The Kansas City Field Guide to Pathology
Ed Friedlander MD
scalpel_blade@yahoo.com

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INTRODUCTION

You see only what you know.-- Goethe

This book was written for students at the University of Health Sciences (now Kansas City University of Medicine and Biosciences) to help them recognize the common pathological lesions. Our students receive the D.O. degree. D.O.'s can do the same things as M.D.'s under the laws of all fifty states. Traditionally, D.O.'s focus on musculoskeletal problems and on primary care services.

The book's sequence follows the traditional order for the introductory pathology course. It was intended to save time for our students, so they would have more time to spend on the most important content of pathology -- understanding why things happen, and why specimens appear as they do.

No matter what your own school is like, the author knows that your faculty wants you to be actively involved in learning. Students are not sponges (to soak up content without thinking) or parrots (to mouth words without understanding). Students are sharks, and it's our job to bloody the waters. Hence this book -- so that you won't ever need to feel lost or helpless, but can get right into the feeding frenzy. Oh by the way, don't get behind in your study of pathology.

Obviously, this book is no substitute for your own hospital or classroom pathologist! The sequence is traditional for a pathology course; hence, there is no table of contents. But notice that this book has an index, which should come in especially handy if you are using it in conjunction with a videodisc guide.

Don't study this too hard. Use it, review it, and enjoy it!

* * *

ABOUT THE AUTHOR

The author is Chairman of the Dept. of Pathology at the Kansas CIty University of Medicine and Biosciences, the osteopathic medical school in Kansas City, Missouri. He is board-certified in anatomic and clinical pathology, and focuses on undergraduate medical education and autopsy pathology.

In his spare time, he enjoys advising the local chapter of the Lambda Chi Alpha general social fraternity, reading the classics, playing keyboard, singing psalms with the brothers, writing for children, and jumping out of perfectly good airplanes. He has no idea whether he is related to the real Dr. Friedlander, 19th century pathologist Carl who discovered "Friedlander's bacillus".

Comments, suggestions, and corrections for this little book are welcome. So are friendly calls. Phone the author at 816-283-2208.


Edward R. Friedlander, M.D.
Chairman, Dept. of Pathology
University of Health Sciences
1750 Independence Blvd.
Kansas City, Missouri 64124

First Edition -- 1993 Instructions: This will get you on the right track most of the time when you are dealing with biopsy or autopsy microscopic slides.

START:

    Can you recognize the organ from your "Histology" class?
        Yes:
          Go to 15
        No:
          Go to 2

2:
    Can't identify organ: Tumor, granuloma, necrosis
      Is this a granuloma?
        Yes: Go to 3
        No: Go to 9

3:
    Granuloma
      Is there also necrosis?
        Yes:
          Go to 4
        No:
          Go to 8

4:
    Necrotizing granuloma
      Which kind of necrosis?
        Caseous:
            Go to 5
        Suppuration:
          Go to 6
        Coagulation:
          Go to 7

5:
    Caseating granuloma
      Consider TB, DEEP FUNGUS, WEGENER'S.

6:
    Suppurating granuloma
      Consider
        LYMPHOGRANULOMA VENEREUM, PLAGUE, CAT SCRATCH, GLANDERS, YERSINIA, LISTERIA, BRUCELLA, TULAREMIA

7:
    Coagulation necrosis in granuloma
      Consider SYPHILITIC GUMMA

8:
    Non-necrotizing granuloma
      Consider FOREIGN BODY REACTION, SARCOIDOSIS, BERYLLIOSIS

9:
    No identifiable organ, no granuloma
      Is this bone marrow packed with living, non-cohesive cells?
        Yes:
          LEUKEMIA / PLASMA CELL MYELOMA
        No:
          Go to 10

10:
    No identifiable organ, no granuloma, not leukemia-myeloma
      Does this lesion appear solid, i.e., are the cells cohesive?
        Yes:
          Go to 12
        No:
          Go to 11

11:
    Liquefaction or caseous necrosis
      Is this...
        Fluid in brain with lipid-laden macrophages:
          CEREBRAL INFARCT OR CEREBRAL TRAUMA
        Fibrin and debris with abundant neutrophils:
          PUS (think first of classic BACTERIAL INFECTION)
        Crumbly remnants of cells
          CASEOUS NECROSIS (think first of TB, DEEP FUNGI)

12:
    Solid tumor
      Do you see bizarre cells, cells arranged topsy-turvy, cells with large hyperchromatic nuclei, non-lymphoid cells with very little cytoplasm, several mitotic figures, a bizarre mitotic figure, hemorrhage, necrosis, and/or invasion of surrounding normal tissue?
        Yes:
          Go to 13
        No:
          Go to 14

13:
    Cancer
      Do you see...
        Round, not-very-cohesive cells with lymphocyte markers:
          MALIGNANT NON-HODGKIN'S LYMPHOMA
        Bizarre individual "Reed-Sternberg" cells in a background of normal white cells:
          HODGKIN'S DISEASE
        Cells containing melanin and positive for S-100:
          MALIGNANT MELANOMA
        Papillae (not on urothelium) and/or cells making glands and/or positive for mucin and/or positive for CEA:
          ADENOCARCINOMA
        Cells forming pearls and/or keratin and/or showing desmosomes and/or tonofilaments
          SQUAMOUS CELL CARCINOMA
        Papillae on the urothelium, or bizarre urothelium:
          TRANSITIONAL CELL CARCINOMA
        Cells about 15-20 microns across, with very little cytoplasm:
          MALIGNANT LYMPHOMA, EWING'S SARCOMA, MEDULLOBLASTOMA, ALVEOLAR RHABDOMYOSARCOMA, OAT CELL CARCINOMA, NEUROBLASTOMA
        Cytotrophoblast plus syncytiotrophoblast:
          CHORIOCARCINOMA
        Cancer cells making cartilage or osteoid, bizarre spindle cells, bizarre fat cells, bizarre muscle cells, or bizarre vessels:
          SARCOMA
        Something else:
          Take your cue from the cells at the site of origin.

14:
    Benign tumor or carcinoid
      Identify any benign tumor by the feature most closely resembling something from your "Histology" course.

15:
    Recognizable organ
      Is this a bit of some normal organ but in the wrong place?
        CHORISTOMA ("ECTOPIA")
      Is this the proper tissues of the organ sampled, but in the wrong mix?
        HAMARTOMA
      Is there a granuloma? Go to 3
      None of the above: Go to 16

16:
    Inflammatory, infectious, birth defect, metabolic, or degenerative
      Do you see abundant inflammatory cells?
        Yes:
          Go to 17
        No:
          Go to 18

17:
    Inflammation, active
      Do you see a preponderance of:
        Neutrophils:
          ACUTE INFLAMMATION, BACTERIAL INFECTION, IMMUNE VASCULITIS, RECENT INFARCT, ULCER, PSEUDOMEMBRANE
        Eosinophils:
          ALLERGY, WORMS
        Lymphocytes:
          VIRUS, RICKETTSIA, CELL-MEDIATED IMMUNE INJURY
        Plasma cells:
          SYPHILIS, LYME DISEASE
        Macrophages:
          TYPHOID, TB, DEEP FUNGI
        Fibroblasts, angioblasts, macrophages:
          GRANULATION TISSUE

18:
    Non-inflammatory, non-neoplastic
      Look for:
        Cell ghosts, crumbly:
          CASEOUS NECROSIS (TB, DEEP FUNGI, ETC.)
        Cell ghosts, solid:
          COAGULATION NECROSIS (INFARCT, CANCER, GAS GANGRENE ETC.), APOPTOSIS
        Cholesterol needles:
          ATHEROSCLEROSIS-ATHEROEMBOLI, CASEOUS NECROSIS
        Connective tissue elements separated by fluid: EDEMA
        Damaged elastic in a scarred blood vessel:
          OLD NEUTROPHILIC VASCULITIS
        Dead, calcified fat: ENZYMATIC FAT NECROSIS
        Dense collagen where it doesn't belong:
          OLD SCARRING, FIBROSIS
        Distended business cells: STORAGE DISEASE, FATTY CHANGE
        Fibrin with laminations ("lines of Zahn"):
          PRE-MORTEM THROMBUS
        In a blood vessel but not liquid blood:
          THROMBUS, EMBOLUS (THROMBO-, OTHER), FIBRIN-PLATELET THROMBI (DIC, TTP, ETC.)
        Lipid-laden macrophages:
          LIPID PNEUMONIA, XANTHOMA, DAMAGE IN CNS OR FAT
        "Hyaline":
          alpha-1PI, AMYLOID, BASEMENT MEMBRANE, FIBRIN, FIBRINOID, KELOID, MALLORY'S HYALINE, OSTEOID, RUSSELL BODY, VIRAL INCLUSION
        Hyaline larger vessels, large hyperchromatic nuclei:
          RADIATION INJURY
        Normal mucosa herniating through a weak spot in a wall:
          PSEUDO-DIVERTICULUM
        Pigment:
          CARBON, LIPOFUSCIN, HEMOSIDERIN, MALARIA, MELANIN
        Red cells not in a vessel: HEMORRHAGE
        Too many cells of one kind: HYPERPLASIA
        Too-small cells: ATROPHY

      If you're here and you're still stumped, look for the most distinctive feature on the slide. Usable knowledge comes only from experience. Good luck!
LOOKING AT GROSS ORGANS


Tell me, and I forget.
Show me, and I might remember.
Involve me, and I understand.

    --Teacher's lore


Consistency

Soft:...Like your earlobe.
Firm:...Like your strongest, leanest muscle when you flex it.
Hard:...Like your knuckle.

Remember the normal consistencies of organs, and that fixed organs are harder than unfixed ones.


Color

Red: ...Fresh blood or fresh myoglobin
Red-orange:...Bilirubin; hemosiderin (sometimes)
Orange:...Carotene
Yellow:...Lipid (adipose tissue; adrenal cortex; most necrosis); elastic fibers (vessels; yellow ligaments)
Green:...Biliverdin
Blue:...Something non-white seen through a reflective surface (blood in your veins through your skin; carbon pigment under the pleura; blue iris; cornea in osteogenesis imperfecta).
Purple:... ???
White:...Tumor; granuloma; collagen (fibrous tissue; scar; etc.); calcium flecks
Gray: ...Lung alveolar tissue
Brown:...Feces; hemosiderin; lipofuscin; melanin; cytochromes (as in the liver); formalin-fixed or stale hemoglobin/myoglobin; debris
Black:...Carbon ("anthracotic pigment"); very abundant melanin; homogentisic acid ("alkapton"); formalin-fixed hemoglobin turns dark brown or black

SELECTED CLASSIC STAINS


Hematoxylin and Eosin: Blue : Nucleic acid (DNA, messenger RNA, ribosomes, transfer RNA), bacteria, calcium
...Pink : Protein (arginine and lysine)

Periodic acid - Schiff (PAS): Magenta : Basement membrane, glycogen, mucin, fungus, cartilage, alpha-1PI

Diastase PAS (dPAS): Magenta : Basement membrane, mucin, fungus, cartilage, alpha-1PI; NOT glycogen

Congo red : Brick red with apple green birefringence : All amyloids

Trichrome: Green or blue : Collagen

Reticulin: Black : Reticulin fibers

Alcian blue: Blue : Acid mucopolysaccharide, acid ground substance

Mucicarmine: Purple-pink : Epithelial mucin

Elastic (Verhoeff, van G.): Black : Elastic tissue

Fontana: Black : Melanin

Hydrogen peroxide: Bleached : Melanin

Acid-fast ZN Red : Mycobacteria, nocardia, lead inclusions, ceroid

Prussian blue: Blue : Hemosiderin

Rubeanic acid / rhodanine: Coppery : Copper

Silver: Black : Fungi, bacteria, pneumocystis, argentaffin/argyrophil (depends on the recipe)

Luxol fast blue: Blue : Phospholipid (i.e., myelin)

Oil Red O: Red : Lipid phase, fat, exogenous oils

SELECTED IMMUNE STAINS
"Mud"

Alpha-1 antitrypsin (alpha-1AT = alpha-1PI): Macrophages and their tumors

Alpha-1 antichymotrypsin (à1CT): Macrophages and their tumors

Carcinoembryonic antigen: Adenocarcinomas

CD1 (T6): Dendritic macrophages ("Langerhans histiocytes") and their tumors (i.e., "histiocytosis X")

Cytokeratin (keratin): Almost all epithelial cells and their tumors (adenomas, papillomas, carcinomas); myoepithelial cells and their tumors; meningiomas; embryonal cell carcinomas; mesotheliomas

Desmin: Smooth, skeletal, and cardiac muscle cells and their tumors

Epithelial membrane antigen (EMA): Exocrine glands, exocrine adenocarcinomas; renal cell carcinomas; other things

Factor VIII: Endothelial cells and their tumors

Glial fibrillary acid protein: Glial cells and their tumors; a few others

HMB-45: Malignant melanomas

Leukocyte common antigen (LCA): Lymphocytes and malignant lymphomas, other white cells and some leukemias

Neurofilament protein: Neurons; neuroblastomas; neuroectodermal cells and their tumors

Neuron specific enolase (NSE): Neurons; neuroblastomas; neuroectodermal cells and their tumors

Myoglobin: Skeletal and cardiac muscle cells and their tumors

OC125 (CA125): Serous tumors of the ovary

S100: Glial cells, Schwann cells, Langerhans histiocytes, Schwann cells, melanocytes, chondrocytes, reticulum cells of lymphoid tissue, myoepithelium, salivary gland cells, sweat gland cells, and most tumors derived from any of these.

Ulex lectin: Endothelial cells and their tumors

Vimentin: Most mesenchymal cells and most of their tumors, many other tumors

NOTE: "Not an exact science." Most of these work most of the time.


THE KANSAS CITY FIELD GUIDE TO PATHOLOGY
Edward R. Friedlander M.D.


Does it stain blue with hematoxylin?
Nucleic acid (DNA, messenger RNA, ribosomes, transfer RNA), bacteria, or calcium
Does it stain pink with eosin?
Arginine & lysine (i.e., protein)
Does it stain a gaudy magenta color with PAS (periodic acid- Schiff)?
Basement membrane, glycogen, mucin, fungus, or cartilage
Does it lose its PAS-positivity on treatment with diastase (spit)?
Glycogen
Does it stain brick-red with Congo red, and exhibit the characteristic apple-green birefringence in some direction on polarized light examination?
Amyloid
Does it stain dark blue or dark green on trichrome (Masson / Mallory) stain?
Collagen
Does it stain black on reticulin stain, and does it look like long black threads?
Reticulin
Does it stain purple-pink with the mucicarmine stain?
Epithelial mucin
Does it stain blue with alcian blue?
Acid mucin (i.e., sulfo- or carboxy- mucin), acid ground substance

NOTE: Exactly how the weakly-acidic mucins like carboxymucin stain depends on the recipe used for the stain.

Does it stain red-brown on immunoperoxidase stain, against a pale background?

Does it stain bright green (less often, bright red) on immunofluorescence, against a dark background?

One specific protein, and you must ask which!
Is it dense bone where spongy bone should be?

Is it excess basement membrane material in a vessel wall?

Is it excess basement membrane and/or mesangial matrix in a glomerulus?

Is it an area in the brain where the oligodendroglia have been damaged and have been replaced by astrocytes?

Anywhere else in the body, is it just excess dense collagen?

Sclerosis

Is it a very thick basement membrane anywhere except the bronchial epithelium?
Consider late effect of diabetes
Is it grossly black and obviously gangrenous?

Are the cells intact, but with nuclei that are dark, shrivelled ("pyknosis"), and devoid of chromatin texture?

Are the cells intact, but with nuclei that have broken up into fragments ("karyorrhexis")?

Are the cells intact, but without nuclei at all ("karyolysis"), at least in the business cells (i.e., they are "ghosts")?

Coagulation necrosis

Is it an area of the brain that has softened and melted away after trauma or infarction?

Is it an area in an organ in which something has softened and melted away, maybe from a bacterial infection and/or the action of neutrophils?

Is it pus?

Liquefaction necrosis

Is it myocardial or skeletal muscle cells crossed transversely by hypereosinophilic bands?

Is this perhaps:
...a portion of heart recently infarcted and then re-perfused (calcium influx injury);
...the edge of a muscle biopsy;
...muscle from a child with Duchenne's muscular dystrophy?

Contraction band necrosis
Is it a portion of heart wall that is thinned but still solid, in the distribution of a known artery?

Is it a portion of brain that is swollen or absent, in the distribution of a known artery, or in the watershed areas?

Is it a discrete, wedge-shaped area with its base on the surface, in the lung (bloody), kidney (pale), liver (blue or pale), or spleen (pale)?

Is it a segment of bowel that is dark and engorged with blood?

Is it an area of coagulation necrosis with a sprinkling of neutrophils (alive or dead)?

Infarct

Is it yellow and liquid, like pus?

Is it a free cell with a moderate amount of pinkish-staining cytoplasm, and a segmented live nucleus?

Neutrophils ("PMN's")
Is it a free cell with a bilobate nucleus and abundant, red- staining granules?
Eosinophil
Is it a free cell in a smear, and does it have deep purple- staining granules concealing an inconspicuous nucleus?
Basophil
Is it a free, living cell with a dark-staining, small round nucleus, and scanty cytoplasm?
Lymphocyte (non-proliferating)
Is it a big, oval, purple free cell with an eccentric nucleus with heterochromatin chunks under the nuclear membrane, and a pale Golgi spot next to the nucleus?
Plasma cell
Is it a free cell about twice the size of an RBC, with a reticulated nucleus bearing a dent?

Is it a free cell in connective tissue that you can tell has eaten something?

Monocyte - macrophage
Is it a cluster of cells with abundant, pink cytoplasm, poorly- defined cytoplasmic boundaries, and elongated, reticulated, indented nuclei, typically lying helter-skelter?

Does it meet the above criteria more or less, and does it contain a Langhans or foreign-body giant cell?

Granuloma

NOTE: The "gestalt" is purple rice-krispies spilled on a frayed pink tablecloth.

Is it neutrophils plus cell debris, and does it appear to be liquid?
Pus
Is it pus in a confined space, its wall red (gross) and/or composed of granulation tissue (micro)?


Abscess
Is it flecks of whitish-yellow dead material all over the peritoneal surfaces?

Is it basophilic (i.e., calcium-rich) acellular debris with identifiable remnants of fat cells?

Fat necrosis
Is it obviously-dead, finely-granular, crumbly-looking material?
Caseous necrosis
Is it caseous necrosis with a granuloma?

And do you perhaps have some reason to believe it is tuberculosis, histoplasmosis, blastomycosis, or coccidioidomycosis?

Caseating granuloma
Is it a granuloma with coagulation necrosis, with other evidence of syphilis?
Gumma
Is it a bodybuilder's skeletal muscles?

Is it the heart muscle of an aerobic athlete, or a patient with systemic hypertension?

Is it heart muscle from a patient with aortic stenosis or insufficiency, or mitral insufficiency?

Is it the right ventricle of a patient with longstanding increased pulmonary vascular resistance?
Is it a section showing myocardial cell nuclei that are clearly more than twice as large as the nearby endothelial cells, with squared-off ends ("boxcars")?

Hypertrophy

Is it a proliferation of normal-appearing cells, more than expected in the normal organ, and the inciting agent makes sense physiologically?
Hyperplasia
Is it wasted muscles from someone with nervous system disease, undernutrition, or disuse?

Is it the adrenal cortex of someone on exogenous steroids, or with anterior pituitary insufficiency?

Is it a brain with wide sulci and deep gyri?

Atrophy

Is it a large airway or endocervix with stratified squamous epithelium, without bizarre cellular features?

Is it bone in a scar?

Is it bone in an otherwise-normal cartilage?

Is it some other adult tissue transformed into a different adult tissue?

Metaplasia
Is it an epithelium with bizarre cells, scrambled architecture, mitotic figures off the basement membrane, and/or failure of maturation?
Dysplasia / carcinoma in situ
Are the business cells of the organ unusually basophilic, with large, euchromatin-rich nuclei, and large, round nucleoli?
Regeneration / repair

Is it a V-shaped white depression in the spleen or kidney?

Is it a V-shaped scar with its base against the visceral pleura?

Is it a sharply-circumscribed, liquified area of brain without inflammation or granulation tissue?

Is it a white scar running deep through a portion of myocardium?

Is it patchy fibrosis involving the subendocardial region of the heart?

Healed infarct

Is it bright red and looks like it really hurts?

Are there dilated arteries with lots of neutrophils, especially pavementing neutrophils?

Are there neutrophils in the tissue, outside the blood vessels? (This almost always means acute inflammation.)

Acute inflammation

Is it a granuloma without any visible necrosis, and no large foreign body?

Is there perhaps a strong clinical hint that it is sarcoidosis or berylliosis or zirconium disease ("armpit sarcoid", etc.)?

Non-caseating granuloma
Is it a giant cell with all nuclei located peripherally?
Langhans giant cell
Is it a giant cell with nuclei located more or less randomly throughout the cytoplasm?
Foreign-body giant cell
Does it look like a pink star in a clear, round space, inside a giant cell?
Asteroid body
Is it a calcified, laminated chunk inside a giant cell?
Schaumann body
Is it a ball of concentrically-laden collagen, with or without a caseating center, in a place suspicious for an infectious granuloma (i.e., lung, hilar node, spleen, liver?)
Healed granuloma

Is it a mix of pus and granuloma in the lung, with chunks of stuff that doesn't look like anything from "Histology"?
Aspiration pneumonia
Is it a portion of a normal body surface which has undergone necrosis and sloughed, with loss of both epithelium and at least some of the underlying connective tissue? Is there now a crater filled with fibrin and necrotic debris?
Ulcer
Is it a portion of colon that appears to have sticky green mustard painted over much of its mucosa?

Is it a portion of colonic mucosa with patchy necrosis of its upper half, these areas being covered with tufts of fibrin and debris?

Pseudomembranous enterocolitis
Is it a portion of airway covered with a pseudomembrane?

Is it a yellow heart with fatty change in each myocardial cell?

Diphtheria

Is it a fibrin meshwork with a few, active-looking spindle cells entering it?

Is it a mix of fibrin and spindle-shaped cells, perhaps with some remaining debris?

Is it a mix of spindle-shaped cells and small blood vessels with walls made of simple cuboidal epithelium?

Is it edematous tissue with prominent blood vessels and relatively little collagen or other recognizable features?

Is it fairly well-organized connective tissue with less collagen than you would expect, and more blood vessels?

Granulation tissue

Is it a nice, clean, neatly-sutured healing wound?
Healing by primary intention
Is it a healing wound that isn't nice, clean, and neatly-sutured?
Healing by secondary intention
Is it a large, yellow liver without other pathology?

Is it a liver with one or more oil-drops in most of the cells?

Is it a tiger-striped heart from a patient with extreme anemia?

Is it a heart that is almost entirely yellow? (Do you perhaps know the patient had diphtheria?)

Fatty change

Is it clear, needle-shaped spaces, tending to orient parallel?
Cholesterol crystals

Are they cholesterol crystals within the intima of a blood vessel?

Is it the intima of an artery with unwholesome-looking yellow stuff?

Atherosclerosis

NOTE: More about this later!

Are they cholesterol crystals free in the lumen of an artery, with or without a foreign-body reaction?
Atheroembolization
Is it a yellow nodule around the eyes, or on an extensor surface or elsewhere?

Is it composed of many foamy macrophages stuck tightly together?

Xanthoma

Is it fat cells between normal-appearing cardiac muscle fibers?

Is it real fat in a lymph node, pancreas, or other organ?

Fatty ingrowth
Is it liver, and do the nuclei appear to have pale white centers?
Glycogenosis of nuclei
Is it white and crystalline, and in the joint, kidney, or pinna of a person with gout?
Uric acid
Is it white and crystalline, and in the small pulmonary arteries and capillaries?
IV drug abuser (talc, pill-filler)
Are they red inclusions in the nuclei of proximal tubular cells, with a history suggestive of heavy-metal poisoning?
Lead / bismuth inclusions

Is it a yellow person with kidney failure?
Urochrome pigment
Is it a yellow person with hemolysis, liver cell disease, and/or blocked bile ducts?
Jaundice
Is it a yellow person whose palms and soles are the most yellow?
Carrot eater ("carotenemia")
Is it black pigment in the lung, or in a jailhouse tattoo?
Carbon pigment
Is it brown pigment at the poles of cardiac nuclei?

Is it a tiny, brown heart?

Is it brown pigment in a "tortoiseshell colon" (melanosis coli)?

Is it brown pigment in the liver cells in Dubin-Johnson syndrome?

Lipofuscin

Is it lipofuscin and also acid-fast?
Ceroid
Is it brown pigment in the basal layer of the dermis?

Is it brown pigment in macrophages, not hemosiderin, in or near with a pigmented skin lesion?

Is it a dark-brown or black nodule on the skin?

Does it bleach on exposure to hydrogen peroxide?

Does it stain black with the "Fontana" stain for melanin?

Melanin

Is it brown pigment at the site of repetitive trauma, or near a piece of shrapnel?

Is it a rusty-brown, cirrhotic liver?

Is there a history of hemochromatosis or multiple blood transfusions for aplastic anemia?

Does it look like barbells in a microscopic view of lung, i.e., is it covering an asbestos fiber?

Does it stain blue (gross or microscopic) with ferrocyanate ("Prussian Blue")?

Hemosiderin

Is it black cartilage?
Alkaptonuria / ochronosis
Is it gray matter in the brain, and is it yellow?
Kernicterus
Is it calcified, and is it a scar, caseous necrosis, a dead worm, an old granuloma, tissue with scleroderma or a scleroderma variant, a deformed cardiac valve, an old blood vessel, an atherosclerotic plaque, a Schaumann body, old fat necrosis, old cartilage, pseudogout, malakoplakia, or a papillary tumor with psammoma bodies?
Dystrophic calcification

Is it calcified, and is it still the normal shape from "Histology", and is it lung, renal tubular basement membrane, gastric fundus basement membrane, or the internal elastic membrane of a small blood vessel?
Metastatic calcification

Is it pink-staining, without an internal structure that is visible on light microscopy?
"Hyaline"
Is it hyaline, and is it a perfect sphere in or near a plasma cell?
Russell body
Is it hyaline, not inflamed, not necrotic, and is it the wall of an arteriole? Is there perhaps a history of benign high blood pressure and/or diabetes?
Hyaline arteriolar sclerosis

Is it hyaline, and is it in the nucleus of a cell, and is it surrounded by a clear zone?
Probably a DNA-virus inclusion ("Cowdry A inclusion")
Is it hyaline, and spherical, and in the cytoplasm of a non-pigmented neuron?
Negri body of rabies
Is it hyaline, and irregularly shaped, and inside a liver cell?
Mallory's alcoholic hyaline
Is it an extremely hard scar with a smooth, elevated surface?

Is it collagen in a scar that is so densely woven that it appears hyaline?

Keloid
Is it large round masses of hyaline basement-membrane material in a glomerulus?
Nodular diabetic glomerulosclerosis
Is it amyloid, and does it lose its congophilia on treatment with potassium permanganate?
Amyloid A ("amyloid AA")
Is it the solid, sealant material that forms the framework of a scab?

Is it a shaggy meshwork of threads, like spider web, at a site of tissue injury?

Is it masses of hyaline material, perhaps with cells invading and devouring it, at a site of tissue injury?

Is it the crusty stuff on a mat burn or other very superficial abrasion of the skin?

Is it masses of hyaline material in granulation tissue?

Is it the non-cellular, solid component of a blood clot?

Is it "hyaline membranes" lining the small air spaces of injured lung?

Is it shaggy stuff hanging off the external surface of the heart?

Is it sticky stuff "loculating" an accumulation of inflammatory fluid?

Fibrin

Is it shaggy, sticky material binding together two internal surfaces, but easily broken with a finger?
Fibrinous adhesions

Is it dense scar or string-like white cords binding together two internal surfaces, too tough to break with a finger?
Fibrous adhesions

Is it fluid that is visible grossly, but is not apparent microscopically?

Is it an effusion, and the principal diagnosis cirrhosis, congestive heart failure, nephrotic syndrome, or protein malnutrition?

Is it an effusion with a relatively low specific gravity and protein content?

Transudate
Is it fluid that persists as pink-staining material in a section after processing?

Is it free fluid from cancer or inflammation?

Is it an effusion with a relatively high specific gravity and protein content?

Exudate
Is it edema most severe around the ankles?
Cardiac edema
Is it edema most severe around the eyes?
Renal edema
Is it edema of an extremity or the genitals, often with roughening of the skin, after surgery, cancer, or filariasis has obliterated lymphatic channels?
Lymphatic obstruction
Is it a brain with flattened gyri and narrow sulci?
Cerebral edema
Is it red blood cells not in a vessel?
Hemorrhage
Is it a hemorrhage in the tissues, under 3 mm?
Petechia
Is it a hemorrhage in the tissues, over 3 mm?
Purpura / Ecchymosis
Is it a hemorrhage in the tissues resulting from trauma?
Contusion / bruise / ecchymosis
Is it a palpable mass of blood outside the vessels?
Hematoma
Is it a red, throbbing organ?
Hyperemia
Is it a blue, non-throbbing, blood-filled organ?

Is it a "nutmeg liver"?

Has something occluded the venous drainage?

Is the heart unable to pump enough blood out of the organ?

Congestion

Is it an artery with several small lumens instead of one large one?
Recanalized thrombus
Is it a mass of blood with lines of Zahn?
Ante-mortem thrombus
Is it blood in a vessel or elsewhere, and it has separated into one layer each of "chicken fat" and "current jelly"?

Are all the RBC's on one side of the lumen, with a meniscus?

Post-mortem thrombus
Is it a mass of fat, with or without marrow, in a pulmonary or other artery?

Is it a brain with lots of petechiae distributed throughout the white matter?

Fat embolus / bone marrow embolus
Is it a mass of squamous cells in a pulmonary artery?
Amniotic fluid embolus
Is it an artery with pink stuff in its media, with abundant inflammatory cells?
Probably type III immune injury; if living bacteria are present, consider mycotic aneurysm
Is it an artery with pink stuff in its media, with scanty inflammatory cells, but with other evidence of recent injury such as necrosis and/or intimal swelling?
Malignant hypertension or radiation injury
Is it sections of artery, not in the lung, with type III immune injury lesions of different ages (acute, chronic, healed)?
Probably polyarteritis nodosa; rule out lupus, etc.
Is it an artery with fibrosis and large discontinuities in the elastica?
Probably old healed type III immune injury

Less likely: Old healed bacterial vasculitis ("mycotic aneurysm"), old trauma

Is it an artery in the head, throat, ear (any portion), nose, lung, kidney, or elsewhere, with evidence of both type III and type IV injury?

Is it a patient with several of the following:
...autoantibodies against proteinase 3 (anti-neutrophil cytoplasmic antibodies);
...hemoptysis and/or a lung cavity;
...unexplained ear, eye, nose, and/or joint problems;
...hematuria and/or azotemia; segmental necrotizing glomerular disease on biopsy?

Wegener's granulomatosis

NOTE: Miss it and the patient dies. Make the diagnosis and treatment is relatively easy and very effective.

Is it an amyloid spleen with most of the amyloid in the white pulp?
Sago spleen
Is it an amyloid spleen with most of the amyloid in the red pulp?
Lardaceous spleen
Is it a butterfly rash on the face?
Lupus or dermatomyositis or acne rosacea
Is it an immunofluorescence photo with green granules along the basement membrane of the skin?

Is it an immunofluorescence photo with all different kinds of green chunks in a glomerulus?

Is there impressive fibrous onion-skinning of the adventitia of the splenic arterioles?

Lupus
Is it a photomicrograph of muscle, with atrophy of the cells worst at the edges of the bundles?

Are there purple pads on the knuckles?

Does the patient perhaps have an autoantibody (anti-Jo, etc.) against a transfer RNA synthetase?

Polymyositis / dermatomyositis

Are there lymphocytes wrecking havoc on the salivary or lacrimal glands?
Sjogren's syndrome
Is his or her face so stiff that a smile is impossible?

Does some other part of the skin look like thick, smooth linoleum?

Is the skin smooth and shiny, with telangiectasias?

Is it a skin biopsy with thinning of the epidermis, flattening of the dermal-epidermal junction, and very dense collagenization of the dermis, in the absence of a history of exposure to radiation?

Does the patient perhaps have an autoantibody (anti-Scl-70, etc.) against topoisomerase and/or a nucleolar anti-nuclear antibody pattern?

Scleroderma or morphea
Is there dystrophic calcification of the finger pads?

Is the esophagus fibrotic and inflexible along its length?

Are there only a few big blood vessels in the nail bed, instead of lots of little ones?

Scleroderma or CREST

Is this a newborn with tetany and immunodeficiency, hypoplastic or absent thymus, few or no T-cells, absent parathyroids, and perhaps also a cleft palate, a cardiac septal defect, and/or some other midline deformity?
DiGeorge's thymic hypoplasia
Is it a brain disease with lots of microglial cells and multinucleate cells?
AIDS encephalopathy
Is it a silver stain of lung, showing silver-positive organisms in the alveoli, looking like squashed ping-pong balls?

Is it an H&E stain of lung, showing pink froth in the alveoli, and no inflammatory reaction?

Is it a Giemsa stain of lung washings, showing cysts with eight little round creatures in them?

