Bandhlish Anshu, Liu Yajuan J, Fang He, Gandhi Jatin, Paulson Vera, Chen Eleanor Y
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Int J Surg Pathol. 2025 Jan 7:10668969241300497. doi: 10.1177/10668969241300497.
The diagnosis of primary leiomyosarcoma (LMS) of bone is generally established based on integrative findings of morphologic features, immunohistochemical staining, and clinical and radiological findings. There are no specific genetic alterations that can be used to confirm the diagnosis of LMS in challenging diagnoses of bone sarcomas with myogenic differentiation. In this study, we assessed the utility of a DNA methylation-based classifier as an ancillary diagnostic tool for subclassifying bone sarcomas with myogenic differentiation. DNA methylation profiling using the Deutsches Krebsforschungszentrum classifier system was performed on 5 patients with available formalin-fixed paraffin-embedded tissue blocks. The original diagnosis of LMS was retained in 2 of 5 patients. Three patients were reclassified as having malignant giant cell tumor of the bone, malignant peripheral nerve sheath tumor, or undifferentiated pleomorphic sarcoma/myxofibrosarcoma after integrating the results of the DNA methylation-based classifier with the clinicopathologic, immunohistochemical, and radiologic findings. While a DNA methylation-based classifier can serve as a useful ancillary tool for refining the subclassification of primary bone sarcomas with myogenic differentiation, especially for diagnostically challenging tumors, integrating clinical, histopathological, and radiological findings is essential for obtaining a final diagnosis.
骨原发性平滑肌肉瘤（LMS）的诊断通常基于形态学特征、免疫组化染色以及临床和影像学检查结果的综合判断。在具有肌源性分化的骨肉瘤诊断存在挑战时，尚无特定的基因改变可用于确诊LMS。在本研究中，我们评估了基于DNA甲基化的分类器作为辅助诊断工具对具有肌源性分化的骨肉瘤进行亚分类的效用。使用德国癌症研究中心分类系统对5例有可用福尔马林固定石蜡包埋组织块的患者进行了DNA甲基化分析。5例患者中有2例维持原LMS诊断。将基于DNA甲基化的分类器结果与临床病理、免疫组化和影像学检查结果相结合后，3例患者被重新分类为骨恶性巨细胞瘤、恶性外周神经鞘瘤或未分化多形性肉瘤/黏液纤维肉瘤。虽然基于DNA甲基化的分类器可作为有用的辅助工具，用于完善具有肌源性分化的原发性骨肉瘤的亚分类，尤其是对于诊断具有挑战性的肿瘤，但综合临床、组织病理学和影像学检查结果对于获得最终诊断至关重要。
