Hepatosplenic T Cell Lymphoma

Definition

• 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

• Non-hepatosplenic T cell lymphoma
• T large granular lymphocytic leukemia
• Mucosal / skin T cell lymphoma

Clinical

• 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

Lists

Mature T and NK cell neoplasms (WHO classification)

• Leukemic
  • T cell prolymphocytic leukemia
  • T cell large granular lymphocytic leukemia
  • Aggressive NK cell leukemia
  • Adult T cell leukemia/lymphoma
• Predominantly cutaneous
  • Mycosis fungoides
  • Anaplastic large cell lymphoma, primary cutaneous
  • Lymphomatoid papulosis
  • CD4+/CD56+ hematodermic neoplasm (Blastic NK cell lymphoma)
• Predominantly extranodal, noncutaneous
  • Extranodal NK/T cell lymphoma, nasal type
  • Enteropathy type T cell lymphoma
  • Hepatosplenic T cell lymphoma
  • Subcutaneous panniculitis-like T cell lymphoma
• Predominantly nodal
  • Peripheral T cell lymphoma unspecified
  • Angioimmunoblastic T cell lymphoma
  • Anaplastic large cell lymphoma, primary systemic

Bibliography

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