Abstract

Primary cutaneous T-cell gamma-delta lymphoma (PCγδTCL) is a rare type of non-Hodgkin lymphoma that arises from mature, post-thymic cytotoxic γδ (gamma delta) T cells and it accounts for less than 1% of primary cutaneous T-cell lymphomas. The exact cause of PCγδTCL is not known, but it is believed to be related to the abnormal proliferation of γδ T cells in the skin. The common molecular variation involved in PCγδTCL includes mutations that affect cancer genes (CDKN2A, IDH2, TP53) as well as tumor suppressors (TNFAIP3, FAS, PDCD1) and involved pathways include JAK/STAT signaling (STAT3, STAT5B, JAK3, SOCS1), MAPK signaling, MYC pathway (MYC, MYCN, FBXW7), and chromatin modification (ARID1A, TRRAP, TET2, KMT2D). We report a case of PCγδTCL with atypical immunophenotypic features, showing positivity for CD5 and absent cytotoxic markers and unusual molecular alteration of FYN deletion at exon 8 on next-generation sequencing. Deletion of the area between FYN exon 8 and TRAF3IP2 intron 2 is known to result in an FYN::TRAF3IP2 fusion, which is a novel recently described fusion transcript in primary cutaneous T-cell lymphoma, not otherwise specified. At a 4-week follow-up after diagnosis, a new leukocytosis with lymphocytosis was identified, and flow cytometric analysis was performed showing involvement by an increased abnormal γδ T-cell population with immunophenotype similar to the lymphoma involving the skin, consistent with rapid systemic progression of PCγδTCL.