Title:        White Cell Disorders I & II
Date & Time:  Monday, November 12, 2012 at 12 nooon (White Cell Disorers I)
Date & Time:  Wednesday, November 14, 2012 at 12 nooon (White Cell Disorers II)
Lecturer:     The Pathology Team

QUIZBANK -- Blood & Lymph #'s 133-139, 178-333


    You will refer to this material every time you feel a large lymph node or spleen, or have a patient with an abnormal CBC.

    "Leukemias and lymphomas" is the most difficult unit in Medical Pathology except for glomerular disease. You can't learn it if you are not continually asking yourself, "Why?"

    You are already familiar with the development of the different kinds of white cells, and the locations of lymphoid tissue throughout the body (lymph nodes, Waldeyer's ring, Peyer's patches, spleen, large airways).

      T-cell zones: thymus, lymph node parafollicular cortex, splenic white pulp near arteriole

      B-cell zones: germinal centers and their mantles, splenic white pulp at its margins

      Among circulating lymphocytes, 80% are T-cells, and 20% are B-cells.

      * You are also familiar with the common reaction patterns of various white blood cells: acute inflammation, pus, granulomas, and accumulations within phagocytes. (There's no need, for example, to talk right now about xanthomas, lipogranulomas, etc., etc.)

      Mycobacterial lymphadenitis
      Pittsburgh Pathology Cases

    In discussing diseases that affect numbers of white blood cells in the peripheral blood, it is much more useful to talk about ABSOLUTE CELL COUNTS than "percentage counts".

      Of course, you can estimate the absolute count by multiplying the total WBC count x the % for a particular cell.

      Healthy absolute counts:

        Basophils: * few- 100/cu mcL (heads up -- basophil granules are soluble and can wash out during slide preparation)

        Eosinophils: few- maybe 400 (fewer in AM, more in PM)

          (* "Hypereosinophilia" was once defined to be more than 1500 for more than six months without an obvious reason, and some evidence of organ involvement; today, as soon as one of the hypereosinophilic syndromes causing organ damage is suspected, diagnose if you can and start treatment even if you can't)

        Lymphocytes: 1200-3400 (* 3000-7000 for kids)

          T4 helper lymphocytes: >=1000

        Monocytes: 100- 590

        Neutrophils: 1800-6500

        Note that "95% lymphocytes" might mean either agranulocytosis (if the total white count is 2000) or chronic lymphocytic leukemia (if the total white count is 100,000). This is why I like white cell differential counts reported in absolute numbers, and why all labs do this nowadays.

        * Current smokers average 25% higher neutrophil counts; those who've quit in the last five years still average higher (Am. J. Clin. Path. 107: 64, 1997). This won't matter in your clinical decision-making.

      A good "normal range" for total white count is 4000-11000/cu mcL. "Leukocytosis" is present when the white count exceeds 12,000/cu mcL.

    The most important "white cell diseases" are neoplastic. These are:

      (1) the MALIGNANT LYMPHOMAS (HODGKIN'S AND NON-HODGKIN'S), solid tumors of lymphocytes (the rare tumors that truly arise from monocyte-macrophages are also included here; no one knows the true cell of origin of the malignant cells of Hodgkin's disease, which is also included here)

      (2) the LEUKEMIAS and their close relatives, the MYELOPROLIFERATIVE DISORDERS, in which sick hematopoietic stem cells proliferate

      (3) the PLASMA CELL DISORDERS, which typically produce antibodies and/or fragments thereof

      (4) the LANGERHANS CELL HISTIOCYTOSIS FAMILY ("histiocytosis X"; "disseminated histiocytosis") of quasi-cancers, much less common than the others

      Probably because it is so easy to harvest the cells, and since chemotherapy has been more successful for these diseases than for most other cancers, a tremendous amount of study has gone into clarifying their molecular pathology.

      There can be no such thing as a truly benign neoplasm of white blood cells, since by their very nature they infiltrate tissues. Some of these entities (for example, the acute leukemias) are far more aggressive than others ("benign plasmacytoma", "benign monoclonal gammopathy").

    White cell markers oversimplified:

      TdT: immature lymphocytes

      E-rosettes: T-cells

{16282} E-rosette, around a T-cell

      CD3, CD4, CD8, αTcR, βTcR, γTcR, δTCR, others: the more mature T-cells (various kinds)

      CD1a (T6): some T-cells, all Langerhans macrophages

      CD5: mantle cell lymphoma, many CLL

      * CD10 (CALLA): most B-cells (mantle cell lymphoma is negative)

      CD15: Most Reed-Sternberg cells; some others

      * CD19: B-cells, but not plasma cells

      * CD20: all but the most primitive B-cells, but not plasma cells

      * CD22: most B-cells (EBV receptor)

      * CD34 : primitive blood cells -- great for counting "blasts" in leukemia / preleukemia

      CD45 ("common leukocyte antigen" / LCA): all white cells (* exception: Reed Sternberg cells and some leukemias)

      * CD65: Most consistent marker for the natural-killer lymphocytes, non-B, non-T cells making up maybe 10% percent of your circulating white cells. (They tend to be big and have granules. Update on their neoplasms: Cancer 112: 1425, 2008).

      CD68: common macrophages

      * CD79a: The mantle lights up best

      BCL-2 (apoptosis-preventer): turned OFF during hypermutation (i.e., germinal centers); turned ON in most nodular lymphomas

      surface Ig(M, etc): B-cells

      kappa, lambda: mature B-cells, plasma cells -- especially useful for showing clonality (i.e., neoplasia)

        * Future pathologists only: To look for clonality, you can also have the lab check to see if the rearrangements that produce the specificity of a lymphocyte for a specific antigen are clonal (IgH Gene Clonality for B-cells, TcR-gamma Gene Clonality for T-cells).

      cyclin D1: mantle cell lymphoma stains strongly

      cytoplasmic Ig: plasma cells

      * nonspecific esterase: monocytes

      Fc receptor: B-cells, monocytes

      TRAP: hairy-cell leukemia

      HLA-D/DR /Ia: Langerhans cells and other antigen-presenting macrophages; some other cells

      lysozyme: monocytes

      * alpha1-antichymotrypsin: monocytes

      erythrophagocytosis: monocytes

      (myelo-)peroxidase: granulocytes

      * Sudan black: granulocytes

      * chloroacetate esterase: neutrophils, basophils, mast cells

      platelet markers: megakaryocytes

      * PAS+ diffusely: erythrocytes, megakaryocytes/platelets

      * PAS+ chunks ("blocks"): immature lymphocytes or M6 leukemia

      S-100, CD1/T6: dendritic ("Langerhans") macrophages

    I would ask you NOT to worry about differentiation markers beyond what's been listed above. A pathologist MUST know them, as a Hodgkin or non-Hodgkin lymphoma cannot be properly classified without immunohistochemistry (update Arch. Path. Lab. Med. 132: 441, 2008). A sub-subclassification for epidemiologists: Blood 110: 685, 2007.

      * There has been talk of diagnosing and classifying lymphomas based on little biopsies (less invasive than taking out a whole lymph node.) As you'd expect, unless there's an easy trademark finding or two (mantle-cell lymphoma, T-lymphoblastic lymphoma), it can't be done reliably (Am. J. Clin. Path. 128: 474, 2007).

{16517} neutrophil, chloroacetate esterase stain


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Eosinophil and lymphocyte

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White Cell Quiz!

