Comprehensive Genomic Profiling In Malignant Myoepithelioma To Suggest Potential Alternative Diagnosis.

e23530 Background: Malignant myoepithelioma of soft tissue (MM) is a rare tumor affecting patients (pts) of any age without sex predilection. MM has varied histopathologic findings, with epithelioid and spindle components and differentiation along osseous, chondroid or other lineages. Morphologic features suggest MM, however histologic overlap with other lesions exists. Diagnosis requires ancillary immunohistochemical &/or molecular studies; EWSR1 rearrangement with various fusion partners has been reported. Clinical behavior is varied and poorly understood due to disease rarity. Here, we undertook comprehensive genomic profiling (CGP) of MM to evaluate for potential targetable molecular alterations and report clinical outcomes. Methods: We identified pts with MM treated at University of Michigan (UM) from 2000-2017, obtained clinical data and reviewed pathology on 10 available samples and performed integrative sequencing through Michigan Oncology Sequencing Program (MI-ONCOSEQ) on 6. For 31 additional FFPE samples, hybrid capture-based DNA CGP (n = 16) or DNA+RNA CGP (n = 15) was performed (Foundation Medicine, FM). Results: 13 pts were treated at UM; median age at diagnosis was 52 (22-88) with male predominance (9/13). Primary tumor size was 3 cm (2-9.5) and most common location was trunk (4/13) and extremity (3/13). Four pts with metastatic disease (mets) underwent systemic chemotherapy with 0 responses. Median progression free and overall survival in mets was 20 (5-75) and 57 (12-91) months, respectively. CGP analyses of all samples (Table) revealed EWSR1 rearrangement in 8.1% (3/37) and presence of PHF1-TFE3 and CIC:DUX4 rearrangements in 16% (6/37). Independent blinded histopathology review of whole slides and tissue is underway. Conclusions: MM is a rare malignancy with variable clinical course. In our series, pts with mets derived little benefit from systemic therapy. CGP revealed CDKN2A/B alteration as the most prevalent with few harboring EWSR1 rearrangement. PHF1-TFE3 was recently described in ossifying fibromyxoid tumor (OFMT) that may represent a subset of OFMT not yet expressing bone markers. The presence of hypermutation and CIC:DUX4 fusions also suggests potential alternate diagnosis. These results indicate that CGP could complement histopathologic evaluation to aid in diagnoses and treatment of this entity. [Table: see text]