Fuentes Harry E, Suleiman Riham, Graham Rondell P, Villasboas Bisneto Jose C, Garcia Joaquin J, Halfdanarson Thorvardur R
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, United States.
Department of Pathology, Mayo Clinic, Rochester, MN 55905, United States.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyae333.
Sarcomatoid carcinomas (SC) are rare tumors with both epithelial and mesenchymal characteristics, linked to aggressive behavior and poor prognosis. Sarcomatoid carcinoma of unknown primary (SCUP) is an exceedingly rare subset with limited literature and no standardized management guidelines. This study aims to characterize the clinical presentations, treatment patterns, and genomic landscape of SCUP.
Data were retrospectively collected from the Mayo Clinic Rochester Cancer of Unknown Primary Registry. Patients included had biopsy-proven SC with no identifiable primary tumor despite comprehensive diagnostic evaluations. Baseline characteristics, immunohistochemistry (IHC) results, next-generation sequencing (NGS) data, and treatment outcomes were analyzed. Statistical analyses included descriptive statistics, Kaplan-Meier survival estimates, and Cox proportional hazards regression.
Fifty-two SCUP patients were identified, with a median age of 60 years. Most patients presented with widely metastatic disease, particularly lytic bone lesions. Elevated alkaline phosphatase (ALP) was noted in nearly half of the patients. IHC showed high positivity for AE1/AE3 and OSCAR antibodies. Tumor NGS revealed 247 alterations, with TP53 being the most common mutation. Patients receiving definitive therapy had a median overall survival (OS) of 72 months, significantly longer than those receiving systemic therapy (14 months). Immunotherapy was a significant prognostic factor, reducing the risk of death by 90%.
This study provides essential insights into the clinical and genomic characteristics of SCUP, advocating for the integration of definitive therapy and immunotherapy in treatment protocols. Further prospective studies are needed to validate these findings and improve patient outcomes.
肉瘤样癌（SC）是一种罕见的肿瘤，具有上皮和间充质特征，与侵袭性生物学行为和不良预后相关。原发灶不明的肉瘤样癌（SCUP）是一个极其罕见的亚组，相关文献有限，且没有标准化的管理指南。本研究旨在描述SCUP的临床表现、治疗模式和基因组特征。
数据回顾性收集自梅奥诊所罗切斯特原发灶不明癌症登记处。纳入的患者经活检证实为SC，尽管进行了全面的诊断评估，但仍未发现可识别的原发肿瘤。分析了基线特征、免疫组织化学（IHC）结果、二代测序（NGS）数据和治疗结果。统计分析包括描述性统计、Kaplan-Meier生存估计和Cox比例风险回归。
共确定了52例SCUP患者，中位年龄为60岁。大多数患者表现为广泛转移的疾病，尤其是溶骨性骨病变。近一半的患者碱性磷酸酶（ALP）升高。免疫组化显示AE1/AE3和OSCAR抗体呈高阳性。肿瘤二代测序揭示了247个改变，其中TP53是最常见的突变。接受确定性治疗的患者中位总生存期（OS）为72个月，显著长于接受全身治疗的患者（14个月）。免疫治疗是一个显著的预后因素，可将死亡风险降低90%。
本研究为SCUP的临床和基因组特征提供了重要见解，主张在治疗方案中整合确定性治疗和免疫治疗。需要进一步的前瞻性研究来验证这些发现并改善患者预后。