Pneumocystosis

Is it brown spots from the skin of someone with AIDS or a transplant?

Is the histopathology something in a range from granulation tissue to a vascular spindle-cell sarcoma, but it either
...comes from an AIDS patient, a transplant patient, or a person from Africa;
...is multiple brown spots on the legs of an older person?

Kaposi's sarcoma

Is it a tumor of small blue cells from an AIDS patient?
Lymphoma

Is it a gross lesion that is round like a ball, and isn't anywhere in your "Gross Anatomy" book?

Is it an orderly group of euploid-looking cells, but in a place or arrangement not in your "Histology" book?

Benign tumor (or maybe a choristoma or a hamartoma or a carcinoid)
Is it a cauliflower-shaped growth?

Is it an ulcer formed by necrosis of a cauliflower-shaped growth?

Is the growth (grossly or microscopically) extending tentacles into the surrounding healthy tissue?

Are its cells bizarre and/or variably-sized?

Is the nuclear-cytoplasmic ratio higher than you would expect for it tissue?

Are there lots of mitotic figures where you don't expect them?

Are the cells arranged helter-skelter, and it is more than just an intra-epithelial process?

Is there a tripolar mitosis, or some other really bizarre mitotic figure?

Is it a tumor with hemorrhage and/or necrosis, grossly or microscopically?

Is it a tumor that has metastasized?

Cancer

Is it a benign tumor making glands?
Adenoma
Is it a benign tumor composed of a fibrous stalk, like the trunk of a tree, surrounded by benign cells, like the leaves of a tree?
Papilloma (papillary adenoma)
Is it a cancer with singly keratinized (i.e., orange-staining, glassy- looking on H&E) cells?

Is it a cancer in which it is easy to see desmosomes (i.e., "prickles") between the cells?

Is it a cancer making "pearls" (i.e., poor attempts to make hairs)?

Is it a cancer with cells seen on electron microscopy to be packed with tonofilaments?

Squamous cell carcinoma

Is it a cancer making glands?

Is it a cancer making inside-out glands (i.e., does it exhibit a papillary growth pattern)?

Is it a cancer that stains positive for epithelial mucin (i.e., mucicarmine positive)?

Is it a cancer that stains positive for CEA (carcinoembryonic antigen) and/or EMA (epithelial membrane antigen)?

Adenocarcinoma

NOTE: Biphasic, mixed adenocarcinoma-and-spindle-cell tumor? Think of mesothelioma or synovial sarcoma

Is it a round, apparently well-circumcised tumor, arising where there is endoderm, with a white or yellow color on cross-section?

In addition to the above, are the cells benign-appearing and uniform, making nests, ribbons, or little gland-like structures?

In addition, does it show neurosecretory granules on electron microscopy?

Does the patient perhaps have:
...carcinoid syndrome (paroxysms of wheezing, flushing, and/or diarrhea);
...problems with the valves on the right side of the heart, and/or
...elevated urinary 5-hydroxy indoleacetic acid?

Does the tumor perhaps take the argentaffin and/or argyrophil silver stains?

Carcinoid tumor
Is it a cancer composed of cells with very scanty cytoplasm?
"Malignant tumor of small blue cells" / "LEMON tumor"

Consider:
Lymphoma
Ewing's sarcoma
Medulloblastoma / Muscle sarcoma ("alveolar rhabdomyosarcoma")
Oat cell carcinoma
Neuroblastoma

Is it individual cancer cells invading the epidermis?
Paget's disease or malignant melanoma

NOTE: Paget's disease cells usually stain positive for CEA and/or mucin. Melanoma cells usually show melanin and/or S100 staining.

NOTE: "Paget's disease of bone" / "osteitis deformans" is a different entity.

Is it respiratory epithelium bearing "smudge cells", epithelial cells with large, homogenized nuclei?
Adenovirus pneumonitis
Is it respiratory epithelium with prominent multinucleated cells which are clearly of epithelial origin?
Respiratory syncytial virus

Is it a white Koplik's spot by the duct from the parotid gland?

Is it a multinucleated giant cell bearing large, herpes-like intranuclear inclusions?

Measles

Is it skin vesicles, each bearing a central dimple, all of nearly- identical age and appearance?

Is it vesicle fluid with cells bearing large intracytoplasmic inclusions ("Guarneri bodies")?

Smallpox
Is it a group of little blisters on the lip, hand, or genitals, or along a dermatome?

Is it an acute vesicular eruption over most of the skin, with lesions of different ages?

Is it a cell from a necrotizing lesion with one or several pale, very swollen nuclei, each bearing a large, eosinophilic intranuclear inclusion?

Herpes (simplex / zoster)

Varicella ("chickenpox"), shingles, and fever blisters should be familiar to you.

Is it a very large cell, with a very large nucleus bearing a single very large inclusion? Are there perhaps also many small, hard-to-see intracytoplasmic inclusions?
Cytomegalovirus (CMV)
Is it liver with little inflammatory infiltrate, and necrosis primarily in the mid-zonal areas?
Yellow fever
Is it a cell from the cornea with many small intracytoplasmic bodies?

Is it a urethral discharge in a man without gonorrhea or trichomonas or a jalape¤o habit?

Chlamydia
Is it a tiny bacterium in an endothelial and/or capillary smooth muscle cell?

Is it a severe vasculitis involving capillaries, with necrosis of endothelial cells?

Rickettsial disease

(Organisms also in smooth muscle: RMSF)

Is it stellate microabscesses with some granuloma formation, in lymphoid tissue?
Lymphogranuloma venereum,
cat scratch fever, brucellosis, plague, tularemia,
glanders,
melioidosis, listeria, or yersinia infection
Is it a blood cell, about 15-25 microns across, with a reticulated nucleus and abundant, pale-gray staining, vacuolated cytoplasm?
Atypical lymphocyte of infectious mononucleosis, etc. (activated T- cell, "virocyte")
Is it large gram-positive cocci in clusters?
Staphylococci
Is it large gram-positive cocci in chains?
Streptococci
Is it pairs of slightly-elongated, gram-positive cocci, joined at their poles, usually encapsulated?
Pneumococci (Streptococcus pneumoniae)
Is it pairs of small gram-negative cocci, typically inside neutrophils?
Neisseria (i.e., gonococci or meningococci)
Is it tiny bacilli that needed to be stained with silver for photography?
Cat scratch fever or Legionnaire's disease
Is it a mix of various shaped bacteria, mostly gram-negative?
Anaerobes
Is it a gram-negative rod attached firmly to the respiratory mucosa, but without invasion?
Whooping cough
Is it a wiggly-looking, gram-negative rod, seen best on Giemsa or silver stain, in an "upset stomach" or a gastric or duodenal ulcer crater?
Helicobacter
Are all of his or her muscles maximally tensed, bent into opisthotonos, with a "sardonic smile" of lockjaw?
Tetanus
Is it a rapidly-spreading, necrotizing process without inflammation but with gas formation? Are there large, gram-positive bacilli here?
Gas gangrene
Is it a systemic infection or serious lung infection caused by gram- positive bacilli in a person who contacted infected wool?

Is there a blackened eschar where the person contacted wool?

Anthrax
Is there an ulcer where the person touched a sick rabbit?
Tularemia
Is it a tiny gram-negative coccobacillus in a person with fever of unknown origin and a history of exposure to livestock?
Brucellosis
Is it a necrotizing, suppurative lymph node infection with rapidly- progressing, severe systemic complaints?
Plague
Is it an infection by a spiral organism?
Syphilis, relapsing fever, Helicobacter, Lyme disease, rat-bite fever (Spirillum)
Is it a painless, indurated ulcer on the genitals, mouth, or anus? Does the darkfield view perhaps show syphilis spirochetes?
Chancre of primary syphilis
Is it a widespread rash that involves the palms and soles?
Syphilis, RMSF, Kawasaki's mucocutaneous lymph node syndrome, toxic- shock / scalded skin syndromes
Is it a necrotizing lesion centered on the periosteum?
Is it a granuloma with a center containing coagulation necrosis and/or with other evidence of tertiary syphilis?

Is it demyelinated posterior columns in the absence of cobalamin deficiency?

Is it a dilated proximal aorta without severe atherosclerosis, or with a tree-bark intima?

Is it an atrophic brain without evidence of Alzheimer's or other idiopathic neuro-degenerative disease? Are the meninges perhaps also opalescent?

Tertiary syphilis
Was it person born with a collapsed nose, or Hutchinson teeth, or mulberry molars, or a rash on palms and soles, or rhagades?
Congenital syphilis
Is it a vasculitis with endothelial cell swelling and a predominantly plasmacytic perivascular infiltrate?
Syphilis, any stage
Is it a spreading, ring-like erythematous rash, perhaps relapsing, around a site of a (remembered or forgotten) tick bite?
Lyme disease, primary ("erythema chronicum migrans")
Is this a patient with some or all of the following:
..."arthritis";
...cranial nerve palsies;
...non-suppurative meningitis;
...encephalitis;
...myocarditis;
...stillbirth?
And do the lesions show inflammation with an infiltrate mostly of lymphocytes and (especially) plasma cells? And is serology positive for Lyme disease? And is there perhaps a history of tick bite?
Lyme disease, secondary / tertiary
Is it a caseating granuloma without visible organisms on H&E even if you look very carefully?

Is it caseous necrosis without visible organisms on H&E, especially if there is nothing to suggest Wegener's?

Is it a necrotizing lesion with acid-fast bacilli, especially if they appear beaded?

Tuberculosis
Does he or she have the typical leonine facies?

Does he or she have a neuropathy and/or erythema nodosum, plus an infiltrate of macrophages bearing bacilli?

Is it a plaque on the skin, bearing macrophage-laden bacilli?

Leprosy
NOTE: Pathology varies tremendously depending on how good the person's immune response is.
Is it weakly acid-fast filamentous bacteria in a lung infection?

Is it weakly acid-fast bacteria in a mutilating, chronic foot infection in a poverty victim?

Nocardiosis
Is it a colony of "ray fungi", i.e., a sulfur granule, in a tonsillar crypt or surrounded by pus?
Actinomycosis
Is it pseudohyphae, considerably larger than bacteria, that bud but do not branch? Does it look like toy balloon animals?

Is it oral, cutaneous, esophageal, or genital thrush, i.e., uncomfortable white patches that scrape off easily?

Candida
Is it a mold with 45ø angle branching, septate hyphae, and perhaps even a fruiting body?

Is it a brown ball in a lung cavity?

Aspergillus
Is it a mold with broad, nonseptate hyphae, branching at 90ø angles, typically invading a blood vessel?
Mucor (Rhizopus, others)
Is it 2-4 micron yeasts, some perhaps budding, perhaps with shrinkage artifact creating the illusion of a "capsule", and typically inside a living macrophage?
Histoplasmosis
Is it a thick-walled, large (maybe 25 micron) yeast with broad-based single buds?
North American blastomycosis
Is it a large yeast with many buds?
South American blastomycosis (Para-coccidioidomycosis)
Is it a 5-10 micron yeast with a large polysaccharide capsule and perhaps one narrow-based bud, typically in a very immunosuppressed person and with no inflammation?
Cryptococcus
Is it a large, dPAS-positive cell in fibrin or an ulcer in the gut, often with erythrophagocytosis?

Is it flask-shaped ulcers in the colon, with their bases on the muscularis mucosa, with organisms as above?

Is it a mass of granulation tissue in the cecum, with organisms as above?

Is it spreading necrosis of the liver, with minimal inflammation, with organisms as above?

Amebiasis

Is it a crescent-shaped creature on the brush-border of the bowel, in a section?

Is it the familiar "friendly ghost face" in a smear?

Giardia
Is it tiny, hematoxyphilic, acid-fast spherules living in the brush border of the gut?
Cryptosporidiosis
Is it a tumbling, pear-shaped protozoan with flagella and a fin-like structure, in a vaginal swab or prostatic fluid?
Trichomonas
Is it a parasite in an RBC?
Malaria or babesiosis
Is it wavy trypanosomes in the blood?

Is it a trypanosomal disease primarily with an encephalopathy?

African sleeping sickness
Is it C-shaped trypanosomes in the blood?

Is it a trypanosomal disease with the chief problem weakness of the esophagus, colon, bladder, or heart?

Chagas's disease ("American trypanosomiasis")
Is it protozoans growing inside the cells of eye, brain, heart, or lymphoid tissue?
Toxoplasmosis
Is it a worm that looks like a very long piece of macaroni?
Ascaris
Is it a little worm that lays its eggs on the anoderm?
Pinworm
Is it a little worm with vicious fangs chomping on the duodenum? Is the patient perhaps iron-deficient and/or shoeless?
Hookworm
Is it a large worm in a contemporary American?
Consider Strongyloides
Is it a large worm encysted beneath the skin?

Is your instructor grinning as if he or she is about to explain the origin of the medical caduceus?

Guinea worm ("Dracunculus")

Is it a baby worm coiled in a little shell in muscle or brain?
Trichina
Is it a worm in the blood or a lymph node of a person with elephantiasis?
Microfilariasis
Is it a calcified, mummified baby tapeworm that made it to the brain to die?
Cysticercosis
Is it a cyst full of thousands of baby tapeworms, in the lung, liver, or spleen?
Echinococcus (hydatid cyst)
Is it a fluke in the bile duct?
Clonorchiasis or fasciolopsiasis
Is it the lung fluke?
Paragonimiasis
Is it a dead, calcified worm in a lung?
Dirofilaria
Is it a mated pair of worms in a vein?
Schistosomes
Is it an oval schistosome egg with a large lateral spine?
Schistosoma mansoni egg
Is it an oval schistosome egg with a large terminal spine?
Schistosoma haematobium egg
Is it a round schistosome egg with a small lateral spine?
Schistosoma japonicum egg
Is it non-caseating granulomas without organisms or eggs or foreign bodies visible?
Sarcoidosis or berylliosis or zirconium ("armpit sarcoid") granulomas
Is he or she a child, very malnourished, with extreme tissue wasting, and perhaps with tetany?

Is he or she a malnourished adult with extreme tissue wasting?

Marasmus
Is he or she a malnourished child with ascites, dependent edema, fatty liver, and pigment loss?
Kwashiorkor
Is this a malnourished person's eye with Bitot's spots (debris) and hyperkeratosis of the cornea (xerophthalmia) leading to corneal maceration and ulcers?

Is he or she a malnourished person or patient with malabsorption, now complaining of night blindness?

Is it squamous metaplasia of a gland's duct, or the airways of a non- smoker?

Is it fatal measles pneumonia in a poor child?

Vitamin A (retinoic acid) deficiency
Is it increased CSF pressure in a vitamin faddist or child of a vitamin faddist?

Is he or she a person who is sick after eating polar bear liver?

Is it fatty change confined to the little Ito cells of the liver?

Is it loss of the sebaceous glands or even columnar metaplasia of the epidermis?

Vitamin A (retinoic acid) toxicity
Is there normal osteoid which fails to mineralize?

Is there nodularity of a child's costochondral junctions ("rosary")?

Is there depression of a child's costochondral junctions? Does the child perhaps also have frontal bossing, a square head and/or lumbar lordosis?

Are the legs of a malnourished, dark-skinned or house-bound child bowed?

Are the bones of an older person living on a diet deficient in calcium, or with vitamin D deficiency or resistance, failing to mineralize?

Rickets / vitamin D (cholecalciferol) deficiency / osteomalacia
Is he or she a chronic alcoholic or malnourished adult with ophthalmoplegia and cerebellar ataxia, especially on re-feeding with carbohydrate?

Does he or she have a history of chronic alcoholism or extreme malnutrition? Does the person now "create a personal reality" (i.e., ties a knot in a non-existent string, invents an autobiography)?

Is he or she badly nourished and now in high-output heart failure?

Is he or she a past or present alcohol abuser, or a person with a history of malnutrition, with a peripheral neuropathy in the glove- stocking distribution?

Thiamine (vitamin B1) deficiency (wet or dry beriberi, Wernicke- Korsakoff syndrome)
Is he or she a malnourished person with rhomboid, hyperkeratotic dermatitis, especially where the sun shines or the skin is irritated?

Is he or she a malnourished person with diarrhea and/or dementia and/or "schizophrenia"?

Is he or she a malnourished person eating primarily maize ("corn", "grits", "hominy", etc.)?

Pellagra (niacin deficiency, vitamin B3 deficiency)
Is he or she a person with megaloblastic anemia and nervous system complaints?

Is he or she a person with either of the above, and atrophic gastritis?

Is he or she a person with either of the above, a negative test for syphilis, and demyelinization of the dorsal columns of the spinal cord?

Is he or she a food cultist who will eat nothing of animal origin, ever?

Cobalamin (vitamin B12) deficiency

NOTE: "Pernicious anemia", etc., etc.

Is he or she a malnourished person with severe gum changes?

Is it petechiae around the body hairs, which have become tightly coiled?

Is he or she a malnourished person with a severe hemorrhagic tendency?

Scurvy (vitamin C deficiency)
Is he or she a malnourished person with megaloblastic anemia, with normal cobalamin levels and no nervous system problems?

Is he or she somebody who just plain won't eat those vegetables?

Folic acid deficiency
Is he or she somebody with a hypochromic, microcytic anemia that isn't thalassemia?

Does the peripheral smear show elongated, pale RBC's ("pencil cells")?

Is that somebody a teenaged girl living on junk food, or somebody with a bleeding ulcer or gut cancer or hematuria or hookworm?

Iron deficiency
Is it a lung with extremely abundant black pigment concentrated in nodules around 1-3 mm across?

Is it a cluster of carbon-laden macrophages packing an alveolus adjoining a respiratory bronchiole, without significant fibrosis?

Coal macules (simple coal worker's pneumoconiosis)
Is it "eggshell calcification" in a hilar lymph node?

Is it a lung or mediastinal lymph node that contain many sharply- demarcated, hard white spheres like pearls?

Is it concentrically-layered fibrosis near a respiratory bronchiole, rimmed by macrophages?

Silicosis

Is it rheumatoid nodules in the lung of a person with coal or silica dust exposure?
Caplan's syndrome
Is it a massive, dense, black lesion occupying most or all of one lobe of the lung of a coal worker?
Progressive massive fibrosis
Is it silicosis plus abundant carbon?
Anthracosilicosis
Does it look like a hemosiderin barbell in the lung?

Is it alveolar septa thickened by collagen in a person with a history or other evidence of asbestos exposure?

Is it a dense fibrous plaque on the pleura, especially the parietal pleura?

Is it a malignant mesothelioma?

Asbestos exposure
Is it cherry-red livor mortis in a body not dead from cold exposure or cyanide?

Is it symmetric necrosis of the globus pallidus on either side?

Is it a body found dead in a car in a closed garage, with the ignition on and the gas tank empty?

Is it a body found in a house adjoining such a suicide?

Is it an entire family with ill-defined symptoms including headache, all sick at the same time, and all recovering soon after leaving their house?

Carbon monoxide
Is it birefringent crystals found in the kidney and meninges in a person with profound metabolic acidosis?
Ethylene glycol (antifreeze) poisoning
Is it birefringent crystals in the pulmonary vasculature?
Is he or she a person with many depressed skin craters?

Is he or she a person with many fibrous scars over the veins?

Injected drug abuse

Is it tissue with hyalinized muscular arteries, perhaps with endothelial swelling, together with abnormally large and hyperchromatic nuclei in cells outside the vessels?
Radiation effect
Is it arborizing marks on the skin?

Is it a gray char mark where the skin contacted metal or was grounded?

Is it calcified collagen (not just dystrophic calcification, but electroplating)? Is there perhaps a history of modern style torture?

Electrical burn
Is it fluid in a circular area under a newborn's scalp?
Caput succedaneum

Is it a circular bleed under a newborn's scalp?
Cephalhematoma
Is it a brachial plexus injury, perhaps leading to a withered arm, sustained during birth?
Erb's palsy or Klumpke's palsy
Was it person born with seal limbs (phocomelia)?
Consider thalidomide effect

NOTE: There are other causes.

Is he or she a child with short palpebral fissures, a small maxilla, and mental retardation?
Fetal alcohol syndrome
Are the nose and ears flattened, and the limbs bent out of shape?
Oligohydramnios sequence
Are some or all of the organs in the body backwards (i.e., heart on the right, liver on the left, spleen on the right)?
Situs inversus (complete or partial)

NOTE: Ask about ciliary dyskinesia / Kartagener's!

Is it an atelectatic lung from a newborn, with fibrin lining the respiratory bronchioles?
Hyaline membrane disease (respiratory distress of the newborn)
Is it squames in the alveoli of a baby born alive or dead?
Aspiration of amniotic fluid
Is it many nucleated red cells circulating in the blood of a newborn?
Hemolytic disease of the newborn
Is he or she a child with cataract, mental retardation, and liver problems?

Is it a child's liver with fat-laden hepatocytes arranged like daisy petals, with or without cirrhosis?

Galactosemia (the bad kind)
Is he or she a child with excess salt in the sweat?

Is he or she an older child or teen who has had many bacterial lung infections, perhaps with bronchiectasis, without immotile cilia or defective neutrophils or lymphocytes?

Is he or she an older child with exocrine pancreatic insufficiency, atrophy of the acini, and viscous plugs in the pancreatic ducts?

Is it a man with normal testes but a missing vas deferens? (May be one-dose of the gene.)

Cystic fibrosis ("mucoviscidosis")
Is it the body of a baby, aged 1-11 months, with no internal or external evidence of disease or trauma, no botulism spores in the small bowel, normal sweat glands and coronary arteries, not found face-down on bedding with mouth and nose occluded, and an adequate death scene investigation has been carried out to remove strong suspicion of smothering, shaking, hyperthermia, or murder by insulin, digitalis, or succinylcholine?
Idiopathic sudden infant death syndrome
Is it a tumor on a newborn's sacrum?
Sacrococcygeal teratoma
Is it a swollen mass of lymphatic vessels under a child's chin?
Cystic hygroma
Is he or she a retarded person with several of the following:
...a flat facial profile;
...oblique palpebral fissures;
...a large tongue;
...epicanthic folds;
...hypotonic muscles;
...horizonal palmar creases;
...a bent little finger;
...midline cardiac defects;
...mild hypothyroidism?
Trisomy 21 (Down's syndrome)
Is he or she a profoundly retarded child with several of the following:
...increased muscle tone;
...a small jaw;
...a short sternum;
...index and little fingers overlapping middle and ring fingers;
...rocker-bottom feet?
Trisomy 18 (Edward's syndrome)
Is he or she a retarded child with a small head, tiny eyes, arhinencephaly, polydactyly, and multiple other defects, or at least most of these?

Does the child have only one eye (cyclops), and/or only one cerebral hemisphere (holoprosencephaly)?

Trisomy 13 (Patau's syndrome)
Is he or she a retarded child with a tiny head and who mews like a cat?
5p- (cri du chat)
Is he or she a retarded person with most of these:
...strabismus;
...almond-shaped eye folds;
...a great tendency to overeat and to steal and hide food;
...a gentle demeanor punctuated by violent outbursts?
Prader-Willi syndrome
Is he or she a profoundly retarded person with a large jaw, jerky movements, and who laughs a lot for no apparent reason?
Angelman syndrome
Is he or she a retarded child with a single, very thick eyebrow?
Cornelia de Lange syndrome
Is he a sterile, gentle, smooth man with gynecomastia and long arms and legs?

Is it a section of testis with Sertoli-only tubules (i.e., no trace of spermatogenesis), and an enormous excess of Leydig interstitial cells?

XXY (Klinefelter's syndrome)
Is he a tall, wiry, uncoordinated man with acne and a temper?
Suspect XYY ("super male")
Is she a short woman with a webbed neck, small breasts, a shield- shaped chest, outward-turning elbows, fibrous nubbins ("streak gonads") instead of ovaries, and who has never menstruated?
XO (Turner's syndrome)
Is she a mildly retarded woman whose periods are irregular?
Suspect XXX ("super female")
NOTE: Most XXX's are normal women.
Do you have histologic evidence that he or she has both ovarian and testicular tissue?
True hermaphrodite
Is she apparently a woman, but she has no uterus or cycle, and never develops body hair?
Testicular feminization
Is she a woman with a large clitoris and excessive body hair? And was the clitoris large from birth?
Suspect congenital adrenal hyperplasia (enzyme deficiency) causing virilization
Is he or she a tall, light-boned person with some of:
...arm span greater than height;
...aortic dissection;
...pectus excavatum;
...displacement of the lens of the eye;
...hyper-extensible joints;
...mitral valve prolapse?
Marfan's syndrome
Is he or she a person with six or more smooth-edged caf‚-au-lait spots?

Is he or she a person with two or more neurofibromas or acoustic neuromas?

Is he or she a person with elephant-like skin overlying a neurofibroma?

Neurofibromatosis (von Recklinghausen's disease)
Is he or she a person with several of the following:
...ash-leaf poorly-pigmented spots on the skin, with long axis parallel to the dermatomes;
..."adenoma sebaceum" fibrous bumps on nose and chin;
...glial hamartomas lining the cerebral ventricles ("candle gutterings");
...glial hamartomas ("tubers") replacing the normal cortex;
...scrambled neurons instead of the normal cortical layers;
...cardiac rhabdomyoma;
...renal angiomyolipoma;
...mental retardation;
...seizures;
...behavior problems;
...this seems to be an autosomal dominant affliction with widely variable penetrance?
Tuberous sclerosis ("epiloia", "Bourneville's disease")
Is he or she a person with little or no pigment, even in the eyes?
Albinism
Is he or she a person with precocious osteoarthritis and black cartilages, who notes his or her urine turns dark if it stands in the light?
Alkaptonuria (ochronosis)
Is it huge crumpled-kleenex ("watered silk") macrophages packing bone marrow or spleen?
Gaucher cell (Gaucher's disease)
Is it huge foamy macrophages packing bone marrow or spleen?
Niemann-Pick cell (Niemann-Pick disease)
Is he a mildly retarded male with a long maxilla?
Fragile X syndrome
Is it masses of glycogen under the sarcolemmal membrane?
McArdle's myophosphorylase deficiency
Is it excess glycogen in the hepatocytes and proximal tubular epithelial cells?
von Gierke's G6Pase deficiency
Is it glycogen packing the heart and skeletal muscle cells of a baby?
Pompe's acid maltase deficiency
Is he or she a person of normal intelligence but with severe, bizarre facial deformities?
Treacher-Collins syndrome
Is he or she a person with fragile, stretchable cigaret-paper skin, hyper-extensible joints, and perhaps a history of bleeding from fragile vessels?
Ehlers-Danlos syndrome

Is it non-caseating granulomas in a person exposed to beryllium?
Berylliosis
Is he or she a person with fused fingers and a depressed center of the face?
Apert's syndrome
Is it a wound without bruising or tissue bridging, and with sharp edges, and deeper than it is wide?
Stab wound
Is it a wound without bruising or tissue bridging, and with sharp edges, and wider than it is deep?
Incised wound
Is it an open wound with rough, bruised edges, and tissue bridging in its depths?
Laceration
Is it a massive wound which penetrates to, or even through, the bone?
Chop wound
Is it a gunshot wound with stellate tearing of the skin, an abrasion ring, a muzzle imprint, no soot and no powder tattooing, and cherry red color of the surrounding tissues, or at least most of these?
Tight contact entry wound

Is it a gunshot wound with an abrasion ring, perhaps a muzzle imprint, and a ring of soot, or at least most of these?
Loose contact entry wound
Is it a gunshot wound with an abrasion ring, no stellate tearing, no muzzle imprint, no cherry red color, and powder tattooing?
Intermediate range (6"-3' or so) entry wound
Is it a gunshot wound with an abrasion ring, no stellate tearing, no muzzle imprint, no cherry red color, and no powder tattooing?
Long range entry wound
Is it a gunshot wound with no abrasion ring, and perhaps with stellate tearing? And is there an entry wound someplace else?
Exit wound
Is it a gunshot wound to the skull with inward beveling?
Entry wound

Is it a gunshot wound to the skull with outward beveling?
Exit wound
Is it a body with nail marks on the neck and conjunctival petechiae?
Manual strangulation
Is it a body found hanged without the usual a V-shaped rope abrasion with vital reaction?
Post-mortem hanging; homicide
Is it a burned body without soot in the trachea?
Post-mortem burning; suspect homicide plus arson

Is it a yellow, minimally-elevated streak on the inner surface of a large artery?

Is it a mass of lipid-laden foam cells in the intima of a large artery, without fibrosis?

Fatty streak of atherosclerosis ("the precursor")
Is it a firm, white, slightly-raised fibrous lesion on the inner surface of a large artery?

Is it a lesion on the intima of an artery with a fibrous cap overlying a variable mixture of lipid-laden foam cells, more fibrous tissue, and debris containing lipid and cholesterol "needles"? Is there perhaps some loss of the underlying elastic of the media?

Fibrous plaque of atherosclerosis ("the time bomb")
Is it a fibrous plaque of atherosclerosis which has ruptured, causing a thrombus to form on its surface?

Is it a fibrous plaque of atherosclerosis in a small artery, into which there has been a hemorrhage, so as to elevate its surface and occlude the artery?

Complicated plaque of atherosclerosis ("the killer")
Is it a mass of blood tracking between elastic layers of the aorta and/or one or more of its branches?
Dissecting hematoma
Is it dystrophic calcification of the media of an artery, without compromise of the lumen or involvement of the intima?
M”nckeberg's medial calcific sclerosis
Is it a small artery or arteriole in which the media is altered and now consists primarily of hyaline, basement membrane-type material instead of smooth muscle? And has it process narrowed the lumen?
Hyaline arteriolar sclerosis

NOTE: Think hypertension,
diabetes, or radiation effect

Is it a small artery in which there has been rapid, concentric proliferation of the intima, with severe narrowing of the lumen?
Hyperplastic arteriolar sclerosis

NOTE: Think malignant hypertension, scleroderma, hemolytic-uremic syndrome, or radiation effect

Is it a small artery in which the intima is thickened by fibrous tissue?
Intimal fibrosis of hypertension / old age
Is there "fibrinoid" necrosis of the small arteries, often with thrombus formation, perhaps with intimal edema, intimal myxoid change, or intimal onion-skinning, without much other evidence of vasculitis?
Malignant hypertension
Is it a granulomatous process concentrated on the inner elastic membranae of a branch of the external carotid artery?
Temporal arteritis

Is it a fibrous and/or granulomatous process compromising the aortic arch and its great vessels?
Takayasu's pulseless disease
Is he or she a child with skin and oral lesions, large lymph nodes, perhaps a coronary artery aneurysm, and a lesion resembling polyarteritis nodosa on biopsy? Is the child perhaps of Japanese ancestry, though living anywhere in the world?
Kawasaki's mucocutaneous lymph node syndrome
Is it an inflamed neurovascular bundle, the artery having undergone thrombosis, from the extremity of a smoker?
Buerger's thromboangiitis obliterans
Is it an aneurysm of the distal aorta or an iliac artery?
Atherosclerotic aneurysm
Is it red streaks running from a primary focus of infection toward the regional lymph node?
Lymphangitis

Is it a vascular malformation or birthmark composed primarily of vascular channels containing many RBC's?
Hemangioma
Is it a mass of bizarre vessels, with anaplastic endothelial cells, and lumens containing red cells?
Hemangiosarcoma ("angiosarcoma")
Is it a malformation or birthmark composed primarily of vascular channels containing no RBC's?
Lymphangioma
Is it a mass of bizarre vessels, with anaplastic endothelial cells, and lumens devoid of red cells? Is there perhaps a history of radiation and/or lymphedema?
Lymphangiosarcoma
Is it a fast-growing mass of little capillaries in a gelatinous stroma, in the mouth or on the skin?
"Pyogenic granuloma"
Is it a tumor composed of well-differentiated spindle cells, and the reticulin stain reveals they are surrounded by reticulin just as normal pericytes are?
Hemangiopericytoma
Is it an adult's left ventricle thicker than 1.5 cm?

Is it an adult's right ventricle thicker than 0.5 cm?

Is it heart with very thick fibers with squared ("boxcar") nuclei that appear more than twice as large as the nuclei of the endothelial cells?

Myocardial hypertrophy
Is there a major abnormality of the anatomy of the heart, in the absence of rupture or suppuration?
Congenital heart disease

NOTE: Yes, Doc, you can puzzle it out!

Is there an irregular mound of calcified tissue in each sinus of Valsalva of an older person's otherwise-normal aortic valve?
Calcific aortic stenosis
Is it an aortic valve with only two cusps, whether or not the valve is stenotic or calcified?
Congenital bicuspid aortic valve
Is it an aortic root which has dilated, rendering the aortic valve incompetent?
Syphilis / HLA-B27 inflammatory disease / Marfan's / aortic dissection
Is it a mitral valve with the posterior leaflet nearly as long as the anterior leaflet?

Is it a mitral, aortic, or tricuspid valve with the leaflets or cusps billowing and redundant, like the cells of a parachute?

Barlow's mitral valve prolapse
Is it a person who recently had a streptococcal throat infection, and now has several or all of the following:
fever;
...migratory polyarthritis;
...a bad EKG;
...painful subcutaneous nodules
...erythema marginatum;
...Sydenham's chorea ("St. Vitus Dance")?

Is it a cardiac valve with little red wart-like excrescences all along its lines of closure?

Is it a cluster of cells that look like shrunken cardiac myocytes but with the histochemistry of macrophages, and with caterpillar-like heterochromatin if the nucleus is sectioned lengthwise (i.e., it is an Aschoff nodule)?

