Recurrent Activating PDGFRB Mutations in Fibroblastic Connective Tissue Nevus

Fibroblastic connective tissue nevus is an uncommon benign cutaneous lesion first described in 2012. It is characterized by an irregularly disposed intradermal spindle cell proliferation and is sometimes associated with papillomatous epidermal hyperplasia and/or admixed adipose tissue. Fibroblastic connective tissue nevus shows some morphologic overlap with a second benign cutaneous lesion known as dermatomyofibroma, and some authors have speculated that the 2 lesions might represent a morphologic spectrum of a single entity. Recurrent activating mutations in the cell-surface receptor tyrosine kinase PDGFRB have recently been identified in dermatomyofibroma. Here, we identified similar recurrent activating PDGFRB mutations in fibroblastic connective tissue nevus, supporting the notion that the 2 lesions are indeed closely related. Direct comparison of the 2 lesions suggests that the most reliable distinguishing characteristics are the lesional architecture and immunoprofile. Whereas fibroblastic connective tissue nevus typically shows an irregular or haphazard architecture, dermatomyofibroma typically shows a horizontal band-like arrangement relative to the overlying epidermis. Immunohistochemically, fibroblastic connective tissue nevus shows frequent expression of CD34 with relative lack of SMA, while dermatomyofibroma shows frequent SMA expression with much less frequent CD34. These results provide insight into the relationship between fibroblastic connective tissue nevus and dermatomyofibroma, and place fibroblastic connective tissue nevus in the broader context of dermal spindle cell neoplasms characterized by activation of the PDGFB pathway.