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Lymphocyte and neutrophil

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Lots of neutrophils

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Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

NEUTROPENIA: A low absolute neutrophil count in the peripheral blood for any reason. (NOTE: "Leukopenia" is a not-very-useful word that describes any low total white count.)

    Possible causes include


        "The aplastic anemias" (better, "bone marrow failure")

        Bad stuff in the marrow

          Space-occupying lesions ("myelophthisic anemias")

            Solid cancers


          Hematologic malignancies that suppress granulopoiesis (i.e., some leukemias and lymphomas)

        DNA problems

          Cancer chemotherapy

          Radiation sickness

          "The megaloblastic anemias"

          Hereditary cyclic (q. 3 wk., severe; dominant mutation usually in the ELA2 elastase gene, molecular biology Blood 92: 2629, 1998; one cause is mutated neutrophil elastase that itself damages the cellular machinery; also Nat. Genet. 35: 90, 2003; Blood 108: 493, 2006)

          * Shwachman-Diamond (genetic, also fatty pancreas)

          Typhoid fever

          Occasional virus infections (mild suppression, especially parvo B19(Am. Fam. Phys. 75: 373, 2007))

          * Some childhood acute leukemias going back to the stem cells

          * MYELOKATHEXIS (group of genetic diseases with accelerated neutrophil precursor apoptosis; surviving neutrophils are hypersegmented and have very long bars between nuclear lobes: Blood 95: 320, 2000; Am. J. Hem. 62: 106, 1999).

          * Kostmann's -- genetic disease (several loci); almost all of the developing neutrophils die at the myelocyte stage. The usual cause of very low absolute neutrophil count at birth and after.


          * The lab machine didn't count them.

          • The blood sat in EDTA too long and the neutrophils stuck together.
          • The patient has one of leukemias / preleukemias in which the neutrophils don't make much myeloperoxidase, and the machine used the myeloperoxidase reaction to count neutrophils


          Autoimmune (rare, think of lupus)

          Hypersplenism (see below)

          Sequestration in a rapidly-growing abscess (??)


        DRUGS: The mechanisms are typically obscure (Ann. Int. Med. 146: 657, 2007).

          This is a dread complication seen with many different medications.

          The most common offenders today:

          • carbimazole

          • clozapine

          • dapsone

          • dipyrone

          • methimazole

          • procainamide

          • propylthiouracil

          • rituximab

          • sulfasalazine

          • ticlopidine


          Some people of African descent people just have slightly low neutrophil counts

          Some women get a mild neutropenia around their periods

      AGRANULOCYTOSIS is a time-honored misnomer for neutropenia sufficiently severe to put a person at risk for serious infection (i.e., neutrophil counts of 1000 or less, often much less; <500 is a big emergency).

        The first sign is typically mouth ulcers ("there's lots of germs in there") with their pseudomembranes laden with infectious bacteria and/or fungi.

          * There may also be ulcers in the cecum; these can actually kill ("acute typhlitis") by providing a portal of entry to the blood for bacteria.

        Later, the body is overwhelmed by bacteria, with death ensuing in a few days. Until the very end, patients are likely to complain only of "just not feeling quite right".

        The usual cause of "agranulocytosis" problems is medications. Future docs: If you notice that somebody has an absolute neutrophil count <1800 or so, stop all medications that can be stopped, and check again in a week.

    LYMPHOCYTOPENIA is less common and less perplexing than neutropenia. Think of hereditary immunodeficiency, HIV, radiation injury, marasmus/kwashiorkor, Cushing's syndrome, or just "stress".

      Apart from AIDS, the most important cause clinically is "multiple organ failure" of the severely sick / very septic; lymphocytes undergo apoptosis throughout the body, and this is mirrored in lymphoid depletion at autopsy (J. Imm. 174: 3765 2005).

LEUKOCYTOSIS: It's worth remembering the following NON-NEOPLASTIC CAUSES OF ELEVATED WHITE CELL COUNTS. Most of them make sense:

    You remember that in health, about half the neutrophils in the blood are circulating, and the other half are marginated, at any time.

    LOTS OF NEUTROPHILS ("granulocytosis"):

    • pyogenic bacterial infection (the usual cause)
    • burns
    • widespread tissue necrosis from any cause
      • (don't forget surgery and myocardial infarcts)

    • late pregnancy (common, mild)
    • really bad "collagen-vascular disease"
    • just plain "stress", nausea, and/or physical pain (un-marginates neutrophils)
      • glucocorticoids and epinephrine do the same thing;

        glucocorticoids also prevent neutrophils from entering tissues

      NOTE: Typhoid patients and some super-septic patients may become neutropenic because granulopoiesis is suppressed and/or all the neutrophils have emigrated from the blood. Beware of relying on white count as your chief marker for infection!

      NOTE: The super-sick, septic patient is likely to have TOXIC GRANULATION (extra-prominent azurophilic granules), CYTOPLASMIC VACUOLES ("from doing all that phagocytosis"), and/or DOHLE BODIES (rough endoplasmic reticulum remnants). By contrast, if the neutrophil count simply rises from acute pain and "stress", there will be no toxic granulation, vacuolization, or left shift. More about these in "Clinical Pathology".

{13646} Dohle body
{13661} Dohle body
{16213} Dohle body

        * Future pathologists: The latter two "Dohle bodies" are fakes; they are from cases of May-Hegglin's (say "Muh-HAY-lun") semi-disease, an autosomal dominant trait with too-few, too-big platelets and lots of "Dohle bodies" and big granules; the neutrophils function normally. May-Hegglin "Dohle bodies" are actually non-muscle myosin A, gene mutated in May-Hegglin: Nat. Genet. 26: 106, 2000; Blood 97: 1147, 2001. There are several different phenotypes at the locus (Blood 102: 529, 2003).

      NOTE: LEFT SHIFT refers to presence of immature white cells ("bands") in the peripheral blood, i.e., they're being mobilized early from the bone marrow. To tell an extreme case (WBC>up to 100,000 or so, i.e., a LEUKEMOID REACTION, as in sepsis, overwhelming TB, or carcinomatosis) from chronic granulocytic leukemia (see below), remember the following:

        (1) In chronic granulocytic leukemia, the LEUKOCYTE ALKALINE PHOSPHATASE tends to be low. In sepsis and the non-leukemic myeloproliferative disorders, it tends to be high.

          Leukocyte alkaline phosphatase is a completely different test from the "serum alkaline phosphatase" on the chemical profile. DON'T talk about them together.

        (2) In chronic granulocytic leukemia, the ABSOLUTE BASOPHIL COUNT is generally high, too. This would be unusual in sepsis.

        (3) In chronic granulocytic leukemia, there is virtually always a switch of material between chromosomes 9 and 22 (i.e., the PHILADELPHIA CHROMOSOME (Ph') or at least its molecular equivalent). You won't see this except in cancer.

        (4) And of course, toxic granulation (very easy-to-see granules on stained blood; nobody really knows why)/ toxic vacuolization says "infection", not "leukemia".

        (5) When in doubt, it's a leukemoid reaction. An indolent leukemia can wait for a few days; deadly infection can't.

        Philologists: RIGHT SHIFT refers to the hypersegmented granulocyte nuclei of pernicious anemia (etc., any major impediment to normal DNA synthesis will produce this "megaloblastic" change). "Right" and "left" derive from spaces on the old do-it-by-hand tally sheets.

