{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:21:43Z","timestamp":1771935703797,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti-TIF1\u03b3-positive dermatomyositis (DM) is a classic paraneoplastic syndrome in adults, but its coexisting with lymphoepithelial carcinoma (LEC) of the parotid gland is exceptionally rare. This rarity poses significant challenges for clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To report a unique case of parotid LEC emerging three years after a diagnosis of anti-TIF1\u03b3-positive DM, followed by a post-oncologic DM recurrence. We aimed to investigate the underlying immunopathogenesis through peripheral blood mononuclear cell (PBMC) analysis and genetic profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 28-year-old male presented with anti-TIF1\u03b3-positive DM. Three years later, he developed parotid LEC, with Epstein-Barr virus (EBV) detected in both tumor tissue and serology. He was treated with surgical resection and adjuvant therapy, achieving a near-complete oncologic response. However, DM recurred eight months after the cancer diagnosis. Initial cyclophosphamide treatment was effective, but its withdrawal led to relapse; subsequent therapies with methotrexate and tofacitinib provided minimal benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PBMC analysis during the DM recurrence revealed a highly active B-cell population and a reduction in cytotoxic cells. This B-cell expansion subsequently decreased 10 months later, suggesting a delayed effect of the documented EBV activation. Germline genotyping identified a panel of deleterious germline mutations in immune regulation genes, including a variant in\n                      <jats:italic>CR2<\/jats:italic>\n                      (rs367567954), which encodes a receptor for EBV on B cells and may contribute to their aberrant activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates that refractory anti-TIF1\u03b3-DM can persist even after the associated malignancy is well controlled and underscore the need for long-term vigilance and personalized management strategies in paraneoplastic DM.<\/jats:p>\n                  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