Extraskeletal Myxoid Chondrosarcoma Mimicking Myoepithelial Tumor

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma defined by its characteristic multinodular myxoid architecture and distinctive clinicopathological features. Although EMC typically exhibits a multinodular myxoid architecture, its histologic variability and frequent immunophenotypic overlap with other myxoid tumors can make diagnosis challenging. We report a case of EMC arising around the left knee of a 73-year-old male patient. Histologically, the tumor exhibited abundant myxoid stroma with lace-like and haphazard cellular arrangements and focal epithelioid morphology. Immunohistochemically, the lesion showed diffuse positivity for several myoepithelial markers, including epithelial membrane antigen, α-smooth muscle actin, HHF35, calponin, and p63. However, the absence of cytokeratin and SOX10 expression raised diagnostic uncertainty despite the myoepithelial-like immunoprofile. Because immunohistochemistry remained inconclusive, targeted RNA sequencing was performed on formalin-fixed, paraffin-embedded tissue. A TAF15::NR4A3 fusion transcript was identified, leading to revision of the initial diagnosis to EMC. At 3-year follow-up, the patient remains free of recurrence or metastasis. This case demonstrates the potential for EMC to mimic myoepithelial tumors and supports the use of molecular analysis when histologic or immunohistochemical findings are insufficient for diagnosis.