Deep‐penetrating‐nevus‐like melanoma arising in patients with familial adenomatous polyposis syndrome

Abstract

Deep penetrating nevi (DPN) are uncommon but distinctive melanocytic neoplasms that show an epithelioid to spindle cell morphology, prominent pigmentation with melanophages, and a plexiform growth pattern. Molecularly, most DPN are thought to be characterized by dual activation of the mitogen‐activated protein kinase and the wingless‐related integration site (Wnt) pathways, the latter being most commonly driven by activating β‐catenin mutations. DPN‐like melanomas are very rare but can be recognized through their overlapping morphologic and architectural features with DPN. Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome associated with multiple tumor types including colorectal carcinoma and desmoid fibromatosis. Like DPN, FAP is also driven by activation of the Wnt pathway, most commonly through loss of function mutations in APC, which is a major negative regulator of β‐catenin. Here we report two cases of DPN‐like melanoma arising in FAP patients. While the small number of cases precludes definitive establishment of an etiologic link between these entities, the shared molecular pathogenesis of DPN‐like lesions and FAP suggests that FAP patients may be at increased risk for this rare subtype of melanoma.