Abstract

Cutaneous fibromyxoid neoplasms (CFMN) comprise a vast category of benign and malignant tumors that include, but are not limited to, low-grade fibromyxoid sarcoma, myxofibrosarcoma, myxoid DFSP, myxoid solitary fibrous tumor, and myxoid neurofibroma with differing implications for treatment and prognosis. Herein, we expand this growing list to include a yet unclassified CFMN in a 53 year-old female harboring a YAP1-TFE3 gene fusion. To date, the YAP1-TFE3 fusion has only been identified in a subset of epithelioid hemangioendotheliomas and clear cell stromal tumors of the lung. The patient presented with a painless, slow-growing, small, flesh-colored mass located on the left dorsal forearm which was surgically removed by local wide-excision. The mass was diagnosed as myxofibrosarcoma at the referral hospital. Histologic sections demonstrated a tumefactive lesion composed of copious amounts of myxoid material with banal spindle cells dissecting the collagen table. Focal perivascular accentuation of spindle cells was identified in the absence of vasoformative features. By immunohistochemistry, the lesional cells were strongly and diffusely positive for CD34, multifocally positive for Factor XIIIa and EMA and negative for CD31, ERG, FLI-1, D2-40, SMA, Desmin, S100, HMB-45, STAT6, MUC4, and cytokeratins. Whole transcriptome RNA-Seq identified a YAP1-TFE3 gene fusion. This finding was further corroborated by fluorescence in situ hybridization (FISH) showing rearrangement of the TFE3 Xp11.2 locus and strong and diffuse TFE3 immunoreactivity. In summary, this is the first report of a CFMN featuring a YAP1-TFE3 fusion. These results underscore the importance of expert consultations in evaluating difficult soft tissue lesions and the need for integrating valuable adjunctive platforms such as Next Generation Sequencing in routine clinical diagnostics. The clinical behavior of this novel entity remains to be fully characterized.

Financial Disclosure: No current or relevant financial relationships exist.