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 7 additional cases of cutaneous ossifying plexiform tumors harboring a TNC::PDGFD fusion transcript. Four patients were female. Tumors were located on the nose (n = 2), hand (n = 2), forearm (n = 1), flank (n = 1), and foot (n = 1), with a median size of 6 (range, 4-9) mm. 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 the 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.