Recurrent TNC::PDGFD Fusions in Ossifying Plexiform Tumors of the Skin

PDGFB or, more rarely, PDGFD rearrangements are well-established oncogenic drivers of dermatofibrosarcoma protuberans (DFSP). Recently, a TNC::PDGFD fusion has been identified in a superficial spindle cell tumor distinct from DFSP but similar to the tumor entity described as ossifying plexiform tumors of the skin. Herein, we report seven additional cases of cutaneous ossifying plexiform tumors harboring TNC::PDGFD fusion transcript. Four patients were female. Tumors were located on the nose (n=2), hand (n=2), forearm (=1), flank (n=1), and foot (n=1) with a median size of 6 mm (range: 4-9). Microscopically, these neoplasms were located in the dermis (n=6) and subcutaneous tissues (n=1). All specimens exhibited a lobulated architecture and a biphasic appearance, characterized by the association of cellular areas composed of bland spindle cells with central regions of bone formation. Immunohistochemistry showed SATB2 positivity in all tested tumors (n=4). RNA sequencing analysis confirmed the presence of a TNC::PDGFD fusion transcript in all cases and revealed a transcriptomic profile that was distinct from other soft tissue tumors, including DFSP. Our findings support that TNC::PDGFD is the oncogenic driver of ossifying plexiform tumor of the skin, a rare tumor distinct from DFSP.