Hepatosplenic gamma-delta T-Cell Lymphoma as a Late-Onset Posttransplant Lymphoproliferative Disorder in Renal Transplant Recipients

Abstract

We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.

TIA-1 expression in hairy cell leukemia

“…15 They therefore considered that hepatosplenic T-cell lymphoma cells may be functionally immature and not yet capable of cytotoxic function. 15 Although TIA-1 expression, in the absence of granzyme and perforin expression, is similar between the cases of hairy cell leukemia and hepatosplenic T-cell lymphoma, 15,16 the mechanism underlying their expression might be different. Since hairy cell leukemia is a B-cell lymphoma, it is not expected to have a role in cytotoxic function.…”

“…[1][2][3] Expression of these proteins has been reported in cytotoxic T cells [4][5][6] and natural killer cells (NK cells). 6,7 These proteins are also expressed in T-cell or NK-cell neoplasms, [8][9][10][11] including large granular lymphocyte leukemia, NK-cell leukemia/lymphoma, [12][13][14] hepatosplenic T-cell lymphoma, [15][16][17] subcutaneous panniculitic T-cell lymphoma, 18,19 enteropathy-type T-cell lymphoma, 20 and anaplastic large-cell lymphoma. 21 Perforin functions by making a hole in the target cell membrane.…”

Small B-cell lymphomas of the spleen: how to tell them apart

“…Some cases occur in the setting of immunosuppression due to prior transplantation or therapy with immunosuppressive agents for other reasons [58,59]. Similar to SMZL, rare cases have been reported in the setting of Plasmodium falciparum malaria infection, which is associated with an expansion of γδ-T cells in the peripheral blood and spleen [60].…”

“…I n a d d i t i o n , p r o m i n e n t erythrophagocytosis in the spleen, present in many cases, may be a clue to the diagnosis. Molecular genetic analysis shows clonal T-cell receptor gene rearrangements and the most common cytogenetic abnormalities are isochromosome 7q and trisomy 8 [59].…”

Hepatosplenic T-cell lymphoma and TNF-α inhibitors

“…Although the majority of these cases seem to have developed de novo, approximately a third have been associated with immunosuppressive therapy for various reasons, mostly for organ transplantations and other conditions that require immune-modifying agents; most cases involving thiopurines [5,23,24]. Several immunocompromised conditions described in the literature include renal transplantation, heart transplantation, Hodgkin lymphoma, acute myelogenous leukemia, inflammatory bowel disease and malaria infection [4][5][6]13,[23][24][25][26][27][28][29][30][31][32]. Cases of HSTCL are also associated with viral infections, including human herpes virus 6, hepatitis B virus, and Epstein-Barr virus [33,34].…”