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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Hepatosplenic T cell lymphoma


Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 29 October 2011, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Hepatosplenic T cell lymphoma (HSTL) is an extranodal and systemic neoplasm derived from cytotoxic T cells usually of γδ (gamma delta) T cell receptor type
● A minority of cases appear to be of αβ (alpha beta) type (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Epidemiology
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● Rare, <1% of all non-Hodgkin lymphomas
● Adolescents and young adults, median age ~35 years
● Male predominance

Etiology
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● 20% arise in the setting of chronic immune suppression (regarded as late-onset PTLD)
● Post-therapy with azathioprine and infliximab for Crohn's disease (especially children)
● Often associated with renal transplant recipients (Am J Clin Pathol 2001;116:41, Am J Clin Pathol 2000;113:487, Hum Pathol 2002;33:253)

Sites
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● Spleen, liver, bone marrow
● Usually no significant nodal involvement
● Peripheral blood involvement late in disease; may have blastic transformation

Clinical features
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● Hepatosplenomegaly, B symptoms, moderate anemia, marked thrombocytopenia, leukopenia, no lymphadenopathy
● Peripheral blood involvement uncommon at presentation

Case reports
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● 16 year old boy with alpha-beta variant presenting with hemolytic anemia and thrombocytopenia (Am J Surg Pathol 2000;24:459)
● 19 year old man with prominent bone marrow involvement and large atypical blastic cells (Soc Heme CQ 2010, May)
● 20 year old woman with S100+ tumor (Arch Pathol Lab Med 2003;127:e119)
● 39 year old man post-infliximab therapy for Crohn disease (Med J Aust 2008;189:464)
● 57 year old man with no production of cytotoxic molecules (J Clin Pathol 2003;56:631)

Treatment and prognosis
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● Aggressive course with relapse in the vast majority of cases
● Median survival <2 years
● Active agents: platinum-cytarabine and 2-deoxycoformycin

Postulated normal counterpart
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● Peripheral γδ (or less commonly αβ) cytotoxic memory T cells of the innate immune system

Gross description
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● Large spleen with diffuse red pulp involvement; no discrete lesions
● Diffusely enlarged liver

Micro description
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● Lymphoid infiltrates in splenic red pulp (cords and sinuses), white pulp atrophy, hepatic sinusoids and bone marrow sinuses
● Intermediate sized monotonous tumor cells with scant to moderate pale/clear cytoplasm, round/oval nuclei, slightly dispersed/loosely condensed chromatin, inconspicuous nucleoli
● Cytologic atypia with large/blastic cells may occur, especially with disease progression
● Bone marrow aspirate smears contain malignant cells resembling blasts, occasionally with fine cytoplasmic granules; display sinusoidal pattern in core biopsies

Micro images
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Bone marrow biopsy: atypical but somewhat inconspicuous intrasinusoidal lymphoid infiltrate


Liver and spleen


CD3 epsilon and TIA1


Liver: H&E, CD3, CD20


Various images


Wright's stained bone marrow aspirate: highly atypical malignant cells with prominent nucleoli and rather abundant cytoplasm with occasional pseudopod formation

Positive stains
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● CD2, CD3, CD7, CD16 (sometimes), CD56 (usually) or CD57, TIA1, granzyme M, Fas ligand, aberrant coincident expression of multiple KIR isoforms
● TCRδ1, Vδ1 (γδ variant) or TCRαβ, βF1 (αβ variant)

Negative stains
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● CD4, CD5, CD8 (usually), perforin, granzyme B, CD94 (usually), EBV (usually)
● TCRαβ (γδ variant) or TCRδ1 (αβ variant)

Genetics and Molecular
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TRG@ (γδ variant) or TRB@ (αβ variant) gene rearrangements
● Non-productive TRB@ gene rearrangements reported in some γδ cases
● Isochromosome 7q (most cases), trisomy 8 (Am J Clin Pathol 2001;116:410)
● Also multiple copies of i(7)(q10), aberrant second chromosome 7, ring 7, loss of sex chromosome

Molecular images
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PCR for TCRγ, Image 3


FISH, Figures 9 & 10

Additional references
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● Review articles: Am J Clin Pathol 2007;127:869, Leukemia 2000;14:991, Am J Surg Pathol 2001;25:285, Am J Surg Pathol 2001;25:970, Am J Surg Pathol 2000;24:1027, Inflamm Bowel Dis 2007;13:1024, Blood 1996;88:4265

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Hepatosplenic T cell lymphoma


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