Background: Soft tissue sarcoma (STS) typically originates in the muscles and is associated with a poor prognosis. Undifferentiated pleomorphic sarcoma (UPS) is the most commonly diagnosed subtype of STS; however, UPS occurring in the sinonasal region is exceedingly rare and lacks effective treatment options.Objective: This case report presents a patient with sinonasal UPS who experienced disease progression after surgery and chemotherapy but showed a positive response to combination therapy with toripalimab and anlotinib. Additionally, it explores the underlying biomarkers associated with this case.Case: A 63-year-old woman with no significant past medical history was diagnosed with sinonasal UPS. The lesions recurred despite seven extensive surgical resections, and standard chemotherapy failed to control the disease, leading to progressive disease (PD).Results: The patient was treated with a combination of toripalimab and anlotinib, resulting in a significant partial response (PR) after just two cycles. Continued PR was observed after an additional six cycles, indicating the potential for a prolonged response with ongoing therapy. Genotyping and immunohistochemistry revealed that the sarcoma cells were rapidly dividing and enriched in vasculature prior to systemic treatment.Conclusion: These findings suggest that the combination of toripalimab and anlotinib may be an effective treatment option for advanced cases of UPS in the sinonasal region.

Background: Anti-TIF1γ-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. Objective: To report a unique case of parotid LEC emerging three years after a diagnosis of anti-TIF1γ-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. Case presentation: A 28-year-old male presented with anti-TIF1γ-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. Results: 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 CR2 (rs367567954), which encodes a receptor for EBV on B cells and may contribute to their aberrant activation. Conclusion: This case illustrates that refractory anti-TIF1γ-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.

Introduction: Dermatomyositis (DM), particularly the anti-TIF1γ‑positive subtype, is associated with a substantially elevated risk of malignancy. However, the peripheral immune landscape of this autoantibody-defined subset, especially in patients without concurrent cancer, remains incompletely understood. Methods: We performed single‑cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from five patients with anti‑TIF1γ‑positive DM (the subtype with the highest malignancy risk) and compared their profiles with those of two other DM subtypes: anti‑MDA5‑positive DM (intermediate malignancy risk) and anti‑synthetase syndrome (ASyS, low malignancy risk). Results: All three subtypes exhibited profound immune remodeling, characterized by reduced frequencies of cytotoxic lineage cells. Anti‑TIF1γ‑positive DM showed a compensatory shift toward humoral immunity, with increased B‑lineage cells, whereas classical monocyte elevation was specific to the anti‑MDA5‑positive DM and ASyS subtypes. Notably, anti‑TIF1γ‑positive DM was uniquely distinguished by an increased frequency of immunosuppressive regulatory T (Treg) cells, a finding validated by immunohistochemistry in patient skin tissue. Conclusion: These results delineate a peripheral immunological signature of anti‑TIF1γ‑positive DM, marked by compromised cytotoxic surveillance, aberrant humoral responses, and selective Treg enrichment. We hypothesize that this Treg elevation may contribute to an immunosuppressive milieu that favors malignancy, although this mechanism remains speculative and requires functional validation in prospective cohorts.