PA16 Uncharted territory: metastasizing atypical deep penetrating naevus/melanocytoma in a teenage patient

Abstract Deep penetrating naevi (DPN) are benign melanocytic lesions. Atypical DPN can rarely spread to lymph nodes with a fatal outcome. We present the only case, as far as we know, of paediatric metastatic atypical DPN. In 2021, a 14-year-old boy presented with a rapidly enlarging homogeneous naevus on his left cheek. This was clinically diagnosed as a blue naevus. He had no significant history of sun exposure or family history of atypical mole syndrome or cutaneous malignancies. The naevus was excised. Histopathology revealed an intradermal pigmented spindle cell melanocytic tumour with a cellular appearance. BRAF V600D and APC (beta-catenin pathway) mutations were identified. Preferentially expressed antigen in melanoma (PRAME) was negative and P16 was diffusely positive. Evidence of a high mitotic rate, cytological atypia and pleomorphism were noted, indicating the atypical nature of the naevus. A diagnosis of atypical DPN/melanocytoma was made and a wide local excision was performed. One year later he developed a submental swelling. Pathological lymph nodes were discovered on magnetic resonance imaging. Lymph node dissection revealed three nodes with metastatic melanocytic tumour-containing spindle-shaped pleomorphic cells with high mitotic activity and extensive areas of necrosis. PRAME was minimally positive and P16 positive. TERT mutation was positive in the lymph node and not in the original tissue sample, indicating progression. Whole-body imaging found no distant metastases. Our patient presented a unique and very difficult management challenge. Treatment similar to that of melanoma was commenced with pembrolizumab, which he completed without significant side-effects. The uncertainties of the long-term prognosis had a profound effect on his mental health. He is now in remission and remains under long-term follow-up with psychological support. A review by Cosgarea et al. found that of 48 patients with atypical DPN, five had positive lymph nodes. All of these five patients were adults. Of those five, four had local recurrence and three had metastatic disease (Cosgarea I, Griewank KG, Ungureanu L et al. Deep penetrating nevus and borderline-deep penetrating nevus: a literature review. Front Oncol 2020; 10: 837). The pathological findings usually associated with malignant variants of DPN are positive PRAME, complete loss of P16 expression and TERT promoter mutations (Ebbelaar CF, Schrader AMR, van Dijk M et al. Towards diagnostic criteria for malignant deep penetrating melanocytic tumors using single nucleotide polymorphism array and next-generation sequencing. Mod Pathol 2022; 35: 1110–20). Management of atypical DPN in children is particularly challenging given the rarity of presentation, histopathological diagnostic difficulties and absence of literature and guidelines for classification, management and risk stratification. Paediatric metastatic atypical DPN is not documented. Paediatric oncology supraspecialist MDT consensus was mandatory for management and support for our patient.