Abstract

While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance in primary cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histology that are difficult to classify based on morphology. Herein, we report a heterogenous group of 13 cases of primary cutaneous and superficial mesenchymal and adnexal neoplasms, each driven by a recurrent fusion which led to more definitive diagnostic classification. Thirteen cases occurred in 7 female and 6 male patients, with a median age of 16 years (range: 1-83) at diagnosis. Tumors involved the extremities (7), scalp (5) and head and neck (1). Predominant features included myoepithelial (4), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (2) and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (3) with LIFR (2), TRPS1 (1). Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 and a novel fusion ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), myoepithelioma (4), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (1), clear cell sarcoma (2) and angiomatoid fibrous histiocytoma (1). Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Further, it can allow for identification of potential therapeutic targets in some instances.