      The machine-counting of immature neutrophils has always been a challenge. Review and new equipment: Am. J. Clin. Path. 128: 454, 2007. Today we know that the band count is very low in health, around one white cell in 500.

Hypersegmented poly

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Hypersegmented poly
Pernicious anemia
KU Collection

LOTS OF EOSINOPHILS (big review Mayo Clin. Proc. 80: 75, 2005):

    The "Loeffler" family of eosinophil-mediated diseases -- now being sorted out; while most remain idiopathic, a few have known mutations

    CHRONIC EOSINOPHILIC LEUKEMIA, an entity removed from the Loeffler's wastebasket by the discovery of FIP1L1-PDGFRalpha (Haematol 95: 696, 2010) -- treat with imatinib.

    type I immune injury

      food allergy, hay fever, eczema, extrinsic asthma (supposedly -- you won't be impressed)

      bronchocentric granulomatosis (aspergillus superinfection in asthma; this one's important)

      * hyper-IgE ("Job's") immunodeficiency

    Tissue parasites


      filariasis (includes "tropical eosinophilia" of the Far East -- future pathologists: filaria worms will be pushed to the "feather edge" of the smear)





      visceral larva migrans (dog and cat roundworms)

      cutaneous larva migrans (dog and cat hookworms)

    Drug allergy (most any; but notoriously gold therapy for arthritis, where eosinophilia is almost expected)

    Hodgkin's disease (a large minority of cases)

    Churg-Strauss (a vasculitis, often with granulomas, usually with ANCA; it's not clear whether this is a separate disease, or simply the way Wegener's / polyarteritis manifests in folks with allergies)

    Dermatitis herpetiformis

    Familial hypereosinophilia (locus unknown, autosomal dominant, mild: Blood 103: 4050, 2004)

    * Well's eosinophilic cellulitis

    Eosinophilia-myalgia syndrome (from the tainted tryptophan)

    * Any AIDS patient with a rash (Am. J. Med. 102: 449, 1997)

    * Pemphigus (I don't know why)

    * Dermatitis herpetiformis

    * Crohn's

    * Acute liver transplant rejection (almost all have it, no one knows why)


    Polyarteritis nodosa (don't miss this one)

    * Kimura's angiolymphoid hyperplasia with eosinophilia (very high IgE, eosinophil-lymphoid pseudotumors of head and neck, germinal centers loaded with eosinophils; marked peripheral eosinophilia; common in middle-aged Asian men, Asia, rare elsewhere; making the call Pediatrics 110: e-39, 2002; probably a low-grade lymphoproliferative disorder Am. J. Surg. Path. 26: 1083, 2002; Arch. Path. Lab. Med. 131: 650, 2007)

    * mastocytosis with eosinophilia (molecular signature known, response to imatinib/Gleevic likely)

    * T-cell neoplasms making interleukin-5: NEJM 341: 1141, 1999

    * "Clonal eosinophilia" -- FIP1L1-PDGFRA fusion gene

    * Eosinophilic leukemia -- looks like CML without proof of clonality

    NOTE: In the developed world, among clinically healthy patients with isolated elevated eosinophil counts, you will often not find the cause.

    NOTE: I did CBC's for years on medical students, many of whom have hay fever, etc., and have never found one with an elevated eosinophil count.

    NOTE: Remember that eosinophilic counts are up in the afternoon and down in the morning because the morning's cortisol surge suppresses them; I'd suggest taking a serious look at an absolute eosinophil count over 350 or so in the morning, and over 650 in the afternoon.

    NOTE: The "Loeffler's eosinophilic" problems are a curious, mixed-bag of diseases with excessive numbers of eosinophils in various tissues that cause tissue damage.

      The most common form is probably caused by a benign neoplasm of some sort, hidden somewhere, with a fusion gene called FIP1L1-PDFGRA (Cancer 110: 955, 2007) This has sometimes responded well to imatinib.

      Sometimes the underlying problem is a proliferation of mutated T-cells producing excessive eosinophil attractants (NEJM 330: 35, 1994).

      * In other cases, the eosinophils themselves seem to be the mutated clone: Blood 93: 1651, 1999.

      In 2004, I predicted the success of the anti-IL5 antibody mepolizumab as treatment (J. Allerg. Clin. Imm. 113: 115, 2004); it has been a spectacular success (NEJM 358: 1215, 2008).

{14099} eosinophilic leukocytes (buffy coat)
{09207} eosinophil granule with crystal (electron micrographs; these crystals will combine to form large Charcot-Leyden crystals under some conditions)

Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery


    typhoid fever

    bad granulomatous problems

      Crohn's disease
      deep fungi

    * chronic autoimmune disease

      rheumatoid arthritis is worth remembering

    * rickettsial disease (often; red flag)

    * disseminated cancer (occasionally)


    "infectious mononucleosis" (see below)

    whooping cough ("pertussis"; little cleaved lymphocytes; the toxin keeps the T-cells from homing to lymphoid tissue; Am. J. Clin. Path. 114: 35, 2000)

    infectious lymphocytosis (mild kids' disease, with T-cells, caused by various non-herpes viruses notably coxsackie B2; a "chronic form" also exists without marrow abnormalities; leave this to the pediatric hematologists; Acta. Paed. 74: 633, 2008.)

    "transient stress lymphocytosis" (absolute counts 4000-10000; on the evidence we've overlooked this for years; all major lymphocyte subsets go up, and neutrophils go up too: Am. J. Clin. Path. 117: 819, 2002)

    * really bad "collagen-vascular disease"

    * phenytoin ("Dilantin") or para-amino salicylic acid ("PAS") therapy

    NOTE: INFECTIOUS MONONUCLEOSIS is a family of diseases featuring fever, malaise, fatigue, lymphadenopathy, and circulating benign atypical lymphocytes. The syndrome results from first meeting one of these four micro-organisms: (1) Epstein Barr virus; (2) cytomegalovirus; (3) toxoplasmosis; (4) HIV.

    BENIGN ATYPICAL LYMPHOCYTES are activated cells (B- or T-) seen typically in the blood in "infectious mononucleosis" and certain other infections; you may see a few in any viral illness.

      There is no such thing as a "typical atypical lymphocyte." There are three "Downey" types:

      • Lymphocytes just a bit larger than usual, with a nuclear cleft and dark cytoplasm
      • Most familiar: the cytolasm is abundant and pale, bluer where the red cells indent them; the nucleoli are small, the nucleoplasm is reticulated
      • immunoblasts -- big cells, bit nucleoli, plenty of blue-staining cytoplasm

      Probably more important in spotting infectious mono and telling it from leukemia when you're a beginner is that when there are bunch of "atypical lymphocytes", no two look the same.

Infectious mononucleosis
Blood picture
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Infectious Mononucleosis
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery


      chronic myelogenous leukemia

      other "chronic myeloproliferative disorders"

        polycythemia vera

        * primary hemorrhagic ("essential") thrombocythemia

      * supposedly in lots of other things; this will not be important clinically.

    NOTE: None of these "classic findings" is either particularly sensitive, or particularly specific, for any particular disease. Use this information in the setting of the "whole person".


    We have already mentioned CHRONIC GRANULOMATOUS DISEASE, a poorly-named group of defects in the ability of neutrophils to kill common bacteria, with the macrophages needing to become involved as well.

      The most familiar is "X-linked chronic granulomatous disease", which has now been cured by gene therapy (Nat. Med. 12: 401, 2006).

    FAMILIAL MEDITERRANEAN FEVER, long-mysterious, has now yielded up its secrets.