Acute rheumatic fever

NOTE: Jones criteria if the patient is living.

Is it a cardiac valve with leaflets thickened by white scar tissue, and stuck together for some distance at their edges?

Is it a mitral or tricuspid valve with thickened, or even fused, chordae tendineae?

Is it mitral stenosis?

Damage from rheumatic fever
Is it masses containing a variable mix of bacteria, fibrin, and neutrophils, hanging on a previously-normal cardiac valve, which is now perhaps damaged?
Acute bacterial endocarditis
Is it masses, perhaps quite large, containing a variable mix of bacteria, fibrin, and neutrophils, hanging on a previously-damaged cardiac valve or the site of turbulence in a malformed heart?
Subacute bacterial endocarditis
Is it a mass of fibrin without bacteria, on the valve of a person who has a chronic, debilitating sickness?
Marantic (non-bacterial thrombotic) endocarditis
Is it fibrin vegetations over various surfaces of a cardiac valve, in a lupus patient?
Libman-Sacks endocarditis
Is it fibrosis of the tricuspid and pulmonic valves, with normal mitral and aortic valves?
Carcinoid heart disease
Is it lymphocytes densely infiltrating a heart?
Coxsackie / autoimmune / allograft myocarditis
Is it myocardium that is just too stiff to beat?
Restrictive cardiomyopathy (i.e., probably amyloid)
Is it a heart with irregularly thickened muscle, typically occluding the outflow track from the left ventricle?

Is it myocardial cells arranged crisscross on a light micrograph? Is there also some thickening of the intima of the small arteries?

Is it myocardial sarcomeres arranged crisscross on an electron micrograph?

Hypertrophic cardiomyopathy (á-myosin gene, others)
Is it a heart with muscle that is just too weak to beat properly? Are the ventricles flabby and much-dilated, perhaps with mural thrombi?
Dilated cardiomyopathy (innumerable causes)
Is it a heart with a hypertrophic left ventricle, and there is no explanation other than past or present hypertension?
Hypertensive heart disease
Is it a heart, clinically from a recent myocardial infarct victim or with a fresh occlusive coronary artery lesion, and you see, under the microscope, only wavy fibers at the border of where the infarct should be, or perhaps contraction bands?
Myocardial infarct, 0-4 hours
Is it a heart, clinically from a recent myocardial infarct victim or with a fresh occlusive coronary artery lesion, and you see, under the microscope, early coagulation necrosis and perhaps a few neutrophils?
Myocardial infarct, 4-12 hours
Is it a heart with a soft spot in the distribution of an artery or the subendocardial watershed?

Is it a heart, and you see, under the microscope, obvious coagulation necrosis and more than just a few neutrophils?

Myocardial infarct, 12-24 hours
Is it a heart, and there is yellow discoloration in the distribution of an artery or the subendocardial watershed?

Is it a heart, and you see, under the microscope, widespread karyorrhexis, lost cross-striations, and lots and lots of neutrophils?

Myocardial infarct, 24-72 hours
Is it a heart with a visible infarct with a thin red rim?

Is it a heart, and you see, under the microscope, resorption of the myocardial fibers and a thin rim of granulation tissue at the edges?

Myocardial infarct, 3-7 days
Is it, grossly and microscopically, a fully-developed scar at the site of a myocardial infarct?
Myocardial infarct, 7 weeks or more
Is it a person with a serious primary lung disease who also has a much-hypertrophied right ventricle?
Cor pulmonale
Is it a person with three-vessel coronary disease each with 70% or greater stenosis, or a serious coronary artery malformation? And did it person die suddenly without other evidence of disease, poisoning, or injury? And at autopsy, did you find no infarct, or at most a few wavy fibers?
Sudden cardiac death
Is it endocardial fibrosis causing restrictive cardiac disease, in a young person from Africa?
Endocardial fibroelastosis
Is it endocardial fibrosis causing restrictive cardiac disease, and are there excess eosinophils in blood, heart, and elsewhere?
Loeffler's eosinophilic endocarditis
Is it a shaggy covering on the pericardium?
Fibrinous pericarditis
Is it a pericardial cavity packed with soft white tumor? And there is no other apparent primary?
Pericardial mesothelioma
Is it a round mass, like a wrecking ball, in the left atrium, hanging on the interatrial septum?
Atrial myxoma
Is it a hamartoma in the heart muscle of a person with tuberous sclerosis?
Cardiac rhabdomyoma
Is it several tumor nodules embedded in the myocardium?
Metastases to the heart
Is it a peripheral smear with spherocytes, i.e., RBC's without central pallor, and the person has a lifelong mild anemia and is Coombs negative?
Hereditary spherocytosis
Is it a peripheral smear with spherocytes, i.e., RBC's without central pallor, and the person is Coombs positive?
Autoimmune hemolysis with spherocytosis
Is it a peripheral smear with an excess (more than 1-2%) of slightly large, slightly-purple staining RBC's (young reds, reticulocytes)?
Anemia of blood loss or increased destruction or early release of red cells
Is it a peripheral smear with RBC's containing small round masses of condensed DNA?
Howell-Jolly bodies (think of absence of spleen)
Is it a peripheral smear with RBC's containing iron-laden mitochondria?
Pappenheimer bodies (think of absence of spleen or sideroblastic anemia)
Is it a peripheral smear, perhaps specially prepared, containing Heinz bodies?
Erythrocyte enzyme defect or hemoglobin H disease
Is it a peripheral smear bearing many target cells and some sickled cells?
Sickle cell disease ("Hemoglobin SS")
Is it a peripheral smear with an unusually large number of target cells, but no sickled cells?
Think of hemoglobin C or E diseases or traits or thalassemia
Is it a smear made at low pH, with target cells and rod-shaped intracellular crystals?
Hemoglobin C
Is it a smear with many target cells and RBC's with bizarre ("birds in flight", etc.) crystals?
Sickle-C disease
("Hemoglobin SC disease")
Is it a smear with target cells, and some cells with coarse basophilic stippling, from a person with Hgb around 11 and MCV around 67?
Beta thalassemia minor
Is it a smear from a child with severe anemia, a crewcut skull x-ray, skull deformity, and many bizarre and/or basophilic stippled RBC's?
Beta thalassemia major
Is it a smear from a person with mild or no anemia and mild microcytosis, without other evidence of illness?
Alpha thalassemia trait (2 deletions)
Is it a person with small red cells, hemolysis and hemoglobin H?
Hemoglobin H disease (à-thal, 3 deletions)
Is it an edematous (i.e., anemia led to high-output congestive heart failure) stillborn with abundant hemoglobin Bart's (four gamma chains)?
Hydrops fetalis thalassemia (à-thal, 4 deletions)

NOTE: There are other causes of an edematous stillborn, notably hemolytic disease of the newborn

Is it a peripheral smear with RBC's fragmented into schistocytes (helmet cells, blister cells, etc.)?
Microangiopathic hemolysis; think of DIC, TTP, vasculitis, malignant hypertension, burns
Is it a peripheral smear with hypersegmented ("right-shifted") neutrophils (one with >5 lobes, 5% or more with 5 lobes) or hypersegmented eosinophils (one with >2 lobes)?

Do you recognize megaloblasts in the bone marrow?

Is the MCV well above 100 fL and you're not dealing with alcoholism, thyroid disease, or liver disease, and the MCV is not elevated due to reticulocytosis?

Is the MCV 130 fL or more?

Megaloblastic anemia
NOTE: Common to all these is difficulty making DNA. The RBC cytoplasm matures, but the nucleus can't.

Think of cobalamin (vitamin B12) deficiency, folic acid deficiency, or antimetabolite therapy.

Is it a peripheral smear with small RBC's?

Is the MCV lower than about 80 fL?

Microcytic anemia

NOTE: The problem is inability to make hemoglobin. it may be due to absolute or functional lack of iron ("iron-deficiency anemia", "anemia of chronic disease", or "sideroblastic anemia"), inability to make porphyrin rings (lead poisoning, erythropoietic porphyria), or inability to make globin chains (thalassemia).

Is it a peripheral smear with small RBC's, but the serum ferritin is high and there are abundant marrow iron stores, and there is chronic inflammation somewhere in the body?
Anemia of chronic disease

NOTE: Interleukin 1 is preventing uptake of storage iron into normoblasts.

Is it a peripheral smear with small RBC's, perhaps also with a population of normal RBC's, and there are abundant marrow iron stores with a few ringed sideroblasts (i.e., normoblasts with iron-rich mitochondria)?
Sideroblastic anemia
NOTE: The normoblasts are having difficulty getting iron into the heme rings.
Is it a peripheral smear with teardrop RBC's and erythroid and myeloid marrow elements?
Leukoerythroblastic smear

NOTE: Think of tumor or TB in the marrow, or agnogenic myeloid metaplasia.

Is it a peripheral smear with RBC's with projections having bulbous ends?
Acanthocytes; think abetalipoproteinemia
Is it a peripheral smear with RBC's with short, stubby projections like gears?
Crenated red cells, artifact, usually means nothing
Is it a peripheral smear with RBC's innumerable radiating grooves on their edges, like plastic checkers pieces?
Artifact; somebody dripped water in the Wright's stain
Is it a peripheral smear with fewer than around 6 platelets per high power field?
Thrombocytopenia
Is it thrombocytopenia, and are there some very large (i.e., rush-job) platelets?
Platelet lysis; think of ITP
Is it thrombocytopenia, and are there also schistocytes?

And are there tiny fibrin-platelet thrombi in the small vessels of many organs, outstandingly the renal glomeruli?

Probably DIC (disseminated intravascular coagulation, and you must find out why!)
It is a person with a fever, neurologic defects, schistocytes, thrombocytopenia, and renal failure?

Are there tiny, very hyaline-looking fibrin-platelet thrombi in the small arteries and capillaries of many organs?

TTP (thrombotic thrombocytopenic purpura)
Is it mouth ulcers in a neutropenic person?

Is it a blood smear with very few neutrophils as the principal abnormality?

Agranulocytosis
Is it a smear with many immature (band, maybe even younger) neutrophils?
"Left shift"
Is it a neutrophil with very prominent, blue-staining granules?
Toxic granulation
Is it a neutrophil with very prominent, red-staining granules?
Alder-Reilly anomaly, i.e., Hunter's, Hurler's
Is it a pale blue blob inside a neutrophil?
D”hle body
Is it a cell that stains positive for CD4?
T-helper lymphocyte or dendritic macrophage ("Langerhans histiocyte")
Is it a cell that stains positive for CD8?
T-suppressor lymphocyte
Is it a small cell with a surface that stains positive for kappa chains or lambda chains?
B-lymphocyte
Is it a cell that with cytoplasm that stains positive for kappa chains, lambda chains, and/or one of the heavy chain types?
Plasma cell
Is it a cell that stains positive for lysozyme, nonspecific esterase, or anti-chymotrypsin?

Is it a cell that has eaten one or more RBC's?

Monocyte - macrophage
Is it a free cell that stains positive for tartrate-resistant acid phosphatase?

Is it a lymphocyte with many apparent hairs sticking from it, as seen on a smear of peripheral blood? And was the bone marrow tap dry?

Hairy cell leukemia
Is it a cell that stains positive for myeloperoxidase, chloroacetate esterase, or with the Sudan Black lipid stain?
Granulocyte
Is it a lymphocyte about 8 microns across, with a dense, smooth-surfaced nucleus and scanty cytoplasm?
Normal B or T lymphocyte, or well-differentiated lymphocytic lymphoma or chronic lymphocytic leukemia.
Is it a lymphocyte about 8 microns across, with an irregular nuclear membrane?
Small cleaved activated B-lymphocyte
Is it a lymphocyte about 16 microns across, with an irregular nuclear membrane?
Large cleaved activated B-lymphocyte
Is it a lymphocyte about 16 microns across, with a smooth nuclear membrane?
Small non-cleaved activated B-lymphocyte
Is it a lymphocyte about 25 microns across, with a smooth nuclear membrane?
Large non-cleaved activated B-lymphocyte
Is it a lymphocyte about 30 microns across, with a very large nucleus, a very large nucleolus, and basophilic cytoplasm?
B- or T-immunoblast
Is it a peripheral smear with striking granulocytosis and left shift, and is there abundant staining for leukocyte alkaline phosphatase, and are Philadelphia chromosome and bcr/abl absent? And you know something's seriously wrong (cancer, bad infection, other) with the patient?
Leukemoid reaction
Is it a peripheral smear with striking granulocytosis and left shift, and is there very poor staining for leukocyte alkaline phosphatase, and is Philadelphia chromosome (or at least bcr/abl present?
Chronic granulocytic ("myelogenous") leukemia
Are the neutrophil nuclei hypo-segmented, with "peanuts" and "eyeglasses", but the patient is not sick?
Pelger-Huet anomaly
Is it a benign lymph node with tremendously enlarged follicles, all rimmed by the normal mantle?
Follicular (i.e., B-cell) hyperplasia

NOTE: Think of AIDS-related complex, rheumatoid disease, syphilis, common variable immunodeficiency

Is it a benign lymph node with prominent follicles and puny granulomas?
Toxoplasmosis
Is it a benign lymph node with lots of activated cells in the cortex between normal-appearing lymphoid follicles?
Paracortical (i.e., T-cell) hyperplasia

NOTE: Think of phenytoin effect, infectious mononucleosis, lupus

Is it a benign lymph node with very prominent macrophages in the sinusoids?
Sinus histiocytosis (i.e., macrophage hyperplasia)

NOTE: Think of a node draining a cancer

Is it a benign but hyperplastic lymph node, with both lipid and melanin in the macrophages?
Dermatopathic lymphadenitis
Is it a lymph node with abundant blood vessels and sheets of immunoblasts?
Angioimmunoblastic lymphadenopathy
Does it stain positive for CD1 (T6) and S100?

Does it contain a Birbeck pentalaminar tennis-racket shaped structure?

Dendritic macrophage / Histiocytosis X / Langerhans cell histiocytosis
Is it a proliferation of normal appearing or activated lymphocytes, destroying the architecture of a tissue?

And is monoclonality demonstrated by finding only kappa or only lambda chains?

And is monoclonality demonstrated by morphologic uniformity of cells?

And is there scanty, if any, vascular proliferation in response to the growth?

And are the monoclonal cells perhaps invading surrounding tissue?

And is there perhaps necrosis, in the absence of some cause of inflammation?

And if nodularity is present, do the nodules lack a proper mantle?

Are classic gene rearrangements (immunoglobulin for B-cells, receptors for T-cells) perhaps present?

Malignant lymphoma
Is it a small lymphoma-leukemia cell with an extremely convoluted nucleus?
S‚zary cell
Is it an aggressive lymphoma or leukemia arising in the setting of chronic lymphocytic leukemia or low-grade lymphocytic lymphoma?
Richter's syndrome
Is it a diffuse lymphoma composed of cells that exactly resemble normal resting lymphocytes?

Is it the solid phase of chronic lymphocytic leukemia?

Well-differentiated lymphocytic lymphoma / small lymphocytic lymphoma
Is it a diffuse lymphoma composed of cells that resemble normal resting lymphocytes but have slightly more cytoplasm, which stains basophilic?

Is there, perhaps, also a Waldenstr”m's IgM pentamer paraprotein? And/or are there apparent intranuclear immunoglobulin deposits (Dutcher bodies)?

Is the primary in the gut, and the tumor makes alpha heavy chains?

Does the tumor make gamma or mu heavy chains?

Plasmacytoid small lymphocytic lymphoma / Waldenstr”m's macroglobulinemia / heavy chain disease
Is it a nodular or diffuse lymphoma composed of cells that resemble normal resting lymphocytes but have irregular nuclear membranes?
Small cleaved cell lymphoma
Is it a nodular or diffuse lymphoma made up of a mix of small cleaved and larger lymphocytes, both being neoplastic?
Small cleaved and large cell lymphoma
Is it nodular or diffuse lymphoma composed of larger lymphocytes, typically larger than an endothelial cell? (An endothelial cell is around 15 microns.)
Large cell lymphoma
Does it look like a diffuse large cell lymphoma, but is composed of cells that truly bear histiocytic markers?
True histiocytic "lymphoma"
Does it look like a diffuse anaplastic lymphoma, with erythrophagocytosis?
Malignant histiocytosis
Is it a diffuse lymphoma composed of B- or T-immunoblasts?
Immunoblastic lymphoma
Is it a T-cell lymphoma from the thymic region of a young person? And are the nuclei a bit clefted?
T-lymphoblastic lymphoma
Is it a lymphoma composed of fairly large cells with almost no cytoplasm and very little in the way of differentiation, with tiny lipid droplets in the cytoplasm which concentrate (when the tumor cells die) inside macrophages, imparting the "starry sky" appearance? And is the famous 8:14 myc-immunoglobulin translocation, or something similar, present?
Burkitt's lymphoma

NOTE: If this is from an African child, it's usually in the jaw and the child is EBV positive. In the U.S. form, it can be from anyplace.

Is it a T-cell lymphoma, perhaps composed of S‚zary cells, with little clusters of neoplastic cells ("Pautrier microabscesses") in the epidermis?
Mycosis fungoides / S‚zary syndrome

Is it an aggressive T-cell lymphoma in an adult who is HTLV-1 positive?
Aggressive adult T-cell lymphoma-leukemia
Is it a large cell with a convoluted nucleus, appearing in section as two or more nuclei, each with an eosinophilic nucleolus around 7 microns across, and marginated chromatin? Further, is the background fitting for some form of Hodgkin's disease?
Reed-Sternberg cell
Is it sheets and sheets of normal-appearing lymphocytes, punctuated with occasional Reed-Sternberg cells and their "uninuclear" variants?
Lymphocyte predominance Hodgkin's disease
Is it a mix of lymphocytes, plasma cells, histiocytes, and eosinophils, with frequent Reed-Sternberg cells and their popcorn variants?
Mixed cellularity Hodgkin's disease
Is it a hideously anaplastic tumor, recurring in a patient with a previous diagnosis of Hodgkin's disease?
Lymphocyte depletion Hodgkin's disease
Is it a mix of lymphocytes, plasma cells, histiocytes, and eosinophils, with occasional Reed Sternberg cells and their lacunar variant, in nodules demarcated by more or less impressive fibrous bands?
Nodular sclerosing Hodgkin's disease
Is it a blood cell about 15 microns across, with a big all-euchromatin primitive nucleus, several nucleoli, and scanty, basophilic cytoplasm?
Blast
Is it a blast with an Auer rod in its cytoplasm?

Is it a blast that stains positive for chloroacetate esterase?

Granulocytic blast
Is it a blast that stains positive for nonspecific esterase?
Monocytic blast
Is it a peripheral smear with abundant circulating blasts?

Is it a bone marrow smear or section with abundant blasts?

Acute leukemia
Is it acute leukemia, determined to be of lymphoid origin, and the blasts are <15 microns and look just plain primitive? And is the patient a younger child?
Acute lymphoblastic leukemia, L1
Is it acute leukemia, determined to be of lymphoid origin, and the blasts are >15 microns with clefted nuclei and lots of nucleoli? Is the patient perhaps a teen or adult?
Acute lymphoblastic leukemia, L2
Is it acute leukemia, with cells maybe 20 microns, with intracellular lipid and a Burkitt chromosome translocation?
Acute lymphoblastic leukemia, L3
Is it acute leukemia with generic, undifferentiated myeloblasts?
Acute myelogenous leukemia, M1
Is it acute leukemia with some promyelocytic differentiation and perhaps an Auer rod or two?
Acute myelogenous leukemia, M2
Is it acute leukemia with a preponderance of obvious promyelocytes, many Auer rods (red crystalloids in the cytoplasm), and a tendency for the patient to develop DIC?
Acute myelogenous leukemia, M3 / Acute promyelocytic leukemia
Is it acute leukemia with blasts featuring both granulocytic and monocytic differentiation?
Acute myelogenous leukemia, M4 / Acute myelomonocytic leukemia
Is it acute leukemia with blasts featuring only monocytic differentiation?
Acute myelogenous leukemia, M5 / Acute monocytic leukemia
Is it acute leukemia with blasts featuring normoblast-like differentiation, with big chunks of PAS-positive material?
Acute myelogenous leukemia, M6 / DiGuglielmo's erythroleukemia
Is it acute leukemia with a fibrotic bone marrow and blasts with platelet markers?
Acute myelogenous leukemia, M7 / Acute megakaryocytic leukemia
Is it a solid, discrete mass from someone with acute myelogenous leukemia, and did the mass turn green on exposure to air?
Chloroma
Is it a peripheral smear with a preponderance of normal-appearing lymphocytes, some of which have been smashed ("smudged") on preparation of the smear?
Chronic lymphocytic leukemia
Is it a spleen bearing erythroid islands and megakaryocytes?
Extramedullary hematopoiesis
Is it sheets of plasma cells in bone marrow?

Is it large, bizarre plasma cells?

Is it punched-out lesions of bone with other findings suggestive of plasma cell myeloma?

Is it precocious osteoporosis with other findings suggestive of plasma cell myeloma?

Is it urine containing immunoglobulin light chains ("Bence-Jones" protein)?

Is it kidney with non-pigmented casts in the tubules and a foreign-body reaction to these casts?

Is it a monoclonal gammopathy, with depression of albumin and other globulins?

Plasma cell myeloma
("multiple myeloma")
Is it bone marrow replaced by fibrous tissue?
Think of myelofibrosis, agnogenic myeloid metaplasia, acute megakaryocytic leukemia, burned-out polycythemia vera
Is it an apparent tumor that stains strongly for CD1 (T6), and/or exhibits Birbeck granules (pentalaminar tennis rackets) on electron microscopy? Does your instructor perhaps appear extra excited over this specimen?
Langerhans cell histiocytosis / histiocytosis X / Letter-Siwe / Hans- Schuller-Christian / Eosinophilic granuloma
Is it a newborn's lung that appears never to have been aerated, but grossly resembles India rubber?

Is it a lung crunched very small because of a pleural effusion, a pneumothorax, massive ascites, obstruction of a large airway, or ischemic from a large pulmonary embolus?

Is it the basal portion of the lung from a patient with recent abdominal surgery, in which deep inspiration is painful?

Is it lung in which the large majority of alveoli are collapsed, due to one of the reasons above, or because of diffuse alveolar damage (respiratory distress syndrome) with loss of surfactant?

Atelectasis
Is it a lung that is beefy red throughout, perhaps worst in its dependent areas?

Is it lung with much-dilated venules, and perhaps some small hemorrhages without apparent vasculitis?

Acute pulmonary congestion

Is it brown lung, perhaps more brown in the dependent areas, perhaps with some fibrosis?

Is it lung with many hemosiderin-laden macrophages, and perhaps also with interstitial fibrosis?

Chronic pulmonary congestion
Is the lung wet and heavy, but there is still air in the alveoli (i.e., there is still crepitus)?

Is it lung with thickening of the alveolar septa, which appear pale on microscopy?

Is it heavy lung without excessive fibrosis, from which a modest among of fluid runs on sectioning?

Interstitial pulmonary edema
Is it heavy, wet lung with frothy bubbles in the large airways? And is the lung relatively airless (i.e., lacking in crepitus)?

Is it lung with interstitial edema, and some fluid still visible in the alveoli after processing?

Intra-alveolar pulmonary edema
Is it very heavy, pale lung, perhaps with focal hemorrhages, and is the history short (days to weeks)?

Do you see most or all of the following:
...interstitial and intra-alveolar pulmonary edema;
...necrotic debris in the alveoli;
...hyaline (mostly fibrin) membranes along air space walls;
...replacement of simple-squamous type I pneumocytes with cuboidal type II pneumocytes;
...new interstitial pulmonary fibrosis?

Diffuse alveolar damage (adult respiratory distress syndrome, ARDS, "shock lung", "bronchopulmonary dysplasia" of newborns, Da Nang lung, etc., etc.)

Causes: Shock, massive trauma, oxygen toxicity, sepsis, near- drowning, aspiration, viruses, radiation injury, drug idiosyncracy, etc., etc.

Is it a laminated thrombus in a pulmonary artery, perhaps with some adhesion to the wall, perhaps with propagation in the distal arterial tree, and not at a site of surgery on the lung?

Is it a laminated thrombus in a pulmonary artery seen histologically, perhaps being entered by fibroblasts and angioblasts where it adheres to the endothelium, and not at a site of surgery on the lung?

Pulmonary thromboembolus
Is it a pulmonary artery or arteriole with any of these:
...atherosclerosis;
...extra layers of cells in its intima and/or media;
...reduplicated elastic lamina;
...the multi-channel "plexiform" lesion replacing the single lumen?
Vascular changes suggestive of pulmonary hypertension
Is it squamous metaplasia of the bronchial epithelium?

Is it patchy loss of cilia on the bronchial epithelium?

Is it extra goblet cells in the bronchial epithelium in the absence of asthma?

Is it bronchial glands that extend more than half the way between epithelium and cartilage ("Reid index" > 0.5 or so)?

Is it a very thick basement membrane under respiratory epithelium?

Is there a big yellow hocker in an airway?

Is there a mass of mucus laden with neutrophils (microscopic appearance of a big yellow hocker) in an airway?

Suspect cigaret smoking as the cause; consider "chronic bronchitis" if clinical picture warrants

NOTE: "Cigaret" is the preferred spelling. "-ette" means little and cute, the tobacco habit isn't.

Is it a lung with poor elastic recoil (i.e., a finger impression holds water 5 seconds after release)?

Is it a diaphanous, relatively insubstantial lung with blebs?

Is it a pair of lungs so hyperinflated that they overlap in front of the heart?

Is it a section of lung with relatively few alveolar septa, and those that are present relatively depleted of vessels? Are many loose septa apparently flapping in the breeze?

Emphysema
Is it a properly-prepared emphysematous lung, and the worst damage is right around the respiratory bronchioles, where the smoke arrives first?
Centrilobular emphysema, suspect cigaret smoking
Is it a properly-prepared emphysematous lung, and all portions of the lobule seem equally damaged?
Panacinar emphysema, suspect à1-protease inhibitor ("antitrypsin") deficiency
Is it an autopsy lung without significant emphysema, scarring or bronchiectasis, but with all the medium-sized airways occluded by thick mucus plugs?

Is it a lung with goblet cell hyperplasia and/or a thick basement membrane, but not enough exposure to tobacco smoke or air pollution to explain these?

Is it sputum laden with "Curschmann's spirals"? If there is allergy, are there perhaps Charcot-Leyden crystals (elongated red-staining lozenges of eosinophil protein)?

Asthma
Is it a lung with dilated large airways, their mucosa disfigured by running sores?

Is it a photomicrograph of a lung airway which is extensively ulcerated, or bearing regenerating epithelium and surrounded by granulation tissue, or perhaps even replaced by fibrin and pus?

Bronchiectasis

Consider cystic fibrosis ("mucoviscidosis"), post-pertussis, post- necrosis, Kartagener's immotile cilia, immune deficiency, or near an obstructive lesion

Is it lung with consolidation, suppuration, and probably hemorrhage, involving a single lobe, stopping only at the interlobar boundaries? Is the involved lung pretty much airless (i.e., there is little or no crepitus)? And on microscopy, are the alveolar spaces packed with neutrophils?
Lobar pneumonia "red hepatization"

Think pneumococci, klebsiella

Is it an electron micrograph of a cilium, lacking the dynein arms? Does the patient have bronchiectasis, nasal sinus problems, and perhaps also situs inversus?
Immotile cilia / Kartagener's
Is it lung with patchy consolidation, suppuration, and maybe little hemorrhages, involving several portions of several lobes? Is the involved lung pretty much airless (i.e., there is little or no crepitus)? And on microscopy, are the alveolar spaces packed with neutrophils?
Bronchopneumonia
Is it lung with patchy or lobar consolidation but more gray- appearing? Is the involved lung pretty much airless (i.e., there is little or no crepitus)?

Is it lung with balls of loose collagenous tissue forming within the alveoli amid debris of macrophages, dead cells, fibrin, and perhaps polys?

Resolving bronchopneumonia or resolving lobar pneumonia "gray hepatization"
Is it a lone caseating granuloma in the lung, typically under the pleura of the midportion?

And do acid-fast stains show mycobacteria, and/or are stains for fungi (i.e., histoplasmosis) negative?

Healed primary tuberculosis, probably an old "Ghon focus"
Is it a lone caseating granuloma of tuberculosis under the lung pleura, and is there a second lone caseating granuloma of tuberculosis in the hilar lymph node draining this portion of lung?
Ghon complex of primary tuberculosis
Is it caseous necrosis with a variable granulomatous response at the pulmonary apex? Has a cavity with a white rim perhaps formed? And again, do acid-fast stains show mycobacteria, and/or are stains for fungi (i.e., histoplasmosis) negative?
Secondary, reactivation tuberculosis
Is it innumerable caseating granulomas throughout the lung, spleen, liver, and/or peritoneal cavity? And again, do acid-fast stains show mycobacteria, and/or are stains for fungi (i.e., histoplasmosis) negative?
Miliary tuberculosis
Is it a lung "whited-out", grossly or on x-ray, by caseation with a variable granulomatous response? And again, do acid-fast stains show mycobacteria, and/or are stains for fungi (i.e., histoplasmosis) negative?
Progressive pulmonary tuberculosis
Is it a lung with widespread fibrosis, a few air spaces pulled extra- wide ("honeycomb lung") especially at the periphery, and there is no other evident pathology or apparent cause?
Diffuse interstitial fibrosis ("usual interstitial pneumonitis", fibrosing alveolitis, "honeycomb lung", "Hamman-Rich")

Rule out: Bleomycin lung, busulfan lung, nitrofurantoin lung, amiodarone lung, other drugs; old diffuse alveolar damage (ARDS) from any cause, etc. etc.

Is it an inflamed lung or portion of lung with more air ("crepitus") than in the familiar lobar pneumonia or bronchopneumonia?

Is it lung with an inflammatory infiltrate, primarily in the interstitium, probably composed primarily of lymphocytes (though perhaps with neutrophils early)? Does the picture develop into ARDS in fatal cases?

"Primary atypical pneumonia" / pneumonitis

Consider viral, rickettsial, chlamydial, or mycoplasmal pneumonitis

Is it gray, airless, non-fibrotic lung in a patient with poor T- cell/macrophage function? Are the alveoli filled with eosinophilic, frothy-looking material? And do special stains (silver is best) show pneumocystis organisms?
Pneumocystosis
Is it a lung cavity containing a solid brown mass?
Aspergillus
Is it a pneumonitis with smudge cells in the bronchial epithelium?
Adenovirus
Is it a pneumonitis with huge owl-eye inclusion-bearing cells?
CMV pneumonitis
Is it a pneumonitis or bronchiolitis with syncytial (i.e., multinucleated) cells in the epithelium of the bronchioles?
Respiratory syncytial virus
Is it a pneumonitis with giant cells with nuclei bearing large inclusions (i.e., Warthin-Finkeldey giant cells)?
Measles pneumonitis
Is it a fibrosing alveolitis with clumps of macrophage-like cells adhering to one another in the centers of the alveoli?
Desquamative interstitial pneumonitis
Is it a fibrosing alveolitis with abundant non-caseating granulomas?
Sarcoidosis or berylliosis
Is it a pneumonitis with a variable mix of eosinophils, neutrophils, macrophages, and/or acute vasculitis? And is the patient exposed to bacterial spores (i.e., farmer, sick building)?
Organic pneumoconiosis
Is it a fibrosing process in the lungs with an abundance of eosinophils and of macrophages with grooved nuclei?

Is it a lung lesion, and your instructor is showcasing a positive CD1 (T6) stain and/or a Birbeck pentalaminar tennis-racket granule on an electron micrograph?

Eosinophilic granuloma variant of Langerhans cell histiocytosis
Is it a diffuse fibrosing alveolitis with an occupational history of asbestos exposure? And is your instructor showcasing a ferruginous body, or is a malignant mesothelioma or a large pleural plaque present?
Asbestosis
Is the lung packed with eosinophils, but this is not eosinophilic granuloma variant of Langerhans cell histiocytosis?
Pulmonary eosinophilia / "eosinophilic pneumonitis"

Consider Loeffler's pneumonia, microfilariasis, nitrofurantoin lung, allergy

Is it a lung with recent (red cells) and/or old (hemosiderin-laden macrophages) hemorrhage in the alveoli, but with little else wrong? And is there a positive anti-GBM antibody in the serum and/or a linear pattern of fluorescence for IgG in the glomerulus and/or alveolar septa?
Goodpasture's disease
Are normal-appearing alveoli more-or-less uniformly packed with a homogeneous, gelatinous, very finely-granular eosinophilic material?
Alveolar proteinosis

Consider acute silicosis, immunosuppression, opportunistic lung infection, lymphoma; many are "idiopathic"

Are the alveoli packed with foamy macrophages without a lot of necrosis?
Lipid pneumonia

Consider aspiration of animal, vegetable, or mineral oil; obstruction of a large airway

Is it a lung cancer (bronchogenic carcinoma) with histology showing single-cell keratinization, pearl formation, and/or obvious intercellular bridges?
Is it a lung cancer with obvious and abundant desmosomes and/or tonofilaments on electron microscopy?
Squamous cell carcinoma of the lung

Most of these present as hilar masses, and they tend to cavitate.

