Nodal gamma-delta T-cell lymphoma: expression of TFH-markers causing diagnostic difficulties in a newly described...

Gamma-delta T-cell lymphomas are rare, aggressive neoplasms derived from γδ T-cells, typically presenting with extranodal disease. Recently, a distinct lymphonodal subtype, nodal gamma-delta T-cell lymphoma (NGDTCL), has been recognized, which is not well reflected in current lymphoma classifications.We here report a unique case of NGDTCL in a 61-year-old male presenting with cervical lymphadenopathy and refractory disease despite multiple lines of therapy. Histopathological analysis revealed diffuse infiltration of a CD4+ gamma-delta T-cell lymphoma, with loss of CD7 and absence of cytotoxic marker expression. Notably, the lymphoma cells expressed two T follicular helper (TFH) cell markers, PD-1 and ICOS, initially leading to misclassification as a TFH lymphoma. Genomic profiling revealed pathogenic alterations of TP53, CHEK2, and loss of CDKN2A and CDKN2B. Additionally, a rearrangement of the ITK-gene, which is believed to play a role in γδ T-cell development, was identified. To our knowledge, this is the first report of a NGDTCL with co-expression of two TFH markers. This case broadens the phenotypic spectrum of NGDTCL and challenges current diagnostic concepts of T-cell lymphoma classification, particularly the notion that expression of CD4 and two TFH markers are sufficient for diagnosing nodal TFH lymphomas.