Track

Clinical Studies

Abstract

Desmoplastic (sclerotic) nevi (DN) are dermal proliferations of melanocytes within a sclerotic stroma. Although once considered a subtype of Spitz nevus, they are now regarded as a distinct entity. This study expands the molecular characterization of DN and aids distinguishing it from other sclerotic-dermal lesions, e.g., dermatofibroma, hypopigmented blue nevus, and desmoplastic melanoma. We reviewed the clinicopathologic features and performed molecular testing on 10 DN cases using massively parallel sequencing with the PGDx Elio Tissue Complete platform targeting 505 cancer-related genes. The average age was 38.7 years, with a 1:1 male-to-female ratio and an average lesion size of 5 mm. Clinically, lesions presented as pink, flesh-colored, or brown papules involving the lower extremity (4), upper extremity (3), and trunk (3). Histologically, all cases showed dense sclerotic stroma; in most, dermal melanocytes formed two populations: small nests of epithelioid cells in the upper reticular dermis and singly arranged spindle cells in the deep reticular dermis. Junctional nests were present in 5 cases. Nuclear atypia was observed in 2 cases. HMB45 showed stratified expression in 6/6; p16 was preserved in 5/5. Molecular testing failed in 4 cases; 2 were negative, and 4 harbored variants of potential clinical significance. All cases had low tumor mutation burden, except one (20 mut/Mb). Alterations identified included GNA11 p.L232F; AXIN1 p.E355G; ATRX p.L1284F with TP53 p.R282W; and ERBB4 p.E996K with NTRK1 p.D270N. All were negative for common MAPK pathway mutations seen in conventional nevi (e.g., BRAF, NRAS) and showed no recurrent alterations.