Ed Friedlander, M.D., Pathologist

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

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Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

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More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
What is Cancer?
Cancer: Causes and Effects
Immune Injury
Other Immune
HIV infections
The Anti-Immunization Activists
Infancy and Childhood
Environmental Lung Disease
Violence, Accidents, Poisoning
Red Cells
White Cells
Oral Cavity
GI Tract
Pancreas (including Diabetes)
Adrenal and Thymus
Nervous System
Lab Profiling
Blood Component Therapy
Serum Proteins
Renal Function Tests
Adrenal Testing
Arthritis Labs
Glucose Testing
Liver Testing
Spinal Fluid
Lab Problem
Alternative Medicine (current)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

KCUMB Students
"Big Robbins" -- Bones / Joints / Soft Tissue Tumors
Lectures follow Textbook


SYNOVIAL FLUID (JAMA 264: 1009, 1990, still the best)




Inflammation in the joint space damages the hyaluronic polymers, shortening them.




ANTI-CCP ANTIBODIES (anti-cyclic citrullinated antibodies; now anti-CCP1 and anti-CCP2; updates Rheumatology 45: 478, 2006; Ann. Rheum. Dis. 65: 845, 2006; J. Imm. 175: 5575, 2005)

ANTI-NUCLEAR ANTIBODIES ("ANA's"): Pathology evidence-based consensus document Arch. Path. Lab. Med. 124: 71, 2000. Simple update: J. Allerg. Clin. Imm. 117(2): S-445, 2005.
RIM PATTERN Probably anti-dsDNA. Your patient probably has SYSTEMIC LUPUS.
HOMOGENEOUS PATTERN Probably anti-histones / anti-chromatin. Your patient probably has DRUG-INDUCED LUPUS.
SPECKLED PATTERN Could be anti-Sm and/or anti-Ro/SSA and/or anti-La/SSB and/or anti-U1snRNP and/or any of several others, or nothing at all that anybody knows. You'll need to decide whether to continue your workup!
CENTROMERE PATTERN An especially fine speckling with little background staining. This is anti-centromere, the marker for CREST / pulmonary hypertension.
NUCLEOLAR PATTERN anti-Th/To or anti-fibrillarin / anti-U3snRNP or anti-U17RNP. Think of SCLERODERMA, though most scleroderma patients don't show the nucleolar pattern.

{33205} positive lupus band test

{29557} ANA, speckled pattern
{33154} ANA, rim pattern
{33248} ANA, nucleolar pattern
{08457} ANA, nucleolar pattern




Tapping the joint

Consider doing this especially when there is a hot joint with an effusion

Heparin tube for crystals and CBC-diff;

Plain tube(s) for viscosity, mucin clot, complement, glucose, gram stain, and culture

* Synovial fluid complement

Acute lupus, acute RA

Likely to be low in active autoimmune disease.

* Synovial fluid RF

Early adult RA

Becomes positive before serum RA. Limited usefulness.

Serum rheumatoid factor

Adult RA

75% of adult RA's will be positive

Many positives in old age, SLE, SBE, syphilis

Negative in juvenile arthritis, osteoarthritis, others

* Serum IgG RF

Adult RA

Available. Of doubtful value.

* Serum anti-RANA

Adult RA

Old test based on the idea that Epstein-Barr virus causes many cases of rheumatoid arthritis, an idea that is still floating around after decades.

Serum f-ANA

Those multi-organ autoimmune diseases

Screening test. Titers 1:20 to 1:160 are nonspecific.

Rim: Classic lupus

Speckled: Classic lupus, Sjogren's, MCTD, others

Homogeneous: Drug-induced lupus

Nucleolar: Scleroderma ... again, this is NOT specific (J. Clin. Path. 61: 283, 2008)

Serum anti-dsDNA


Same as anti-nDNA and anti-DNA. Higher titers are very specific for lupus. Rising titers predict an exacerbation. Titers fall on successful treatment.

Now being seen after infliximab therapy also. Stay tuned.

Serum C3


Usually low in lupus; of course this is not specific. Value rises to normal on successful treatment

Serum anti-Sm


Very specific for lupus, positive in 30% of cases.

