Hepatosplenic T-Cell Lymphoma

Hepatosplenic T-cell lymphoma (HSTL) is an aggressive peripheral T-cell lymphoma with specific localization to the spleen, liver, and bone marrow. It preferentially affects young adults with a male predominance. A small subset of cases occur in the setting of iatrogenic immunosuppression and treatment with thiopurines and/or tumor necrosis factor (TNF-α) inhibitors. Morphologically, HSTL cells infiltrate the sinuses and cords of the red pulp of the spleen. It shows sinusoidal infiltrate pattern in the liver and bone marrow. The HSTL cells are typically medium sized with mature chromatin and no cytoplasmic granules. But cytological variation is not uncommon. Most cases of HSTL are γδ T-cells with double-negative CD4/CD8, loss of CD5, and expression of CD56 and TCL1. A minority of cases of HSTL are αβ T-cells. There is no significant clinical or prognostic difference between γδ and αβ HSTLs. The HSTL cells show a characteristic inactivated cytotoxic T-cell phenotype with expression of TIA1 and negative granzyme B and perforin. The most common recurrent cytogenetic finding is isochromosome (7q). Commonly mutated genes in HSTL include STAT3 and STAT5b. Given the sinusoidal infiltrate pattern, the differential diagnosis includes T-cell large granular lymphocytic leukemia, which can be resolved by a combination of clinical, histologic, and cytogenetic analysis.