Is it a lung cancer making mucin and/or forming good glands and/or forming good papillae?

Is it a lung cancer with intracellular lumens on electron microscopy?

Is it a cancer that immunostains positive for surfactant?

Adenocarcinoma of the lung

Most of these present as peripheral masses.

Rule out metastasis to lung.

Is it a lung cancer (bronchogenic carcinoma) presenting as masses of mucoid material within the lung parenchyma?

Is it lung cancer with well-differentiated columnar or cuboidal cells growing single-file along the alveolar septa? Are they perhaps producing mucin which fills the alveoli?

Bronchioloalveolar lung cancer

A variation on adenocarcinoma.

Rule out metastasis to lung.

Is it lung cancer (bronchogenic carcinoma) composed of large (more than 20 microns or so), anaplastic cells without obvious glandular or squamous features?
Large cell undifferentiated lung cancer

Most of these present as large masses near the hilum.

Is it lung cancer (bronchogenic carcinoma) composed of small (around 15 microns), fragile cells with very little cytoplasm ("small blue cells")? And is there little or no tendency to form a collagenous stroma?

Does this lung cancer stain strongly with neuron-specific enolase or some other neuroendocrine marker?

Does this lung cancer exhibit neurosecretory granules on electron microscopy?

Small cell undifferentiated lung cancer ("oat cell")

The primary is usually fairly small, and the soft white tumor tends to spread widely among peribronchial lymphatics

Is it a round, soft lung mass which in microscopy shows benign- appearing cuboidal cells in clumps or ribbons? And are neurosecretory granules seen on electron microscopy?
Bronchial carcinoid ("bronchial adenoma")
Is it a lung or pair of lungs bearing several rounded tumor nodules throughout the parenchyma, without a dominant mass?
Metastases to the lung
Is it a popcorn-shaped mass in the lung, composed primarily of cartilage?
Chondroid hamartoma of the lung
Is it pus in the pleural cavity, or packing the gallbladder?
Empyema
Is it shaggy strands on the pleural surface?
Fibrinous pleuritis
Is it milky-white fluid in the pleural cavity, and there has been trauma or cancerous involvement of the thoracic duct?
Chylothorax
Is it air in the pleural cavity?
Pneumothorax
Is it a pneumothorax with the mediastinal contents markedly shifted toward the opposite side?
Tension pneumothorax
Is it a fibrous mass attached to the visceral or parietal pleura, and showing no invasive tendency?
Benign mesothelioma

NOTE: No asbestos link

Is it a white solid or semi-liquid mass filling a pleural cavity? (Or perhaps the pericardial or peritoneal cavity?)

On microscopy, is it tumor composed of spindle cells, gland-and/or- papillar, or (typically) both?

Is it cancer with very long, spaghetti-like microvilli on electron microscopy?

Malignant mesothelioma

NOTE: The cause is asbestos exposure. Tobacco is not a contributor.

Is it a tumor of small, blue cells, similar to a neuroblastoma, arising from the olfactory epithelium?
Olfactory neuroblastoma ("esthesio-neuroblastoma")
Is it a fibrovascular tumor from the throat of a teenaged male?
Angiofibroma
Is it a lymphocyte-rich squamous cell carcinoma of the throat?

Is the patient perhaps Chinese? Did your instructor perhaps mention a link to Epstein-Barr virus?

"Lymphoepithelioma"
Is it a rounded mass on the true vocal cord? Is the patient perhaps a singer, a teacher, and/or a drill sergeant?
Laryngeal polyp
Is it a wart-like, non-invasive tumor on the vocal cord? Did the instructor perhaps mention a link to human papillomavirus? Are they perhaps multiple, and did they obstruct a child's airway?
Laryngeal papilloma
Is it an invasive, cauliflower-like mass on the mucosa of any portion of the larynx? Histologically, is it malignant?
Laryngeal carcinoma

NOTE: Most of these are squamous cell carcinomas.

Is it a painful ulcer, lasting a few days, somewhere on the oral mucosa (not the vermilion border of the lip), perhaps related to minor trauma or stress, but not to more serious illness? Do you recognize it as the familiar "canker sore"?

Or is it a similar ulcer on a mucosal surface from a patient with Beh€et's disease or Crohn's regional enteritis?

Aphthous ulcer

NOTE: "Not caused by herpes."

Is it a blistering eruption on the lip, perhaps at a time of stress or sunburn? Do you recognize the familiar "fever blister"?

Is it little blisters and ulcers throughout the mouth of a baby or immunosuppressed person?

Herpes stomatitis
Is it leukoplakia or erythroplakia of the oral mucosa with considerable cellular atypia on biopsy?

Is it a cauliflower-like mass or malignant ulcer on the oral or lip mucosa? Does biopsy perhaps confirm malignancy?

Mouth cancer

NOTE: Most of these are squamous cell carcinomas.

Is it enlarged salivary gland in an adult with dry eyes and dry mouth? Does the person perhaps also have rheumatoid arthritis, lupus, scleroderma, anti-SSA/Ro, anti-SSB/La, and/or B-cell lymphoma?

Is it a biopsy showing major or minor salivary gland with most of the acini gone and replaced by a mass of lymphoid tissue, with or without germinal centers?

Sjogren's syndrome
Is it a round, benign-appearing, shiny, grayish mass in a salivary gland?

On microscopy, does it look like cartilage with a variable mix of primitive stellate myxoid tissue, acini and duct-like structures, hair structures, and/or other stuff?

Pleomorphic adenoma (mixed tumor of salivary gland)
Is it a round, very soft, brown mass in the parotid gland?

Is it a parotid tumor composed of tall, benign-appearing cells, strongly eosinophilic and packed with mitochondria? And is there a heavy lymphoid infiltrate?

Warthin's tumor (papillary cystadenoma lymphomatosum)
Is it a salivary gland, mouth or bronchial tumor that exhibits both the keratinization, desmosomes, and/or pearls of a squamous cell carcinoma, and the mucin and/or dPAS-positivity of an mucin-producing adenocarcinoma?
Mucoepidermoid carcinoma
Is it a salivary gland tumor composed of well-differentiated cells, consistent with salivary acini (eosinophilic, basophilic, or pale- staining), but without ducts?
Acinic cell carcinoma
Is it a salivary gland, mouth or bronchial tumor with a striking cribriform (glands-within-glands, i.e., Swiss cheese) pattern? Do the cells look pretty much benign? Do you perhaps see perineural invasion? And can you perhaps tell that the mucus in the glands stains slightly differently from the ground substance of the rest of the stroma?
Adenoid cystic carcinoma
Does the proximal portion of the esophagus terminate abnormally and/or communicate abnormally with the trachea or a bronchus?
Esophageal atresia / tracheo-esophageal fistula
Is the esophagus abnormally dilated along most of its length, but without any evidence that the gastroesophageal sphincter fails to open?
Megaesophagus
Think of Chagas's disease
Is the esophagus abnormally dilated, but the gastroesophageal sphincter tightly closed?
Achalasia
Is it a fibrous ledge in the upper esophagus?
Esophageal web
Is it a fibrous ledge at the level of the squamocolumnar junction between esophagus and stomach?
Schatzki's ring
Is it the proximal portion of the stomach which appears to have been pulled up into the thorax by the esophagus?
Sliding hiatus hernia
Is it a portion of the stomach that has herniated up into the thorax next to the esophago-gastric junction?
Para-esophageal hiatus hernia
Is it a portion of the esophageal mucosa which has herniated out past the cricopharyngeus muscle?
Zenker's pulsion esophageal diverticulum

Note: Pseudo-diverticulum

Is it a portion of the esophageal wall that has been pulled sideways into a blind pouch, perhaps by scar contraction in an adherent tuberculous mediastinal lymph node?
Traction esophageal diverticulum

NOTE: True diverticulum

Is it a small tear in the esophageal mucosa, resulting from severe retching? Did it perhaps bleed copiously?
Mallory-Weiss esophageal laceration
Is it an esophagus with its wall diffusely scarred and thickened, most severely near the stomach?

Is it a biopsy of the esophageal mucosa showing some of the following:
...eosinophils in the epithelium;
...layers of basal-like cells 20-50% or more of the way up the epithelium;
...hydropic change of some stratified squamous epithelial cells?

Gastroesophageal reflux
Is it a biopsy of the esophageal mucosa showing any columnar cells in the surface epithelium?
Barrett's esophagus
Is it dilated, thick-walled veins in the mucosa of the distal esophagus?
Esophageal varices
Is it a fungating or ulcerating cancer in the esophagus? Is the patient perhaps known heavy drinker and heavy smoker? Or is the patient perhaps known to suffer from Barrett's esophagus?
Esophageal cancer

NOTE: Most are squamous cell carcinoma; in Barrett's mucosa, expect adenocarcinoma

Are some of the abdominal viscera in one pleural cavity or the other, because part of the diaphragm did not form properly?
Diaphragmatic hernia
Is the pyloric muscle much too thick, obstructing outflow from the stomach? Is the patient perhaps a 1-month old male infant with projectile vomiting?
Pyloric stenosis
Is the gastric mucosa acutely inflamed? In other words, do you perhaps see hyperemia grossly and neutrophils in the lamina propria microscopically? In bad cases, are there lots of little ulcers and bleeding points?
Acute gastritis
Has the fundus of the stomach lost the velvety appearance of its mucosa? On microscopy, do you see the epithelium transformed into a nondescript simple cuboidal epithelium, perhaps with atypia? Does the patient perhaps have antibodies against parietal cells, antibodies against intrinsic factor, pernicious anemia, Hashimoto's disease, and/or autoimmune Addisonism?
Type A chronic gastritis
Is the gastric antrum selectively inflamed? Does the patient perhaps have a duodenal ulcer as well? Do you know that the patient makes excess stomach acid? Is the antrum infested with Helicobacter ?
Type B "hypersecretory" chronic gastritis
Is the gastric antrum, and perhaps the fundus, involved in a process with some or all of the following:
...chronic inflammation;
...atrophy;
...intestinal metaplasia of some type;
...carcinogenesis?
And does the process begin on the surface and spread deep into the glands as it progresses?
Type AB "environmental" chronic gastritis
Is it a wiggly-looking bacterium adhering to the surface of antral-type gastric mucosa (in the antrum, or metaplasia elsewhere in the gut)? Are the surfaces of the mucus-producing cells disrupted?
Helicobacter
Are the mucosal folds excessively thick grossly and microscopically? Does histologic examination show excessive numbers of mucus cells? Is there excess mucus production, perhaps leading to protein wasting?
M‚n‚trier's hypertrophic gastritis

Or some related condition.

Is the gastric mucosa abnormally thick and lush, as a result of a gastrinoma somewhere else inside the patient? Does the patient (probably) have ulcers and/or diarrhea?
Zollinger-Ellison syndrome
Are there several small (ó1 cm) superficial ulcers in the gastric fundus? Is the patient perhaps under marked physical (burns, intracranial catastrophe, deadly illness) and/or emotional stress? Or did the patient perhaps take a lot of alcohol, tobacco, coffee, aspirin, or glucocorticoids?
Acute gastric erosions / acute stress ulcers
Is it a sharply-demarcated benign ulcer in some portion of the gut exposed to peptic juice and perhaps Helicobacter?

If it is an ulcer in the stomach, has scar contraction produced a radiating pattern of the rugae?

Peptic ulcer
Is it one of several small, smooth exophytic growths on the gastric mucosa?

Is it a stomach tumor composed primarily of benign-appearing glands resembling normal gastric pits?

Hyperplastic gastric polyp
Is it an exophytic gastric tumor, microscopically composed of tubular or villous glandular structures, perhaps with some dysplasia or even a tiny focus of cancer?
Neoplastic gastric polyp ("adenomatous polyp of the stomach")
Is it an exophytic and/or ulcerating gastric mass, composed either of tall, bizarre columnar cells or large, bizarre polygonal cells or signet-ring cells?

Is it a stomach with its wall more or less diffusely thickened ("linitis plastica"), with cancer cells singly or in small clusters infiltrating through the wall?

Stomach cancer

NOTE: Most gastric cancers are adenocarcinomas

Is it a malignant mass in the mucosa of the stomach composed of monotonous cells with scanty cytoplasm and which do not adhere to each other?
Gastric lymphoma
Is it a grossly and microscopically benign-appearing stomach tumor that takes a silver stain, produced carcinoid syndrome, or is positive for neurosecretory granules?
Gastric carcinoid
Is it a portion of small intestine with creatures on its brush border, presenting crescent shapes in cross-section?
Giardiasis
Is it a portion of small intestine with little, round, basophilic, acid-fast creatures living in its brush border?
Cryptosporidiosis

Or some similar organism

Is it a portion of small intestine with epithelial cells packed with clear lipid? Does the patient perhaps have malabsorption and/or acanthocyte red cells?
Abetalipoproteinemia
Is it a portion of small intestine (or perhaps someplace else) with large pools of fat plus abundant macrophages loaded with PAS-positive bacilli, both in the lamina propria? Does the patient have malabsorption, and perhaps also arthropathy and/or encephalopathy?
Whipple's disease
Is it a non-neoplastic disease of the small bowel with ulcers with their long axes oriented parallel to the long axis of the bowel?

On section, do you see an infiltrate composed primarily of macrophages, with phagocytosis of necrotic debris and normal red cells?

Are there excessive macrophages in other lymphoid tissues of the body?

Typhoid fever

Tip: Use a metachromatic stain to see the bacteria!

Is it a portion of bowel that shows dusky-brown to gangrenous changes as a result of thrombosis or other occlusion of the superior mesenteric artery?

Is it a portion of bowel that showed hemorrhagic necrosis as a result of being trapped in a hernia, in an intussusception, or under an adhesion?

Is it a large intestine with dusky-brown to gangrenous changes at the splenic flexure or in the midportion of the rectum ("watershed zones")? Was the patient perhaps in shock, and/or receiving digitalis, norepinephrine, or dopamine?

Is this a mild case in which there is acute inflammation with or without necrosis (which if present simulates a pseudomembrane) involving the superficial mucosa?

Ischemic bowel
Is it small intestinal mucosa, the only abnormality being deepened crypts and absent villi?
Sprue (including "celiac disease"/ "gluten enteropathy" and "tropical sprue")

Is it small intestinal mucosa packed with eosinophils?
Consider food allergy
Is it small intestinal mucosa with plenty of lymphocytes but no plasma cells?
Agammaglobulinemia

NOTE: You win the sharp-eyes prize if you noticed this!

Is it a portion of small bowel, or some other portion of the gut or large airways, exhibiting several of the following:
...lesions are sharply focal ("string sign", "garden hose segments", and all that);
...some pathology in all three layers of the gut
...fissure ulcers running parallel to the long axis of the gut;
...ulcers resembling the familiar aphthae;
...non-caseating granulomas;
..."creeping fat" growing up around the side of the gut wall;
...fistula formation;
...most common site of involvement is the terminal ileum?
Crohn's regional enteritis ("terminal ileitis")
Is it a tough, thin fibrous band connecting two periteonalized surfaces?
Peritoneal adhesion
Is it a mass of mucus and fibrous tissue matting together the peritoneal surfaces? And are there at least a few cancer cells in the mucin?
Pseudomyxoma peritonei
Is it a loop of bowel telescoped into itself?
Intussusception
Is it a loop of bowel twisted around its mesentery?
Volvulus
Is it a birth defect in which a portion of small or large bowel has no lumen?
Atresia of the bowel
Is it a two-inch true diverticulum of the ileum, two feet proximal to the cecum? Does it perhaps contain gastric mucosa? Has it perhaps ulcerated or bled or become inflamed?
Meckel's diverticulum
Is it a grossly and microscopically benign-appearing intestinal tumor that takes a silver stain, produced carcinoid syndrome, or is positive for neurosecretory granules?
Intestinal carcinoid
Is it a grossly and microscopically benign-appearing tumor of the bowel? Histologically, is there a mix of normal-appearing glands, abundant collagenous stroma, and a tree-like pattern of smooth muscle?

Does the patient perhaps have dark freckles especially on the lips?

Peutz-Jegher type hamartomatous intestinal polyp
Is it large intestine grossly distended because of lack of motility, and thorough examination of the involved wall shows few or no ganglion cells?
Hirschsprung's megacolon
Is it large intestine grossly distended because of lack of motility, and the underlying cause is serious intrinsic disease of the colon (i.e., ulcerative colitis, pseudomembranous colitis, bacterial colitis)?
Toxic megacolon
Is the lamina propria of the large bowel packed with macrophages laden with brown pigment? Does the patient perhaps recall having used cascara or rhubarb?
Melanosis coli
Is it a portion of large bowel, especially a portion of sigmoid, with little blebs sticking out its sides at 120ø from the mesentery?

Has a portion of the mucosa herniated through the muscularis propria of the large bowel? Is there perhaps a big fecalith in the lumen? Or did the little tiny artery get scraped and bleed like crazy?

Diverticular disease of the colon ("diverticulosis")

NOTE: Yes, these are really pseudo-diverticula.

Has a portion of the mucosa herniated through the muscularis propria of the large bowel? And is the surrounding area now a mess of acute inflammation and scarring?
Diverticulitis of the colon
Is it a dilated vein in the hemorrhoidal plexus around the anus? And has it been persistently dilated?
Hemorrhoid
Is it a large bowel or portion thereof exhibiting most of the following:
...rectum is most severely involved, and there are no discontinuities;
...the mucosa is ulcerated, with some spared areas appearing like cobblestones;
...the ulcers are superficial, polygonal craters instead of deep longitudinal fissures
...the mucosa is heavily infiltrated with plasma cells;
...some crypts are distended and packed with neutrophils ("crypt abscesses")
...the process is confined to the mucosa except in the most severe cases;
...regenerating mucosa appears as pseudopolyps ("inflammatory polyps");
...except perhaps for "backwash ileitis", no other portion of the gut is involved;
...there are no granulomas;
...nothing looks like an amoeba, and the shigella culture came back negative;
...is there perhaps some dysplasia, or even a frank cancer?
Ulcerative colitis

NOTE: "Crypt abscesses", while usually present, are by no means pathognomonic

NOTE: Shigella and some other infections can produce a very similar picture.

Is it a large intestine with a greenish pseudomembrane covering its inner surface, at least in patches?

Is it a microscopic picture of large intestine with the upper half of the mucosa replaced in patches by tufts of fibrinous and necrotic debris?

Pseudomembranous colitis

NOTE: Ischemic colitis can look quite similar. Clinical correlation (Clostridium difficile , antibiotic use) required!

Is it a portion of large intestine with an extra dense, collagenous layer underneath the epithelium? And are the crypts basically normal, without crypt abscesses?
Collagenous colitis
Is it an extensively ulcerated colon, with ulcers widening just above the muscularis mucosae, where they stop ("Erlenmeyer flasks")?

Are there large, round, dPAS-positive, multinucleate, erythrocyte- eating blobs that could be amoebas?

Amebic colitis

NOTE: Masses of granulation tissue in the cecum in this disorder are amebomas

Is it a severe inflammatory and perhaps necrotizing lesion of the bowel of a newborn, perhaps a premature baby? And was the child perhaps not breast-fed?
Necrotizing enterocolitis
Is it a portion of colonic mucosa with several tiny nodules that look like rice grains, and no other abnormality?

Is it a biopsy of one such lesion, showing mucus epithelial cells of variable heights, imparting a scalloped or sawtooth appearance to the crypts?

Hyperplastic polyp of the colon
Is it a pedunculated ("berry on a stem") or sessile ("bump"), benign- appearing lesion on the colonic mucosa? And does microscopy show epithelial cells that:
...are too tall for their width;
...have large, elongated nuclei, with too little cytoplasm;
...make very little mucin?
Adenoma ("adenomatous polyp") of the colon

NOTE: Look at the architecture to distinguish the villous adenoma from the tubular adenoma. Both can turn malignant; the villous adenoma is more worrisome.

Is it a colonic polyp, typically from a child, with abundant stroma and a pattern of normal-appearing glands? (I.e., is this a hamartoma?)
Juvenile colon polyp
Does the colon contain hundreds of adenomatous polyps? Has it been perhaps removed by a savvy physician to prevent cancer?
Familial adenomatous polyposis coli

NOTE: Anti-oncogene deletion syndrome.

Variants:
Gardner's syndrome: F.A.P. plus bone and fibroblast tumors

Turcot's syndrome: F.A.P. plus brain tumors

Is it an exophytic (cauliflower), endophytic (ulcer), and/or diffusely-infiltrating (napkin-ring, radiologist's apple-core) lesion of the colon?

Microscopically, is it an adenocarcinoma composed of tall, basophilic cells with elongated nuclei? Or is it perhaps a more anaplastic adenocarcinoma, or even an infiltrating signet-ring adenocarcinoma?

Adenocarcinoma of the colon ("colon cancer")
Is it an appendix that is obviously acutely inflamed and perhaps ruptured, gangrenous, and so forth?

Is it a histologic section of appendix, and neutrophils are present?

Acute appendicitis
Is it an appendix bearing a yellow tumor, without other pathology? If you have additional information, does it suggest carcinoid?
Appendiceal carcinoid
Is it an appendix that is distended with mucus?
Mucocele of the appendix

NOTE: This can result either from distention following obstruction, or from a mucus-producing adenoma or adenocarcinoma.

Is it a retroperitoneum with an overgrowth of very dense connective tissue, eventually compromising the ureters? Did the patient perhaps take a lot of ergot?
Retroperitoneal fibrosis ("sclerosing retroperitonitis")
Is it a section of liver parenchyma with most or all of the following:
..."lobular disarray" (i.e., you do not see the usual separate liver plates)
...a lymphocytic infiltrate among the hepatocytes, or at least in the portal areas;
...hydropic change ("ballooning degeneration")
...single-cell necrosis ("apoptosis", "Councilman-body formation");
...extra Kupffer cells, with some perhaps packed with lipofuscin indicating recent hepatocyte necrosis;
...necrosis of small groups of cells, typically disappearing ("dropout necrosis"), with the reticulin, sinusoids and Kupffer cells collapsing together here?
Viral-type hepatitis

Think of acute hepatitis A, B, C, D, or E, or yellow fever

Also consider autoimmune "lupoid" hepatitis, Wilson's disease, or drug effect (remember isoniazid hepatitis, alpha-methyldopa hepatitis, others).

Is it a gross or microscopic section of liver, with the lobular architecture more or less gone, and divided instead by fibrous bands into well-defined nodules?
Cirrhosis

For the likely cause, check the size of the nodules, and look for additional hints.

Is it a cirrhotic liver with nodules mostly less than 3 mm across?
Micronodular cirrhosis
Think first of alcoholism, then of other processes that involved lobules more or less uniformly, i.e., Wilson's disease, iron overload ("hemochromatosis"), primary biliary cirrhosis, methotrexate toxicity, or alpha-1 protease inhibitor ("antitrypsin") deficiency
Is it a cirrhotic liver with nodules greater than 3 mm across?
Macronodular cirrhosis

Think first of autoimmune "lupoid" hepatitis or hepatitis B, C, or D, because these processes involved lobules non-uniformly. Remember that cirrhosis from any cause may progress to large nodules when it reaches the end-stage of "postnecrotic cirrhosis".

Is it a cirrhotic liver with extreme scarring, no matter how big the nodules are?
Postnecrotic cirrhosis

NOTE: This is a dumb name for the end-stage of cirrhosis from any cause.

Is it a pale, flabby, shrivelled liver with a wrinkled capsule? Did the patient die, or is the patient near death?

Is it a section of liver with dropout or apoptosis of most of the liver cells? If there are live cells, are they proliferating from the tiny bile ducts?

Massive hepatic necrosis ("acute yellow atrophy")

Think of acute hepatitis B, C, or D, amanita toadstool poisoning, carbon tetrachloride toxicity, acetaminophen overdose, halothane idiosyncracy

Does it look like massive hepatic necrosis but not quite so bad, and patient is perhaps not dead or near death?
Sub-massive hepatic necrosis

Think of the same causes as for massive hepatic necrosis

Is it a portion of liver with a heavy portal infiltrate, composed primarily of lymphocytes? Is the patient (probably) known to be six- months post the onset of viral hepatitis, and still has elevated serum transaminases? Do you see NO tendency of the infiltrate to spill into the liver parenchyma? If there is any hepatitis-like change in the parenchyma, do you at least see NO "piecemeal necrosis" of groups of cells at the limiting plate? And finally, are you confident the patient does not have lymphoma or Hodgkin's disease?
Chronic persistent hepatitis

Think of a person recovering from hepatitis B.

The prognosis is generally good.

Is it a portion of liver with a heavy portal infiltrate, composed largely of lymphocytes? Does the infiltrate tend to spill into the liver parenchyma? And do you see at least groups of a few cells undergoing apoptosis or dropout next to the limiting plate ("piecemeal necrosis")? And do you perhaps even see bands of necrosis running from portal area to central vein ("bridging necrosis")?
Chronic active hepatitis

Think of hepatitis B, C, or D, autoimmune "lupoid" hepatitis, Wilson's disease, alpha-1 protease inhibitor ("antitrypsin") deficiency, or drug effect.

The prognosis is generally bad. The process leads to cirrhosis.

Is it a bile duct or canaliculus distended by green-brown material?

Is it a mass of green-brown material surrounded by a ring of hepatocytes?

Are there perhaps some nearby Kupffer cells that have phagocytized bile? Do you perhaps see "feathery degeneration" of hepatocytes laden with bile salts?

Bile plug / bile lake

Think of some cause of intrahepatic (alcoholism, hepatitis, cirrhosis, tumor) or posthepatic (gallstone, tumor) bile duct obstruction

Is he or she a person with a mild (2-6 mg/dL) unconjugated hyperbilirubinemia and no other problem? Does this level double when the person fasts for a few days? If somebody actually biopsied the liver (and I'm not recommending this), is it normal?
Gilbert's non-disease
Is he or she a person with a mild (2-6 mg/dL) conjugated hyperbilirubinemia and no other problem? And is the liver dark brown grossly, and are the hepatocytes laden with brown pigment?
Dubin-Johnson non-disease

NOTE: No pigment? Rotor non-disease

Do 75% or more of the hepatocytes contain Prussian-blue stainable iron?

Is there stainable iron in the bile duct epithelium?

Are the spleen, pancreas, adrenals, heart, and duodenum a rusty color, with abundant stainable iron on microscopy?

For any of the above, is the patient's skin perhaps a curious bronze- brown color? Is there perhaps cirrhosis? Is there perhaps diabetes? Is there perhaps arthritis worst in the knuckles? Is there perhaps loss of libido? Is there perhaps a cardiac rhythm disturbance? Is the transferrin saturation (serum Fe/TIBC) greater than 82% (or at least high)?

Severe iron overload, probably primary hemochromatosis

NOTE: Also ask about previous transfusions for insufficient red cell production

Are the Kupffer cells packed with hemosiderin?
Chronic hemolysis
Are the Kupffer cells packed with a pigment that looks like hemosiderin but does not take the Prussian blue stain?
Malaria
Is it liver from a child with lobular disarray and formation of hepatocyte syncytia (giant cells) of hepatocyte origin?
Neonatal hepatitis

NOTE: Many causes

Is it neonatal or adult hepatitis, perhaps with widespread necrosis, with large, eosinophilic inclusions in the hepatocyte nuclei?

In the neonate, is there widespread hepatic necrosis as well as necrosis of the brain and adrenals?

Herpes simplex hepatitis
Is it a liver with microvesicular steatosis? Did it come from a child with cerebral edema following a mild viral-type illness? And was blood ammonia preposterously high? And did electron microscopy perhaps show widespread severe damage to the body's mitochondria?
Reye's syndrome
Is it a liver containing random grooves across its surface?
Hepar lobatum

NOTE: Textbooks cite congenital syphilis with deep gummas and scar contraction; much more often today, this is a mere congenital curiosity

Is it a liver with a series of "rib" grooves on its right diaphragmatic surface?
Costal grooves

NOTE: Lots of emphysema patients develop them.

Are the portions of the sinusoids closest to the central veins distended with blood?

Are the hepatocytes dead or dying around the central vein ("centrilobular necrosis", "ischemic hepatitis") without a history of poisoning?

Are the Kupffer cells in the central area packed with hemosiderin (from broken-down red cells) and lipofuscin (from dead hepatocytes) and bile (couldn't be processed in the hypoxic environment)?

Is the patient in shock or right-sided heart failure, and the underlying problem is not liver disease?

Congested liver / hypoxic liver

NOTE: These usually occur together. Congestion doesn't damage the liver

Is there a bit of scarring just around the central veins, perhaps enough to produce "pigskin" dimples on the liver surface? And has the patient had problems with right heart function (notably, tricuspid insufficiency) for a while?
Cardiac hepatic sclerosis

NOTE: Usually a non-problem. I bet you never see "cardiac cirrhosis", with central-central bridging.

Is it a blue or pale wedge-shaped area in a liver? Is it perhaps atrophic? And has either a portal vein or hepatic artery branch been occluded?
Zahn hepatic infarct
NOTE: Dual blood supply prevents necrosis, and "infarct" is a figure of speech. The blue color is from slow blood flow (how?)
Is the liver very congested, and you see a gross thrombus in a large hepatic vein, and/or a microscopic thrombus in a central vein? And does your patient perhaps have polycythemia vera, or is pregnant, or has hepatocellular carcinoma?
Budd-Chiari syndrome
Is it a photomicrograph of congested liver, with veins showing greatly thickened walls (check the reticulin or elastic stains), perhaps with little thrombi?
Hepatic veno-occlusive disease
Are the hepatocytes dead or dying, worst around the central vein?
Centrilobular hepatic necrosis

Think of ischemia, carbon tetrachloride, chloroform. Lowest oxygen tension in the liver makes these cells most vulnerable.

Are the hepatocytes dead are dying, worst in the midzonal area? Do you see Councilman bodies but not much inflammation?
Midzonal hepatic necrosis / yellow fever

Nobody knows why.

Are the hepatocytes dead or dying, worst in the periportal ("peripheral) areas?
Peripheral hepatic necrosis / periportal hepatic necrosis

Think of phosphorus or some other exotic poisoning; if there are little fibrin thrombi, and bleeds all over the liver, it's probably eclampsia. Bad things in the blood reach these cells first.

Is it a hepatocyte with a "ground glass" homogeneously-staining cytoplasm? Do you perhaps have a picture showing it staining positive with orcein?
Hepatitis B carrier or Hepatitis B chronic liver disease
Is it obvious suppuration along the biliary tree?

Is it a bile duct with two or more neutrophils in its lumen?

Acute cholangitis
Is there a lymphocytic infiltrate concentrated around the bile ducts in the portal triads? And is there some clinical evidence of cholestasis, but no other abnormal anatomy?
Pericholangitis
Are certain bile ducts, inside and/or outside of the liver, narrowed by chronic inflammation and dense scarring? And there has been no biliary surgery? Do the bile ducts perhaps look like a string of white beads? And does the patient perhaps also have ulcerative colitis?
Primary sclerosing cholangitis
Is it pus in a confined space in the liver?
Liver abscess

NOTE: Nothing subtle. The underlying cause is usually ascending cholangitis from obstruction.

Is it an area of necrosis in the liver with little or no inflammatory reaction? And if you look (or have a dPAS stain), do you see amebas?
Amebic liver abscess
Is it fatty change in the liver, and most of the cells have a single fat vacuole?
Macrovesicular steatosis

Think of alcoholism, ischemia, methotrexate toxicity or other drug effect, Wilson's disease, galactosemia, other rare metabolic kinks, hepatitis C

Is it fatty change in the liver, and most of the cells have several small fat vacuoles?
Microvesicular steatosis

Think of ischemia, drug effect, Reye's syndrome, pregnancy, outdated tetracycline, heavy aspirin use, rare metabolic kinks, hepatitis C

Is it fatty change in the liver, without inflammation, Mallory's alcoholic hyaline, neutrophils, cell necrosis, or cirrhosis? And is the patient known to overindulge in alcohol?
Alcoholic fatty liver

NOTE: Liver function and serum enzymes may be very abnormal, but this is NOT cirrhosis, and should be reversible upon abstinence.

Is it a liver with fatty change plus cell necrosis, neutrophils, and Mallory's alcoholic hyaline? And is cirrhosis not (yet) present? And is the patient known to overindulge in alcohol?
Alcoholic hepatitis

NOTES: (1) Liver function and serum enzymes will be very abnormal, but this is not cirrhosis, and should be reversible upon abstinence. (2) Drug effects and Wilson's disease can give identical histology.

Is it a cirrhotic (micronodular or massively-scarred postnecrotic) liver in a patient who is or was known to overindulge in alcohol, which you assume to be the cause? Are alcoholic fatty change or even alcoholic hepatitis perhaps also present (if the patient was recently drinking, that is)?
Alcoholic ("Laennec's") cirrhosis
Is it a liver showing changes similar to alcoholism, acute viral hepatitis, or chronic active viral hepatitis, but special stains for copper (rhodanine, rubeanic acid) show abundant copper deposition in hepatocytes?

Does the patient have a Kayser-Fleischer ring in the cornea?

Does the patient perhaps have neurologic problems and/or hemolysis in addition to / instead of obvious liver problems?

Wilson's disease

NOTE: Don't goof on this one.

