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

ABSTRACT

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.