Hepatosplenic T-cell lymphoma with STAT5B and SETD2 mutations recurring as cells with NK-cell immunophenotype

A 58-year-old man with a history of T-cell receptor (TCR) γδ–positive hepatosplenic T-cell lymphoma (HSTCL) with STAT5B and SET2D mutations involving the spleen, liver, and peripheral blood underwent chemotherapy and autologous stem cell transplantation with persistent disease detected in the blood. He received pralatrexate for 6 months with improvement in leukemic disease but developed headache, left eye blurriness, and emesis. Brain magnetic resonance imaging (MRI) demonstrated asymmetric enhancement of the left optic nerve concerning for CNS involvement (panel A, MRI short tau inversion recovery image). A lumbar puncture demonstrated atypical lymphoid cells (panel B, Wright-Giemsa, magnification ×1000) expressing CD2, CD7, CD56, and CD16 and lacking CD3, CD5, TCRαβ, and TCRγδ (panel C, orange population). Despite the lack of surface CD3 and TCRγδ and apparent “NK-cell” immunophenotype, mutational analysis revealed STAT5B and SET2D mutations. A subsequent lumbar puncture showing persistent disease additionally demonstrated TRG and TRB gene rearrangements (panel D).

This case is an example of HSTCL with aberrant loss of the CD3/TCR complex, an extremely rare phenomenon typically occurring in the posttreatment setting. This case highlights the diagnostic difficulty of distinguishing HSTCL with loss of CD3/TCR vs reactive NK-cells based solely on immunophenotyping, and highlights the use of molecular analysis for confirming recurrent disease in T-cell lymphomas that have undergone an immunophenotypic shift.

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