De Novo CD3 Negative Hepatosplenic T-cell Lymphoma: Diagnostic Challenges and Pitfalls

Abstract

Hepatosplenic T-cell lymphoma is a rare and aggressive peripheral T-cell malignancy that is distinctively characterized by sinusoidal infiltration of mature medium-sized T lymphocytes in the spleen and liver. The neoplastic cells are classically surface CD3+, CD2+, CD5−, CD4−, and CD8+/− and manifest variable expression of markers associated with natural killer (NK) cells such as CD16 and CD56. In this article, we report the first case to date of a newly diagnosed de novo surface CD3− hepatosplenic T-cell lymphoma with circulating blastlike neoplastic cells expressing NK-cell–associated markers. The lack of surface CD3 expression, together with the expression of NK-cell–associated markers and the leukemic presentation, leads to significant diagnostic challenges in differentiating this CD3− hepatosplenic T-cell lymphoma from NK-cell neoplasms, in particular aggressive NK-cell leukemia. The related literature is reviewed, and the approaches for adequate diagnosis of this novel situation are described.