Are there variably-sized round globules of dPAS-positive material inside hepatocytes? Is there perhaps hepatitis or cirrhosis?
Alpha-1 protease inhibitor ("antitrypsin") deficiency
Is it a liver with lymphocytes, histiocytes, and plasma cells surrounding and apparently destroying the portal bile ducts? Are the ducts either gone or proliferating bizarrely? Is there visible cholestasis? Has the process perhaps progressed with fibrosis toward, or to, a true cirrhosis? Is there perhaps also some granuloma formation, some Mallory's hyaline, or some local excess of copper?
Primary biliary cirrhosis
Is it fibrosis progressing to cirrhosis as a result of biliary obstruction? Are the bile ducts still intact?
Secondary biliary cirrhosis

Is it a liver with widespread scarring, with many plasma cells in the scars?
Congenital syphilis

NOTE: You'll probably never see this today.

Is it a sharply-circumscribed, homogeneous-looking red or blue blotch in the liver?

Is it a vascular hamartoma in the liver on microscopic examination?

Hemangioma of the liver

Future surgeons: Don't biopsy.

Is it a circumscribed bump (typically yellow) in the liver, with a central, star-shaped scar?

Microscopically, does it look like a nodule of cirrhosis plus fatty change, in an otherwise-normal liver? Is the patient perhaps (but not necessarily!) a man taking anabolic steroids, or a woman taking the oral contraceptive pill?

Focal nodular hyperplasia of the liver

NOTE: "Fool's cirrhosis"

Is it circumscribed bump (typically yellowish) in the liver, with prominent blood-engorged sinusoids?

Microscopically, is there no or mild cellular atypia? Is the patient perhaps (but not necessarily!) a man taking anabolic steroids, or a woman taking the oral contraceptive pill?

Liver cell adenoma ("hepatic adenoma")
Is it a circumscribed white bump in the liver, microscopically with many little bile ducts in fibrous tissue and not much else?
Bile duct adenoma ("von Meyenberg complex"; "bile duct hamartoma")
Is it a variegated red, yellow, green, brown, and/or white mass, arising singly or multifocally in the liver, particularly in a setting of hepatitis B and/or iron overload and/or exposure to aflatoxin mold in a poor person's diet and/or anabolic steroid use?

Is it an apparent primary malignancy of the liver that shows a tendency, grossly or microscopically, to invade blood vessels?

Is it a cancer composed of trabecular, rings, or sheets of cells that look like hepatocytes? Do they perhaps contain Mallory's hyaline and/or à1-protease inhibitor globules?

Is it a cancer, anywhere in the body, that produces bile?

Is it "normal liver, no portal areas identified" obtained from a lung biopsy? And the clinicians swear they hit the lung mass, not the liver?

Hepatocellular carcinoma ("hepatoma")

NOTE: You can also see Mallory's hyaline in occasional lung adenocarcinomas.

Is it a single mass in a non-cirrhotic liver? Microscopically, is it composed of plates of hepatocytes separated by sheets of collagen?
Fibrolamellar hepatocellular carcinoma
Is it a childhood liver cancer composed of malignant hepatocytes, perhaps with an admixture of other mesenchymal elements?
Hepatoblastoma
Is it a desmoplastic adenocarcinoma arising in the liver? Are the cells perhaps mucin positive but without anything to suggest hepatocyte differentiation?
Cholangiocarcinoma

NOTE: These tumors will never produce bile.

Is it a mixed cancer in the liver, composed of both hepatocellular carcinoma and cholangiocarcinoma?
Mixed hepatocellular carcinoma - cholangiocarcinoma
Is it a mass of bloody nodules in the liver? And microscopically, do you see cords of polygonal cells making poorly-defined vascular channels, and perhaps some metaplastic bone marrow? Has the patient perhaps been exposed to vinyl chloride monomer?
Angiosarcoma of liver
Is it tumor nodules in an otherwise-normal liver, the larger ones bearing a central dimple ("umbilication")?
Metastases to the liver
Is the patient a baby with cholestatic jaundice due to failure of portions of the intrahepatic and/or extrahepatic bile ducts to form lumens?
Biliary atresia
Is it a gallstone that is mostly yellow?

Is it a large solid common gallstone?

Cholesterol gallstone
Is it a gallstone that is mostly black, with a bumpy surface? And is it small, under 5 mm or so? And does the patient perhaps have longstanding intramedullary (megaloblastic anemia, thalassemia) or intravascular (hemoglobinopathy, spherocytosis) hemolysis?
Bilirubinate gallstone
Is it bile that is so pasty-thick with suspended micro-particles that it can plug things?
Biliary sludge
Is the gallbladder acutely inflamed, with neutrophils in the lamina propria as a minimum? Is there also cholelithiasis?
Acute cholecystitis
Has the entire gallbladder undergone dystrophic calcification after a bout of acute cholecystitis?
Porcelain gallbladder
Are there lots of little yellow flecks (groups of cholesterol-laden macrophages) among the mucosal folds of the gallbladder? Do they remind you of the seeds on a strawberry?
Cholesterolosis of the gallbladder ("strawberry gallbladder")
Is the gallbladder laden with opalescent, mucoid fluid? Is the outlet occluded by a stone or by scar?
Hydrops of the gallbladder
Is it a gallbladder with several of the following:
...hyperplastic smooth muscle;
...scarring of the lamina propria;
...scarring of the serosa;
...pseudodiverticula, in which the mucosa herniates into or through the muscle ("Rokitansky-Aschoff sinuses")
...an inflammatory infiltrate with lymphocytes?
Chronic cholecystitis
Is it an exophytic, ulcerating, or infiltrating cancer of the gallbladder? Does the patient perhaps have gallstones too?

Microscopically, is it composed of malignant glandular or glandular- and-squamous elements?

Adenocarcinoma of the gallbladder
Is it a malignant tumor of the bile ducts composed of glandular elements? Does the patient perhaps have infestation with the liver fluke, or suffer from ulcerative colitis?
Adenocarcinoma of the bile ducts
NOTE: No relationship to gallstones
Is it a bile duct adenocarcinoma at the junction of the right and left hepatic ducts?
Klatskin tumor
Is it a malignant tumor of glandular origin at the ampulla of Vater?
Periampullary adenocarcinoma

NOTE: Consider doing a Whipple procedure! You've got a good chance of cure if tumor is localized.

Are the two portions of the pancreas inappropriately wrapped around the duodenum?
Annular pancreas
Is it a pancreas with atrophy and loss of the acini, and viscous plugs in the ducts?
Cystic fibrosis
Is it a pancreas with more or less homogeneous atrophy and loss of the acini, and perhaps scarring of the interstitium, and this is not cystic fibrosis?
Obstructive pancreatic atrophy
Is it a pancreas that is transformed into a mess of bloody, necrotic stuff?

Microscopically, do you see hemorrhage, necrosis, fat necrosis, and acute inflammation?

Acute hemorrhagic pancreatitis

Ask about alcoholism, trauma, common duct stone or sludge

Is it a pancreas with uneven atrophy and loss of acini, with impressive scarring?

Are there perhaps protein or calcific blobs in the surviving ducts (suggesting alcoholism)?

And are you confident that no "acinus" or "duct" contains one nucleus more than four times bigger than another in the same structure, and that you see no mitotic figures, and that you see no obviously incomplete "acini" or "ducts"?

Chronic pancreatitis

NOTE: Misnomer. This is scarring from old damage.

Is it a hollowed-out region in the pancreas or surrounding fatty tissues, or perhaps even the lesser sac, lined by scar tissue, with no inner epithelial layer?
Pancreatic pseudocyst
Is it an obvious cancer in the pancreas, composed of cells of glandular origin?

Could it be a pancreatic scar, but there are "acini" or "ducts" which are incomplete or which contain one cell with a nucleus four times larger than another in the same structure, or you see mitotic figures?

And does the patient perhaps have unexplained depression and/or unexplained venous thrombosis?

Pancreatic adenocarcinoma / "cancer of the pancreas"
Is it an islet of Langerhans packed with eosinophils?
Child of a diabetic mother
Is it an islet of Langerhans packed with lymphocytes?
Type I diabetes, early
Is it a section of pancreas that should contain islets, but doesn't?
Type I diabetes, late

NOTE: The best place to find lots of islets is in the tail of the normal pancreas.

Is it an islet of Langerhans that contains abundant fibrous tissue and/or amyloid?

Is it a section of pancreas that contains some oversized islets? And does this surprise somebody, because the patient is diabetic?

Type II diabetes
Is it a sharply-circumscribed, round nodule in the pancreas?

Does it have the histology of a very large islet of Langerhans, perhaps with a collagenous and/or amyloid stroma? And is your instructor perhaps showing you an immunoperoxidase stain for some endocrine hormone?

Islet cell adenoma

NOTE: Some of these will turn out to be cancers. This is pretty much unpredictable.

Is it an islet cell adenoma, and does it stain for insulin and/or is the patient suffering from Whipple-triad hypoglycemia and/or has the patient become massively obese recently?
Insulinoma / beta cell adenoma
Is it lots of little clumps of endocrine-looking cells in the pancreas, especially near the ducts? Do they stain positive for insulin? Is the patient suffering from fasting hypoglycemia?
Nesidioblastosis
Is it an islet-cell adenoma, and does it stain for glucagon and/or does the patient have a sore tongue and/or necrotizing skin lesions?
Glucagonoma / alpha cell adenoma
Is it an islet-cell adenoma, and does it stain for gastrin and/or does the patient have Zollinger-Ellison syndrome with lots of stomach ulcers and diarrhea?
Gastrinoma

NOTE: Ask about multiple endocrine neoplasia type I (Wermer's MEN- I)

Is it an islet-cell adenoma, and does it stain for vasoactive intestinal polypeptide and/or does the patient have watery diarrhea and achlorhydria?
VIPoma
Is it an islet-cell adenoma, and does it stain for somatostatin?
Somatostatinoma / delta cell adenoma
Is he or she a patient with hematuria of glomerular origin (i.e., perhaps your found a red cell cast in the urine)? And does the patient also have azotemia, hypertension, oliguria, and mild edema?
Nephritic syndrome ("nephritis")
Is he or she a patient with heavy proteinuria of glomerular origin (ò3.5 gm per day for an adult, selective or nonselective), plus the expected hypercholesterolemia, hypoalbuminemia, and generalized edema?

Is the kidney grossly yellow at autopsy due to lipid accumulation in the proximal tubules?

Are there "lipid casts" in the renal tubules or urine?

Regardless of what else is wrong, are most of the foot processes obliterated on electron microscopy?

Nephrotic syndrome

NOTE: Dumb name!

Think of:
...diabetes
...amyloidosis
...membranous glomerulopathy
...foot process disease (i.e., minimal change glomerulopathy, focal- segmental glomerulosclerosis)

Is he or she a patient with nephritic syndrome who is taking a rapidly-downhill course?

On biopsy, are there fibrinous-proliferative crescents in ò80% of glomeruli?

Rapidly-progressive glomerulonephritis
Is he or she a patient who is wasting something into the urine because of proximal tubular failure?
"Fanconi syndrome"

NOTE: Terminology is loose here.

Is he or she a patient who is unable to concentrate urine well (i.e., complains first of nocturia)?
Renal medullary dysfunction
Is he or she a patient with oliguria, azotemia, and isosthenuria following either:
...ingestion of a tubular poison (mercury, gentamicin, many others);
...an episode of hypotension;
...an episode of massive hemolysis or rhabdomyolysis
...a big dose of non-steroidal anti-inflammatory drugs?

Is this a section of kidney with several of the following:
...obvious edema between the cortical tubules;
...flattening of the cortical tubular epithelium;
...loss of occasional single cells in the cortical tubules;
...necrotic cells in the lumens of the tubules;
...mitotic figures and/or multinucleate cells in the cortical tubules
...abundant white cells resembling myeloblasts in the capillaries in the renal medulla (don't ask me why!)

Acute tubular necrosis / "acute renal shutdown" / "shock kidney" / "vasomotor nephropathy"

NOTE: Other names exist

Is he or she a patient with the clinical picture of acute renal tubular necrosis, and you see red pigment casts (hemoglobin or myoglobin) in the tubules?
Pigment nephropathy
Is this a patient with hepatic failure, dilute urine, and bile- stained casts in the renal tubules?
Hepatorenal syndrome

NOTE: The morphology doesn't really define this poorly-understood process.

Is this a newborn with some or all of one or both kidneys composed of irregular cysts and fibrous tissue, as a result of failure of the blastema to obtain proper drainage?

Is it a portion of one kidney found to exhibit similar changes in an older person?

Is it a mess of fibrous tissue, cysts, and perhaps cartilage, bone, and/or muscle where kidney tissue ought to be?

Renal cystic dysplasia

NOTE: This is not polycystic kidney, but a sporadic birth defect.

Is it a pair of kidneys that began developing cysts in youth, and were gradually transformed into two huge cystic masses by later middle age?
Autosomal dominant polycystic kidney disease / "adult polycystic kidney"
Is it a pair of massively-enlarged, smooth-surfaced white kidneys in a newborn, with long, narrow cysts arranged radially?
Autosomal recessive polycystic kidney disease / "infantile polycystic kidney"

Is it a few dilated distal portions of collecting ducts, and the patient seems none the worse or perhaps developed a stone here, or got an infection, or has hematuria, or complains of back pain?
Medullary sponge kidney

NOTE: This is not polycystic kidney. Nobody knows the cause.

Is it a bunch of cysts in the medulla and at the corticomedullary junction, and the patient has isosthenuria and eventually renal failure?
Medullary cystic disease / nephronophthisis

NOTE: Several hereditary disorders.

Is it a single cyst (or a very few cysts) on a kidney with nothing else wrong except perhaps small-vessel disease?
Simple renal cyst
Is it a kidney that failed years ago, and the patient has been kept alive on dialysis or with a transplant? And has the kidney developed a mess of cysts, with scars and/or oxalate crystals and/or little yellow tumors?
Acquired dialysis cystic disease / trans-stygian kidney

NOTE: Dialysis isn't the cause. This is the inexorable progression of the end-stage kidney.

Is it a pair of kidneys fused at their lower poles?
Horseshoe kidney

Is it an intensely-eosinophilic, more-or-less round blob in a sick glomerulus?
Hyalinosis lesion

Think of FSGS / hyperfiltration lesion and/or diabetes. Hyalinosis is supposed to be a marker for hyperfiltration from any cause.

Are the glomeruli diffusely hypercellular, maybe with 5 or more neutrophils per glomerulus, and the hypercellularity is sufficient to compromise the capillary lumens?

Does immunostaining for IgG and C3 give a coarsely-granular, lumpy- bumpy pericapillary pattern?

Does electron microscopy show large, unevenly-spaced subepithelial deposits?

And the patient probably has nephritic syndrome, and you probably see some red cells in the tubules?

Diffuse proliferative glomerulonephritis

Think of post-streptococcal disease, deep bacterial infection, (remember bacterial endocarditis), bad (WHO IV) lupus

Is it rapidly-progressive (i.e., crescentic) glomerular disease, and do you have either of the following:
...positive anti-GBM antibodies in a significant titer, performed by a competent lab;
...linear fluorescence for IgG along the glomerular basement membrane;

Rapidly-progressive glomerulonephritis type I (anti-GBM disease)

NOTE: "Goodpasture's disease" is anti-GBM disease with hemoptysis because antibodies also attack lung.

Is it rapidly-progressive (i.e., crescentic) glomerular disease, and do you see either:
...non-linear staining on immunofluorescence;
...immune deposits on electron microscopy?
Rapidly-progressive glomerulonephritis type II (bad immune complex disease)
Is it rapidly-progressive (i.e., crescentic) glomerular disease with:
...negative immunofluorescence;
...positive anti-neutrophil cytoplasmic antibody disease?

Is there perhaps also focal-segmental necrosis (which is unusual in other forms of RPGN) and/or a systemic vasculitis syndrome?

Rapidly-progressive glomerulonephritis type III (Wegener's granulomatosis / polyarteritis)
Is it a glomerulus with its basement membrane diffusely thickened, and the patient doesn't have diabetes?

Does dPAS or silver staining of the glomerulus show spikes projecting upward from the GBM?

Does immunofluorescence show a finely-granular pericapillary pattern of immune complex deposition?

Does electron microscopy show small, evenly-spaced subepithelial deposits?

And the patient probably has heavy nonselective proteinuria leading to the nephrotic syndrome?

Membranous glomerulopathy

Think of lupus (WHO V), chronic hepatitis B infection, chronic pyelonephritis, many others. Most cases remain idiopathic.

There's no inflammation, but many people insist on calling this something "-itis".

Is it a kidney with glomeruli that look normal by light and immunofluorescence, and show only loss of foot processes by electron microscopy?

Is the patient probably a child (or an adult with Hodgkin's) with mild nephrotic syndrome and selective proteinuria?

Minimal change glomerulopathy ("lipoid nephrosis", "nil disease")
Is it a kidney with glomeruli that are unusually large, exhibit focal (i.e., some glomeruli are involved) and segmental (portions of glomeruli are involved) sclerosis (i.e., too much mesangial matrix / basement membrane, obliterating capillary loops)? And is the immunofluorescent picture nonspecific (i.e., just a little IgM and C3 in the sclerotic areas, as you can see in any scar?) And are all the foot processes lost on electron microscopy?

And does the patient have nephrotic syndrome with nonselective proteinuria?

Focal-segmental glomerulosclerosis ("FSGS")

NOTE: This infamous lesion is often idiopathic, but can result from heroin abuse, HIV infection ("AIDS glomerulopathy") or a few glomeruli working overtime because the others are shut down ("hyperfiltration"). You'll see some FSGS in any end-stage kidney.

Is it a glomerulus with most or all of the following:
...a cloverleaf accentuation of the lobular architecture;
...splitting (reduplication) of the basement membrane ("tram tracks"; silver stain and dPAS show this well);
...irregular granules in immunofluorescence;
..."mesangial cells invading the capillary loops" on electron microscopy.

And is the patient probably a child with both hematuria and heavy proteinuria?

Membrano-proliferative glomerulonephritis type I / mesangiocapillary glomerulonephritis type I
Is it a glomerulus with splitting (reduplication) of the basement membrane ("tram tracks"; silver stain and dPAS show this well) by an electron-dense deposit which stains negative for immunoglobulin and strongly positive for C3? Is the deposit metachromatic, and stains brown with silver?

And is the patient probably a child with both hematuria and heavy proteinuria?

Membrano-proliferative glomerulonephritis type II / mesangiocapillary glomerulonephritis type II / dense deposit disease
Is it a kidney with glomerular proliferation, perhaps segmental, perhaps with some scarring? And is there primarily a mesangial deposition, primarily of IgA?

And is the patient probably a young person with some degree of hematuria?

IgA nephropathy ("Berger's disease")
Is he or she a patient with some or all of the following:
...bad IgA nephropathy, perhaps with some segmental necrosis and/or crescents;
...vasculitis, with predominantly IgA in the vessel walls;
...GI bleeding;
...arthritis;
...purpura?
Henoch-Sch”nlein purpura
Is it a kidney with focal-segmental, rather than diffuse-global, proliferation in the glomeruli?
Focal-segmental proliferative glomerulonephritis

Think of bacterial endocarditis (first!), IgA nephropathy, lupus (WHO III); mild versions of other causes of RPGN.

Is it a kidney with proliferation of mesangial cells (i.e., it's easy to count 5 or more nuclei in some mesangial areas), but without compromise of capillary lumens (until late)?
Mesangial proliferative glomerulonephritis

Think of IgA nephropathy, mild lupus (WHO II), Zuni nephropathy, mild or resolving proliferative glomerulonephritis, mild or resolving cases of other glomerular diseases.

Is it a kidney with variable glomerular lesions and abundant foam cells? On electron microscopy, is there a basket-weave GBM? And is the patient hard of hearing?
Alport's hereditary nephritis
Is it a kidney with most of the glomeruli hyalinized really bad, with relatively little vascular disease or interstitial scarring?
Chronic glomerulonephritis

NOTE: This is end-stage glomerular disease. In an end-stage kidney, don't expect to be able to determine the exact cause.

Is it a glomerulus with diffusely thickened GBM (light or electron microscopy), even to the point of obliterating the capillary lumens, but no immune deposits? Is there perhaps a hyalinosis lesion?

Is it a glomerulus bearing a lens-shaped droplet of hyalinosis-like material on the inner surface of Bowman's capsule ("capsular drop")?

Is it a glomerulus with both arterioles about equally hyalinized?

Is it a glomerulus with diffusely thickened GBM plus variably-sized rounded nodules ("balls") of mesangial matrix material ("nodular Kimmelstiel-Wilson lesion")?

Diabetic glomerulopathy

NOTE: Common usage calls these lesions "diffuse" or "nodular" glomerulosclerosis, depending on the absence or presence of Kimmelstiel-Wilson lesion.

Is it an electron micrograph of a glomerulus showing lamellar storage product?
Fabry's disease
Is it a massive subendothelial deposit visible on electron microscopy, taking up much or all of the rim of the capillary?
Wire loop

Your patient has lupus, bad membrano-proliferative glomerulonephritis type I, or cryoglobulinemia

Is it a solid mass of protein, not a fibrin-platelet thrombus, plugging a capillary? Is there some kind of glomerular disease that goes with it?
Cryoglobulinemia

NOTE: D'ya know how to test blood for it?

Is the renal pelvis dilated and inflamed?

Are there lots of little abscesses through a greatly swollen kidney?

Are there two neutrophils together in a renal tubule?

Is the renal interstitium packed with neutrophils? (And the glomeruli are spared, and appear normal?)

Acute pyelonephritis
Are the renal papillae necrotic?
Renal papillary necrosis

Think of diabetes (all papillae equally dead), phenacetin abuse, very severe pyelonephritis, sickle cell disease or even trait, Wegener's granulomatosis (all show papillae unequally dead).

Is this kidney acute inflamed and perhaps even shut down, probably with some kind of inflammatory infiltrate (neutrophils, eosinophils, lymphocytes, and/or plasma cells) in the interstitium, but you cannot identify a bacterium?
Acute interstitial nephritis

NOTE: Consider lupus or other immune, drugs, others.

Is it a kidney with irregular scarring, with broad pitting, especially at the poles, suggesting damage from repeated bouts of acute infection? And is there some obstructive or reflux-producing lesion, or a stone, that could have exacerbated the tendency to infection?

Microscopically, do you see interstitial scarring, perhaps with lots of lymphocytes, but with more or less normal glomeruli and vessels? Do you perhaps even see an area in which scar contraction has dilated cast-filled tubules ("thyroidization")?

Chronic pyelonephritis

NOTE: Another misnomer. It's scarring from previous infection. Perhaps bacteria persist.

Is this a kidney with the microscopic picture of chronic pyelonephritis, but no history of acute pyelonephritis?

Are there perhaps abundant plasma cells as well, suggesting autoimmunity?

Chronic interstitial nephritis

Consider drug effect, anti-tubular basement membrane disease, lupus, Sjogren's, many others.

Did the patient take a non-steroidal anti-inflammatory drug, and is now in renal failure, and do you see some or all of the following:
...fused foot processes;
...acute tubular necrosis;
...papillary necrosis (severe cases)?
Analgesic nephropathy
Are there uric acid crystals in the kidney tubules or insterstitium?

Are there perhaps tophi and/or urate stones?

Urate nephropathy

Consider gout treated primarily with probenecid, massive tissue necrosis, others.

Does the patient have plasma cell myeloma, and as a result, is there one or more of the following:
...amyloid B in the glomeruli;
...metastatic calcification;
...casts in the tubules with foreign-body reaction;
...infection?
"Myeloma kidney"
Is it a glomerulus that has been obliterated by fibrous tissue, and does dPAS or silver staining reveal a shrivelled glomerular tuft, reduplicated Bowman's membrane, and the remainder of the space filled by dense collagen?
Ischemic end-stage glomerulus

NOTE: The cause was damage to the blood vessels, probably hypertensive.

Is this a kidney with most or all of the following:
...finely-granular surface;
...hyalinized arteriolar sclerosis of afferent arterioles with sparing of efferent arterioles;
...concentric intimal fibrosis of the intrarenal arteries;
...many glomeruli hyalinized as a result of chronic ischemia (i.e., shrivelled tuft, urinary space packed with collagen)?

And is there a history (maybe, sort-of) of "benign essential hypertension"?

Or did the opposite kidney have renal artery stenosis, and the patient had Goldblatt hypertension? (Why the opposite kidney?)

Hypertensive kidney / "nephrosclerosis"

NOTE: "Arterial nephrosclerosis", due to narrowing of big vessels, produces wedge-shaped scars that show better in books than in real life. Ischemic atrophy causes them to look more like pits.

"Arteriolar nephrosclerosis" is a sandpaper-surfaced kidney due to nephrons dropping out randomly from arteriolar disease.

Is this a kidney with most or all of the following:
...hemorrhages throughout its substance;
...fibrinoid necrosis/thrombosis of the small arteries, arterioles, and glomeruli;
...striking myxoid and/or onion-skin proliferation of the intima of small arteries?

Does the patient also have spectacular high blood pressure and other resulting problems?

Malignant hypertension
Are glomerular capillaries distended by hyaline pink masses?
Fibrin-platelet thrombi

Consider DIC, TTP, hemolytic-uremic syndrome, eclampsia.

Is it a glomerulus with its capillary loops thickened by a subendothelial layer of finely-granular material composed of fibrin and platelet debris? Do you perhaps also see fragments of red cells here? Do you perhaps also see impressive onion-skin changes of the intimal layers of the small arteries?
Hemolytic-uremic syndrome
Is it a kidney with its cortex more or less diffusely yellow, and this is sudden, total renal failure rather than nephrotic syndrome? And do you perhaps know the patient had shock and/or DIC?
Diffuse renal cortical necrosis
Is it a depressed, white, V-shaped scar of the kidney?
Old renal infarct
Are the renal pelvis and calyces massively inflated due to obstruction distally?
Hydronephrosis

Beginners: Tell this from adult polycystic kidney because the dilated portions of kidney all communicate with one another!

Is it a yellow nodule in the renal cortex, and is it less than 3 cm and free of histologic evidence of malignancy?
Renal cortical adenoma

NOTE: This lesion really exists, but it's impossible to tell from a tiny low-grade cancer without DNA study.

Is it a yellow (usually) mass in the kidney of an adult, with hemorrhage (usually) and necrosis (usually)?

Is it a renal mass composed of clear (usually) polygonal (less often, spindle) cells with distinct intercellular boundaries, and do you see any of:
...invasion of a vein;
...invasion of a lymphatic;
...bizarre cells;
...a mitotic figure;
...hemorrhage;
...necrosis;
...the DNA lab says it has a 3p deletion?

Renal cell carcinoma / "hypernephroma" / Grawitz tumor / "kidney cancer" / adenocarcinoma of the kidney
Is it a grossly malignant primary tumor in the kidney of a child?

Does it contain some or all of the following:
...primitive cells resembling renal blastema;
...attempts at tubule formation;
...spindle cell areas;
...various mesenchymal structures, including perhaps muscle, cartilage, and/or bone?

Did the guy in the DNA lab say that the WT locus is deleted?

Wilms' tumor / nephroblastoma
Is it a white and yellow, grossly benign nodule from the renal cortex?

Is it a renal mass composed of a mix of fat, smooth muscle, and blood vessels?

Does the patient perhaps have tuberous sclerosis?

Angiomyolipoma
Is it a round, sharply-circumscribed, tan tumor in the kidney, exhibiting a central white, star-shaped scar?

Is it a histologically benign kidney tumor with cells packed with mitochondria ("oncocytes"; "Hšrthle cells")?

Hšrthle cell adenoma / oncocytoma

NOTE: These may occasionally metastasize.

Is it a papillary tumor apparently arising from the epithelium of the renal pelvis?
Urothelial (transitional cell) carcinoma of the kidney
Are there chunks of transitional epithelial cells apparently lying in the lamina propria below the normal transitional epithelium?
Brunn's nests
Are there tiny cysts lying in the lamina propria below the normal transitional epithelium?
Cystitis cystica / ureteritis cystica
Is the urothelium dotted with abundant lymphoid follicles?
Cystitis follicularis / ureteritis follicularis
Is it a ureter that is substantially dilated for any reason?
Hydroureter
Is it a bladder with an out-pouching of the entire wall, or mostly mucosa with perhaps some muscularis visible?
Bladder diverticulum
Does the bladder mucosa communicate with the skin over the pubis because of a birth defect? Is there perhaps associated bladder infection, squamous metaplasia, and/or adenocarcinoma of the bladder?
Exstrophy of the bladder
Is it a voiding urogram showing contrast medium from the bladder refluxing into the ureter or even the renal pelvis?
Vesicoureteral reflux
Is it a communication between the bladder mucosa and the umbilicus?
Persistent urachus
Is it one or more cysts lying between the bladder and the umbilicus?
Urachal cysts
Is the bladder acutely and/or chronically inflamed?
Cystitis
Are all layers of the bladder wall chronically inflamed and scarred?
Ulcerative interstitial cystitis / Hunner's ulcer
Is it a urinary bladder with several slightly-raised yellow plaques on its mucosa?
Is it a lesion from the urinary bladder (or perhaps elsewhere) composed of macrophages containing abundant lipid and round, calcified "Michaelis-Gutmann" bodies?
Malakoplakia
Is it flat (i.e., not a papillary tumor) transitional epithelium with more than 7 apparent layers of nuclei (the exact number varies depending on your authority)?
Transitional cell hyperplasia
Is it a papillary growth on the urothelium with transitional epithelium with 7 or fewer apparent layers of nuclei?
Transitional cell papilloma
Is it a papillary growth on the urothelium, with more than 7 apparent layers of nuclei?

Is it an invasive carcinoma apparently arising from urothelium, with or without a papillary component, without obvious glandular or squamous features in most areas?

Transitional cell carcinoma / bladder cancer
Is it flat transitional epithelium with obvious cellular atypia?
Transitional cell atypical hyperplasia / carcinoma in situ
Is it a squamous cell carcinoma of the bladder, and there is a curious foreign body which might be a Schistosoma haematobium egg?
Squamous cell carcinoma of the bladder in schistosomiasis
Is it a man with an acutely inflamed urethra, with pain and at least some discharge?
Urethritis

In addition to gonorrhea and chlamydia, remember trichomonas (after intercourse), meningococcus (after oral sex), and eating lots of those little jalape¤o peppers

Is it an uncomfortable, small red mass at the external urethral meatus of a woman? If someone was foolish enough to biopsy it, do you see apparent granulation tissue?
Urethral caruncle
Is it a hexagonal crystal in the urine?
Cystine or uric acid

NOTE: Cystinuria is serious and treatable. Uric acid crystals are normal in acid urine.

Is it an octahedral crystal in the urine?
Calcium oxalate

NOTE: Normal to have a few.

Is it a coffin-lid crystal in the urine?
Magnesium ammonium phosphate (struvite)

NOTE: Proteus infection.

Is it plate-like crystals in the urine?
Cholesterol crystals
Is it needle-shaped crystals in the urine, gathered as sheaves?
Tyrosine or contrast medium
Is this a bicycle-wheel crystal in the urine?
Leucine
Is this a male with the urethra opening on the dorsal surface of the penis?
Epispadias
Is this a male with a foreskin which cannot be retracted backwards over his corona?
Phimosis
Is this an uncircumcised male with phimosis or extremely poor personal hygiene, who now is infected and sore?
Balanoposthitis
Is this a male with a tight foreskin which he did manage to retract backwards over his corona, and now cannot put it back over his glans?
Paraphimosis
Is this one or more large, benign warts on the genitals of a man or a woman?

Is this skin from the genitals, and do you see some or all of the following:
...plenty of shrivelled, crinkled nuclei in the spiny layer;
...a perinuclear halo surrounding most of these nuclei;
...acanthotic epithelium overlying a papillary fibrous stroma.

Is this a lesion from the genitals, and somebody showcases human papillomavirus (HPV) using a DNA probe?

Condyloma acuminatum

NOTE: Very large, locally invasive ones are verrucous carcinoma / giant condyloma of Buschk‚-Lowenstein; these shouldn't metastasize however.

Is it one patch of red skin on the external genitals of an older man (scrotum, shaft) or older woman, (or perhaps skin someplace else), with marked cytologic atypia of the epidermis but no invasion?
Bowen's disease
Is it several patches of brown, warty lesions on the genitals of a younger man or younger woman, with marked cytologic atypia of the epidermis but no invasion? Has HPV type 16 perhaps been showcased in the lesion?
Bowenoid papulosis
Is it a red patch on a man's glans, with marked cytologic atypia of the epidermis but no invasion?
Erythroplasia of Queyrat
Is it a fungating squamous cell carcinoma arising around the coronal sulcus? Is the patient (probably) an uncircumcised, un-hygienic man? Has HPV perhaps been showcased in the lesion?
Cancer of the penis
Is at least one testis undescended?
Cryptorchidism
Is it an adult man's testis, but there is no sperm production in any of the tubules?
Testicular atrophy

Consider cryptorchidism, XXY Klinefelter's, pituitary insufficiency, old torsion, old mumps, taking estrogen, radiation injury, chemotherapy, old age, liver failure, kwashiorkor-marasmus, mild cystic fibrosis, obstruction from vasectomy or other

Is it a mass in the testis composed primarily of granulomas both within and between the tubules, with some plasma cells and no obvious cause?
Granulomatous orchitis
Has the cremaster muscle gone into spasm, twisting the spermatic cord 540ø, occluding the pampiniform plexus, and causing venous infarction of the testis?
Torsion of the testis
Is it a soft, yellow testicular tumor? And on microscopy, do you see cells with abundant cytoplasm and round, centrally-located nuclei, and very sharply-defined cell borders, arranged in nests ("organoid pattern"), separated by thin fibrous bands rich in lymphocytes? Do you perhaps see granulomas? Do you perhaps see syncytiotrophoblast (but never cytotrophoblast)?
Classic seminoma
Is it a soft, gray testicular tumor? And on microscopy, do you see tumor cells resembling spermatocytes, with great variability in tumor cell size, and no lymphocytes?
Spermatocytic seminoma

NOTE: Almost benign.

