Updates on superficial mesenchymal neoplasms: emerging novel entities and an old foe revisited

Abstract

Understanding the molecular underpinnings of oncogenesis has led to an expansion of the spectrum of superficial mesenchymal neoplasms. The present review aims to provide an overview of the clinicopathologic and molecular characteristics of emerging entities with disease-defining molecular alterations. These include benign and indolent tumors such as hemangioma with epithelioid features harboring TPM3/4::ALK fusions, OGT-rearranged mesenchymal neoplasm, acral fibrochondromyxoid tumor, superficial FET::ETS neurocristic tumor, as well as hybrid peripheral nerve sheath tumors (hPNSTs), a subset of which harbor recurrent VGLL3 rearrangements or alternative rare and unique fusions. A concise review of the main characteristics of recently described biologically aggressive to overtly malignant tumors is also presented, including nodular necrotizing fibroblastic tumor, superficial GLI1-altered mesenchymal tumor, CRTC1::TRIM11 cutaneous tumor, and TFCP2-rearranged rhabdomyosarcoma. The review concludes with an update on dermatofibrosarcoma protuberans (DFSP). A subset of DFSPs harbor PDGFD rearrangements, and approximately 5% of both PDGFB- and PDGFD-rearranged DFSPs show S100 expression, which may pose a diagnostic challenge for practicing pathologists. These findings have further elucidated the molecular background and associated morphologic characteristics of superficial mesenchymal tumors, leading to the recognition of novel entities and further subclassification of existing ones, with important implications for diagnosis and patient management.