The skin knew first: A diagnostic chase for primary diffuse leptomeningeal melanocytosis

Abstract

Primary diffuse leptomeningeal melanocytosis (PDLM) is a rare and clinically aggressive primary tumor of the central nervous system that arises from leptomeningeal melanocytes. We report the case of a 38-year-old male presenting with subacute-onset headache, nausea, and vomiting, without focal neurological deficits. Magnetic Resonance Imaging (MRI) of the brain revealed diffuse leptomeningeal enhancement with cystic changes and mild ventriculomegaly. Despite an extensive infectious and inflammatory workup, no etiology was identified. Surgical biopsy during temporal craniotomy revealed a melanocytic neoplasm with atypical pigmented cells invading the cortex. Immunohistochemistry was positive for S100 and HMB-45, with a Ki-67 index of 7–8%, confirming the diagnosis of primary diffuse leptomeningeal melanocytosis. Whole-body 18F-fluorodeoxyglucose emission tomography (FDG-PET/ CT) excluded systemic melanoma, establishing the primary CNS origin. The patient underwent whole- brain radiotherapy and temozolomide-based chemotherapy but succumbed during treatment. This case underscores the diagnostic challenges of primary diffuse leptomeningeal melanocytosis, which mimics more common infectious or inflammatory meningitides. A high index of suspicion, especially in the presence of congenital melanocytic nevi and characteristic radiological findings, should prompt early tissue diagnosis. Given its rapid progression and dismal prognosis, prompt recognition is crucial for initiating timely intervention.