      The cause is a lack of pyrin, a neutrophil protein that slows down neutrophils when enough have reached an area. Gene found Cell 90: 797, 1997; molecular genetic diagnosis: Ann. Int. Med. 129: 539, 1998.

      Lacking pyrin, neutrophils mob body cavities every once in a while. In addition to fever, patients may have pleuritis, arthritis, peritonitis, and/or a hot rash (looks like a strep infection) on the ankles.

      Colchicine, famous for its ability to slow down neutrophils (as in acute gout), controls the attacks and prevents the dread complication of secondary amyloidosis.

      As you can imagine, acute FMF can mimic many diseases. The amyloidosis AA that often develops in these patients can mimic most of the rest. Don't miss it.

      * A similar, thankfully-rare periodic fever syndrome is caused by a mutation in the TNF-receptor (TNFR1): Blood 108: 1320, 2006. Yet another is caused by mutated cryopyrin (includes serious neurologic problems; anti-interleukin-1 treatment brings about full resolution: Neurology 74: 1267, 2010).

    You recall CHEDIAK-HIGASHI SYNDROME, in which there are several problems with organelle membrane synthesis. synthesis.

      Neutrophil lysosomes are large and prominent (they fuse with each other) and do not fuse with phagosomes, so there's poor bacterial killing and a lot of infections.

      Melanosomes don't form properly, so there is partial albinism.

      The lack of platelet dense granules results in a bleeding tendency.

      * The gene has been cloned (LYST, lysosomal traffic regulator). Most of these patients go on to develop a lethal non-neoplastic hyperplasia of the lymphocytes. Marrow / stem cell transplant is now routine and prevents this. Review Blood 95: 979, 2000.

      * There is a report that long-term survivors of bone marrow transplantation develop a neurodegenerative disease after decades (Blood 106: 40, 2005). Stay tuned.

    In the autosomal dominant PELGER-HUET ANOMALY, the neutrophil nuclei fail to segment normally, producing "peanuts" and "pince-nez eyeglasses". ("Look! This clinically healthy patient has a horrible left shift / leukemia!") This is a fairly common laboratory curiosity (maybe one person in 5000), and of no significance. Explain to the physician and the patient, and check their close kin before somebody gets sick and everybody gets confused (Am. J. Clin. Path. 137: 358, 2012). (* Double doses get no segmentation whatever. And they don't seem to have any obvious troubles with bacteria or anything else: Acta. Hem. 66: 59, 1981. "Look! This clinically healthy patient has all myelocytes!" "No, look around, they're pelgeroid.")

      * Acquired / pseudo-Pelger-Huet can been seen when there are mutations (i.e., myelodysplasia, leukemia) or for some mysterious reason as a medication side-effect (Arch. Path. Lab. Med. 130: 93, 2006; Am. J. Clin. Path. 135: 291, 2011). These tend to be a minority of neutrophils, tend to be hypogranular, and tend to have denser chromatin. Let us worry about them.

{16208} Pelger-Huet, one dose
{16209} Pelger-Huet, one dose
{13658} Pelger-Huet, two doses

Blood picture
WebPath Photo

Pseudo-Pelger Huet
Wikimedia Commons

    * ALDER-REILLY ANOMALY merely refers to large, mucopolysaccharide-laden granules in some of the storage diseases (Hunter's, Hurler's, Tay-Sach's, occasionally as an acquired trait in myelodysplasia). You will see it in all five types of white blood cells. Don't mistake this for "toxic granulation."

    * Thankfully rare: Lack of endothelial adhesion molecules for phagocytes (J. Clin. Invest. 103: 97, 1999) or lack of CD18 integrin on neutrophils (Blood 91: 1520, 1998).

    Bacilli in neutrophil vacuoles: Usually DF2 (dog bite)

    * And you know that drumsticks are the inactivated X-chromosomes of lyonization.

    MORULAE OF EHRLICHIOSIS can help you diagnose this famous "spotless fever"; this "granulocytic" variant of ehrlichiosis can be fatal (NEJM 334: 209, 1996). "Morule" is Latin for "mulberry".

    Morules in macrophages
    CDC photo


    LYMPH NODES are soft (i.e., reticulin-framework) ovoids, up to about 2 cm in health. Afferent lymphatics penetrate and travel within their capsules (metastatic cancer first sets up here). Afterwards, lymph percolates through the cortex, and then the medulla, leaving by the hilum.

      Within the cortex, there are generally some germinal centers ("lymphoid follicles"), sites of actively-proliferating B-cells. Each germinal center is surrounded by a mantle of resting B-cells, which are in turn surrounded by "parafollicular" T-cells. (If there is no antigenic stimulus, you'll see only "primary follicles" of sleepy B-cells in the cortex.)

        The next time you get to look at a germinal center under the microscope, check out those proliferating B-cells. The sequence from small B-cell to plasma cell is interesting and unsung in most histology courses. You'll need to know this to understand classical acconts of lymphomas:

Resting small B-lymphocyte

Small cleaved ("clefted", i.e., folded-nucleus) B-lymphocyte

Large cleaved B-lymphocyte

Small non-cleaved B-lymphocyte

[NOTE: This cell is as large as a large cleaved B-lymphocyte]

Large non-cleaved B-lymphocyte


Memory B-cells . . and . . Plasma cells

    Within the medullary cords, expect to see a mix of B- and T-cells and plasma cells. The sinusoids are lined by fixed phagocytes.

    Despite the elegant pictures in histology books, lymph nodes are seldom "normal", especially in adults.

LYMPHADENITIS: Inflammation of the lymph nodes

    ACUTE LYMPHADENITIS described in "Big Robbins" is not much more than the hyperplasia in a reactive node.

      Localized lymphadenitis is most often due to a bacterial infection in the area drained by the lymph node.

        Really bad cases have polys and even abscess formation within the nodes. The end result will be a scarred-up lymph node. You have one or more.

      Generalized lymphadenitis suggests a systemic viral infection.

      "Mesenteric adenitis", often indistinguishable from acute appendicitis, is caused by Yersinia enterocolitica.

      Acute lymphadenitis, since it comes up suddenly and stretches the capsule, is likely to make the node tender.

    CHRONIC NON-SPECIFIC LYMPHADENITIS falls in one of three distinctive patterns.

      FOLLICULAR HYPERPLASIA (i.e., lots and lots of big follicles) results from longstanding contact with organisms or "other things" that stimulate the B-cells. If perplexed, think of:

      • toxoplasmosis (* look for mini-granulomas touching the germinal centers at their edges, this is supposedly pathognomonic; some of these are groups of macrophages; some are big "monocytoid B-cells" especially in the medulla)
      • rheumatoid arthritis (often lots of plasma cells)
      • syphilis (plasma cells in the medulla, mini-granulomas, spirochetes)
      • AIDS-related complex / persistent generalized lymphadenopathy of HIV infection.
      • common variable immunodeficiency (ineffective B-cell activation)

{36371} toxoplasmosis; many bugs in a cell
{40654} toxoplasmosis; tissue reaction (lame-looking granulomas)

Syphilis in a lymph node

Yutaka Tsutsumi MD

Toxoplasma lymphadenitis

Yutaka Tsutsumi MD

Follicular hyperplasia

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Follicular hyperplasia

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Follicular hyperplasia

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HIV lymphadenopathy

Yutaka Tsutsumi MD

      PARACORTICAL LYMPHOID HYPERPLASIA (i.e., lots and lots of lymphocytes, including turned-on ones, in the T-cell regions of the cortex -- often easiest to recognize the the presence of prominent blood vessels) results from longstanding contact with organisms or "other things" that stimulate the T-cells. If perplexed, think of

