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  • Surgical Pathology Criteria

    Hepatosplenic T Cell Lymphoma


    • Lymphoma of cytotoxic T cell phenotype with a marked predilection for sinusoidal involvement of liver, spleen and bone marrow

    Alternate/Historical Names

    • Hepatosplenic gamma delta T cell lymphoma

    Diagnostic Criteria

    • Infiltrate confined to sinusoids of liver, spleen and bone marrow
      • May be rather inconspicuous
      • Portal spaces and white pulp generally spared
      • Peripheral blood may be involved late in disease
      • Lymph nodes only rarely involved
    • Uniform medium sized cells in most cases
      • Clumped chromatin and inconspicuous nucleoli
      • Occasional cases show more pleomorphism and mixture with large cells
      • Progression to larger cells with blastic features has been described in some cases
    • All cases T lineage with cytotoxic protein expression
    • Most cases have gamma delta T cell receptors
      • A subset of cases may have alpha beta T cell receptors
      • Other types of lymphoma may express gamma delta T cell receptors

    Dita Gratzinger MD PhD
    Yasodha Natkunam MD PhD
    Robert V Rouse MD

    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Initial posting : September 1, 2007

    Supplemental studies

    Immunohistology and Flow

    • T lineage
    • CD3
    • Virtually 100%
    • CD2
    • Virtually 100%
    • CD4
    • Negative
    • CD8
    • <10%
    • CD5
    • Negative
    • >90% express gamma/delta T cell receptors
      • <10% express alpha/beta T cell receptors
    • Cytotoxic granule protein antigens
      • TIA1 100%
      • Granzyme B <5%
      • Perforin negative
    • CD56 >90%
    • EBV about 10%

    Genetic study

    • T cell receptor gamma genes rearranged in most cases
      • A subset may show instead beta gene rearrangement
    • Isochromosome 7q has been identified in most cases studied
      • Other abnormalities may also be seen

    Differential Diagnosis

    Hepatosplenic T Cell Lymphoma Non-hepatosplenic T Cell Lymphoma
    Involves liver, spleen, marrow Variable
    Granzyme B usually negative Granzyme B often positive
    Perforin usually negative Perforin often positive
    EBV usually negative EBV positive in subset

    Hepatosplenic T Cell Lymphoma T Large Granular Lymphocytic Leukemia
    Involves liver, spleen, marrow Involves blood and marrow
    Granzyme B usually negative Granzyme B positive
    Perforin usually negative Perforin positive
    Clinically aggressive Clinically indolent

    Hepatosplenic T Cell Lymphoma Mucosa / Skin Associated T Cell Lymphoma
    Predominantly involves liver and spleen Involves mucosa and/or skin but does not predominantly involve liver or spleen
    Frequently involves marrow Usually does not involve marrow
    Immunophenotype overlaps and morphology of both is variable


    • Rare, <5% of peripheral T cell lymphomas
    • Predominantly young adult males
      • alpha beta T cell receptor subtype seen predominantly in females with wide age range
    • Presents with hepatosplenomegaly
      • Peripheral adenopathy rare
    • Fever, anemia, thrombocytopenia and neutropenia usually present
      • Leukocytosis may be present
    • Cases have been reported following organ transplants
      • Present later but with poorer prognosis than B cell PTLD
    • Poor prognosis

    Grading / Staging / Report

    Grading is not applicable

    Ann Arbor Staging System

    • Stage I
      • I if involvement of a single lymph node region
      • IE if involvement of a single extralymphatic organ or site
    • Stage II
      • II if two or more lymph node regions on same side of diaphragm
      • IIE if localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm
    • Stage III
      • III if Involvement of lymph node regions on both sides of the diphragm
      • IIIS if spleen involved
      • IIIE if extralymphatic site involved
    • Stage IV
      • Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement
    • Systemic Symptoms in 6 months preceding admission
      • Fever, night sweats, 10% weight loss
      • A = absent
      • B = present
    • Extranodal sites are also designated
      • M+ = marrow
      • L+ = lung
      • H+ = liver
      • P+ = pleura
      • O+ = bone
      • D+ = skin and subcutaneous tissue
    • Although originally designed for Hodgkin lymphoma, the Ann Arbor System is also used for non-Hodgkin lymphoma

    The pathology report should contain the following information:

    • Diagnosis in the World Health Organization (WHO) classification
      • Equivalent diagnosis in other classifications used by relevant clinicians
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient
    • Information relevant to staging if available


    Mature T and NK cell neoplasms (WHO classification)


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