Melanoma In Situ Within a Congenital Nevus: A Rare Pediatric Case With Molecular Profiling

Summary: INTRODUCTION Pediatric cutaneous melanoma is exceptionally rare, accounting for only 1-3% of all pediatric malignancies. Melanoma in situ occurring within a congenital nevus is exceedingly uncommon and must be distinguished from benign junctional anomalies that can occur in pediatric nevi. CASE Clinical presentation: A 12-year-old female presenting with a 0.8 × 0.4 cm asymptomatic brown macule on the posterior shoulder (Figure A), present since birth. Clinical examination revealed an irregular pigment network. Her family history was significant for skin cancer, including melanoma. Histopathological examination of the biopsy showed a compound melanocytic proliferation with two distinct populations (Figure B). An atypical intraepidermal population of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and vesicular chromatin, showing prominent pagetoid scatter (Figure C). A subjacent infiltrate was present. An adjacent benign compound melanocytic nevus (Figure D). Dermal mitotic figures were absent. Immunohistochemical findings: Atypical intraepidermal melanocytes: Diffusely positive for PRAME (Figure G) with complete loss of p16 (Figure E) Adjacent nevus melanocytes: PRAME-negative (Figure H) with retained p16 (Figure F). NGS identified a BRAF V600E mutation and a CDKN2A inactivating mutation. Final diagnosis: Melanoma in situ arising within a congenital melanocytic nevus. DISCUSSION While most pediatric melanocytic lesions are benign, this case highlights the rare occurrence of true melanoma in situ in a child. Distinguishing benign junctional anomalies from melanoma in situ requires careful histopathologic evaluation, with PRAME and p16 immunohistochemistry serving as useful diagnostic adjuncts. Atypical junctional anomalies in congenital and early-onset acquired nevi can closely mimic melanoma in situ, displaying architectural asymmetry, irregular nests, pagetoid scatter, and lentiginous growth. Features to support benignancy include small, monomorphic melanocytes and absence of a dense inflammatory infiltrate. REFERENCE Barnhill RL. Childhood melanoma. Semin Diagn Pathol. 1998 Aug;15(3):189-94. PMID: 9711668. LeBoit, Phillip E. Histological Diagnosis of Nevi and Melanoma. Springer, 2014.