Hepatosplenic T-cell lymphoma

Signs and symptoms

The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegaly.

The spleen and liver are always involved, and bone marrow involvement is common. Nodal involvement is exceedingly rare.

Cause

The cell of origin for this disease is an immature cytotoxic T-cell clonally expressing the γδ T-cell receptor. The disease is seen more often in immunosuppressed recipients of solid organ transplants, an association that has led to the hypothesis that long-term immune stimulation in the setting of immunosuppression is the causative agent.

Cases of hepatosplenic T-cell lymphoma have been reported in patients treated with the immunosuppressants azathioprine, infliximab, and adalimumab. The majority of cases occurred in patients with inflammatory bowel disease. Adolescents and young adult males were most frequently affected. They presented with a very aggressive disease course, and all but one died. The Food and Drug Administration required changes to the drugs' labeling to inform users and clinicians of the risk.

Diagnosis

The neoplastic cells in hepatosplenic T-cell lymphoma show a monotonous appearance, with a small amount of cytoplasm and inconspicuous nucleoli.

Laboratory findings

The constellation of thrombocytopenia, anemia, and leukopenia is common in patients with hepatosplenic T-cell lymphoma.

Spleen and liver

The disease shows a distinct sinusoidal pattern of infiltration which spares the splenic white pulp and hepatic portal triads.

Bone marrow

While the bone marrow is commonly involved, the detection of the neoplastic infiltrate may be difficult due to a diffuse, interstitial pattern. Immunohistochemistry can aid in diagnosis.

Peripheral blood

Cells of a similar morphology observed in solid organs are observed in peripheral blood.

Immunophenotype

The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature T-cell.

Genetic findings

Clonal rearrangement of the γ gene of the T-cell receptor is the hallmark of hepatosplenic T-cell lymphoma. A few cases have shown rearrangement of the T-cell receptor β gene. Isochromosome 7q has been observed in all cases described so far, sometimes in conjunction with other chromosomal abnormalities such as trisomy 8.

Treatment

The CHOP chemotherapy regimen frequently induces remission but has proven weak compared to treatments that integrate cytarabine, with Hyper-CVAD being particularly effective. When treated solely with chemotherapy, most patients relapse and die within two years. Treatment solely with doxorubicin can make the disease worse.

Allogeneic bone marrow transplantation has been shown to induce remission for more than five years and possibly cure hepatosplenic lymphoma. Autologous bone marrow transplantation is currently being investigated.

Epidemiology

Hepatosplenic lymphoma is rare, comprising less than 5% of all lymphoma cases, and is most common in young adults and adolescents. A distinct male gender preference has been described.

References

References

1. (2015). "Outcomes of allogeneic stem cell transplantation in hepatosplenic T-cell lymphoma". Blood Cancer Journal.
2. (February 2007). "Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease". J. Pediatr. Gastroenterol. Nutr..
3. (June 1990). "Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta". Blood.
4. Elaine Sarkin Jaffe, Nancy Lee Harris, World Health Organization, International Agency for Research on Cancer, Harald Stein, J.W. Vardiman. (2001). "Pathology and genetics of tumours of haematopoietic and lymphoid tissues". IARC Press.
5. FDA Warning concerning azathioprine and Hepatosplenic T-cell lymphoma [https://web.archive.org/web/20110619042340/http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm258794.htm]
6. (September 1994). "Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen". Am. J. Clin. Pathol..
7. (March 2001). "Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas". Am. J. Surg. Pathol..
8. (2011). "Hepatosplenic T-Cell Lymphoma". Indian Journal of Hematology and Blood Transfusion.
9. (August 1997). "Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma". Leukemia.
10. (December 1996). "Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin". Blood.