Lymphoma and plasma cell neoplasms
T / NK cell disorders
Hepatosplenic T cell lymphoma


Topic Completed: 12 December 2019

Minor changes: 13 March 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Hepatosplenic T cell lymphoma[TI] pathology

Mario L. Marques-Piubelli, M.D.
Roberto N. Miranda, M.D.
Page views in 2019: 1,096
Page views in 2020 to date: 849
Cite this page: Marques-Piubelli M, Ferrufino-Schmidt M, Miranda R. Hepatosplenic T cell lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBhepatosplenic.html. Accessed June 1st, 2020.
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)
ICD coding
  • ICD-0: 9716/3 - hepatosplenic T cell lymphoma
Epidemiology
Pathophysiology
  • Neoplastic clonal proliferation of γδ T cell induced by up regulation of the JAK / STAT (STAT3 and STAT5B) pathway or mutations of chromatin modifiers (SETD2, INO80 and ARID1B) (Hum Pathol 2018;74:5)
Etiology
Clinical features
  • Hepatomegaly and splenomegaly are the most common clinical manifestations (Ann Diagn Pathol 2017;26:16, Am J Surg Pathol 2017;41:82)
    • 70 - 80% of patients
    • Massive splenomegaly is found in most patients, defined as ≥ 6 cm below costal margin or ≥ 20 cm in greatest dimension or splenectomy > 1,000 g
  • B symptoms (Am J Surg Pathol 2016;40:676)
  • Lymphadenopathy is uncommon (< 25%); when present, splenic peripheral lymph nodes are the most commonly compromised (Histopathology 2014;64:171)
  • Peripheral blood involvement at initial presentation is uncommon
    • Cytopenia or pancytopenia: moderate anemia, thrombocytopenia and neutropenia (Blood 2003;102:4261)
      • Pathogenesis not well defined
    • Severity correlates with disease progression
  • Elevated levels of lactate dehydrogenase (LDH), β2 microglobulin and bilirubin (Hum Pathol 2018;74:5)
  • Bone marrow (BM) usually involved at initial presentation (Hum Pathol 2016;50:109)
  • Cutaneous involvement is rare
Prognostic factors
Case reports
Gross description
  • Diffuse and homogeneous enlarged liver and spleen; without distinct macroscopic lesions (Blood 2003;102:4261)
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Roberto N. Miranda, M.D.

Bone marrow infiltration

Bone marrow infiltration by hepatosplenic T cell lymphoma

Bone marrow dyspoietic changes

Small size cells (bone marrow aspirate)

Intermediate size cells (bone marrow aspirate)

Blastic morphology (bone marrow aspirate)


CD3 sinusoidal pattern

CD4 negative

CD8 negative

TCR βF1 negative

TCRγδ positive

Liver portal infiltration


Liver sinusoidal infiltration

Liver sinusoidal pattern CD3

Kupffer cells CD4 positive

Lymphoma cells CD8 positive

Lymphoma cells TIA1 positive

Cytology description
Negative stains
Flow cytometry description
  • Helpful for diagnosis
  • TCRγδ in 80% cases
  • CD2+, CD3+, CD7+, CD56+, KIR+
  • CD4-, CD5-, CD8- and CD57- (Am J Surg Pathol 2017;41:82)
  • Variable CD16 and CD94 (dim or negative)
Flow cytometry images

Contributed by Roberto N. Miranda, M.D.

Flow cytometry of hepatosplenic T cell lymphoma

Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:

PCR for TCRγ

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 male, who has a history of Crohn's disease for which he was receiving azathioprine and tumor necrosis alpha receptor antagonist. Patient refers that 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 are 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 pattern correspond 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 answer #1
B. CD2+, CD3+, CD4-, CD5-, TIA1+, Granzyme M+, TCRγδ+

Reference: Lymphoma and plasma cell neoplasms - Hepatosplenic T cell lymphoma

Comment here
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 answer #2
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