Etmr-21. Primary Diffuse Leptomeningeal Melanomatosis (Pdlm) Associated With Intracranial Bleeding and Rapid Progression in a Child

Abstract BACKGROUND PDLM is a rare and aggressive disease with limited cases reported worldwide and few cases in the pediatric population. Herein we report on clinical, histologic, and molecular/genetic findings of a young child with PDLM and rapid clinical progression. CASE STUDY A 12-year-old right-handed male presented with two months of intermittent fevers, progressive frontal headaches, lethargy, vomiting, and weight loss, and one month of focal seizures with altered awareness, speech arrest, eye deviation, and tonic posturing. Examination revealed bilateral papilledema and signs of increased intracranial pressure. A brain CT demonstrated increased density of the anterosuperior right frontal lobe and punctate focus of increased density along the left frontal lobe suggestive of hemorrhage. MRI revealed diffuse leptomeningeal thickening and enhancement throughout the brain and spinal cord. At biopsy, the frontal lesion was noted to be grossly abnormal and discolored, and on pathology demonstrated a melanocytic neoplasm infiltrating the subarachnoid space and extending into Virchow-Robin spaces. Tumor cells stained strongly for HMB45, vimentin, Melan-A, and PRAME and were BRAFV600E negative. RNA sequencing was negative for structural variants, Whole exome sequencing revealed a Tier I missense variant in NRAS (c.181CA) among other copy number variations and loss of heterozygosity. Comprehensive ophthalmologic and dermatologic examinations as well as whole body PET/CT did not reveal any other sites of disease. He was due to commence immunotherapy with combination PD-1/CTLA-4 inhibitors but developed status epilepticus and raised intracranial pressure, warranting ventriculoperitoneal shunt insertion. Three days later, he had further deterioration with altered level of consciousness, hypertension, eye deviation, and vomiting. CT brain revealed large bifrontal hematomas with mass effect and care was redirected to palliation. CONCLUSION PDLM can be challenging to diagnose with a rapidly progressive course. Advanced molecular diagnostics may provide new targets for precision therapy, though overall outcomes remain dismal.