      • infectious mononucleosis, CMV
      • phenytoin ("Dilantin") exposure
      • weird reactions to a vaccine
      • infectious mononucleosis family (those angry T-killers, etc.; * expect to see lots of big lymphoid cells with pale cytoplasm, plenty of necrosis and mitotic figures; see any CMV cells?; this can be a real fooler for lymphoma, see Arch. Path. Lab. Med. 117: 269, 1993)
      • lupus (look for frank vasculitis and even regions of infarction)

      SINUS HYPERPLASIA (formerly "sinus histiocytosis"; i.e., sinusoids with swollen endothelial cells and lots of histiocytes). If perplexed, think of:

      • nodes draining a cancer (by no means specific!)
      • * nodes injected with permanent radiology contrast medium ("lymphangiogram dye") or for some reason containing mineral oil ("oleogranulomas")
      • Whipple's disease (Whipple cells)
      • * Castleman's giant angiofollicular lymphoid hyperplasia (far beyond your learning objectives; NEJM 330: 642, 1994); one cause (especially when multifocal and rich in plasma cells) seems to be herpes 8 / KSHV (Am. J. Path. 151: 1517, 1997; West. J. Med. 167: 38, 1997; Blood 93: 3643, 1999). It is a famous cause of paraneoplastic pemphigus (Lancet 363: 525, 2004).

        Great photos
        Pittsburgh Pathology Cases

      • * hemolysis (Coombs-positive, or macrophages rendered hungry by infection; the latter situation is "erythrophagocytic reticulosis")
      • * "sinus histiocytosis with massive lymphadenopathy and lymphocyte emperipolesis" (Rosai-Dorfman disease): a presumably viral, generally self-limited semi-disease of young people. B- and T-cells live inside macrophages ("emperipolesis"), which in turn light up with S100 and for lipid. There is a more ominous extranodal form as well. No one understands it.
      • Rosai-Dorfman
        S100 for dendritic macrophages
        Wikimedia Commons

      MIXTURES OF THE ABOVE cause diagnostic problems. In all the above, capillary endothelial cells are likely to be hyperplastic (rare in cancer).

        The most common cause of "unexplained" lymph node enlargement, especially in the groin: DERMATOPATHIC LYMPHADENITIS, melanin and sebum-laden nodes draining chronically inflamed skin. You're likely to see a mix of reaction types.

{35609} dermatopathic lymphadenitis (the red-brown is melanin, the white is sebum)

      WARNING: Any of these patterns can be (and occasionally is) mistaken for malignant lymphoma by the inept. Note that the finding of mitotic figures or necrosis doesn't necessarily point to malignancy, while the presence of a variety of cell shapes actually suggests a benign diagnosis. Know your pathologist, and ask for consultation if you are in doubt.


      Granulomas with central CASEOUS NECROSIS are probably tuberculosis, some other mycobacterial infection (atypical mycobacteria, leprosy)

      Well-made granulomas with NOTHING else are probably sarcoidosis. Also remember Crohn's, berylliosis, and nodes draining Hodgkin's disease.

      Granulomas with PUS in their centers are probably caused by one of the following: (1) lymphogranuloma venereum, (2) cat scratch fever, (3) brucellosis, (4) plague, (5) tularemia, (6) glanders-melioidosis, and (7) other yersinia infections. If you can find none of these, consider (8) X-linked chronic granulomatous disease (the neutrophil dysfunction problem).

      * Granulomas with central necrosis with much karyorrhexis but no pus: Kikuchi-Fujimoto. See below.

Tuberculous lymphadenitis
Great labels
Romanian Pathology Atlas

Cat scratch fever
Yutaka Tsutsumi MD

    You have probably already seen the Warthin-Finkeldey giant cells of measles within germinal centers. They show variable immunologic markers -- B-cell, T-cell, and/or dendritic macrophages. Some have intranuclear measles virus inclusions; some do not.

    * KIKUCHI-FUJIMOTO NECROTIZING HISTIOCYTIC LYMPHADENITIS (J. Am. Acad. Derm. 59: 130, 2008; Am. J. Clin. Path. 131: 174, 2009): Nobody knows the cause of what seems to be a viral illness (the herpes family exonerated Arch. Path. Lab. Med. 131: 604, 2007); the molecular biology is not that of a lymphoma: Am. J. Clin. Path. 117 627, 2002. Nepalese study: Arch. Path. Lab. Med. 127: 1345, 2003. Big review Am. J. Clin. Path. 122: 141, 2004. It looks like lupus in the lymph node, but there's lots more cytotoxic CD8+ than CD4+ T-cells. I've got a story about this I'll tell you personally.

Subacute necrotizing lymphadenitis
Kikuchi's disease
Yutaka Tsutsumi MD

    LYMPHADENOPATHY is a clinician's word for a big lymph node.

NON-HODGKIN'S LYMPHOMAS: By definition, monoclonal, malignant tumors of the B- or T-cells, and not of plasma cells, and not Hodgkin's disease. By custom, soft tumors of monocytes are included here because they look similar.

    These are the common primary tumors arising in the lymphoid tissue (lymph nodes, tonsils, adenoids, spleen, Peyer's patches, non-epitehlial thymus) and there are some special cases. (We cover CNS lymphomas in the "neuro" section; the outlook for primary CNS lymphoma is still "dismal": Cancer 110: 1803, 2007.)

    There are about forty kinds at most recent count, each with its own personality. Together, the non-Hodgkin's lymphomas are common. Update, with a focus on molecular markers: Br. Med. J. 362: 139, 2003; also Lancet 362: 139, 2003; J. Clin. Path. 58: 561, 2005.

    Most pathologists use the 2008 World Health Organization classification. It is elaborate even by WHO standards and only the highlights can be covered here.

Lymphomas and Plasma Cell Neoplasms
"Pathology Outlines"
Nat Pernick MD

CD Markers
"Pathology Outlines"
Nat Pernick MD

Bryan Lee

Lung lymphoma
Lung pathology series
Dr. Warnock's Collection

FCC lymphoma
Pittsburgh Pathology Cases

B-cell lymphoma
Pittsburgh Pathology Cases

Diffuse large cell lymphoma
Pittsburgh Pathology Cases

B-cell lymphoma
Large cell
Pittsburgh Pathology Cases

Follicular lymphoma, spleen
Wikimedia Commons

{23581} nodular lymphoma

Nodular lymphoma

WebPath Photo

Nodular lymphoma

KU Collection

Lymphoma in lymph node
Invasion of surrounding fat
Tom Demark's Site

{09040} electron micrograph of a malignant lymphoid cell. Note the lack of distinguishing features.

{23575} small lymphocytic lymphoma. There is a small vessel running across the picture. Use the endothelial cell nuclei to gauge the sizes of cells.

{23854} CLL, transforming into a more aggressive cancer. Note the numerous small lymphocytes and the blasts.

