De novo CD3 negative hepatosplenic T-cell lymphoma: diagnostic challenges and pitfalls

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.