Primary Cutaneous Gamma-Delta T-Cell Lymphoma Complicating Long-Standing Immunosuppressed Dermatomyositis.

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare cytotoxic lymphoma with key oncogenic drivers in the JAK/STAT pathway. Also primarily involving the subcutaneous adipose tissue, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is more frequently encountered in scenarios of autoimmune disorders. SPTCL shares clinicopathologic overlap with lupus panniculitis. However, the link between autoimmunity and PCGD-TCL is much less established, particularly in the setting of long-standing, immunosuppressed dermatomyositis (DM). We report two cases of PCGD-TCL arising in women with chronic anti-TIF1-γ DM following years of immunosuppressive therapy. Case 1 is a 47-year-old woman with a 19-year history of DM on azathioprine/prednisone who developed rapidly progressive, painful subcutaneous nodules. Incisional biopsy confirmed a TCR-delta+, CD8+ cytotoxic T-cell lymphoproliferative disorder (TCLPD) compatible with PCGD-TCL. She achieved complete remission following pralatrexate and subsequent allogeneic hematopoietic stem cell transplant. Case 2 is a 27-year-old woman with DM on mycophenolate/rituximab who developed subcutaneous nodules with an indolent course and some spontaneous regression. A biopsy revealed a similar panniculitic infiltrate with an atypical TCR-delta+, CD8+ phenotype. Notably, both cases were negative for high-risk JAK/STAT pathway mutations. These cases identify PCGD-TCLPD/TCL as a potential complication of chronic, immunosuppressed DM. The shared, atypical CD8+ immunophenotype and absence of canonical driver mutations suggest a distinct pathogenic mechanism possibly linked to long-term immune modulation. Unlike classic PCGD-TCL, which is characterized by an aggressive course and < 2-year median survival, the clinical courses in these two cases were variable, with one requiring transplant and the other showing indolent behavior and responsiveness to therapy.