Assessing the Utility of DNA Methylation Profiling in the Classification of Myogenic Sarcomas of Bone

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.