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Hepatosplenic T cell lymphoma

Last author update: 2 May 2022
Last staff update: 4 October 2023

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PubMed Search: Hepatosplenic T cell lymphoma

Mario L. Marques-Piubelli, M.D.
Roberto N. Miranda, M.D.
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Cite this page: Marques-Piubelli ML, Ferrufino-Schmidt MC, Miranda RN. Hepatosplenic T cell lymphoma. website. Accessed May 19th, 2024.
Definition / general
Essential features
  • Rare, aggressive extranodal neoplasm that originates from cytotoxic T cells; it usually expresses the T cell receptor (TCR) γδ (gamma delta) (Am J Surg Pathol 2017;41:82)
  • Hepatomegaly and splenomegaly are the most common clinical manifestations (Ann Diagn Pathol 2017;26:16)
  • Liver and bone marrow: sinusoidal infiltration (Histopathology 2014;64:171)
  • Spleen
    • Diffuse involvement; expansion of the red pulp cords and sinusoids, with atrophy or absence of white pulp (Hum Pathol 2018;74:5)
  • Cytology: variable
    • Usually monotonous, small to intermediate size cells with pale agranular cytoplasm, round / oval nuclei, moderately condensed chromatin and inconspicuous nucleoli (Blood 2003;102:4261)
  • Obsolete term: erythrophagocytic Tγ lymphoma
ICD coding
  • ICD-O: 9716/3 - hepatosplenic T cell lymphoma
Clinical features
Radiology description
  • CT or MRI (Blood 2020;136:2018):
    • Homogeneous hepatosplenomegaly
  • Fluorodeoxyglucose (FDG) PET / CT (Blood 2020;136:2018):
    • Diffuse FDG uptake in affected areas
      • Usually liver, spleen and bone marrow
Prognostic factors
Case reports
Gross description
  • Diffuse and homogeneous, enlarged liver and spleen; without distinct macroscopic lesions; lymph nodes are usually not enlarged (Blood 2003;102:4261)
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Roberto N. Miranda, M.D.

Bone marrow infiltration

Bone marrow with dyspoietic changes

CD3 positive

CD4 negative

CD8 negative

TCR βF1 negative

TCRγδ positive

Liver infiltration

HSTCL: CD3 positive

HSTCL: CD4 negative

CD8 positive

TIA1 positive

Small size morphology

Intermediate size morphology

Blastic morphology

Cytology description
Negative stains
Flow cytometry description
Flow cytometry images

Contributed by Roberto N. Miranda, M.D.

Positivity for CD2, TCRγδ and CD56

Molecular / cytogenetics description
Sample pathology report
  • Bone marrow (right iliac crest) core and clot specimen; aspirate smears and peripheral blood:
    • Hepatosplenic T cell lymphoma
    • Flow cytometry immunophenotype demonstrated aberrant T cells with loss of CD4 and CD8, positive for T cell receptor gamma delta chain (see comment)
    • Comment: According to clinical records, patient is a 28 year old man who has a history of Crohn's disease, for which he was receiving azathioprine and tumor necrosis alpha receptor antagonist. Patient reports malaise and fever for 3 months. On physical exam, patient had massive splenomegaly (8 cm below costal margin) and hepatomegaly. Laboratory findings showed leukopenia, severe anemia and thrombocytopenia. Additional testing proved negative for antiglobulin testing, negative for HIV, hepatitis B, hepatitis C and HTLV1.
    • Bone marrow core biopsy and clot sections show similar features. There is 70% cellularity with trilineage hematopoiesis. Megakaryocytes are adequate in number and range from small, hypolobated forms to megakaryocytes of normal size and shape. There are scattered small clusters of small to intermediate size lymphocytes with hyperchromatic nuclei with irregular nuclear contours.
    • Bone marrow aspirate smears show trilineage hematopoiesis with mild dysmegakaryopoiesis. There are approximately 15% lymphocytes, of small to intermediate size, with clear and agranular cytoplasm and central hyperchromatic nuclei with irregular nuclear contours.
    • Immunohistochemical studies were performed in bone marrow core biopsy and the T cell marker CD3 highlights lymphocytes in an interstitial and sinusoidal pattern, representing approximately 10% of marrow cells. Atypical lymphocytes are also highlighted with CD2, CD7, CD56, TIA1 and granzyme M. The T cell receptor gamma delta is positive in lymphocytes, while the T cell receptor alpha beta (βF1 clone) is negative. CD4 and CD8 are negative in atypical lymphocytes. The following markers are also negative in lymphocytes: CD1a, CD5, CD10, CD57, EBER (EBV in situ hybridization), TCL1 and TdT.
    • Concurrent flow cytometry immunophenotype demonstrates that approximately 15% of marrow cells are T lymphocytes, positive for CD2, CD7, CD52, CD56 and T cell receptor gamma delta. The atypical lymphocytes are negative for CD4, CD5, CD8, CD57 and T cell receptor alpha beta. The B lymphocytes are polytypic.
    • Molecular testing revealed monoclonal T cell receptor gene rearrangement of gamma (V gamma 4 family) and beta chains. Next generation sequencing showed mutation of STAT5B. The specimen was negative for IGH gene rearrangement.
    • Cytogenetic analysis revealed isochromosome 7 and trisomy 8
    • Clinical correlation and followup is recommended.
Differential diagnosis
Board review style question #1

Which of the following immunophenotypic patterns corresponds to hepatosplenic T cell lymphoma?

  1. CD2+, CD3+, CD4+, CD5-, TIA1+, granzyme B+, TCRγδ+
  2. CD2+, CD3+, CD4-, CD5-, TIA1+, granzyme M+, TCRγδ+
  3. CD2+, CD3-, CD4+, CD5+, CD7+, CD8+, TCRγδ+
  4. CD2+, CD3-, CD4+, CD5+, CD7-, CD8-, TCRγδ+
  5. CD2-, CD3-, CD4-, CD5+, CD7-, CD8-, TCRγδ+
Board review style answer #1
B. CD2+, CD3+, CD4-, CD5-, TIA1+, granzyme M+, TCRγδ+

Comment here

Reference: Hepatosplenic T cell lymphoma
Board review style question #2
Which of the following cytogenetic and molecular abnormalities are found in hepatosplenic T cell lymphoma?

  1. Del(6q) and RHOA1 mutation
  2. Inversion 14 and TCL1 rearrangement
  3. Isochromosome 7 and STAT5B mutation
  4. t(2;5) and JAK / STAT activation
  5. 6p25 and DUSP22 / IRF4
Board review style answer #2
C. Isochromosome 7 and STAT5B mutation

Comment here

Reference: Hepatosplenic T cell lymphoma
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