Recurrent PDGFRB-Mutations in the Epithelioid Variant of Fibrous Papules.
TL;DR
In summary, epithelioid fibrous papule is characterised by distinct morphologic features and harbours recurrent, activating PDGFRB mutations.
Abstract
Fibrous papule (FP) is a common benign dermal mesenchymal lesion presenting as a solitary, dome-shaped papule mostly located on the nose. The morphologic spectrum is broad, and a number of variants have been described, including hypercellular, clear cell, pigmented, pleomorphic, granular, inflammatory, and epithelioid. The latter is very rare. In the current study, we present a comprehensive morphologic, immunohistochemical, and molecular characterization of 16 additional cases of epithelioid fibrous papule (EFP). The cohort included 7 females and 9 males, with a median age at diagnosis of 42 years (range: 7 to 83 y). Anatomic distribution showed predilection for the head and neck region (n=14). Microscopically, all lesions presented as a dome-shaped, well-circumscribed dermal proliferation composed of epithelioid and spindle-shaped cells arranged in nests or individual units and embedded in an abundant eosinophilic stroma. Neoplastic cells displayed uniform morphology with abundant pale cytoplasm and medium-sized nuclei. Focal immunoreactivity for CD68 and CD163 was detected in 7 and 5 cases, respectively. Molecular analysis revealed pathogenic alterations in the PDGFRB gene in all 16 cases, including missense mutations p.Y562C (n=5), p.N666K (n=5), p.N666H (n=1), p.P584L (n=1), p.R562C (n=1), and p.V568A (n=1). One case each exhibited an in-frame deletion, p.R561_R565del and p.W566_S574delinsC, respectively. In summary, epithelioid fibrous papule is characterised by distinct morphologic features and harbours recurrent, activating PDGFRB mutations.