Is it a variegated gray, typically hemorrhagic and necrotic testicular tumor composed of sheets, cords, rings and/or papillae of very primitive cells with poorly-defined borders and abundant purple cytoplasm?
Embryonal cell carcinoma
Is it a multinucleated cell, in any testicular tumor, that stains positive for hCG?
Syncytiotrophoblast
Is it a cell in any testicular tumor that stains positive for à- fetoprotein (AFP)?
Yolk sack cell
Is it a pale yellow, gelatinous testicular tumor, perhaps from a boy, with rings-within-rings ("Schiller-Duvall bodies") recalling embryonic vitelline duct, and hyaline globules staining positive for à- fetoprotein (AFP) and à1-protease inhibitor?
Yolk sack tumor ("endodermal sinus tumor")
Is it a soft, mushy, bloody-red tumor of the testis that contains both syncytiotrophoblast and cytotrophoblast? Is hemorrhage obvious grossly and microscopically?
Choriocarcinoma
Is it a testicular tumor composed microscopically of a mix of identifiable benign tissues, without cancer or primitive material?
Mature teratoma
Is it a testicular tumor composed microscopically of a mix of identifiable benign tissues and some very primitive tissues such as are seen in an embryo?
Immature teratoma
Is it a testicular tumor composed microscopically of a mix of identifiable benign tissues plus an obvious cancer (typically squamous cell carcinoma or carcinoid)?
Teratoma with malignant transformation
Is it a round, golden-brown testicular nodule composed of pink, polygonal cells, with perhaps a Reinke crystalloid?
Leydig cell tumor ("interstitial cell tumor")
Is it a pale testicular tumor composed of cords of cells that tend to take a wedge-shape?
Sertoli cell tumor ("androblastoma")
Is it a round, white nodule in the epididymis? Microscopically, is it a mix of fibrous tissue and epithelial cells without other distinguishing features?
Adenomatoid tumor
Is it excess fluid in the tunica vaginalis?
Hydrocele
Is it a bunch of little rough red bumps on an older man's scrotum?

Is it lots and lots of little rough red bumps on the penis and scrotum of a patient with Fabry's disease?

Angiokeratomas
Is it an older man's prostate with large soft-to-firm nodules around the urethra, compressing the surrounding tissue?

Is it an older man's prostate with nodules forming a "median bar" protruding upward into the bladder outlet?

Is it an older man's prostate that is very large?

Is it prostate nodules composed of collagen and/or muscle and/or two- cell-layer-thick glands with exaggerated papillary infoldings?

Prostatic hyperplasia ("benign prostatic hypertrophy")
Is it a dominant hard mass in an older man's prostate?

Is it an apparent cancer arising in an older man's prostate, typically in the posterior lobe, and invading the surrounding tissue?

Is it glands in the prostate that are crowded, or that seem to invade among benign glands distorting the normal architecture, or that have prominent nucleoli, or that have nuclei with marginated chromatin, or that have lost their myoepithelial cell layer?

Prostate cancer (prostatic adenocarcinoma)
Is it a vulvitis or vaginitis with white patches that scrape off? Do you see pseudohyphae in the scrapings under the microscope?
Candida
Is it a vaginitis with considerable redness ("strawberry"), with superficial inflammation? Do you see trichomonads in the discharge?
Trichomonas
Is it glands in the vaginal wall, with plentiful cytoplasm? And is there probably a history of exposure to exogenous estrogen (i.e., diethylstilbestrol) in utero?
Vaginal adenosis
Is it a clear-cell adenocarcinoma involving the vagina? And is there probably a history of exposure to exogenous estrogens (i.e., diethylstilbestrol) in utero?
Vaginal adenocarcinoma
Are the oviducts distended and inflamed? Is there pus formation?

Are the folds of the oviduct edematous and rich in neutrophils?

Are the oviducts extensively scarred?

Are the oviducts distended by non-inflammatory fluid held there by scarring?

Pelvic inflammatory disease

NOTE: Consider gonorrhea, chlamydia, others.

Is it a cyst at the vaginal introitus?
Bartholin's gland cyst
Is it a dense, shiny area on the vulvar or penile skin?

Is it a portion of vulvar or penile skin with epidermal thinning, very dense dermal collagen, and an edematous zone under the epidermis?

Lichen sclerosus
Is it vulvar or perineal skin with the epidermis invaded by individual bizarre cells? Are the cells mucin and/or CEA positive?
Extramammary Paget's disease
Is it vulvar or perineal skin with the epidermis invaded by individual bizarre cells? Are the cells mucin negative and CEA negative, but exhibit melanin or S100 positivity?
Malignant melanoma
Is it a bosselated, soft mass in the bladder or vagina? Under the microscope, do you see a dense "cambium layer" under the epithelium, and a looser fibromyxoid stroma deeper? And, do you perhaps see a plausible rhabdomyoblast?
Sarcoma botryoides
Is it a vaginal smear and you see squamous cells with abundant adherent bacteria ("clue cells")?
Gardnerella
Is it a fibromyxoid structure hanging from the cervical os by a peduncle?
Endocervical polyp
Is it a striking hyperplasia of the columnar cells of the endocervix, in a woman receiving extra progesterone or with a progesterone- producing tumor?
Microglandular endocervical hyperplasia
Is it a cervix that appears normal, but fails to stain with iodine ("Schiller test")? Does the skilled culposcopist perhaps believe a lesion is present? Does pap smear or biopsy confirm replacement of the epithelium by abnormal cells without invasion of the stroma?
Carcinoma in situ of the cervix
Is it an invasive squamous cell carcinoma (most common) or adenocarcinoma of the cervix?
Cancer of the cervix

Is it an endometrial biopsy containing at least a few plasma cells?
Chronic endometritis

NOTE: If there are no retained fragments of a pregnancy, and the patient does not have an IUD in place, and the patient does not have gonorrhea, consider blaming chlamydia.

Is it an endometrium or oviduct containing granulomas and perhaps giant cells? Does acid-fast stain perhaps show mycobacteria?
Tuberculosis of the endometrium / oviduct
Do you see at least two of the following, in the same place, outside the endometrial cavity:
...endometrial glands;
...endometrial stroma;
...evidence of old hemorrhage, i.e., hemosiderin-laden macrophages?

Is it a chocolate cyst of the ovary?

Endometriosis

NOTE: If it's in the myometrium, call it adenomyosis.

Is it endometrium from the latter portion of the cycle, with continued mitotic activity and large glands, and without secretory changes?
Anovulatory cycle
Is it endometrium from the latter portion of the cycle, with minimal or no secretory changes?
Inadequate luteal phase
Is it a soft, nodular mass in the endometrial cavity, composed of normal or anovulatory-cycle type endometrium?
Endometrial polyp
Are the endometrial glands markedly variable in size, with some cysts, with perhaps piling-up of the cells, but no increase in number and no cytologic atypia?
Simple endometrial hyperplasia
Are the endometrial glands markedly variable in size and shape, and also increased in number, but with no cytologic atypia?
Complex endometrial hyperplasia ("adenomatous hyperplasia of endometrium without atypia")
Are the endometrial glands markedly variable in size and shape, and crowded, and probably branching, and there is some anaplasia, but the fundamental architecture of discrete glands in a stroma is preserved?
Atypical endometrial hyperplasia ("adenomatous hyperplasia of endometrium with atypia")
Is it endometrium with poorly-developed glands but with a lush, mitotically active, perhaps decidualized stroma?
Oral contraceptive pill effect
Is it a thin endometrium, mostly gone except for the basalis? Are some of the glands perhaps cystically dilated?
Post-menopausal endometrium
Is it an epithelial malignancy of the endometrium, growing as glands and/or sheets?
Adenocarcinoma of the endometrium ("cancer of the uterus")
Is it an adenocarcinoma of the endometrium with benign squamous metaplasia?
Adenoacanthoma of the endometrium
Is it an adenocarcinoma of the endometrium with malignant squamous elements?
Adenosquamous carcinoma of the endometrium
Is it a round, white mass within, hanging off of, or immediately subjacent to the myometrium?

Is it a benign spindle cell tumor of the myometrium?

Has it perhaps undergone central infarction, fibrosis, calcification, and/or "cystic" change?

Leiomyoma ("fibroid")
Is it a spindle cell tumor of the myometrium with mitotic figures?
Leiomyosarcoma or endometrial stromal sarcoma

NOTE: Ask your instructor whether you need to learn to distinguish these.

Is it a spindle cell tumor with scanty cytoplasm, infiltrating between myometrial muscle bundles and invading lymphatics?
Low-grade endometrial stromal sarcoma ("endolymphatic stromal myosis")
Is it a cancer of the uterus with both adenocarcinoma and malignant mesenchymal elements?
Malignant mixed mesodermal tumor ("mixed Mšllerian tumor")

TERMS: "Heterologous" examples contain differentiated mesenchyme (muscle, cartilage, etc.) "Homologous" ones are simply primitive.

Is it a mucus-filled cyst adjacent to an oviduct?
Hydatid of Morgagni / parovarian cyst
Is it a benign ovarian cyst lined by flattened cells?
Follicular ovarian cyst
Is it a benign ovarian cyst lined by luteinized, yellow cells?
Luteal ovarian cyst
Is it a pair of enlarged ovaries with thick outer fibrous layer and innumerable cysts?

Is this a young woman with excess gonadotropins, androgens, and estrogens, as well as amenorrhea? Is she perhaps also hirsute and/or obese?

Stein-Leventhal polycystic ovaries
Is it an ovarian cystic tumor lined by a single layer of benign, ciliated cells like in the oviduct?
Serous cystadenoma of ovary
Is it an ovarian tumor with cells as in a serous cystadenoma, but with a much more abundant stroma and less tendency to form large cysts or papillae?
Cystadenofibroma of ovary
Is it an ovarian cystic tumor lined by atypical ciliated cells, perhaps with some piling up, but without stromal invasion?
Borderline serous cystadenocarcinoma of ovary
Is it an ovarian tumor composed of tall, columnar, non-mucin- secreting malignant cells, perhaps with a cystic and/or papillary growth pattern and/or psammoma bodies, perhaps with cilia, and with stromal invasion? Are both ovaries perhaps involved?
Serous cystadenocarcinoma of ovary
Is it an ovarian cystic tumor, perhaps multi-loculated and/or very large, lined by a single layer of columnar cells like in the endocervix?
Mucinous cystadenoma of ovary
Is it an ovarian cystic tumor lined by atypical mucin-producing cells, perhaps with some piling up, but without stromal invasion?
Borderline mucinous cystadenocarcinoma of ovary
Is it an ovarian tumor composed of mucin-producing malignant cells, perhaps with a cystic growth pattern, and with stromal invasion?
Mucinous cystadenocarcinoma of ovary
Is it an ovarian tumor with back-to-back glands and perhaps squamous areas, as in a familiar-type endometrial adenocarcinoma?
Endometrioid carcinoma of ovary

Is it an ovarian tumor composed of malignant glands with cells exhibiting abundant, clear cytoplasm?
Clear-cell adenocarcinoma of ovary
Is it a solid ovarian tumor with an ovarian spindle-cell type stroma containing islands of transitional cell epithelium?
Brenner tumor
Is it an ovarian tumor with an inner lining surface of skin and a central cyst containing sebum, keratin, and hair? Are all the tissues in "Rokitansky's nodule" in the wall benign, resembling an adult's? Is there perhaps a tooth?
Mature cystic teratoma of ovary ("dermoid cyst")
Is it a solid ovarian tumor containing a variety of tissues, including some primitive elements typical of an embryo?
Immature teratoma of ovary
Is it an ovarian tumor with the typical appearance of a carcinoid? Is carcinoid syndrome perhaps present? Is urinary 5-HIAA perhaps elevated?
Ovarian carcinoid ("specialized teratoma")
Is it an ovarian tumor composed primarily of thyroid tissue?
Struma ovarii ("specialized teratoma")
Is it a soft, yellow ovarian tumor? And on microscopy, do you see cells with abundant cytoplasm and round, centrally-located nuclei, and very sharply-defined cell borders, arranged in nests ("organoid pattern"), separated by thin fibrous bands rich in lymphocytes? Do you perhaps see granulomas? Do you perhaps see syncytiotrophoblast (but never cytotrophoblast)?
Dysgerminoma
Is it a pale yellow, gelatinous ovarian tumor, perhaps from a boy, with rings-within-rings ("Schiller-Duvall bodies") recalling embryonic vitelline duct, and hyaline globules staining positive for à- fetoprotein (AFP) and à1-protease inhibitor?
Yolk sack tumor ("endodermal sinus tumor")
Is it a soft, mushy, bloody-red tumor of the ovary that contains both syncytiotrophoblast and cytotrophoblast? Is hemorrhage obvious grossly and microscopically?
Choriocarcinoma
Is it a solid, white ovarian tumor composed of non-lipid-containing spindle-shaped cells?
Ovarian fibroma
Is it a solid, yellow ovarian tumor composed of luteinized, lipid- containing spindle-shaped theca cells? Has it perhaps produced some hormone, probably estrogen?
Thecoma

NOTE: If small, consider also stromal luteoma.

Is it a solid, yellow, solid or cystic ovarian tumor composed of epithelial-type cells, perhaps making miniature fluid-filled follicles ("Call-Exner bodies")? Do you perhaps see grooved, coffee-bean nuclei? Has it perhaps produced some hormone, probably estrogen?
Granulosa cell tumor
Is it a pale ovarian tumor composed of cords of cells that tend to take a wedge-shape, plus polygonal, pink-staining cells with perhaps a Reinke crystalloid? Has it perhaps produced some hormone, probably androgen?
Sertoli-Leydig cell tumor ("androblastoma"; "arrhenoblastoma")
Is it a pale ovarian tumor composed of entirely of polygonal pink- staining cells with perhaps a Reinke crystalloid? Has it perhaps produced some hormone, probably androgen?
Pure Leydig cell tumor ("Hilus cell tumor")
Is it a yellow ovarian tumor composed of entirely of lipid-rich cells? Has it perhaps produced androgen?
Lipid cell tumor
Is it a yellow ovarian mass composed of cuboidal cells, later in pregnancy, perhaps with virilization?
Pregnancy luteoma
Is it an ovarian tumor composed of embryoid bodies?
Polyembryoma
Is it an ovarian or testicular tumor composed of a mix of germ cell and sex-cord stroma structures, probably including granulosa and Sertoli cells, perhaps with dysgerminoma, Leydig cells, and/or theca cells? Does the patient perhaps have one of the intersex conditions, or undescended testes?
Gonadoblastoma
Is it an ovarian tumor with a mix of granulosa-theca and Sertoli- Leydig elements?
Gynandroblastoma
Is it an ovarian tumor with a mix of serous, mucinous, endometrioid- clear cell, and/or Brenner tumor?
Mixed coelomic ovarian tumor
Is it a portion of umbilical cord with abundant neutrophils?
Funisitis
Is it a portion of fetal membranes with abundant neutrophils?
Chorioamnionitis
Is it a hematoma separating the placenta from the uterine wall prior to the birth of the child?
Abruption of the placenta
Is it a placenta overlying the inner cervical os?
Placenta previa
Is it a placenta which has stuck to the uterine wall and not delivered after birth, because the decidua did not form properly?
Placenta accreta
Is it normal-appearing trophoblastic villi and/or fetal parts outside the uterine cavity?

Is it an oviduct distended with blood?

Ectopic pregnancy

Is she several months pregnant, and do you see some or all of the following:
...intrahepatic hemorrhages;
...periportal hepatic necrosis with fibrin deposition;
...swollen endothelial cells in the glomeruli;
...fibrin deposition under the endothelial cells in the glomeruli;
...fibrinoid necrosis of uterine arteries;
...lipid deposition ("acute atherosis") in the intima of the uterine arteries
...fibrin microthrombi in the brain?
Eclampsia
Is it uterine contents that resemble at least dozens of small grapes?

Is it swollen trophoblastic villi with at least minimal proliferation of the trophoblast, and poor or no development of the vessels in the villi?

Hydatidiform mole
Is it a hydatidiform mole with no fetal parts anywhere, and almost all villi are involved?

Is it a hydatidiform mole and somebody who understands these things says the karyotype is a normal child's but chromosomes are all of paternal origin?

Complete ("classic") hydatidiform mole
Is it a hydatidiform mole with many uninvolved villi and/or at least some fetal parts?

Is it a hydatidiform mole and the karyotype is triploid or tetraploid?

Partial hydatidiform mole
Is it both syncytiotrophoblast and cytotrophoblast invading the wall of the uterus and/or metastatic from a pregnancy or hydatidiform mole?
Invasive mole ("chorioadenoma destruens") or choriocarcinoma
Is it a small accessory nipple or breast somewhere on the line from the axilla to the groin on either side?
Supernumerary nipple / supernumerary breast
Is it a portion of breast tissue that has become inflamed during nursing, perhaps with abscess formation? Has Staph. aureus perhaps been demonstrated on smear or culture?
Acute mastitis / breast abscess
Is it a lump in the breast, perhaps at a site of a blow, in which lakes of free lipid are surrounded by scar, lipid-laden macrophages, neutrophils, calcification, and/or granuloma formation?
Fat necrosis of breast
Is it a dilated duct in a lactating breast, filled with milk?
Galactocele
Is it a lump in the breast composed of a group of dilated ducts fill of inspissated secretion, and surrounded by granulomas and perhaps also plasma cells?
Mammary duct ectasia / plasma cell mastitis
Is it breast tissue with a shotty consistency? Is most of the tissue in both breasts perhaps of similar consistency? Are the breasts perhaps extra tender before menstruation?

Is it an unopened cyst of the breast that appears blue?

Is it a portion of breast with more dense stroma than usual, and scattered cyst formation?

Cyst formation and fibrosis of breast ("fibrocystic disease")
Is it cells proliferating in the ducts and/or lobules of the breast, perhaps extending into the lumen, perhaps with irregular lumen formation within the mass, but without obvious cribriform pattern, hyperchromatic nuclei, or cell uniformity (sic).
Epithelial hyperplasia of breast

Variants: Ductal papillomatosis of breast (good papillae), atypical hyperplasia of breast (cytology and/or arrangement looks malignant)

Is it breast tissue with little ducts and glands surrounded by fibrosis, looking perhaps like cancer but always maintaining the normal lobular architecture?
Sclerosing adenosis
Is it a small lesion in a duct near the nipple that appears to be a papilloma? Has the patient perhaps experienced nipple bleeding? Are at least some of the following present:
...fibrous stalk;
...good myoepithelial cell layer;
...apocrine metaplasia;
...hyalinization;
...no features of carcinoma in situ?
Papilloma of breast
Is it a papillary lesion in a duct near the nipple? Are at least some of the following present:
...cellular atypia;
...cellular uniformity;
...cribriform pattern;
...mitotic figures?
And are these absent:
...fibrous stalk;
...good myoepithelial cell layer;
...apocrine metaplasia;
...hyalinization?
Papillary carcinoma of breast
Is it a sharply-circumscribed, round tumor in the breast, with more-or- less compressed ducts in a more-or-less loose fibrous stroma?
Fibroadenoma
Is it a circumscribed, round, mixed epithelial-and-stromal tumor of the breast divided into lobules by slits "like the veins in a leaf"?
Phyllodes tumor
Is it a phyllodes tumor of breast with mitotic figures, cellular atypia, and/or cellular crowding in the stroma?
Malignant phyllodes tumor
Is it a section of breast containing intraductal carcinoma with necrotic cancers in the centers of the lumens?
Intraductal breast carcinoma, comedocarcinoma pattern
Is it cribriform growth of relatively uniform cells in ducts of breast?
Intraductal breast carcinoma, cribriform pattern
Is it breast with its terminal ducts distended by large cells, pretty much uniform, with small nucleoli?
Lobular carcinoma in situ of breast
Is it a hard lump in the breast, with perhaps a gritty texture, a tendency to retract below the cut surface (elastic effect) and a mixed yellow and white pattern?

Is it breast with more-or-less malignant looking cells invading a desmoplastic stroma as cords ("Indian files"), sheets, tubes, or some other adenocarcinoma-type pattern?

Scirrhous carcinoma of breast
Is it a large, soft breast cancer composed of large, malignant cells in sheets, with abundant lymphocytes between the sheets?
Medullary carcinoma of breast
Is it extremely well-differentiated, one-layered tubes of cells, infiltrating the breast stroma?
Tubular carcinoma of breast
Is it a gelatinous breast cancer with abundant extracellular mucin, in which float cancer cells?
Mucinous carcinoma of breast
Is it small cancer cells with scanty cytoplasm and rather small nuclei, forming single files ("Indian files") as they infiltrate stroma?
Lobular carcinoma of breast
Is it nipple with the epidermis invaded by individual bizarre cells? Are the cells mucin and/or CEA positive?
Paget's disease of the nipple
Is it a portion of male breast with hyperplasia of the ducts, perhaps also with extra connective tissue around the ducts?
Gynecomastia
Is it a round, expansile lesion in the sella turcica?

Is it a clearly-circumscribed nodule of uniform cells within the adenohypophysis?

Is it an electron micrograph of a pituitary lesion showing uniform cells with pituitary-type secretory granules?

Pituitary adenoma

NOTE: Almost all benign. Metastasis is the only proof of malignancy. Consider checking for Wermer's MEN-I.

Is he or she a extra-tall youngster with a pituitary adenoma (probably "acidophilic")?
Pituitary gigantism
Is he or she a person who never grew, and who fails the hGH stimulation test?
Pituitary dwarfism

NOTE: Similar dwarfism, but with high hGH occur in people who lack hGH receptors and/or somatomedin.

Is he or she a person with several of the following:
...tall stature;
...frontal bossing;
...spade fingers;
...thick lips and big tongue;
...deep voice;
...good musculature;
...glucose intolerance;
...myopathy / neuropathy?
Acromegaly

NOTE: The usual cause is a pituitary adenoma, probably "acidophilic".

Is he or she a person with several of the following:
...round, red face;
...extra fat on the back of the neck ("buffalo hump");
...increased appetite and weight gain;
...atrophy of the muscles;
...thinning of the skin, perhaps with purple striae;
...fragile capillaries;
...acne;
...ringworm;
...hypertension;
...glucose intolerance;
...depression;
...psychosis?
Cushing's syndrome
Is it a person with Cushing's syndrome and a pituitary adenoma (probably a basophilic microadenoma) causing adrenal gland hyperplasia?
Cushing's disease
Is she a woman during reproductive life, not a new mother, who has stopped having her periods and is lactating?
Galactorrhea-amenorrhea syndrome

NOTE: This patient has a prolactinoma until proven otherwise.

Is this a pituitary adenoma of any H&E appearance that stain positive for prolactin?

Is he a man who has lost his libido despite perhaps normal testosterone levels, and has elevated blood prolactin and/or a pituitary mass?

Prolactinoma
Is this an adult with an anterior pituitary lesion and at least some of the following:
...weight loss;
...mental changes;
...loss of sexual hair;
...amenorrhea / loss of libido;
...hypothyroidism;
...nausea?
Hypopituitarism ("Simmonds's disease")
Is it an anterior pituitary that has undergone infarction during an episode of shock around the time of parturition?
Sheehan's syndrome

NOTE: Some usage allows "Sheehan's syndrome" to cover massive pituitary infarction from any cause.

Is it an anterior pituitary gland that has undergone pressure atrophy from the arachnoid herniating through the diaphragma sellae?
Empty-sella syndrome
Is it an adenohypophysis from a patient with Cushingism from any cause, and the basophilic cells are packed with intermediate filaments imparting a hyaline appearance?
Crooke's hyaline change

NOTE: A classic bit of the real arcana of pathologic anatomy.

Is it a tumor in the hypothalamic-pituitary region, with at least several of the following:
...cysts containing "machine oil" cholesterol-rich debris;
...myxoid stroma surrounded by columnar cells with basal vacuoles as in ameloblasts
...squamous elements (pearls, desmosomes, keratin) without malignancy;
...calcification?
Craniopharyngioma
Is he or she a patient with several of the following:
...recent weight loss;
...fine tremor (try putting a paper over the outstretched hands)
...anxiety, "nervousness";
...hyperdynamic heart;
...atrial fibrillation;
...diarrhea;
...lid lag;
...feels warm and moist?
Hyperthyroidism
Is he or she a person with most or all of the following:
...mental and physical sluggishness;
...increased mucopolysaccharide ground substance in connective tissue ("myxedema");
...hoarseness;
...constipation;
...cold skin;
...dry, brittle hair;
...cardiomyopathy;
...delayed "hung" brief tendon reflexes;
...high serum cholesterol;
..."depression" and/or "psychosis"?
Hypothyroidism
Is or was he or she a child with mental retardation, delayed development, and other familiar signs of hypothyroidism?
Cretinism
Is it a midline neck mass lined by thyroid and/or squamous epithelium?
Thyroglossal duct cyst
Is it a miniature, white thyroid gland with histology showing mostly fibrosis, with only a few remaining thyroid epithelial cells?
End-stage thyroid ("thyroid atrophy")

Consider burned-out Hashimoto's, burned-out DeQuervain's, hypopituitarism, radiation effect.

Is it a thyroid gland containing abundant lymphocytes, but no germinal centers or Hšrthle cells, perhaps in a hypothyroid patient?
Lymphocytic thyroiditis
Is it a thyroid gland containing abundant lymphocytes and probably plasma cells, with germinal center formation and Hšrthle cell formation?
Hashimoto's thyroiditis
Is it a thyroid gland with loss of follicular epithelial cells and active granuloma formation, apparently a foreign-body reaction to liberated colloid?
DeQuervain's subacute granulomatous thyroiditis

NOTE: If painless, some call it "subacute lymphocytic thyroiditis"

Is it a proliferation of fibroblasts and collagen beginning in the thyroid gland and perhaps adhering to nearby neck structures?
Riedel's thyroiditis
Is he or she a patient with two or more of these:
...hyperthyroidism, usually with autoantibodies against the hTSH receptor;
...exophthalmos due to increased tissue behind the eyeball;
...pretibial myxedema?
Graves' disease
Is this thyroid gland from someone known to be taking medication for hyperthyroidism, and the follicular epithelium is thrown up into elaborate papillae and/or otherwise hyperplastic?
Propylthiouracil effect in thyroid
Is this thyroid gland from someone known to be taking medication for hyperthyroidism, and the follicular epithelium is flat and inactive and there is abundant colloid?
Iodine excess effect in thyroid
Is this a portion of a diffusely enlarged thyroid gland, and you see "scalloping" resorption vacuoles in the colloid adjacent to the epithelial cells (i.e., the colloid is being rapidly metabolized)?

Is this a section of a diffusely enlarged thyroid gland with the colloid almost gone, with tall epithelial cells?

Diffuse thyroid hyperplasia
Is the thyroid gland diffusely enlarged and perhaps hypercellular in simple iodine deficiency and/or the absence of demonstrable thyroid disease?
Simple diffuse nontoxic goiter

NOTE: Growing goiters tend to be hypercellular. When sufficient cell mass is achieved, colloid accumulation becomes possible, producing the "colloid goiter".

Is it an enlarged thyroid with many nodules, and perhaps some of the following:
...colloid-rich nodules;
...colloid-poor nodules;
...irregular scarring;
...irregular calcification;
...irregular hemosiderin deposits.
Multinodular goiter / adenomatous goiter
Is it a single nodule in a thyroid gland, composed of benign cells without papilla formation?
Thyroid adenoma

NOTE: The subtypes aren't of much consequence.

Is it a section of thyroid immunostained to demonstrate the calcitonin-producing C-cells, and they are much more numerous than in your "Histology" book?
C-cell hyperplasia

NOTE: Precursor lesion to medullary carcinoma. The patient almost certainly has Sipple's MEN-II.

Is it a thyroid tumor with any one of the following:
...gross appears as a tiny white stellate scar;
...optically clear "Orphan Annie eye" nuclei;
...widespread papilla formation;
...psammoma bodies?
Papillary adenocarcinoma of the thyroid
Is it an apparently circumscribed thyroid nodule, but histology shows follicles or sheets of cells invading vessels?

Is it a grossly malignant-appearing tumor in the thyroid, calcitonin- negative and perhaps thyroglobulin-positive, composed of reasonably well-differentiated epithelial cells but without features of a papillary carcinoma?

Follicular adenocarcinoma of the thyroid
Is it a fairly well-differentiated thyroid carcinoma which does any of the following:
...produces calcitonin, detected by immunoperoxidase and/or serum assay;
...produces ACTH (Cushingism), VIP (diarrhea), and/or serotonin (carcinoid syndrome);
...has an amyloid stroma composed (if you can check it) of á- pleated calcitonin;
...shows neurosecretory-type granules on electron microscopy?

... In addition to the above, is there perhaps a family history of any of the following:
...Sipple's MEN-II or MEN-IIb
...pheochromocytoma;
...parathyroid adenoma / hyperplasia
...mucosal neuromas?

Medullary carcinoma of the thyroid

NOTE: Always check patient and family for Sipple's MEN-II or MEN- IIb.

Is it a cancer arising in the thyroid gland, composed of relatively small, highly anaplastic cells that lack lymphocyte markers?
Undifferentiated ("anaplastic") thyroid carcinoma, small cell variant
Is it a cancer arising in the thyroid gland, composed of large, highly anaplastic cells?
Undifferentiated ("anaplastic") thyroid carcinoma, giant cell variant
Is it an enlarged parathyroid gland?

Does the patient perhaps have hypercalcemia?
Does the patient perhaps have a personal or family history of MEN-I (pituitary adenoma / gastrinoma) or MEN-II (medullary thyroid cancer / pheochromocytoma / IIb mucosal neuromas)?

Parathyroid hyperplasia or parathyroid adenoma

NOTE: You cannot distinguish these unless you have more information, i.e., about the other glands.

Are all four (three, five, however many there are) parathyroid glands enlarged?

Does the patient perhaps have hypercalcemia (primary, tertiary parathyroid hyperplasia) and/or chronic renal insufficiency (secondary, tertiary parathyroid hyperplasia)?

Parathyroid hyperplasia

NOTE: Consider checking the patient for Wermer's MEN-I and Sipple's MEN-II.

Is only one of the four (three, five, however many there are) parathyroid glands enlarged?
Parathyroid adenoma

Much less likely: Parathyroid carcinoma.

Is it a single enlarged parathyroid gland, and histology shows some or all of these:
...mitotic figures;
...trabecular growth pattern;
...invasion of capsule and/or blood vessels and/or lymphatic vessels?

Is it metastatic cancer with good evidence that the primary is in the parathyroid (i.e., a mass these, etc.)?

Parathyroid carcinoma
Is it the adrenal cortex of a newborn, and there is no fetal layer? And the child is anencephalic?
Anencephalic adrenal hypoplasia
Is it the adrenal cortex of a newborn with adrenal insufficiency, and the cells are large and bizarre?
Cytomegalic adrenal hypoplasia
Is this a patient with several of the following:
...nausea and weight loss;
...low blood pressure;
...weakness and tiredness;
...emotional lability;
...sudden circulatory collapse in a stressful situation?
Adrenal insufficiency ("Addisonism", "Addison's disease")
Is it a patient with adrenal insufficiency and increasing skin pigmentation?

Is it a patient with adrenal insufficiency and you can exhibit the principal lesion to be in the adrenals?

Primary adrenal insufficiency
Is it a patient with primary adrenal insufficiency, demonstrable at least on ACTH stimulation testing, atrophic adrenal cortices packed with lymphocytes?
Autoimmune adrenalitis ("idiopathic Addison's disease")
Is it an adrenal gland with relatively few, relatively small cells in its cortex?

Is it a patient with adrenal insufficiency due to exogenous glucocorticoids or pituitary failure?

Adrenal cortical atrophy / secondary adrenal insufficiency

Is it adrenals with extensive hemorrhage and perhaps necrosis?
Waterhouse-Friderichsen syndrome or birth trauma
Is the adrenal gland enlarged, primarily by a thickened cortex, so that it weighs more than ten grams or so?

Does the adrenal cortex exhibit several yellow nodules?

Under the microscope, is the adrenal cortex notably thickened by endocrine-type cells, with or without abundant cytoplasm, with or with out foamy lipid vacuoles, and with or without metaplastic bone marrow (sic)?
Does the patient have one of:
...lots of physical or emotional stress lately;
...an ACTH-producing pituitary adenoma;
...an ACTH-producing and/or CRF-producing oat cell carcinoma, thymoma, islet cell tumor, carcinoid, or medullary thyroid cancer;
...a physician administering ACTH;
...a physician administering drugs that suppress cortisol production;
...a problem with the enzymes that produce cortisol (21- hydroxylase, 11-á-hydroxylase, licorice abuse, others)
...Conn's primary low-renin hyperaldosteronism, but without a solitary adrenal adenoma;
...a stimulatory anti-ACTH-receptor autoantibody?