Well-differentiated lymphocytic lymphoma
Tom Demark's Site

Pittsburgh Pathology Cases

{13673} heavy chain disease; plasmacytoid cells in intestinal mucosa

{19504} Mediterranean lymphoma, small bowel

{23599} mixed lymphoma; use the endothelial cell at 2:30 as a size marker
{23683} mixed lymphoma

{23596} nodular large-cell; at this power, just appreciate the nodularity
{23581} nodular lymphoma

Large cell lymphoma

WebPath Photo

Large cell lymphoma

WebPath Photo

{23590} diffuse small cleaved lymphoma (all you can tell is that it is small cleaved)
{23593} diffuse small cleaved lymphoma (all you can tell is that it is diffuse)
{46344} diffuse small cleaved lymphoma, marrow

{23581} nodular lymphoma

Small cleaved lymphocyte in blood
Ed Lulo's Pathology Gallery

{08787} large-cell lymphoma
{15389} large-cell lymphoma
{23647} * "angioimmunoblastic lymphadenopathy", a T-cell lymphoma with vascular proliferation -- note the vessels and the monomorphic cell infiltrate)

{23674} true histiocytic lymphoma, trust me

{10935} lymphoma arising in thyroid; my case
{10937} lymphoma arising in thyroid; my case. Notice that the lymphocytes are growing within a follicle.

Body cavity lymphoma and Hodgkin's
Lung pathology series
Dr. Warnock's Collection

Post-transplant lymphoproliferation
Pittsburgh Pathology Cases

Post-Transplant Neoplasia
Great site
Transplant Pathology Internet Services

{00245} immunoblastic lymphoma
{10691} immunoblastic lymphoma, cytology
{10724} immunoblastic lymphoma
{10772} immunoblastic lymphoma
{23623} immunoblastic lymphoma
{23689} immunoblastic lymphoma
{08017} lymphoma in the heart
{11630} lymphoma in the pericardial space
{11633} lymphoma, primary in the heart
{20227} lymphoma, primary in the stomach
{15446} lymphoma, primary in the stomach
{15542} lymphoma, primary in the stomach

{00242} T-lymphoblastic lymphoma. Trust me.

{46189} African Burkitt's
{49035} African Burkitt's

Burkitt's lymphoma
Missionary site

Burkitt's lymphoma
Starry sky
KU Collection

Burkitt's lymphoma
Patient and photomicrograph
KU Collection

Bryan Lee

Wikimedia Commons

Burkitt's after transplant
Pittsburgh Pathology Cases

Wikimedia Commons

Wikimedia Commons

{23620} Burkitt's lymphoma, lipid drops
{46336} Burkitt's lymphoma, lipid drops
{23611} Burkitt's lymphoma, good starry sky
{46332} Burkitt's lymphoma, good starry sky
{23641} * Burkitt's, methyl green pyronine (the red "pyroninophilia" merely tells us that the cytoplasm is rich in ribosomes)
{46326} African Burkitt's, tonsils

{40003} mycosis fungoides
{40004} mycosis fungoides
{12747} mycosis fungoides, plaque phase
{12751} mycosis fungoides
{12754} mycosis fungoides
{13117} mycosis fungoides
{13781} mycosis fungoides
{13784} mycosis fungoides
{24740} mycosis fungoides, histopathology; note Pautrier microabscesses
{12759} mycosis fungoides, Pautrier microabscesses
{13793} mycosis fungoides, Pautrier microabscess
{13796} mycosis fungoides cells in a lymph node (look how wiggly the nuclear membranes are)
{09042} mycosis fungoides cell, electron micrograph

{12757} Sézary patient
{16544} Sézary cell
{23722} Sézary cell
{15409} Sézary cell

{23668} malignant histiocytosis with erythrophagocytosis

Epstein-Barr hemophagocytic syndrome

Yutaka Tsutsumi MD

HODGKIN'S DISEASE ("Hodgkin's lymphoma"; J. Clin. Path. 55: 162, 2002)

{23560} Reed-Sternberg cell
{20057} Reed-Sternberg cell
{36398} Reed-Sternberg cell, not H&E; cytology
{36401} Reed-Sternberg cell, not H&E; cytology
{40423} Reed-Sternberg cell, mitosis

Great labels
Romanian Pathology Atlas

Hodgkin's with Reed-Sternberg variants
Great labels
Romanian Pathology Atlas

Hodgkin's Disease ("Hodgkin's granuloma"
is an ancient misnomer.)
Human Pathology Digital Image Gallery

Hodgkin's disease
Nice Reed-Sternberg cell
KU Collection

Hodgkin's, node

WebPath Photo

Hodgkin's, liver

WebPath Photo

Reed-Sternberg cells

WebPath Photo

Reed-Sternberg cell

WebPath Photo

Hodgkin's disease, spleen
Wikimedia Commons

Wikimedia Commons

{46338} Lymphocyte predominant Hodgkin's
{46339} Lymphocyte predominant Hodgkin's

{23539} mixed cellularity Hodgkin's disease
{46342} mixed cellularity Hodgkin's disease
{46343} mixed cellularity Hodgkin's disease

{23524} lymphocyte depleted Hodgkin's disease. Just plain anaplastic.

{23542} nodular sclerosing Hodgkin's disease
{23545} nodular sclerosing Hodgkin's disease
{23548} lacunar Reed-Sternberg variants
{23551} lacunar Reed-Sternberg variant

Nodular sclerosing Hodgkin's
Bryan Lee

Nodular sclerosing Hodgkin's

WebPath Photo

Nodular sclerosing Hodgkin's

WebPath Photo

Lacunar cells

WebPath Photo

{20056} Hodgkin's disease in a cervical node (we would of course diagnose this only with microscopy)
{46348} Hodgkin's disease in the spleen
{46349} Hodgkin's disease in the spleen


Packed marrow
WebPath Photo

Packed marrow
WebPath Photo

Leukemia / myelodysplasia
"Pathology Outlines"
Nat Pernick MD

{23848} packed marrow; * this was late-stage CLL
{36032} packed marrow; * this was AML
{12347} packed marrow; * this was AML

{16243} blast with Auer rods
{29475} lymphoid blasts, pap stain. Big pale nuclei.

Wikimedia Commons

Acute promyelocytic leukemia
Good Auer rods
KU Collection

Auer rods

WebPath Photo

{23842} acute lymphocytic leukemia, brain
{08734} acute leukemia, liver; as you would expect, the leukemia is blue
{08735} acute leukemia, liver
{08736} acute leukemia, liver

Acute Lymphoblastic Leukemia
Peripheral smear
KU Collection

{06269} fatal cerebral hemorrhage in leukemia
{01735} brain and dura, acute leukemia

ACUTE LYMPHOBLASTIC LEUKEMIA ("ALL"; diagnosis Am. J. Clin. Path. 111: 467, 1999)

Acute lymphoblastic leukemia
Bone marrow
WebPath Photo

Acute lymphoblastic leukemia
Peripheral smear
WebPath Photo

Acute Lymphoblastic Leukemia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Pittsburgh Pathology Cases

{12410} ALL (all you can tell from the smear is "blasts")

{23746} L1
{23833} L1, special stain (cytoplasm is brown)
{23860} L2
{13982} L2, bone marrow
{23758} L3; note the lipid
{13985} L3

Wikimedia Commons

Burkitt's leukemia
Bone marrow
KU Collection

{23857} ALL in the liver
{32027} ALL in the liver
{34513} ALL in the brain
{49316} ALL in the kidney
{49343} ALL in the testis

ACUTE MYELOID LEUKEMIA ("AML", "acute myelogenous leukemia", "poorly differentiated granulocytic leukemia", "acute non-lymphocytic leukemia", "ANLL", etc.)

