An Atypical Deep Penetrating Nevus With Mutations in Beta Catenin , BRAFV600E , and IDH1R132C in an 8-Year-Old Boy

• Published in: The American journal of dermatopathology Vol. 44; no. 8; pp. 607 - 610
• Main Authors: Ireland, Amanda M., Wood, Benjamin A., Whitfield, Joseph, Amanuel, Benhur, Harvey, Nathan T., Mesbah Ardakani, Nima
• Format: Journal Article
• Language: English
• Published: United States The American Journal of Dermatopathology 01-08-2022
• Subjects: beta Catenin - genetics; Child; Humans; Male; Mutation; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented - pathology; Skin Neoplasms - genetics; Skin Neoplasms - pathology
• ISSN: 0193-1091; 1533-0311
• DOI: 10.1097/DAD.0000000000002198

Deep penetrating nevus (DPN) is a pigmented melanocytic tumor which typically displays a wedge-shaped deep penetrating architecture. Some cases show a coexisting component resembling conventional melanocytic nevus. These morphological attributes are correlated with the acquisition of genomic alterations in the Wnt pathway on a background of underlying activating MAPK pathway mutations. Lesions with features of DPN, but displaying expansile architecture, sheet-like arrangement of cells, cytological atypia, and/or more than rare mitotic activity have been described as "atypical deep penetrating nevus" or "deep penetrating melanocytoma." The molecular correlates of these atypical morphological features are not well-established. In this case report, we describe a tumor in an 8-year-old boy with histological features of atypical DPN showing somatic BRAFV600E , beta catenin , and IDH1R132C mutations. The combination of abnormalities in MAPK and Wnt pathways with IDH1 mutations seems to be a reproducible feature in a subset of atypical DPNs. Whether this "three-hit" combination is associated with a significant risk of adverse outcome remains to be established.