Serum anti-histone

Drug-induced lupus

Most patients with this antibody remain asymptomatic. A negative value pretty much rules out drug-induced lupus.

Lupus band test


Requires skin biopsy. Becoming obsolete

Serum anti-snRNP

Mixed CT disease

All MCTD's positive, low titers in other diseases. Ask whether the lab can give you just an anti-U1.

* Serum anti-centriole


Promoted as positive in some patients with scleroderma; not much used nowadays

Serum anti-centromere


High titer defines CREST syndrome

Serum anti-SSA (-Ro)


Often positive but not specific. This is the autoantibody that causes neonatal lupus with heart block.

Serum anti-SSB (-La)


Often positive but not specific

* Serum anti-adrenal

Autoimmune Addison's

Helps rule out other causes of Addisonism. The antigen is (at least usually) 21-hydroxylase.

* Serum anti-islet-cell

New or impending DM type I

Usually positive, doubtful clinical usefulness

Serum anti-insulin receptor

Type II diabetes variant

Insulin resistance caused by blocking autoantibody

Serum anti-sperm antibodies


Husband or wife

Serum anti-AchR

Myasthenia gravis

Anti-acetyl cholinesterase receptor. The first test to order in suspected MG.

* False positives occur in patients injected with bungarotoxin (cobra venom, quack remedy)

Serum anti-AchR Blocking Ab

Myasthenia gravis

Order in suspected MG if Anti-AchR is negative

* Serum anti-striational ab's (StrAbs; anti-titin, anti-ryanodine reeptor)

Myasthenia gravis, thymoma is usually present

If negative in MG, some surgeons will not remove thymus. See Arch. Neurol. 62: 442, 2005.

* Serum Kv1.4 (potassium channel)

Myasthenia gravis

New possible marker for more serious disease (Arch. Neuro. 64: 1121, 2007)

Serum anti-GBM


A few false negatives. If the pathologist who does the test isn't experienced, there will be lots and lots of false positives.

Serum anti-tubular BM

Renal interstitial disease

Anti-TMB disease is an important, under-recognized cause of acute interstitial nephritis.

* Serum anti-intrinsic factor

Pernicious anemia

Probably worthless, less sensitive and less specific than a Schilling test

* Serum anti-parietal cell abs

Pernicious anemia

Probably worthless, less sensitive and less specific than a Schilling test

Schilling test

Pernicious anemia etc.

It's a shame when the reagents aren't available -- here's hoping this good test will be re-instituted

Step 1: Give your patient radioactive vitamin B12 by mouth. See how much comes out in the urine. If very little comes out in the urine, your patient can't absorb straight vitamin B12 (pernicious anemia, fish tapeworm, or ileal disease).

Step 2: If your patient just proved he or she cannot absorb straight vitamin B12, repeat the test by administering a mix of vitamin B12 and intrinsic factor. If, this time, the patient excretes more of the vitamin B12 in the urine, you have established the diagnosis of addisonian pernicious anemia.

Check your protocol. You'll probably want to administer an injection of vitamin B12 before the test, since you don't want the patient actually storing the radioactive substance.

Platelet-associated Ig

Immune thrombocytopenia

Idiopathic thrombocytopenic purpura, also SLE, AIDS

Serum anti-skin

Blistering diseases

Inter-epithelial antibodies: Pemphigus vulgaris

Dermal-epidermal junction: Bullous pemphigoid

Reticulin: Dermatitis herpetiformis (biopsy it instead!)

* Serum anti-reticulin

* Serum anti-endomysium

* Serum anti-gliadin

Sprue / dermatitis herpetiformis

Nowadays some clinicians omit small bowel biopsy when these are positive, and move right to the gluten-free diet trial.

* Anti-collagen (I, IV, etc.)

Various joint diseases Research interest only; nothing's really come of these in humans despite decades of work.

Serum anti-smooth muscle

Lupoid hepatitis 1

Only high titers are significant, low titers occur in many diseases

Serum anti-LKM1 ("liver kidney microsome")

"Lupoid hepatitis" 2

Defines the illness

Anti-liver-kidney-microsome disease.

Serum anti-mitochondrial

Primary biliary cirrhosis

Sensitive and specific, but only high titers are significant health threats

* Serum anti-myocardial


Completely out of use. The existence of Dressler's is very much in doubt anyway.