Adrenal cortical hyperplasia
Is this a boy, girl, or woman with virilization and adrenal hyperplasia?
Congenital adrenal hyperplasia / adrenal virilism
Is it a single yellow nodule in the adrenal gland, composed of benign- appearing glandular cells, perhaps with hyperchromatic nuclei, but without necrosis or metastases?

Does the patient perhaps have:
...Cushingism, and even high-dose dexamethasone does not suppress cortisol production;
...Conn's primary low-renin hyperaldosteronism;
...virilization;
...demasculinization / feminization?

Adrenal cortical adenoma

NOTE: Most of these produce no known hormone and no known syndrome.

Is it a grossly (large size, necrosis, metastases) or microscopically (necrosis, utterly bizarre cells, mitotic figures) malignant tumor arising in the adrenal gland, with lipid in the cells and/or hormone production and/or no evidence of catecholamine production?
Adrenal cortical adenocarcinoma
Is it a round chunk of fat and hematopoietic cells in the adrenal gland?
Myelolipoma
Is it a soft, vascular, very bloody mass in the adrenal, at the origin of the superior mesenteric artery, or where there is some sympathetic or parasympathetic ganglion?

Is it a tumor from the location of an autonomic ganglion, and the cells are large, with abundant pink cytoplasm and perhaps a suggestion of nerve processes?

And does the patient perhaps have most of the following:
...frequent bad headaches;
...paroxysms of hypertension;
...elevated urinary VMA;
...some other positive pheochromocytoma screening test?

Or does the patient perhaps have a personal or family history of
...Sipple's MEN-II or MEN-IIb
...medullary carcinoma of the thyroid;
...parathyroid adenoma / hyperplasia
...mucosal neuromas?

Did your instructor happen to tell you that the tumor turned a pretty mahogany brown when somebody dropped it into chromic acid?

Pheochromocytoma

NOTE: There's no telling the malignant ones from the benign ones until something metastasizes.

NOTE: Consider checking patient and family for Sipple's MEN-II or MEN- IIb.

Is it a soft, gray tumor, arising in or near the adrenals or along the sympathetic trunks (or perhaps elsewhere), perhaps with calcification? And is the patient a young child?

And microscopically, is the tumor composed of cells with very scanty cytoplasm ("small blue cells"), perhaps with Homer-Wright pseudo- rosettes (rings of cells with fibrillary stuff in the middle, as if they were making a neural tube)?

And on electron microscopy, do you perhaps see neurosecretory granules?

Neuroblastoma
Is it a neuroblastoma-like tumor but with Schwann cells and fibrous tissue for a stroma, and at least some recognizable ganglion cells?
Ganglioneuroblastoma
Is it a white nodule in the adrenal or retroperitoneum, or along the sympathetic chains?

And microscopically, is it composed of fibrous tissue with embedded neurons?

Ganglioneuroma

NOTE: Self-curing neuroblastomas differentiate into ganglioneuroblastoma and then into ganglioneuromas.

Is it a thymus gland with germinal centers?
Thymic hyperplasia
Is it a tumor of the thymic epithelium, with or without an admixture of T-lymphocytes?
Thymoma

NOTE: You can only tell these are malignant if you see gross infiltration of nearby structures.

Is it a tumor arising in the pineal gland, with the histopathology of a medulloblastoma or neuroblastoma?
Pinealoblastoma
Is it a pineal tumor resembling a seminoma / dysgerminoma, embryonal cell carcinoma, choriocarcinoma, and/or teratoma?
Pineal germinoma
Is it a pineal tumor composed of various glial and neuronal type cells?
Pineocytoma
Is it furrowed, "weather beaten" skin on an older person?

Is there an amorphous, slightly basophilic appearance to the upper dermis?

Solar elastosis
Is it "hives" a blotchy, red, slightly elevated acute eruption, perhaps following exposure to an allergen?

Is it a more enduring case of "hives" in a person with systemic autoimmune disease, vasculitis, malignant lymphoma, mastocytosis, celiac disease, or dermatographism?

Urticaria
Is it an acute, itchy, at least somewhat oozy-crusty dermatitis?

Is there accumulation of edema fluid within the epidermis (i.e., spongiosis), disrupting its integrity? (Beyond this, the histopathology may vary some with the cause.)

Acute eczematous dermatitis

Consider allergic contact dermatitis, irritant dermatitis, atopic dermatitis, drug eruption, and lots of other things.

Is it an itchy area of skin that looks chronically inflamed and on which the skin lines are exaggerated? Has the patient been scratching it a lot?

And on biopsy, do you see acanthosis, hyperkeratosis, and a thick granular layer?

Lichen simplex chronicus
Is it a rash with target lesions?

Is it an epidermis apparently being attacked by lymphocytes, perhaps with much apoptosis of the cells of the lower layer?

Does the patient perhaps have herpes simplex, mycoplasma, leprosy, deep fungi, typhoid, cancer, lupus, polyarteritis, dermatomyositis, and/or a drug reaction (sulfonamide is notorious)?

Erythema multiforme

With fever and systemic involvement: Stevens-Johnson syndrome

With necrosis and loss of much of the epidermis and mucosae: Toxic epidermal necrolysis

Is it inflamed painful, tender bumps in the fat of the lower leg?

Is it fat with the broad connective septa widened by fibrin and acute inflammation, perhaps later with chronic inflammation and even a few good granulomas?

Erythema nodosum
Is it an inflammatory, necrotizing panniculitis, typically a single lesion, that ulcerates? Histologically, does it look like a vasculitis is the problem?
Erythema induratum
Is it pink plaques on the elbows, knees, scalp, gluteal cleft, and/or glans, with a silvery scale? Does peeling the scale produce punctate bleeding ("Auspitz's sign")?

Is also there perhaps one of more of the following:
...erythroderma;
...pitted yellow nails;
...arthritis?

Does skin biopsy show all or most of the following:
...thick scales exhibiting parakeratosis (i.e., retention of nuclei in the keratin layer);
...thinning of the granular layer of the epidermis;
...acanthosis with elongation of the rete pegs;
...thinning of the epidermis over the dermal papillae;
...clumps of neutrophils in the upper epidermis ("spongiform pustule of Kogoj");
...clumps of neutrophils in the stratum corneum ("Munro microabscesses")?

Psoriasis
Is it chronic, purplish, itchy thickenings on the flexor surface of the wrist, the glans, or elsewhere on the skin?

Is it a filigree of lines on the buccal mucosa?

Do you see the following on biopsy:
...hyperkeratosis;
...thick granular layer of the epidermis;
...apoptosis of basal cells, which may drop into the upper dermis ("Civette bodies", "colloid bodies");
...a sawtooth appearance of the rete pegs;
...a band of lymphocytes in the upper dermis, apparently attacking the basal cells?

Lichen planus
Is it skin with large, more-or-less round, shiny-scaly, red plaques with telangiectatic vessels, loss of hairs, and variegated hypopigmentation and perhaps hyperpigmentation? Do you perhaps see little keratin plugs in the follicles if you look very closely?

Is it a skin biopsy showing most of the following:
...lymphocytes clustered around vessels and adnexal structures;
...a patchy, band-like infiltrate of lymphocytes apparently attacking the basal layer;
...hydropic change of the basal cells near these lymphocytes;
...hyperkeratotic scale overlying these areas;
...keratin plugs in follicles?

Is there a granular deposit of IgG and C3 along the basal lamina ("positive lupus band test")?

Discoid lupus

NOTE: If the "lupus band test" is positive on uninvolved skin, the patient probably also has systemic lupus.

Is it the familiar "acne" of adolescence, etc., with expanding sebum- keratin plugs in follicles with open lumens ("blackheads", "open comedones") and closed lumens ("closed comedones"), the latter perhaps undergoing suppuration?

If someone happened to biopsy this lesion, do you see the keratin plug in the follicle, perhaps with surrounding suppuration?

Acne vulgaris
Is it a skin disease that tends to spread to any site that has been recently injured?
Koebner phenomenon
Consider psoriasis, lichen planus, vitiligo, morphea, others.

Is it a blistering disease involving the skin and perhaps mucosal surfaces, with blisters forming where the skin is rubbed ("Nikolsky's sign")?

And on light microscopy, do you see acantholysis with separation of the epidermis just above the basal layer ("suprabasal acantholytic blister"; basal cells remain below as "tombstones")?

And on immunofluorescence, do you see immunoglobulin deposited on the desmosomes, i.e., as a network between the epidermal cells?

Pemphigus vulgaris
Is it a disease producing warty-blisters on the skin of a patient, usually a Central or South American?

And on light microscopy, do you see acantholysis with separation of the epidermis most marked in the stratum granulosum?

And on immunofluorescence, do you see immunoglobulin deposited as a network between the epidermal cells?

Pemphigus foliaceus
Is it a blistering skin disease with separation of the entire epidermis, including the basal layer, from the basement membrane ("subepidermal non-acantholytic blister")?

And on immunofluorescence, do you see a smooth, linear immunoglobulin deposit along the basement membrane (i.e., antibodies against hemidesmosomes)?

Bullous pemphigoid
Is it a urticarial and/or blistering skin disease, cropping up symmetrically, with extreme pruritis?

And on biopsy, do you see acute inflammation of the tips of the dermal papillae?

And on immunofluorescence, do you see IgA in the tips of the dermal papillae (autoantibodies against reticulin in anchoring fibrils)?

And does the patient perhaps have gluten enteropathy?

Dermatitis herpetiformis
Is it a blistering disease of sun-exposed skin, with subepidermal blisters and considerable hyaline thickening of the nearby blood vessels?

Is the patient perhaps an iron-overloaded alcoholic? Is there perhaps extra hair over the cheekbones? Are the lesions from the backs of the hands or the center of the chest? Does the patient perhaps have hypertrichosis, photomutilation, (and in the worst cases) a taste for blood, and is mistaken for a vampire or werewolf? Etc., etc.

Porphyria

NOTE: The common one is porphyria cutanea tarda. Dracula and friends may have suffered from congenital erythropoietic porphyria.

Is it a single, deep abscess of hairy skin, perhaps caused by a staphylococcus?
Furuncle ("boil")
Is it a large, deep skin infection with suppuration and multiple draining sinuses?
Carbuncle
Is it a red, non-suppurating, spreading skin infection, perhaps caused by a group A streptococcus?
Cellulitis / phlegmon / erysipelas
Does the histology show most of the following:
...bumpy epidermal hyperplasia;
...prominent granular layer;
...vacuoles surrounding nuclei of infected cells ("koilocytosis")?
And do you recognize the lesion grossly as the familiar wart? And if somebody did electron microscopy, do you see viruses in the nucleus?
Wart

Depending on the location, this may be "verruca vulgaris", "condyloma acuminatum", etc.

Is it little pruritic skin lesions from which the patient can express a curd-like center?
Is it a hyperplastic skin lesion containing a crater filled with cells bearing very large, homogeneous, intracytoplasmic viral inclusions?
Molluscum contagiosum
Is it honey-colored crusts on the skin?

Is it a skin lesion with neutrophils just under the stratum corneum? If you have a gram stain, do you see gram positive cocci among the neutrophils?

Impetigo
Is the gross picture recognizable to you as one of these:
...ringworm of the scalp or beard;
...tinea corporis, cruris, or versicolor;
...athlete's foot;
...onychomycosis?

Does PAS or silver stain reveal fungi in the dead keratin layer?

Superficial fungus infection ("dermatophytosis")
Is it a "stuck-on", pigmented, crusty lesion on an older person's skin?

Is it multiple, small, dark hyperkeratotic lesions on a black person's face ("papulosa nigra")?

Do you see hyperplasia of the basal cells of the epidermis, which have piled up, and produced sharply-demarcated keratin pearls ("horn cysts")?

Seborrheic keratosis
Is it darkening and crusty thickening of the skin of the axillae, and perhaps neck and groin? If someone biopsies it, do you see hyperplasia of the basal cells and excess keratin?
Acanthosis nigricans
Is it a rapidly-developing, volcano-shaped lesion with a keratin- filled crater? Does the dermatologist say it will go away by itself?

And histologically, do you see hyperplasia of the epidermis, apparently invading the dermis, but without cytologic atypia?

Keratoacanthoma
Is it a cyst beneath the skin or elsewhere, its center filled with laminated keratin and its wall composed of stratified squamous epithelium?
Epidermoid inclusion cyst
Is it a cyst beneath the skin or elsewhere, its center filled with a mix of keratin and sebum, and its wall resembling the components of the pilosebaceous apparatus?
Pilar cyst ("trichilemmar cyst"; "sebaceous cyst")
Is it a cyst beneath the skin or elsewhere, its center filled with a mix of keratin and sebum, and its wall resembling hairy epidermis?
Dermoid cyst
Is it a cyst beneath the skin or elsewhere, its center filled with a mix of keratin and sebum, and its wall made of sebaceous epithelium?
Steatocystoma multiplex
Is it a papillary lesion of the skin, with a fibrous core with overlying epidermis?
Fibroepithelial polyp ("skin tag")
Is it a small, rough, horny-scaly, perhaps slightly pigmented and/or shiny-atrophic patch typically on sun-exposed skin of an older person (or the palms, if arsenic was a factor)? And on histology, is there atypia of the basal layer, which retains squamous features and is not invading (i.e., is this "squamous cell dysplasia / carcinoma in situ")?
Actinic keratosis ("solar keratosis"; "senile keratosis", "arsenical keratosis")
Is it a skin lesion, especially on sun-exposed hair-bearing skin of an older person, perhaps (but not necessarily) rich in pigment? Is it perhaps telangiectatic, and if ulcerated, is there a pearly, rolled border? And on microscopy, is the lesion an invasive cancer composed of cells with scanty cytoplasm but little other evidence of anaplasia, no intercellular bridges, and a tendency to form a palisade of cells around the edges of the invasive cords?
Basal cell carcinoma
Is it a cancer producing any of the following:
...single-cell keratinization;
...good desmosomes between the cancer cells;
...good keratin pearls?
Is it located:
...on sun-exposed skin of an older person;
...at the edge of a chronic osteomyelitis sinus or other fistula;
...on the palm of someone who has taken arsenic some time ago?
Squamous cell carcinoma of the skin

NOTE: The in-situ phase ranges from an actinic keratosis to an erythematous plaque.

Is it a fleshy nodule on the skin of an older person, composed of cells about 15-25 microns across with very little cytoplasm, neurosecretory granules and positive staining for neuroendocrine markers? Does it look histologically like oat-cell carcinoma of the lung?
Merkel cell carcinoma

NOTE: Cancer of an atavistic touch receptor

Is it an epithelial tumor of the skin that looks like it ought to be a classic example of something, but you don't find it listed here?
Skin adnexal tumor

NOTE: Lots of varieties. Get out a real pathology book.


Is it a firm-to-hard bump in the dermis, with some hyperpigmentation of the overlying epidermis? Does the epidermis (being unattached to the lesion) dimple when it is squeezed? On microscopy, do you see a non- encapsulated lesion composed of spindle and/or foam cells in collagen within the dermis? Is its cut surface perhaps brown or yellowish?
Dermatofibroma ("benign fibrous histiocytoma of skin", "sclerosing hemangioma")

NOTE: A large, mildly-malignant dermatofibroma a with "pinwheel" arrangement of spindle cells is called a dermatofibrosarcoma protuberans.

Have the melanocytes and melanin disappeared from a region of the skin, in the absence of other local pathology?
Vitiligo
Is it a flat, hyperpigmented skin lesion, less than 1 cm and probably one of many, with increased melanin production by melanocytes which may be slightly atypical and/or increased in numbers, but not floridly malignant? Is the owner perhaps a redhead?
Freckle ("ephelis")
Is it the familiar raccoon-eyes "mask of pregnancy", or a similar lesion in a patient taking phenytoin, or with no known predisposing factor? Under the microscope, is there either:
...increased pigmentation of the basal layer;
...pigment incontinence with the dermal papillae packed with melanophages (i.e., melanin-laden macrophages)?
Melasma
Is it a flat, hyperpigmented skin lesion under 10 mm, with hyperplasia of the melanocytes and perhaps some elongation of the rete pegs?
Lentigo
Is it a darkly-pigmented, perhaps spectacular birthmark with nevus cells extending through the dermis and into the fat?
Congenital nevus
Is it a pigmented nevus from a young person, with cuboidal and/or spindly nevus cells at the dermal-epidermal junction and in the upper dermis, perhaps showing cellular atypia, but with a tendency to lose this atypia and "mature" deeper in the dermis?
Spitz nevus
Is it a lightly or darkly pigmented skin lesion which on microscopy shows nevus cells confined to the dermis, without "junctional activity" (i.e., no clumps of cells at the dermal-epidermal border)?
Intradermal nevus
Is it a lightly or darkly pigmented skin lesion which on microscopy shows nevus cells distributed primarily in groups along the dermal- epidermal junction ("junctional activity")?
Junctional nevus
Is it a lightly or darkly pigmented skin lesion which on microscopy shows nevus cells both in groups along the dermal-epidermal junction and in the deeper dermis?
Compound nevus
Is it a benign nevus, perhaps regressing, with depigmentation of the surrounding skin? And on microscopy, do you see both nevus and surrounding skin under attack by lymphocytes?
Halo nevus
Is it a group of darkly-pigmented nevus cells with many branches ("dendritic nevus cells"), deep in the dermis?
Blue nevus
Is it a junctional nevus with some or all of these features:
...6 mm or more across;
...irregular border;
...variegated pigmentation (i.e., the color is not uniform)
...large clusters of nevus cells at the dermal-epidermal junction, perhaps so large that adjacent nests fuse;
...cytologic atypia of the nevus cells;
...a modest infiltrate of lymphocytes near these nests;
...pigment incontinence and melanophages;
...fibrosis in the upper dermis around the rete pegs?

Is there perhaps a personal or family history of other BK moles and/or melanoma?

Dysplastic nevus ("BK mole")
Is it a large, flat, pigmented, perhaps variegated lesion on sun- exposed skin? On microscopy, is it malignant melanocytes only in radial growth phase with cells exhibiting considerable atypia, but mostly growing as individual cells in the basal layer?
Lentigo maligna melanoma ("Hutchinson's freckle")

Is it a pigmented skin lesion, perhaps variegated and/or irregular, on sun-exposed skin or elsewhere? On microscopy, is it malignant melanocytes in groups, perhaps invading the upper epidermis, but still in radial growth phase and not invading dermis?
Superficial spreading melanoma
Is it a malignant melanoma at the edges of the hairless, nonpigmented skin of the palm or sole?
Acral lentiginous melanoma
Is it cancer composed of malignant melanocytes anywhere in the body, whether in radial or vertical growth phase? Is it positive for melanin and/or S100, and do you perhaps find melanosomes on electron microscopy?
Malignant melanoma

NOTE: Your instructors probably want you to know both "Clark's levels" and "Clark's stages"; don't confuse the two conceptually.

Is it bone viewed under polarized light, with its lamellae all parallel?
Lamellar bone

NOTE: All healthy adult bone is lamellar.

Is it bone viewed under polarized light, with crisscrossing of its fibers?
Woven bone

NOTE: Normal in kids, most pathologic and healing bone is also woven.

Is it a broken bone with the overlying skin and soft tissue intact?
Simple ("closed") bone fracture
Is it a broken bone with the fracture site in communication with the outside environment?
Compound bone fracture
Is it bone that has been splintered into several pieces?
Comminuted bone fracture
Is it a cracked bone, not broken into two separate pieces?
Greenstick bone fracture
Is it a "knot" of blood clot, fibroblasts, cartilage, and/or osteoid at the site of a fracture?
Healing bone fracture / callus
Is it a "knot" of blood clot, fibroblasts, cartilage, and/or osteoid at the site of a fracture?
Pseudarthrosis ("false joint")
Is he or she a patient who has excessively fragile bones, perhaps sustaining multiple fractures on being born, or in less severe cases, perhaps deformed and very short? Are the teeth perhaps abnormally shaped? Do the sclerae perhaps appear blue?

Has the biochemist identified some lesion that interferes with proper formation of type I collagen?

Osteogenesis imperfecta ("brittle bone disease")
Are the marrow cavities gradually being filled by solid bone as a result of defective osteoclast resorption? As a result, are the bones prone to be radio-dense yet extra-brittle, and is there perhaps deficient blood cell production?
Osteopetrosis
Is this a dwarf with normal rib development, spine and head, but shortened arms and legs, and perhaps a depressed center to the face? If there is a family history, is it autosomal dominant?
Achondroplasia / achondroplastic dwarfism
Is it pus in the bone marrow cavity, perhaps also with granulation tissue? Is the spongy bone perhaps necrotic (a "sequestrum", i.e., there are no osteocytes in the lacunes)?

Do you perhaps see any of the following:
...septic arthritis nearby
...subperiosteal abscess;
...sterile, walled-off but non-resolving "Brodie's abscess";
...sinus tract to the skin;
...fibrosis and repair by new bone in the surrounding areas?

Pyogenic osteomyelitis
Is it caseous necrosis, probably with granulomas, in the bone marrow? And you see no fungi, and perhaps an acid-fast stain shows mycobacteria?

And has the process perhaps resulted in either of the following:
...psoas abscess;
...Pott's collapse of a vertebra?

Tuberculous osteomyelitis
Is it periosteal disease with proliferative endarteritis narrowing vessels, and abundant plasma cells?
Syphilitic periostitis
Is this bone that has lost its matrix, i.e., abnormally thin cortex, abnormally rarified spongy bone, as part of a systemic process or in an immobile extremity?

Is this a compression fracture of a vertebral body in an older person, perhaps producing a "dowager's hump"?

Are the spicules of spongy bone in a histologic section unusually thin and perhaps unusually few?

Osteoporosis
Is it a mixed picture of osteitis fibrosa cystica ("hyper-parathyroid bone disease") and osteomalacia, in a patient with longstanding renal insufficiency?
Renal osteodystrophy
Is this bone from a person with primary, secondary, or tertiary hyperparathyroidism, and you see masses of fibrous tissue with osteoclasts, where marrow should be, resorbing bone, leading in time to hollowed out "cysts" (misnomer) in the bone?

Is it a random section of adult's bone, without a recent fracture or Paget's disease, and you see an osteoclast? (Even seeing one in a grown-up, without some other good reason, suggests hyperparathyroidism.)

Osteitis fibrosa cystica / Hyper-parathyroid bone disease
Is it bone from an older person that looks and crumbles like dried biscuit?

Is it bony spicules with a mosaic pattern of craze-marks? Are they surrounded by a fibrous tissue with excess osteoblasts and osteoclasts?

Does the patient perhaps have any of these:
...enlarging hat size;
...hearing loss;
...back or pelvic pain;
...bowing of the legs;
...high-output heart failure from arteriovenous shunts in bone?
...lab evidence of "slow paramyxovirus infection" (some people blame canine distemper virus);
...osteogenic sarcoma?

Paget's osteitis deformans
Is part of the bone being replaced by a benign, fibrous tissue with metaplastic woven bone?
Fibrous dysplasia of bone
Do several bones exhibit fibrous dysplasia ("polyostotic")? In addition, does the patient exhibit some or all of:
...caf‚-au-lait spots with ragged borders;
...precocious puberty;
...vitamin D resistance;
...various endocrinopathies?
And is the illness sporadic, the result of a mutation early in embryonic life, the mutation being lethal to the fertilized egg? And does the research lab notice that cells tend to react to activation of cGMP as if it were cAMP?
McCune-Albright's disease
Is new bone forming under the periosteum of the distal ends of long bones, hand bones, foot bones, and finger and toe bones?

And does the patient probably have lung cancer, or some other kind of cancer or some other severe longstanding lung disease, or else cirrhosis?

Hypertrophic osteodystrophy
Is it a lytic lesion in the metaphysis of a long leg bone of a child? Histologically, do you see a cellular mass of fibroblasts without bone formation?
Fibrous cortical defect ("non-ossifying fibroma")

Is it a hard bump of dense bone jutting off the skull or jaw, perhaps into a nasal sinus?
Osteoma
Is it a round, painful lesion of bone, with a lytic center composed of fibrous tissue with miniature bony trabeculae, and a sclerotic rim composed of thick bony trabeculae?
Osteoid osteoma
Is it a non-painful, lytic lesion of bone composed of miniature bony trabeculae?
Osteoblastoma
Is it a malignant tumor in which the cancer cells themselves are making osteoid? (There are several histologic variants.)

Did it perhaps (but not necessarily) arise in one of these settings:
...the metaphysis of the leg bone of a (maybe tall) teenager;
...a site of previous radiation;
...a patient with retinoblastoma, Gardner's, or Li Fraumeni anti- oncogene deletion syndromes, or with multiple enchondromatosis;
...an older person with Paget's osteitis deformans;
...an old fracture site, bone infarct, or osteomyelitis lesion?

Osteosarcoma
Is it a bony bump off the metaphysis of a long bone, with a cartilage cap?

Is it one of dozens of similar lesions from a patient diagnosed with one of the autosomal-dominant "osteochondromatosis" syndromes or Gardner's syndrome?

Exostosis ("osteochondroma")
Is it chunks of mature cartilage in a vascular stroma, popping up as a "bone tumor"?

Does the patient also perhaps have lots of these cartilage bumps ("Ollier's syndrome", not hereditary) over part of the body?

Or does the patient also perhaps have lots of these plus lots of hemangiomas ("Maffucci's syndrome, autosomal dominant)?

Chondroma
Is it a chondroma arising inside of a bone?
Enchondroma
Is it a mixed mess of mature cartilage, dense fibrous tissue, and loose myxoid fibrous tissue, perhaps with some cellular atypia, often (but not necessarily) at the knee of an older male teen?
Chondromyxoid fibroma
Is it a bone tumor composed primarily of little, uninucleate chondrocytes? Do you also perhaps see any of these:
...calcification;
...benign giant cells;
...good cartilage matrix;
...figures;
...hemorrhage;
...necrosis?

Is it perhaps (but not necessarily) an apparently destructive lesion from the knee of a male teen?

Chondroblastoma
Is it a cartilage-based tumor in bone with either multinucleate chondrocytes and/or multiple chondrocytes in one lacune and/or obviously anaplastic chondrocytes?

Did it perhaps (but not necessarily) arise in the pelvis of an older man, or in a patient with an enchondromatosis syndrome or from an exostosis?

Chondrosarcoma
Is it a primary bone tumor, not leukemia-lymphoma, composed of anaplastic cells with scanty cytoplasm, typically filling a marrow cavity, and with no tendency to make a dense collagenous stroma? And are the tumor cells rich in glycogen?

Is the patient perhaps a teenaged male? Is the trademark t(11:22) translocation present?

Ewing's sarcoma

NOTE: Many similar tumors bear neuroendocrine markers, plus the t(11:22) translocation. Ask your instructor.

Is it a primary, soft, vascular, often bloody, locally destructive spindle-cell bone tumor with abundant benign osteoclasts?

Is the tumor perhaps (but not necessarily) from the knee?

Giant cell tumor of bone ("osteoclastoma")

NOTE: Hemorrhage, necrosis, mitotic figures are all poor predictors of behavior.

Is it age-related changes in the hip, knee, or first metacarpophalangeal joints?

Is it "Heberden's nodes" alongside the distal interphalangeal joints of the fingers?

Is the cartilage thinned, frayed, cracked, eroded, overly basophilic, and/or missing live chondrocytes? In the underlying bone, is there eburnation (i.e., thickened from constant rubbing) and/or microcyst formation? As a result, are the sides of the articular surfaces growing outward as bumps ("spurs", "osteophytes")?

Osteoarthritis / degenerative joint disease
Is it arthritis beginning in the small joints of the hands and feet, and perhaps progressing to the familiar mutilating changes?

Is it markedly thickened synovium, with hyperplastic, layered-up synovial lining cells, and infiltrated by lymphocyte, plasma cells, and macrophages? (In other words, is this "pannus"?) As the disease progresses, does the joint undergo destruction?

Do you perhaps also find, elsewhere in the patient:
...immune-complex type vasculitis involving the skin (ulcers) or coronary arteries (heart attack) or some other site;
...hypersplenism ("Felty's");
...amyloidosis A;
...autoantibodies against the modified Fc portion of IgG ("rheumatoid factor")?

Rheumatoid arthritis
Is it a nodule, up to 2 cm across, with a central necrotic mass of fibrinoid, rimmed by a palisade of epithelioid histiocytes? And surrounding this, are there lymphocytes and plasma cells?
Rheumatoid nodule
Is it pus, perhaps also with granulation tissue as the process develops, in a joint?
Suppurative arthritis
Is it a highly destructive arthritis with caseous necrosis? Can no organism be visualized or cultured except mycobacterium?
Tuberculous arthritis
Is it uric acid crystals from an inflamed joint?

Is it a tophus, i.e., a mass of uric acid crystals encased in a granuloma?

Gout
Is it calcium pyrophosphate crystals from an inflamed joint?

Is it a knee or other joint with chalky crystal of calcium pyrophosphate or hydroxyapatite on its articular surfaces?

Pseudogout / calcium crystal deposition arthritis
Is it a proliferation of synovial cells and macrophages in a tendon sheath? Are there perhaps abundant giant cells?
Giant cell tumor of tendon sheath / nodular tenosynovitis
Is it a proliferation of synovium and macrophages covering an articular surface (usually the knee), with hemorrhage and destruction of the joint?
Pigmented villinodular synovitis
Does the muscle perhaps appear normal on H&E section, but special stains reveal the type I and type II fibers to be grouped together rather than at random?
Type grouping of muscle fibers

NOTE: Denervation-reinnervation is the cause.

Are the individual muscle fibers decreased in cross-sectional area?

Do you see angular muscle fibers?

Are the type II fibers of a couch potato, person on glucocorticoids, or other type patient substantially smaller, and perhaps more angular, than the type I fibers?

Atrophy of muscle fibers

NOTE: Don't mistake a golgi tendon organ for atrophy.

Has a segment of a muscle fiber become hypereosinophilic (i.e., stains red instead of pink) and has lost its cross-striations?
Degeneration of muscle fibers
Is this apparent muscle fiber cells with basophilic cytoplasm, a rounded-up, pale-staining nuclei no longer stuck on the sarcoplasmic membrane, and visible nucleoli?
Regenerating muscle fibers
Is it contraction bands (q.v.) in skeletal muscle? And if this isn't Duchenne's muscular dystrophy, are we perhaps looking at the edge of a muscle biopsy near the surgeon's cuts?
Hypercontraction of muscle fibers
Is this muscle fibers with sarcomeres arranged circumferentially in a ring under the sarcolemma, surrounding the properly-oriented sarcomeres deep in the fibers?

Does this patient perhaps have myotonic dystrophy?

Ring muscle fibers
Is it muscle fibers that appear to have clefts, as if they cracked?
Split muscle fibers
Is this muscle exhibiting group atrophy of its fibers as the primary lesion?

Does the finding of type grouping on special stains confirm denervation-reinnervation?

Denervation atrophy of muscle

Is this a younger boy with weakness and pseudohypertrophy of the muscles, or such a boy grown to be wheelchair-bound by age 16?

And on muscle biopsy (which isn't always a good idea), do you see:
...degeneration-necrosis and/or hypercontraction of individual muscle fibers;
...great variation in fiber size;
...split fibers;
...too many central nuclei;
...fibrous and fatty ingrowth?

Duchenne's muscular dystrophy
Is it a Duchenne-like picture, but the boy is less severely affected, and can walk on his sixteenth birthday?
Becker's muscular dystrophy
Is this a patient who first loses the ability to whistle, then loses mass in the deltoids, pectorals, shoulder girdle, and upper arm muscles? Is muscle biopsy nondiagnostic?

Does the family history perhaps suggest autosomal dominant inheritance?

Facioscapulohumoral muscular dystrophy
Does he or she have weakness and, distinctively, difficulty letting go of doorknobs, jar lids, and handshakes?

On muscle biopsy, do you see a lot of ring fibers, central nuclei, and disorganized chunks of non-striated actin and myosin in the cytoplasm?

Does he or she also perhaps have a small chin, frontal balding, a "tapir-nose", and personality problems?

Does this autosomal-dominant disease get worse from generation to generation (Sherman's paradox)?

Myotonic muscular dystrophy
Are there rods of Z-band material running down the centers of the muscle fibers?
Nemaline myopathy
Is this an autosomal dominant disease in which the central regions of the type I fibers lack myofilaments and energy-producing enzymes?
Central core myopathy
Does he or she have unusually well-developed muscles even with little resistance training, but complains of muscle cramps in cold weather?
Myotonia congenita
Is this a disease featuring "ragged red fibers", the ragged red areas being packed with worthless mitochondria? Are the worthless mitochondria perhaps packed with "parking lot" crystalloids?
Mitochondrial myopathy ("Kearns-Sayre myopathy", AZT myopathy, others)
Is this an acquired syndrome of weakness relieved by injection of edrophonium? Does the patient perhaps have thymic hyperplasia and/or a thymoma?

Do you see, perhaps (but not necessarily), clusters of lymphocytes around the motor end plates in the muscles?

Myasthenia gravis
Is this a tumor of the tongue or elsewhere, composed of polygonal cells packed with dPAS-positive granules (phagolysosomes with junk inside them), S100-positive, and inducing hyperplasia in any nearby stratified squamous epithelium?
Granular cell tumor
Is this a sarcoma with cells positive for any of these:
...alpha-1 protease inhibitor (antitrypsin);
...alpha-1 antichymotrypsin;
...lysozyme;
...factor XIIIa?