{12338} AML. Note promyelocyte in center.
{16245} blast, and not much else, M1
{13988} blasts, and not much else, M1
{23830} blast, * chloroacetate-esterase (+), M1
{13940} blast, * chloroacetate-esterase (+), M1
{23839} blast, M1; note nucleolus.
{23770} blasts with a few granules, M2
{13991} blasts with a few granules, M2
{16249} blast with Auer rod, M2
{12344} blast with Auer rod, M2 or maybe M3
{14010} blast with great Auer rods
{23776} blasts with lots of granules, M3
{13994} blasts with lots of granules, M3
{16254} blasts with lots of granules, M3
{10109} blasts with lots of granules, M3
{13997} semi-monocyte like blasts, M4; note indented nucleus and gray cytoplasm
{10133} semi-monocyte like blasts, M4
{13937} non-specific esterase in M4
{23800} monocyte-like blasts in M5
{40449} monocyte-like blasts in M5
{40451} monocyte-like blasts in M5
{23803} non-specific esterase in M5
{14001} monocyte-like blasts in M5
{13928} non-specific esterase in M5
{23949} erythroleukemia, M6. If you don't recognize the malignant cells as red-cell precursors, please check out a histology book.
{14007} erythroleukemia, M6
{16267} erythroleukemia, M6
{23836} erythroleukemia, M6
{23806} erythroleukemia, M6
{16273} erythroleukemia, M6, PAS-positive chunks
{16274} megakaryocytic blasts, M7. See the platelets budding?
{23812} megakaryocytic blasts, M7
{23821} megakaryocytic blasts, M7
{23818} megakaryocytic blasts, PAS-positive, M7
{46340} gingival involvement; this is common in M4 & M5

Pittsburgh Pathology Cases

Pittsburgh Pathology Cases

Acute myeloid leukemia
Tom Demark's Site

With eosinophils
Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

Auer rods in blasts
Wikimedia Commons

M7 marrow
Tiny megakaryocytes
Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

Weird normoblasts in circulation
Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

Wikimedia Commons

M5 -- electron micrograph
Dented nucleus
Wikimedia Commons

THE MYELODYSPLASTIC SYNDROMES ("THE PRELEUKEMIAS", Carl Sagan's disease): Mayo Clin. Proc. 70: 673, 1995; Am. J. Clin. Path. 119(S1): S-58, 2003.

Myelodysplastic syndrome
Odd megakaryocyte / giant platelet

CHRONIC MYELOID LEUKEMIA ("chronic myelogenous leukemia", "well-differentiated granulocytic leukemia"): all about it Lancet 370: 1127, 2007

{10769} CML, splenomegaly
{10763} CML, peripheral blood
{12359} CML
{23863} CML (note the basophil)
{23866} CML, leukocyte alkaline phosphatase stain (black; note the cells are not stained black)

CML, liver
Great labels
Romanian Pathology Atlas

Chronic granulocytic leukemia
WebPath Photo

Chronic myelogenous leukemia
Peripheral smear
KU Collection

Chronic granulocytic leukemia
Automated profile
WebPath Photo

Chronic granulocytic leukemia
WebPath Photo

{12371} Philadelphia chromosome

Chronic granulocytic leukemia
Philadelphia chromosome
WebPath Photo

{23869} CML, blast crisis
{12365} CML, blast crisis

"APLASTIC ANEMIA" (updates Ann. Int. Med. 136: 534, 2002; Lancet 365: 1647, 2005; Blood 110: 1603, 2007)

Aplastic anemia

WebPath Photo

CHRONIC LYMPHOCYTIC LEUKEMIA ("CLL", "well-differentiated lymphocytic leukemia"; "the liquid phase of well-differentiated lymphocytic lymphoma", etc.) Lancet 371: 1017, 2008.

CLL / Melanoma
Pittsburgh Pathology Cases

Pittsburgh Pathology Cases

Pittsburgh Illustrated Case

CLL and melanoma together in marrow
Pittsburgh Illustrated Case

Chronic lymphocytic leukemia

WebPath Photo

Chronic lymphocytic leukemia
Peripheral smear
KU Collection

Chronic lymphocytic leukemia
Classic drawing
Adami & McCrae, 1914

Chronic Lymphocytic Leukemia
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

B-CLL, good smudges
Wikimedia Commons

CLL in liver
Great labels
Romanian Pathology Atlas

{08784} CLL
{12389} CLL
{12404} CLL going bad (some blasts)
{12386} CLL with smudges

HAIRY CELL LEUKEMIA (Mayo Clin. Proc. 87: 67, 2012)

{23872} hairy cell leukemia
{10766} hairy cell leukemia, spleen (top; normal at bottom)
{16543} hairy cell leukemia, TRAP stain (red)
{23875} hairy cell leukemia, TRAP stain (red)
{13925} hairy cell leukemia, TRAP stain (red)
{16541} hairy cell leukemia, TRAP stain (red)
{23881} hairy cell leukemia, bone marrow biopsy (trust me)
{42117} big spleen in hairy cell leukemia, foot ruler

Hairy cell leukemia
Peripheral smear
KU Collection

POLYCYTHEMIA VERA ("Osler's polycythemia", "P. V. rubra", etc.; Mayo Clin. Proc. 78: 174, 2003; Arch. Path. Lab. Med. 130: 1126, 2006)

Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

PRIMARY MYELOFIBROSIS ("myelofibrosis with myeloid metaplasia"; "agnogenic myeloid metaplasia"; "myelosclerosis"); JAMA 303: 2513, 2010; Mayo Clin. Proc. 87: 25, 2012

{12302} teardrop reds

{13799} myelofibrosis, marrow core biopsy
{24788} myelofibrosis, marrow core biopsy
{13802} myelofibrosis, reticulin stain

PLASMA CELL MYELOMA ("multiple myeloma", "malignant plasmacytoma") NEJM 336: 1657, 1997; Lancet 363: 875, 2004; for pathologists dealing with the difficult diagnostic cases Am. J. Clin. Path. 136: 168, 2011 (let us worry about them).

{08462} bony lesions of myeloma (skull and spine)
{27327} bony lesions of myeloma (skull)
{13769} skull lesions of myeloma
{10760} skull lesions of myeloma
{10754} bone lesions of myeloma
{10757} osteoporosis of myeloma
{46197} femur lesions in myeloma
{46198} rib lesions in myeloma
{27329} spike, probably monoclonal gammopathy of uncertain significance, since normal albumin and gamma seem not to be suppressed

Plasma cell myeloma
Marrow smear
Wikimedia Commons

Plasma cell myeloma
Bone marrow smear
KU Collection

Myeloma skull

WebPath Photo

Myeloma skull

WebPath Photo

Myeloma marrow

WebPath Photo

Myeloma cells, section

WebPath Photo

Myeloma cells, section

WebPath Photo

Myeloma cells, smear

WebPath Photo

{16554} plasma cell myeloma, cells
{16556} plasma cell myeloma, cells
{13772} plasma cell myeloma, marrow aspirate
{27330} plasma cell myeloma, marrow aspirate
{13775} plasma cell myeloma, bone marrow section
{10751} * "grape cell"
{42054} * "flame cell" (named for its staining properties)

{17273} myeloma kidney, Bence-Jones casts with foreign body reaction
{17274} myeloma kidney, Bence-Jones casts with foreign body reaction

OTHER PLASMA-CELL PROBLEMS ("plasma cell dyscrasias", an archaic term)

THE LANGERHANS CELL HISTIOCYTOSIS FAMILY ("LCH", "Histiocytosis X", "disseminated histiocytosis"; * R&F "differentiated histiocytosis" is a typo); review for clinicians J. Ped. 127: 1, 1995; Cancer 85: 2278, 1999.

