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BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Background: In this single‐arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first‐line chemotherapy. Methods: Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28‐day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR). Results: In total, 38 patients were enrolled. Of these, 35 patients were evaluable, and the ORR was 20% (95% confidence interval; [CI], 8%–37%). The disease control rate was 71%, and the median duration of response was 21.8 months (range, 7.6 to ≥43.3 months). The median progression free‐survival was 5.6 months (95% CI, 4.5–6.8 months), and the median overall survival was 27.5 months (95% CI, 20.4–34.6 months). Grade 3–4 adverse events occurred in 70% of patients, of which neutropenia was the most common (54%). Immune‐mediated adverse events occurred in five patients (14%; hypothyroidism, n = 3; hepatitis, n = 2). Patients who had a higher density of tumor‐infiltrating lymphocytes (greater than the median) exhibited better ORR (35% vs. 8%; p =.104), progression‐free survival (median, 7.3 vs. 3.3 months; p =.024), and overall survival (median, not reached vs. 21.5 months; p =.027). Conclusions: The combination of avelumab and gemcitabine demonstrated promising efficacy and manageable safety in patients with advanced LMS who progressed on first‐line therapy. Tumor‐infiltrating lymphocyte density may be an important factor in predicting the response to combining immunotherapy with chemotherapy. In this single‐arm, multicenter, phase 2 trial, the efficacy and safety of avelumab plus gemcitabine were evaluated as a second‐line treatment in patients with advanced leiomyosarcoma. The results indicated a 20% response rate with a durable median duration of response of 21.8 months, highlighting the potential of combining immunotherapy with chemotherapy for advanced leiomyosarcoma. [ABSTRACT FROM AUTHOR]