Is this a sarcoma, and the cells are making cartwheels-pinwheels ("storiform arrangement"), myxoid areas, or areas that remind you of a granuloma?

Do you think this is a sarcoma, but it doesn't look like any of the sarcomas you know? (If so, "MFH" is a good bet.) Is your instructor perhaps talking eagerly about "facultative fibroblasts"?

Malignant fibrous histiocytoma

Is it an encapsulated mass of mature fat, typically from under the skin?

Does it perhaps (but usually not) contain prominent blood vessels and/or fibrous septa and/or marrow?

Lipoma
Is it a sarcoma from deeper in the body, with some of these features:
...looks like a lipoma, but has some anaplasia ("well- differentiated liposarcoma");
...myxoid gross and microscopic appearance, with a prominent network of vessels and a few lipoblasts ("myxoid liposarcoma");
...highly cellular, small-cell sarcoma with some vacuolated lipoblasts ("round cell liposarcoma");
...super-ugly lipoblasts, at least a few bearing several fat vacuoles ("pleomorphic liposarcoma")?
Liposarcoma


Is it a sarcoma from deeper in the body, perhaps somewhere where there is skeletal muscle, and you see some of these features:
...primitive cells, strap cells (elongated, eosinophilic cytoplasm, maybe cross-striations), tennis-racket cells, spider cells (central nucleus indented by huge glycogen vacuoles); this is an "embryonal rhabdomyosarcoma"; if there is a cambium layer, it is a "sarcoma botryoides"
...as the above, but a tougher call ("pleomorphic rhabdomyosarcoma");
...undifferentiated cells with scanty cytoplasm, in clusters surrounded by fibrous alveolus-like walls ("alveolar rhabdomyosarcoma")?

Does this cancer stain positive for desmin and/or myoglobin?

Does electron microscopy of this cancer show good sarcomeres?

Rhabdomyosarcoma


Is it a tumor of interlacing smooth-muscle bundles as in the familiar uterine "fibroid"? Is it perhaps (but not necessarily) uncomfortable?
Leiomyoma
Is it a smooth-muscle tumor with several mitotic figures?
Leiomyosarcoma
Is it a well-differentiated spindle-cell tumor making scanty collagen, but with the spindle cells arranged in a herringbone pattern?
Fibrosarcoma
Is it an apparent sarcoma, not arising from a mesothelial surface, with a "biphasic" mix of spindle-cell and gland-like areas?
Synovial sarcoma

NOTE: Monophasic versions exist. Don't worry about them.

Is it an irregular thickening of the palmar fascia, perhaps entrapping one or more finger tendons?
Palmar fibromatosis ("Dupuytren's contracture")
Is it an irregular thickening of the fascia of the penis, perhaps occluding the urethra and/or causing curvature of the erect penis?
Penile fibromatosis ("Peyronie's disease")
Is it a lesion composed of collagen-producing fibroblasts without atypia, but locally invasive? Is the site perhaps the abdominal muscles during or just after pregnancy, or in a big skeletal muscle, or anywhere in a patient with Gardner's syndrome?
Aggressive fibromatosis ("desmoid")
Is it a rapidly-growing lesion composed of fibroblasts that look like the familiar tissue-culture kind, without atypia, but apparently invading muscle and other nearby tissues and probably with mitoses and hemorrhage?
Nodular fasciitis ("pseudosarcomatous fasciitis")

NOTE: Leave this lesion alone, it's benign.

Is it a scleroderma-like lesion of fascia with abundant eosinophils?

Is it a syndrome of rhabdomyolysis-myositis in which eosinophils invade the muscle and bloodstream? And did the patient take tainted "health-food store" tryptophan?

Eosinophilic fasciitis / eosinophilia-myalgia syndrome
Is it skeletal muscle being replaced by fibrous tissue which undergoes metaplasia into bone, either at a single site of injury, or in many different locations for no apparent reason?
Myositis ossificans
Is he or she a trim individual with a large heart and low resting pulse, with lots of mitochondria in the skeletal muscles and impressive physical endurance? Does this person train by making muscles contract and expand repeatedly to the limits of their metabolic capacity, though not against great resistance?
Aerobic athlete
Is he or she a physically strong individual, with increased diameter of the type II fibers, and who trains by making muscles contract only a few times per day against maximal resistance?
Strength athlete
Is he (or even she, heaven forbid) a strength athlete with several of the following:
...rapid, really impressive increase in muscle mass (gee whiz!);
...tell-tale testicular atrophy and sterility;
...greatly increased LDL and/or lowered HDL;
...cholestasis;
...gynecomastia (men) / amenorrhea and hirsutism and guy-smell (women; you have been warned);
...acne getting much worse;
...accelerated masculine-type hair loss;
...impotence (men) or increased libido (either sex);
...aseptic necrosis of a hip;
...hepatic adenoma, focal nodular hepatocyte hyperplasia, or hepatocellular carcinoma;
...personality changes, and not for the better?
Strength athlete on anabolic steroids

NOTE: You'll see a lot more of these specimens than you will "nodular fasciitis". Around 1,000,000 Americans are doing this stuff while you read this.

NOTE: Consider yourselves properly cautioned.

Is the calvarium mostly or entirely absent, and the forebrain represented only by neuroglial nubbins?
Anencephaly
Is there a defect in the bones of the spine, allowing the dura, but not the spinal cord, to herniate out under the skin?
Meningocele
Is the brain of a newborn generally well-formed, but a portion is herniating out through a hole in the skull?
Encephalocele
Is there a defect in the bones of the spine, allowing both dura and spinal cord to herniate out under the skin?
Meningomyelocele
Is the cerebellar vermis ("roof of the fourth ventricle", or whatever) congenitally absent, or at best represented by inert glial scar ("cyst")?
Dandy-Walker syndrome
Is this a brain with:
...elongated cerebellar tonsils that hang through the foramen magnum;
Is there also (usually) hydrocephalus and a problem with the formation of the spine (meningocele, meningomyelocele)?
Arnold-Chiari malformation ("Chiari II malformation")
Is this an adult's brain weighing less than 900 gm, or a child's brain that is proportionally undersized, the result of a birth defect? In addition, are the gyri perhaps not all there, but the brain is otherwise well-formed?
Microcephaly
Is it a brain with a single cerebral hemisphere, lacking the usual midline structures of the prosencephalon?

Is the patient perhaps a cyclops?

Holoprosencephaly
Is this a brain with some or all of the limbic system missing? In its mildest form, is the brain normal except for no olfactory bulbs or tracts?
Arhinencephaly
Is the brain more or less well-formed except that the corpus callosum is partly or completely missing, perhaps with a lipoma or dermoid cyst at the site of a partial defect? Does the patient perhaps have alexithymia?
Agenesis of the corpus callosum
Is it a brain with no development of gyri, and there are only four, rather than six, layers to the cortex?
Agyria ("lissencephaly")
Is it a brain with just a few big, ill-formed gyri, and there are only four, rather than six, layers to the cortex?
Pachygyria
Is it a brain with too many gyri, and there are only four, rather than six, layers to the cortex?
Polymicrogyria
Is it a cleft in the brain that does not actually cause a discontinuity in the cortex, though it severely deforms it?
Schizencephaly
Is it a cleft in the brain that goes so deep that it reaches the ependyma?
Encephaloclastic porencephaly
Is it a congenital "hole in the brain", perhaps the result of a fetal stroke?
Porencephaly
Is it massive destruction of part or all of the cerebrum, perhaps as a result of failure of the carotid arteries to develop properly, or infection of the fetus by CMV or toxoplasmosis?
Hydranencephaly
Is it loss of brain tissue, most severe deep in one or more sulci of the unborn child or newborn, probably as a result of ischemia?
Ulegyria
Is it a "marbled" pattern seen in the putamen and caudate from ischemia or kernicterus around the time of birth?
Etat marbr‚ ("status marmoratus", "marbled state")
Is it necrosis surrounding the ventricles of a child's brain, worst at the angles, resulting from hypoxic-ischemic injury (the periventricular white matter being one watershed area of a child)?
Periventricular leukomalacia
Is this a swollen neuron body with lysis of the rough endoplasmic reticulum ("Nissl substance") except under the cell membrane?
Central chromatolysis ("axonal reaction")

NOTE: In a few locations, this is normal. Otherwise, it means the axon was severed.

Is this a neuron with its nucleus small and dark, and its cytoplasm shrunken and slightly hypereosinophilic?
Red necrotic neuron

NOTE: Think of hypoxia, circulatory arrest, hypoglycemia.

Are the neurons bloated with some abnormal granular material, with the nucleus pushed to one side?
Intra-neuronal storage disease
Is this a round, perhaps laminated, eosinophilic mass in the cytoplasm of a neuron (most often, a pigmented neuron of the substantia nigra), composed of neurofilament proteins?
Lewy body
Is it a weakly basophilic mass filling most of the cytoplasm of a big neuron? Does it stain strongly with the Bielschowsky silver method, which shows it as a tangled mess of filaments?

Does electron microscopy show the filaments to resemble twisted ribbons? Does the lab confirm that the predominant component is altered tau protein?

Does the patient have Alzheimer's disease (or is at least old), or dementia pugilistica, or progressive supranuclear palsy, or Parkinsonism after Von Economo's influenza encephalitis, or Guam ALS?

Neurofibrillary tangle
Does it appear on H&E as a bubbly neuron? Does the Bielschowsky silver stain show it up nicely, as granules in the neuronal cytoplasm surrounded by clear apparent vacuoles? Is the granule also rich in altered tau protein? Does the patient perhaps (probably) have Alzheimer's disease?
Granulovacuolar degeneration
Is it a barrel-shaped intracytoplasmic inclusion that is seen best on Bielschowsky silver staining?
Pick body
Is it an eosinophilic rod on a neuron's dendrite? Does the patient also have Alzheimer's disease?
Hirano body
Is it a dilated portion of an axon, visible as a round or oval structure in the neuropil? And has the patient perhaps suffered trauma (notably, diffuse axonal injury) or an infarct, or something else that disrupts axons?
Axonal spheroid
Is this an astrocyte with an extremely large, extremely hyperchromatic nucleus? And does the patient (probably) have progressive multifocal leukoencephalopathy?
Alzheimer I astrocyte
Is this an astrocyte with a swollen, edematous-looking nucleus, making it conspicuous in the neuropil? And did the patient die with liver failure and elevated blood ammonia?
Alzheimer II astrocyte
Is this an astrocyte with abundant, eosinophilic cytoplasm, and a large nucleus typically with a visible nucleolus? Is it one of a group of similar cells activated for repair?
Gemistocyte
Is it a PTAH-positive red rod in an astrocyte cytoplasm?
Rosenthal fiber
Is it a basophilic, glycogen-positive sphere in the neuropil, especially under the pia and ependyma, especially in older people?
Corpora amylacea
Is it a slightly-basophilic, glycogen-positive, daisy-shaped mass in a neuron? Does the patient (probably) have myoclonus epilepsy?
Lafora body
Is it an activated microglial cell, with its nucleus appearing as a "rod" in the neuropil?
Rod cell
Is it a lipid-laden microglial cell / macrophage in an area in which the brain has undergone necrosis?
Gitter cell
Is it a group of microglia ("microglial nodule") surrounding a dead neuron?
Neuronophagia
Is it an increase in the volume of cerebrospinal fluid from any cause, for any reason?

Is it a child, with sutures not yet fused, with a tremendously enlarged head but normal-sized face, optic nerves stretched so the eyes look downward ("setting sun")?

Is it an adult with the poorly-understood syndrome of "normal pressure hydrocephalus", with apraxia of gait, dementia, and incontinence, which responds to CSF shunting?

Hydrocephalus
Is it an increase in the volume of spinal fluid in some or all of the ventricular system because the flow of spinal fluid is blocked somewhere along its course?
Communicating hydrocephalus
Is it an increase in the volume of spinal fluid because of overproduction (i.e., choroid plexus papilloma) or deficient resorption (i.e., scarring around the arachnoid villi, etc.)
Non-communicating hydrocephalus
Are the ventricles of the brain simply enlarged because of brain "atrophy" (i.e., loss of brain cells for whatever reason)?
Hydrocephalus ex vacuo
Has the cingulate gyrus been pushed, as a result of localized edema and/or a space-occupying lesion, underneath the falx? In addition to the deformity, has the anterior cerebral artery perhaps been compromised?
Cingulate herniation
Has the cerebellar tonsil been pushed, as a result of a shift in intracranial contents due to generalized edema or an expanding lesion, out the foramen magnum? Has the medulla probably been crushed in the process?
Cerebellar tonsillar herniation
Has the uncus of the temporal lobe been pushed downward, as a result of localized edema and/or a space-occupying lesion, into the tentorial notch? In addition to the deformity, has there perhaps been compromise of the ipsilateral third nerve ("blown pupil"), contralateral third nerve (in "Kernohan's notch"), and/or ipsilateral posterior cerebral artery?
Tentorial uncal herniation
Has the skull been massively fractured and/or opened by surgery, and is edematous brain protruding?
Trans-calvarial herniation
Is this a brain with some or all of the cortex so swollen that the sulci have been greatly narrowed and the gyri flattened against the skull?
Cerebral edema
Is there excess fluid between the brain cells? Does water run from the cut surfaces of this edematous brain?

Is the clinical setting a bacterial infection, recent trauma, a recent infarct, cancer, or lead poisoning?

Vasogenic cerebral edema

NOTE: Nothing subtle, just like leaky vessels anywhere else.

Is there excess water actually inside the brain cells? Despite this brain being obviously edematous, does little or no water run from the cut surfaces?

Is the clinical setting ischemia, perhaps a stroke-in-progress or after cardiac arrest?

Cytotoxic cerebral edema
Is this edema primarily in the white matter immediately surrounding the ventricles, in hydrocephalus?
Interstitial cerebral edema
Is it thick pus, perhaps with some organization, covering the brain? Was a classic bacterium probably identified as the etiologic agent?
Acute pyogenic meningitis
Is it an acute inflammation of the arachnoid primarily with lymphocytes? If an etiologic agent has been found, was it a virus?
Acute lymphocytic meningitis
Is it dense white debris encasing the circle of Willis? On microscopy, is there the familiar caseous necrosis of TB, and perhaps granulomas and/or mycobacteria as well?
Tuberculous meningitis
Is it an opalescent thickening of the arachnoid, with fibrosis and a plasmacytic, obliterative vasculitis, perhaps (but not often nowadays) producing infarcts?
Meningovascular syphilis
Is it involvement of the meninges by thickly-encapsulated yeasts, probably with a positive India-ink test? Do the yeasts perhaps grow down into the Virchow-Robin spaces and eventually expand them, producing Swiss-cheese brain?
Cryptococcal meningitis
Does the patient have serologic evidence of syphilis, and any of these:
...manic behavior or other psychosis, progressing to horrible insanity;
...brain atrophy;
...loss of neurons and their replacement with astrocytes ("windswept cortex");
...lots of rod cells in the cortex?
General paresis / paretic neurosyphilis
Does the patient have serologic evidence of syphilis, and any of these:
...loss of sensation in the extremities, especially proprioception;
...loss of deep tendon reflexes;
...Charcot joint deformities;
...Argyll-Robertson pupils that accommodate without reacting;
...lightning pains;
...loss of axons and myelin in the dorsal roots;
...loss of myelin and axons in the dorsal columns?
Tabes dorsalis
Is it a brain infection with a preponderance of lymphocytes, plasma cells, and macrophages? Are glial cells and neuronophagia perhaps prominent?
Viral encephalitis
Is it a meningoencephalitis with widespread necrosis of brain tissue and an impressive lymphocytic vasculitis? Is there perhaps currently an epidemic?
Arbovirus encephalitis
Is it an acute necrotizing viral encephalitis, most severe in the temporal lobes? Under the microscope, do you perhaps see swollen oligodendroglia cell nuclei, with some perhaps bearing intranuclear Cowdry A herpes-type inclusions?
Herpes encephalitis
Is it an infection limited to the anterior horns of the spinal cord, with cells as in viral encephalitis, and neuronophagia of anterior horn cells?

Is this the spinal cord of a known "polio" survivor, with absent anterior horn cells?

Poliomyelitis
Is this an encephalitis with neurons bearing intracytoplasmic, oval, eosinophilic Negri bodies?
Rabies
Is this the spinal cord of an HIV-positive person, with lipid-laden macrophages especially in the lateral columns?
AIDS vacuolar myelopathy
Is this brain from a person with a dementing disorder of several years' duration, and histology shows lymphocytes, plasma cells, and prominent eosinophilic inclusions in oligodendroglia and perhaps also in astrocytes and/or neurons?

Does electron microscopy show measles virus-like particles in those inclusions? Did the lab perhaps identify measles virus acting as a slow virus?

Dawson's subacute sclerosing panencephalitis ("SSPE")
Is this the brain of an immunosuppressed person who suffered from progressive dementia, and have portions of the white matter, and perhaps also the gray, lost their shiny white myelin?

And on microscopy, do surviving oligodendroglia at the edges of the lesions have nuclei that are grossly enlarged, with blobby intranuclear inclusions? And deep in the lesions, are there bizarre hyperchromatic astrocyte ("Alzheimer type I") nuclei?

Progressive multifocal leukoencephalopathy ("PML")
Is the brain cortex almost devoid of neurons, and filled instead with bubbly spaces in the neuropil?

Did the patient have an inexorably-progressive dementing and movement disorder?

Are there perhaps (but by no means necessarily) some amyloid plaques, especially in the cerebellum?

Spongiform encephalopathy / prion disease (includes Creutzfeldt-Jakob disease, kuru, veterinary diseases)
Is it a necrotizing brain lesion in someone who is immunocompromised, and toxoplasma "cysts" are in evidence at the edges of the expanding necrosis?

Is it a necrotizing and calcifying lesion of the brain of an unborn child, and there are no CMV cells or other evidence of CMV infection?

Cerebral toxoplasmosis
Is it a swollen, violaceous brain examined several days following an episode of near-drowning, cardiac arrest, or profound hypoglycemia? Histologically, do you see mostly "red necrotic" neurons?

Is it a brain with a profoundly thinned cortex, nearly or totally devoid of neurons?

Is it brain, not quite so severely involved, but with necrosis and loss of the pyramidal cell layers ("laminar necrosis") in most areas of the cortex?

Is it the familiar pattern of "watershed infarcts" of the brain, particularly involving the parasaggital cortex?

Ischemic ("hypoxic", "hypoglycemic") encephalopathy
Is it any portion of the cortex, following generalized hypoxia, hypoperfusion, or hypoglycemia, or local ischemia, with necrosis and loss of the pyramidal cell layers ("laminar necrosis")?
Laminar necrosis
Is it a linear, parasaggital infarct in the area between the middle and anterior cerebral arterial distributions, following an episode of hypotension or hypoxia?
Watershed infarct ("border zone infarct")
Is it softening and eventual lysis of a portion of brain in the distribution of a blood vessel?

In this setting, is the gray-white junction blurred? Are there petechiae, or perhaps more extensive hemorrhage as blood finds its way back into the damaged vessels?

Microscopically, do you see dying brain cells, perhaps hemorrhage, and usually some foamy macrophages ("gitter cells")?

Is this a portion of brain, after a known or unknown "stroke", which has liquified and been transformed into a cavity without significant collagenous scarring, with a rim of fibrillary gliosis, and with perhaps some lipid-laden macrophages as permanent residents?

Cerebral infarct
Is it an expansile hematoma deep in the brain substance, typically the basal ganglia, surrounded by considerable edema? Do you perhaps see blood pigments in the surrounding tissue, blood forced up the Virchow- Robin spaces of nearby small vessels, or rupture into a ventricle?

Is it a hemosiderin-pigmented slit in the deep brain substance, surrounded by fibrillary gliosis and hemosiderin-laden macrophages? (This is the site of an old hemorrhage which the patient survived.)

Intracerebral hemorrhage
Is it a little aneurysm without good elastica in its wall, arising from the circle of Willis or nearby (most often, the anterior communicating artery)? Did it perhaps rupture?
Berry aneurysm
Is it a tangle of vessels deep in the brain substance? Has there perhaps been hemorrhage here?
Cerebral arteriovenous malformation
Is it a mass of fresh blood or hemosiderin pigment in the subarachnoid space? Was the bleeding site a berry aneurysm or a cerebral arteriovenous malformation?
Subarachnoid hemorrhage
Is it a brain with many small infarcts deep in the brain? Did the patient perhaps have high blood pressure and/or a shower of micro- emboli?
Lacunar infarcts
Is this the brain of a patient with both longstanding hypertension and progressive dementia, simulating Alzheimer's disease? And is there loss of myelin and axons in the centrum semiovale? And is there severe hypertensive arteriolar sclerosis on microscopy?
Binswanger's subcortical leukoencephalopathy
Is this a patient with severe high blood pressure, with headache and convulsions and probably papilledema?

Is it the brain from such a patient, and the principal pathologic finding is cerebral edema?

Hypertensive encephalopathy
Is it a lens-shaped mass of blood forced between skull and dura following fracture of the skull which severed the middle meningeal artery? Was the patient perhaps knocked out, regained lucidity, then sank into coma?
Epidural hematoma
Is it a massive hemorrhage underneath the dura, from avulsion of the bridging veins?
Acute subdural hematoma
Is it a fibrous, hemosiderin-stained membrane overlying the cerebral hemispheres, the site of an old bleed which organized and is now shunting blood away from the cortex? Is the patient perhaps an older person with brain atrophy which stretched the bridging veins, which were avulsed by some mild trauma?
Chronic subdural hematoma
Is it a bruise of the brain following trauma?

Is it a cone-shaped, hemosiderin-pigmented area of obvious brain damage underlying the site of a blow ("coup contusion")?

Is it hemosiderin pigmentation and loss of the lower portions of the prefrontal lobes, as a result of one or more episodes of falling onto the back of the head ("contrecoup contusion")?

Is it hemosiderin pigmentation and loss of tissue where the temporal lobes overlie the ridge of the petrous temporal bone, following one or more episodes of a blow to the head ("contrecoup contusion")?

Cerebral contusion
Is it a brain with petechiae in the middle of the corpus callosum?

Is it a brain, normal by CT scan and perhaps nearly-normal appearing at gross autopsy examination, but from a patient who sustained a head injury and never regained normal mentation?

Is it a section of brain from such a patient, with axonal spheroids and perhaps even clearly ruptured axons? Is there perhaps also localized hemosiderin pigmentation especially in the corpus callosum (where the shearing forces come together), and/or foam cells and microglial cells where axons have been disrupted?

Diffuse axonal injury
Is it a section of brain with pink (active) or yellow-gray (old) plaques of sclerosis (lost oligodendroglia and myelin, increased astrocytes) especially around the ventricles?

Microscopically, do you see demyelinization beginning around vessels and expanding to become the grossly visible plaques? And are the axons preserved?

Multiple sclerosis
Is this a one-time-only demyelinating disease, with loss of myelin beginning around the little veins, with a lymphocytic infiltrate?

Did it follow an infection or immunization ("acute disseminated encephalomyelitis", etc.), and usually take a relatively benign course? Or is it the very lethal, hemorrhagic-necrotizing disease which follows a cold ("acute necrotizing hemorrhagic leukoencephalitis")?

Perivenous encephalomyelitis including "acute disseminated encephalomyelitis" and "acute necrotizing hemorrhagic leukoencephalitis".
Is this the brain of an adult with progressive dementia, and you see some of these things:
...senile plaques (i.e., areas of abnormal, silver-stainable dendrites, surrounding a chunk of amyloid);
...neurofibrillary tangles;
...granulovacuolar degeneration;
...Hirano bodies;
...amyloid in the cerebral vessels ("congophilic angiopathy")?
Alzheimer's disease

NOTE: The best place to look is in the hippocampus. Stay tuned for a better definition of the disease.

Is it changes identical to Alzheimer's, but less numerous, perhaps confined to the hippocampus, and the patient isn't demented?
Alzheimer's senile change
Is this a brain with selective, impressive atrophy of the prefrontal and temporal lobes?

Is this a brain with swollen, edematous-looking neurons and Pick bodies as the predominant histologic changes?

Pick's disease
Is it a section of brain in which the head and body of the caudate have virtually disappeared?

Is it a section of caudate nucleus in which the neurons have mostly disappeared?

Huntington's disease
Is it a section of substantia nigra with loss of most of the pigmented neurons?

Is it several pigmented neurons in the substantia nigra, most bearing one or more Lewy bodies?

Idiopathic Parkinson's disease
Is it pigmented neurons in the substantia nigra, perhaps decreased in number, bearing neurofibrillary tangles?
Post-encephalitic Parkinson's disease
Are the caudate and putamen atrophic, with loss of neurons? Are neurons also lost from the substantia nigra, but you see no Lewy bodies or neurofibrillary tangles here?
Striatonigral degeneration
Is it Parkinsonism, perhaps with the abnormal anatomy of idiopathic Parkinsonism or striatonigral degeneration, plus loss of the intermediolateral column neurons which give rise to the sympathetic nervous system? As a result, does the patient have profound autonomic disturbances including orthostatic hypotension?
Shy-Drager disease

NOTE: More talked-about (whenever a patient is "orthostatic") than seen.

Is there variable loss of neurons in the inferior olives, cerebellar cortex, and basis pontis? Is there perhaps a hereditary tendency?
Olivopontocerebellar atrophy
Is this a nervous system with a small spinal cord with loss of much of the white matter, loss of neurons on the dentate nucleus, and atrophy of much of the cerebellum?

Was the patient a male with a familial disease with ataxia, cranial nerve dysfunctions, and probably death from a cardiomyopathy?

Friedreich's ataxia
Is this an older person with loss of anterior horn cells, motor neurons of cranial nerve, and/or upper motor neurons, without other pathology?
Amyotrophic lateral sclerosis / motor neuron disease
Is this the brain of a prizefighter exhibiting widespread cortical atrophy and neurofibrillary tangles in neurons?
Dementia pugilistica
Is this an extremely floppy baby with a neurogenic atrophy and progressive weakness leading to death in childhood? Do studies show this is autosomal recessive?

Is this the nervous system of a child with profound thinning of the motor roots?

On histologic examination, are most of the muscle fibers profoundly atrophic, with a few groups enlarged? Is type grouping, of course, also present?

On histologic examination of the spinal cord, are the anterior horn cells almost all gone?

Werdnig-Hoffman infantile progressive spinal muscular atrophy
Is this an older person with progressive muscle denervation weakness and atrophy and loss of anterior horn cells? Do studies show this is genetically programmed?
Kugelberg-Welander progressive spinal muscular atrophy
Is this the spinal cord from a patient with B12 deficiency from any cause, with loss of myelin worst in the dorsal columns (look for foam cells), and eventually disruption of the axons and gliosis?

Is this a B12 deficient patient with a sensory neuropathy with paresthesis and ataxia?

Subacute combined degeneration of the cord
Is this an alcoholic or other patient with thiamine deficiency with acute cerebellar ataxia, confusion and nystagmus, and/or with chronic non-intentional confabulation and/or problems moving the eyes?

Is this the brain from such a patient, and you see hemosiderin pigmentation and/or gliosis in the mammillary bodies and/or the dorsomedian nucleus of the thalamus next to the third ventricle?

Wernicke-Korsakoff syndrome
Is this radiation-induced or chemotherapy-induced necrosis of the deep white matter of the hemispheres and/or basis pontis, perhaps with calcification of the remnants of the axons, and with negligible inflammatory reaction?
Iatrogenic leukoencephalopathy ("radiation encephalopathy", "chemotherapy encephalopathy")
Is this a rhomboid-shaped area of loss of myelin centered on the basis pontis? And did the patient have his or her hyponatremia, from whatever cause, corrected too rapidly by the doctor?
Central pontine myelinolysis
Is this an autosomal recessive or mitochondrially-transmitted (yes) disease with widespread necrosis, vascular proliferation, and gliosis in the brain, leading to death in childhood?

And has the lab perhaps identified a deficiency in cytochrome C (from whatever enzyme problem) as the underlying cause?

Leigh's subacute necrotizing encephalomyelopathy
Is it a demyelinating disease that spares the subcortical fibers? Is the disease hereditary, usually with death in childhood?

Does frozen section stained with quickie-stain show an accumulation of metachromatic material?

And has the lab perhaps identified deficiency of arylsulfatase A as the underlying problem, and galactosyl sulfatide as the accumulating substance?

Metachromatic leukodystrophy
Is it a hereditary demyelinating disease with histiocytes around blood vessels, packed with galactocerebroside?
Krabbe's globoid cell leukodystrophy

Is he a patient with an X-linked syndrome of adrenal insufficiency and demyelination? Does the lab find excess very long-chain fatty acids in the blood? Does electron microscopy demonstrate the characteristic inclusions in brain macrophages and the adrenal glands?
Adrenal leukodystrophy
Is it a liquefaction and dilatation of the central portion of the cervical spinal cord, interrupting the spinothalamic tract that carries pain and temperature sensation from the arms to the brain?
Syringomyelia
Is it slit-like, fluid-filled lesions in the brainstem, similar to syringomyelia?
Syringobulbia
Is it an self-limited, ascending paralysis following viral infection, usually followed by full recovery? In those rare cases when pathologic material is available for examination, do you see lymphocytes plus destruction and phagocytosis of myelin in the motor nerve roots?
Guillain-Barr‚ syndrome ("acute idiopathic polyneuritis")
Is it a progressive neurogenic atrophy of the muscles of the legs, producing the striking "upside-down champaign bottle legs"?
Charcot-Marie-Tooth peroneal muscular atrophy
Is it a benign spindle cell tumor on a nerve, with richly cellular ("Antony A") areas containing parallel sets of palisaded cells ("Verocay bodies"), and myxoid ("Antony B") areas? Are the arterioles hyalinized here? And do the involved nerve's axons run along the edge of, rather than through, the tumor?
Schwannoma ("neurilemmoma")

NOTE: "Acoustic neuromas" are really schwannomas.

Is it a tumor that thickens a nerve trunk, and is composed of loosely- arranged, often wiggly spindle cells? And do the involved nerve's axons run through the tumor itself?
Neurofibroma
Is it a malignant tumor that thickens a nerve trunk, and the patient probably has Von Recklinghausen's neurofibromatosis?
Neurofibrosarcoma
Is it a pale gray, infiltrated, poorly-circumscribed tumor of the brain substance or spinal cord, without necrosis?

And histologically, do you see one of these (highly variable) patterns:
...increased astrocyte nuclei but still neurons and oligodendroglia as well (perhaps the only abnormality)
...lots of gemistocytes;
...cells with lots of Rosenthal fibers ("pilocytic astrocytoma", noted for good behavior);
...lots of astrocytic-looking nuclei in a fibrillary background, without much else?

Astrocytoma

NOTE: Vascular endothelial proliferation or more than 1 mitotic figure in ten high power fields makes it "anaplastic", which is bad.

Is it a pale gray, fairly well demarcated, soft brain tumor, usually with calcium flecks?

And histologically, do you see:
..."fried egg cells" with clear cytoplasm, central nuclei, and distinct borders;
...calcium flecks;
...a conspicuous network of capillaries?

Oligodendroglioma
Is it a sharply-demarcated CNS tumor, usually in the spinal cord, with benign-appearing cells, often triangular, against a fibrillary background?

Does the tumor perhaps form "ependymal rosettes" (little neural tubes and/or rings around blood vessels)?

Does PTAH staining perhaps show blepharoplasts?

Ependymoma
Is it a spherical, firm-to-calcified bump attached to the ventricular lining, usually an autopsy curiosity? Histologically, do you see clumps of ependymal cells in a fibrillary background?
Subependymoma
Is it a massive, poorly-circumscribed, widely-necrotic, widely- hemorrhagic brain tumor, microscopically with pseudopalisading of tumor cells and much vascular proliferation? Or are at least most of these features present?
Glioblastoma multiforme
Is it monoclonal lymphocytes proliferating in the brain, perhaps in a person with AIDS or some other immunosuppressive problem?
Cerebral lymphoma
Is this a tumor at the site of the choroid plexus, and almost perfectly reduplicating this structure?
Choroid plexus papilloma
Is it a simple cyst, filled with gelatinous fluid, next to (and probably obstructing) the foramen of Monro?
Colloid cyst of third ventricle
Is it a white mass arising around the cerebellar vermis, perhaps spreading up and down the neuraxis, and composed of very primitive cells with very little cytoplasm?

Do the cells perhaps show both glial (GFAP+) and neural (stains, a few Homer-Wright pseudo-rosettes) differentiation? (Or the tumor may do one, or neither.)

Medulloblastoma
Is it a sharply-circumscribed round mass, compressing but not invading the brain, and arising typically over the sphenoid ridge or the falx?

Microscopically, do you perhaps see one or more of these:
...whorls recapitulating arachnoid granulations (takes some imagination);
...psammoma bodies;
...spindle cells streaming
...surprise, it's really a hemangiopericytoma?

Meningioma
Is it a brain with several (typically) sharply-circumscribed round masses, typically at the gray-white junctions, surrounded by considerable edema?

Is it cancer cells detected in the meninges, perhaps at the autopsy of a patient with mysterious cranial nerve palsies and a normal CT scan?

Metastases to the brain

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