LAUSR

Neurocutaneous melanocytosis (NCM) is a rare neurocutaneous syndrome which typically develops in children with large congenital melanocytic nevi (LCMN) and excessive melanocyte proliferation in the leptomeninges and brain parenchyma. Malignant melanoma develops in an estimated 2.3% of patients with LCMN and 40-60% of patients with NCM. NCM-associated melanomas frequently harbor NRAS mutations with no well-established role for targeted therapy. In a retrospective, single-institution study, we reviewed eleven patients with NCM-associated CNS melanoma evaluated at Memorial Sloan Kettering Cancer Center from June 2000 to January 2020. Five patients had previously identified focal melanocytosis prior to developing melanoma. In this subgroup, the median time from identification of focal melanocytosis to melanoma diagnosis was 80 months (range: 18-200). Median age at melanoma diagnosis was 9.9 years (range: 1.1-25.3). Presentation at the time of diagnosis with CNS melanoma included headache (45%), focal deficits (45%), and seizure (18%). Eight patients had hydrocephalus (73%). Five patients presented with a focal mass (45%) and six patients had focal or diffuse leptomeningeal disease without a mass (55%). Leptomeningeal spread eventually developed in all patients. Where molecular testing was available, three melanomas had NRAS mutations and none were associated with BRAF mutations. Seven patients were treated with cancer-directed therapy including temozolomide, trametinib, ipilimumab, and nivolumab, with each therapy being administered to two patients. Radiation therapy was used in three patients, including whole brain radiation therapy and stereotactic radiosurgery. Median survival from melanoma diagnosis was 9.1 months (range: 1-60.4). The longest surviving patient was initially diagnosed with cutaneous melanoma, surviving 60.4 months after diagnosis with cutaneous melanoma and 22.7 months after diagnosis with CNS melanoma. Prognosis remains guarded in patients with NCM-associated melanoma, and further investigation is warranted to identify effective management strategies.