Serum anti-streptococcal

Sequelae of strep infection

Glomerulonephritis, rheumatic fever. Several tests are available, ask you lab ("ASO", "anti-hyaluronidase" are popular). They will be positive by the time your patient has rheumatic fever or glomerulonephritis.

* Serum anti-teichoic acid

Staph infections

This used to be used to monitor the treatment of osteomyelitis, but is now completely out of use which is fine (Ped. Inf. Dis. J. 17: 1021, 1998)

Serum anti-neutrophil cytoplasmic antigen

Wegener's, polyarteritis

Anti-myeloperoxidase (p-ANCA, p-ACPA) causes many cases of polyarteritis (the "small vessel" variant, now clearly a distinct disease from "classic polyarteritis nodosa"). You'll also see it in most patients with the combination of sclerosing cholangitis and ulcerative colitis.

Anti-proteinase 3 (c-ANCA, c-ACPA) is closely linked to Wegener's granulomatosis.

You can see these in various systemic autoimmune diseases; whatever the "underlying systemic vasculitis.

Certain nonspecific ANCA's probably result from longstanding inflammation, as in rheumatoid arthritis (Art. Rheum. 36: 994, 1993).

Serum C' esterase inhibitor

Hereditary angioedema

Ask for both level and functional assay

Serum complement components

Deficiency states

Deficiencies of C1q, C1r, C1s, C4, C2, C5, and/or C8 simulate SLE

Deficiency of C6, C7, C8 have recurrent neisserial infections

In seeking out genetic birth defects, ask for both level and functional assay.

You can of course also use C3 and C4 to monitor the course of lupus.

Serum CH-50

Screening test for all complement component deficiencies ("titer that hemolyzes 50% of the test red cells")

Has also been used to follow the course of SLE

Serum anti-cardiolipin

SLE, AIDS, aborters, clotters

Newly recognized major disease, with thrombosis and abortion. Also called anti-phospholipid. Biochemically similar (but not identical to) "lupus anticoagulant" and the lupus biologic false positive for syphilis.

Nitroblue Tetrazolium test

Chronic granulomatous disease (i.e., the neutrophil killing defect)

Hereditary immunodeficiency syndrome with defective killing of staphylococci by polys

Serum anti-allergen IgE

Food or penicillin allergy

"RAST", supposed to replace skin tests, expensive.

* Raji cell assay

Circulating immune complexes

Limited usefulness


Ankylosing spondylitis, etc.

Classic example of a result that is unlikely to affect patient management

* Von Willebrand factor


In patients who do not have von Willebrand's disease but who do have some kind of serious systemic vasculitis (lupus, polyarteritis nodosa, Wegener's, Henoch-Schonlein, and so forth), levels of vWFAg are likely to be elevated (why? Arch. Dis. Child. 70: 40, 1994)

* Thrombomodulin


Endothelial thrombin receptor. Serum levels increase in vasculitis (Am. J. Clin. Path. 101: 109, 1994)

Complement 3 nephritic factor

Membranoproliferative glomerulonephritis types I and (now) II

Pathogenic; helps establish the diagnosis



"Heterophile antibodies"

Many inflammatory diseases

Agglutinate sheep red cells. Nobody orders this test.

Forsmann antibodies

Many inflammatory diseases

Heterophile antibodies that are absorbed by guinea pig kidney but not by beef RBC's. Nobody orders this test.

Mono test ("Mono-spot")

EB-virus infectious mono

Heterophile antibodies that are absorbed by beef RBC's, not by guinea pig kidney. Cheap test, sensitive and specific, but often remains negative for many weeks, often never turns positive in children

Serum IgG anti-EBV capsid

EBV infection, past/present

Expensive, high titers suggest current infection. This is the test to order if the "Mono-spot" is still negative but you still suspect EBV mono.

Serum IgM anti-EBV capsid

Current EBV infection

Sensitive and specific, very useful in children

EBV "early antigens"

Early or chronic EBV disease

Ask your infectious disease expert whether these tests are useful.

CMV, toxoplasmosis, HIV tests

Remember these too in "infectious mononucleosis"; "post-viral fatigue syndrome"


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