{09095} Birbeck granules
{09097} Birbeck granules

Histiocytosis X
Pittsburgh Illustrated Case

Histiocytosis X with Birbeck granules
Lung pathology series
Dr. Warnock's Collection

Eosinophilic granuloma of the lung
Lung pathology series
Dr. Warnock's Collection

{23392} Letterer-Siwe disease. Weird histiocytes ("coffee-bean nuclei, even"). Trust me.

{13688} eosinophilic granuloma
{13691} eosinophilic granuloma
{09043} eosinophilic granuloma, EM, coffee-bean nucleus (left) and eosinophil (right)

{10481} Hand-Schüller-Christian disease. Weird histiocytes. Trust me.
{21779} skull in Hand-Schüller-Christian disease

* CHESTER-ERDHEIM DISEASE ("lipid granulomatosis"; "cholesterol granulomatosis") is a rare illness in which lipid-laden non-dendritic-type macrophages infiltrate the tissues. Thankfully rare, it is clonal and seems to be a neoplasm (Hum. Path. 30: 1093, 1999).


* Every man has his own ways of courting the female sex. I should not, myself, choose to do it with photographs of spleens, diseased or otherwise.

        -- Agatha Christie, "The Moving Finger"

Normal spleen

WebPath Photo

Big spleen
ITP case

{00239} Gaucher's disease, spleen
{09864} Gaucher's disease, spleen
{16216} Gaucher's disease, watered-silk ("wadded kleenex") cell from spleen

Big spleen
From a cirrhotic
WebPath Photo

Reed-Sternberg cells

WebPath Photo

Big spleen
Some myeloproliferative disorder
WebPath Photo

Urbana Atlas of Pathology


WebPath Photo

You remember the difference between sections and smears, right?


10110 ff blood

{10766} leukemia, hairy cell and normal
{12275} anemia, iron deficiency; normal
{13715} lymphocyte, normal
{13868} red blood cell, normal blood
{13910} red blood cell, normal
{14702} polymorphonuclear leukocyte, normal
{14703} polymorphonuclear leukocyte, normal
{14704} polymorphonuclear leukocyte, normal
{14705} polymorphonuclear leukocyte, normal
{14705} polymorphonuclear leukocyte, normal
{14706} polymorphonuclear leukocyte, normal
{14707} polymorphonuclear leukocyte, normal
{14708} eosinophil, normal
{14709} eosinophil, normal
{14710} basophil, normal
{14711} basophil, normal
{14712} monocyte, normal
{14713} monocyte, normal
{14714} monocyte, normal
{14715} monocyte, normal
{14716} lymphocyte, large
{14717} lymphocyte, large
{14718} lymphocyte, normal
{14719} lymphocyte, normal
{14720} lymphocyte, normal
{14721} lymphocyte, normal
{14722} reticulocytes, normal
{14723} reticulocytes, normal
{14724} red blood cell, abnormal
{14725} red blood cell, abnormal
{14726} platelets, normal
{14727} platelets, normal
{14728} pronormoblast, normal
{14729} pronormoblast, normal
{14730} basophilic normoblast, normal
{14731} basophilic normoblast, normal
{14732} normoblast
{14733} normoblast
{14734} polymorphonuclear leukocyte & * lymphocyte
{14735} polymorphonuclear leukocyte & * lymphocyte
{14736} normoblast series
{14737} normoblast series labelled
{14738} myelocyte, normal
{14739} myelocyte, normal
{14740} * granulocyte series
{14741} * granulocyte series (labelled)
{14742} myelocyte, band form
{14743} myelocyte, band form
{14744} myelocyte, normal
{14745} myelocyte, normal
{14746} myelocyte, normal
{14747} myelocyte, normal
{14748} myelocyte, normal
{14749} myelocyte, normal
{14750} myelocyte, normal
{14751} myelocyte & megakaryocyte, normal
{14752} myelocyte & megakaryocyte, normal
{15193} plasma cell, #23
{15205} thymus, adult
{15564} thymus, normal
{15565} thymus, normal
{15566} thymus, normal
{15567} thymus, normal
{16175} red blood cell, normal
{20782} polymorphonuclear leukocyte, normal
{20783} monocyte
{20784} platelets, circulating blood
{20785} monocyte
{26230} polymorphonuclear leukocyte, normal
{40179} thymus, normal
{46538} red cell, normal

{11750} spleen, normal
{11751} spleen, normal
{11753} lymph node, normal
{11797} spleen, normal
{11805} spleen, normal unfixed
{14753} thymus, human fetal
{14754} thymus, human fetal
{14755} thymus, juvenile
{14756} thymus, juvenile
{14757} thymus, adult
{14758} thymus, adult
{14759} thymus, juvenile
{14760} thymus, juvenile
{14761} hassall's corpuscles
{14762} hassall's corpuscles
{14763} hassall's corpuscles
{14764} hassall's corpuscles
{14765} thymus (septum)
{14766} thymus (septum)
{14767} spleen, normal
{14768} spleen, normal
{14769} spleen, pulp
{14770} spleen, pulp
{14771} spleen (trabeculae), normal
{14772} spleen (trabeculae), normal
{14773} spleen (trabecular artery), normal
{14774} spleen (germinal center), normal
{14775} spleen (germinal center), normal
{14776} spleen (venous sinus), normal
{14777} spleen (venous sinus), normal
{14778} spleen (scanning em)
{14779} spleen (scanning em)
{14780} lymph node, normal
{14781} lymph node, normal
{14782} lymph node cortex, normal
{14783} lymph node cortex, normal
{14784} lymph node, medulla
{14785} lymph node, medulla
{14786} lymph node, normal
{14787} lymph node, normal
{15189} lymph node and subcapsular sinus, #23
{15190} lymph node, primary nodule
{15191} lymph node, germinal center
{15192} lymph node, medulla
{15194} spleen, #24
{15195} spleen, * red pulp and white pulp
{15196} spleen, central artery
{15197} spleen, central artery and germinal cent
{15198} spleen, trabeculae
{15199} thymus, #25
{15200} thymus, cortex
{15201} thymus, hassall's corpuscle
{15202} thymus, medulla
{15203} thymus, epithelial reticular cell
{15568} spleen, normal
{15569} spleen, normal
{15570} spleen, normal
{15571} spleen, normal
{15769} spleen, normal
{15770} spleen, normal
{20200} spleen, normal
{20799} lymph node, overview
{20800} lymph node, cortex
{20801} lymph node, medulla
{20802} lymph node, subcapsular sinus
{20803} lymph node, secondary nodule
{20804} lymph node, primary nodule
{20805} spleen, normal histology
{20806} spleen, red pulp
{20807} spleen, white pulp
{20808} spleen, central artery
{20809} spleen, red pulp
{20810} spleen, secondary nodule
{20811} spleen, trabecula
{20812} thymus, overview
{20813} thymus, medulla
{20814} thymus, cortex
{20815} thymus, hassall's corpuscle
{20827} tonsil, palatine
{20828} tonsil, pharyngeal
{24782} lymph node, normal
{24783} lymph node, normal
{36344} lymph node, normal
{36347} lymph node, normal
{36350} lymph node, normal cytology
{36353} lymph node, normal cytology