Random cases to test your knowledge! Matt Frank M.D.

Let’s start with an easy one…

Hodgkin Lymphoma Classic Hodgkin lymphoma Nodular sclerosis Mixed cellularity Lymphocyte rich Lymphocyte depleted Nodular lymphocyte predominant Hodgkin lymphoma

Nodular Sclerosis Hodgkin Lymphoma Collagen bands surrounding at least one nodule and lacunar type “HRS” cells 70% of Classical Hodgkin Lymphoma (CHL) Median age of 28 years 80% Mediastinum 10-40% EBV M:F =1:1

Nodular sclerosis Hodgkin lymphoma, “Lacunar cells”

Mixed Cellularity Hodgkin Lymphoma Mixed inflammatory background without nodular sclerosing fibrosis 20-25% of CHL Median age of 37 years Usually peripheral nodes ( but 30% in spleen) 70% male HIV association 75% EBV

Mixed Cellularity Hodgkin lymphoma

Lymphocyte rich Hodgkin lymphoma Nodular (common) or diffuse lymphoid background with scattered HRS cells 5% of all HL Higher median age 70% male Usually peripheral nodes Slightly better prognosis

Lymphocyte depleted Hodgkin lymphoma Diffuse form of CHL rich in HRS cells and/or depleted in non neoplastic lymphs Median age of 37 years 75% male Strongest HIV association Abdomen, retroperitoneum, BM EBV associated Main differential (morphological) is ALCL or Anaplastic DLBCL

Nodular lymphocyte predominant Hodgkin lymphoma

Nodular Lymphocyte Predominant Hodgkin Lymphoma Vaguely nodular architecture with small lymphs, histiocytes, and scattered “L&H” cells Male, years old Cervical, axillary, or inguinal nodes No EBV Malignant cells CD 15 and 30 negative, CD45 positive (opposite of CHL) Main differential is TCRLBCL

Malaria Plasmodium vivax (benign tertian fever) Plasmodium falciparum (malignant tertian fever) Plasmodium ovale (benign tertian fever) Plasmodium malariae (benign quartan fever)

P. vivax (rings) Infects large pale red cells with large rings(> 1/3 size of RBC) Single ring forms Shϋffner’s dots One nucleus

P. vivax (rings)

P. vivax with “amoeboid” trophozoites)

P. vivax (trophozoite)

P. vivax (schizont)

P. falciparum (rings) Any size red cell but more often mature Multiple small ring forms (less than 1/3-1/5 diameter of RBC) often with multiple nuclei Tend to stick to RBC membrane (applique form) Only ring form and gametocyte generally present

P. falciparum (rings)

P. falciparum (gametocyte)

P. ovale

P. malariae Small red cells Single rings and single nuclei No Shϋffner’s dots “Band like ameboid forms Schizonts with <12 merozoites

Babesiosis Northeast U.S. Usually asymptomatic but can be life threatening in elderly and immunocompromised Transmitted by Ixodes tick (what other disease does Ixodes transmit?) Can have ring forms indistinguishable from Plasmodium species Look for characteristic “maltese cross” rings

Anaplastic large cell lymphoma T-cell lymphoma (Hodgkin is a B cell lymphoma) percent of childhood lymphomas Males; First three decades of life Can occur almost anywhere nodal and extranodal (but not skin or should be classified as cutaneous ALCL~much better prognosis) ALK, EMA, and CD 30 positive t(2;5), NPM/ALK fusion protein (not present in skin cases) Several subtypes including “common”, lymphohistiocytic, and small cell

Alder-Reilly anomaly Lot’s of azurophilic (purplish) granules filling cytoplasm of neutrophils but also seen in other cell lines Distinguish from toxic change, Chediak- Higashi, etc. Associated with mucopolysaccharidoses (Hunter’s, Hurler’s, others) Can be isolated abnormality

“Sea blue” histiocytes in marrow Totally non-specific Thought to be secondary to increased bone marrow cell turnover Can be feature of various inflammatory processes and inborn errors of metabolism (Niemann-Pick) Can be associated with lymphoma, myeloproliferative, and myelodysplastic disorders 30% of CML patients have them in marrow (think CML for board purposes)

“Sea blue” histiocyte or ???

Gaucher’s disease Deficiency in glucocerebrosidase A Glucocerebroside accumulates in macrophages throughout body with “crumpled tissue paper” inclusions but can be indistinguishable from “pseudo-Gaucher” cells in CML Three types (I, II, and III) Type I – most common, spares brain, late onset Type II and III – much rarer, brain involved, younger onset, more severe than type I Treatable disease

Acanthocytes Non-specific For board purposes, remember association with abetalipoproteinemia and McLeod phenotype (lack of Kx antigen) Associated with Chronic Granulomatous Disease

Rosai-Dorfman disease Usually painless cervical lymphadenopathy but ~30% are elsewhere Unknown etiology (? HHV-7) Most prevalent in teenagers and blacks but anyone can be affected Often resolves spontaneously but can linger indefinitely Chemotherapy for persistent cases can be offered

AML with inv (16) AKA M4e ~10% of AML Monocytic and granulocytic differentiation with abnormal eosinophil component Shows various myeloid and monocytic markers (CD 13, 33, 14, 11c, 64, MPO) Better prognosis

“5q- syndrome” Myelodysplastic syndrome Variable trilineage dysplastic features present but most megakaryocytes are characteristically hypolobated and/or mononucleated DDx includes CML (micromegakaryocytes), PV, etc Confirm with cytogenetics

Diagnosis? “14 year old with pelvic mass from bowel/mesentery and involving pelvic bones” Intra-operative touch prep performed

PAS stain

Ewings sarcoma (masquerading as sporadic Burkitt’s) Be careful with “small blue cell” tumor~usually best to defer to permanents unless you are absolutely sure of diagnosis Depending on age group, ddx includes Ewings/PNET, neuroblastoma, lymphoma, small cell carcinoma, melanoma, etc.

Langerhans cell histiocytosis Mostly children but can be any age Three clinical syndromes Eosinophilic granuloma Hand-Schuller-Christian disease Letterer-Siwi disease S-100, CD1a Birbeck granules on EM Prognosis variable depending on extent

Mott cell Non-specific Presence of Mott cells should raise the question of plasma cell malignancies Also present in many reactive inflammatory processes involving exuberant immunoglobulin production

Dutcher body

60 year old with enlarged spleen

Splenic marginal zone lymphoma (Splenic lymphoma with villous lymphocytes) Patients over 50 Splenomegaly with involvement of white pulp Polar villi and often contain prominent nucleoli Positive for CD20, 79a Negative for CD 5, 10, 23, 43, 103, cyclin D1, TRAP Indolent

Another splenic MZL?

Hairy cell leukemia Older age group than Splenic MZL Splenomegaly with involvement of red pulp CD25, 11c, 103 and TRAP are characteristically positive Circumferential villi and ribosomal lamellar complexes (EM) Fried egg appearance on biopsy with bean shaped/cleaved nuclei Intermediate prognosis

You are now buffed!