Hepatosplenic T-cell lymphoma (HSTL) is a rare extranodal and systemic lymphoma derived from cytotoxic T cells usually of γδ T cell receptor type. It is characterized by primary extranodal disease with typical sinusoidal infiltration of liver, spleen, and bone marrow by medium-sized lymphoid cells.
A 29-year-old man, with no significant prior medical history, presented with fever and massive splenomegaly. A diagnosis of HSTL was established by histologic examination and immunohistochemistry. Staging workup demonstrated bone marrow involvement by lymphoma. In addition, the patient was found to have hepatitis B infection. The association of these 2 entities has been described rarely.
Hepatosplenic T-cell lymphoma is a distinct T cell lymphoma associated with an aggressive clinical course, a poor response to conventional treatment, and an exceedingly high mortality rate. An association of HSTL with hepatitis B as seen in the present case is exceedingly rare, with few cases reported in the literature.
Tumori 2016; 102(Suppl. 2): e61 - e64
Article Type: CASE REPORT
AuthorsFouzia Siraj, Varsha Dalal, Afaq A. Khan, Deepali Jain
- • Accepted on 17/09/2015
- • Available online on 13/10/2015
- • Published online on 11/11/2016
This article is available as full text PDF.
Hepatosplenic T-cell lymphoma (HSTL) is a rare peripheral T-cell lymphoma derived from cytotoxic T-cells, and manifests as an extranodal systemic lymphoma (1). It is characterized by primary extranodal disease with typical sinusoidal infiltration of the liver and the spleen. The neoplasm is seen mostly in adolescents and young adults with a strong predilection for males (2, 3). Hepatosplenic T-cell lymphoma has been reported in the context of immunosuppressive states and certain infections (1, 4). There is a possibility that proliferation of neoplastic T cells in response to infective agents like hepatitis B, as seen in the present case, plays a role in the pathogenesis of hepatosplenic T-cell lymphoma.
A 29-year-old man presented with fever, abdominal pain, and significant weight loss for a period of 5 months. There was no history of cough, chest pain, vomiting, icterus, or bowel or bladder dysfunction. There was no history of any comorbid condition or significant disease in the family. General physical examination was normal except for mild pallor. Abdomen examination revealed massive splenomegaly and mild hepatomegaly. Laboratory results showed anemia (10 g/dL), thrombocytopenia (40,000/µL), and leukocytosis (15,300/µL). Peripheral smear revealed normocytic, normochromic red blood cells with mild anisocytosis, few target cells, and Howell Jolly bodies. Reticulocyte count was 3.98%, suggestive of a hemolytic picture. Malaria and kala-azar infections were excluded. Liver function tests were abnormal, with bilirubin of 3 mg/dL (normal range 0.3-1.9 mg/dL), alanine aminotransferase 80 IU/L, and aspartate aminotransferase 120 IU/L (normal range 0-40 IU/L). HBeAg was positive with high hepatitis B virus DNA load of 2.4 × 108 copies/mL. Viral serology for hepatitis C, hepatitis D, and human immunodeficiency virus 1 and 2 was negative. Abdominal ultrasonography confirmed marked splenomegaly and mild hepatomegaly. No enlarged lymph nodes were identified. The patient underwent splenectomy and liver wedge biopsy. Subsequently bone marrow aspiration and biopsy was done.
Gross examination revealed an enlarged spleen measuring 33 × 21 × 10 cm and weighing 2900 g. Cut surface was reddish brown, homogenous, and fleshy, with an area of infarction. No nodularity or follicular prominence was noted. Wedge biopsy of liver measured 1 × 0.8 × 0.5 cm. Cut surface was unremarkable.
Microscopic examination of the spleen showed diffuse involvement of the red pulp by small to medium-sized lymphoid cells with a thin rim of pale cytoplasm and irregular nuclei. Few residual follicles of white pulp were identified (
A diagnosis of HSTL was rendered on the basis of clinicopathologic and immunophenotypical features.
The patient was started on tenofovir (300 mg/d) in view of active hepatitis B infection and CHOP regimen comprising cyclophosphamide and prednisolone but died within 4 months of diagnosis due to septicemia following repeated infections.
Peripheral T-cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10%-15% of all non-Hodgkin lymphomas. A rare entity within this group is represented by hepatosplenic γδ T-cell lymphoma, which constitutes less than 1% of all non-Hodgkin lymphomas (1). In 1990, Farcet et al (5) proposed HSTL as a separate entity characterized by a γδ T-cell infiltration of the red pulp of the spleen and by sinusoidal infiltration of the liver without lymphadenopathy. In 2001, the WHO classification of tumors recognized HSTL as a distinct clinicopathologic entity based on the expression of T-cell receptors, the clinical presentation, and the pattern of histologic involvement. Hepatosplenic T-cell lymphoma has a predilection to develop in young men, with a recorded mean age of 32 years. According to Weidmann (2), clinical symptoms at presentation are hepatosplenomegaly, constitutional symptoms, and less frequently jaundice due to hepatic involvement. The predominant laboratory findings are reduced peripheral blood cells, ranging from hemolytic anemia to thrombocytopenia or pancytopenia, high levels of low-density lipoprotein, and mild increase of liver enzymes (2, 3). Pancytopenia is attributed to splenomegaly and secretion of cytokines that suppress normal hematopoiesis (e.g., interferon-γ) by neoplastic γδ T cells (2).
The histologic picture of HSTL is characterized by typical sinusoidal infiltration of liver, spleen, and bone marrow by neoplastic T cells. The affinity towards liver and splenic sinusoids is believed to be due to altered expression of adhesion molecules on the surface of malignant T lymphocytes (3). Immunophenotyping and cytogenetic analysis have become essential diagnostic tools. Usually, the malignant γδ lymphocytes are CD2+, CD3+, CD4−, CD5−, CD7+, CD8−, and TCRγδ+ (1-2-3). Clonal
The majority of HSTLs are primary lymphomas, but about 20% of cases occur in a setting of chronic immunosuppression like solid organ transplantation and Crohn disease (2, 3, 7, 8). Certain viral infections are also implicated, like human herpesvirus 6 and Epstein-Barr virus (4). An extensive literature search revealed only a handful of cases of HSTL with coexistent hepatitis B (9, 10). The present case also highlights the possible association of HSTL with hepatitis B. It is postulated that prolonged antigenic stimulation by the virus leads to an abnormal proliferation of γδ T cells, subsequently resulting in neoplasia. However, more studies need to be done to determine the exact evolution of disease in this scenario.
Hepatosplenic T-cell lymphoma has an aggressive clinical course with an unsatisfactory response to treatment. Various treatment modalities include splenectomy, CHOP-like cytotoxic regimens, purine analogues, and hematopoietic stem cell transplantation (3). However, the long-term outcome is dismal, with the majority of patients dying within 1 year of diagnosis, as was seen in our case.
In conclusion, HSTL is a distinct T-cell lymphoma with characteristic clinicopathologic findings and immunophenotypical profile. It is associated with an aggressive clinical course, a poor response to conventional treatment, and an exceedingly high mortality rate. An association of HSTL with hepatitis B, as seen in the present case, is rare, with few cases reported in the literature.
- Siraj, Fouzia [PubMed] [Google Scholar] 1
- Dalal, Varsha [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Khan, Afaq A. [PubMed] [Google Scholar] 2
- Jain, Deepali [PubMed] [Google Scholar] 3
National Institute of Pathology (ICMR), New Delhi - India
JLNM Hospital, Srinagar, Kashmir - India
Department of Pathology, AIIMS, New Delhi - India