Abstract:

Neurocutaneous melanosis (NCM) is a rare neurological disorder involving accumulation of melanin within the central nervous system. Melanocytic tumors and leptomeningeal involvement are known causes of morbidity and mortality from NCM. We report a rare case of a 2-year old girl with NCM who presented with neuroregression, seizures, and persistent hydrocephalus secondary to malignant transformation. This patient was diagnosed with congenital melanocytic naevi at birth with extensive lesions along her face, scalp, bilateral upper and lower limbs, as well as giant melanocytic nevus extending from her abdomen to perineum and lower limbs. At 2 years of age, she presented with progressive neuroregression over 1 month: she became unable to sit up, walk, or speak. On the day of admission, she developed vomiting, lethargy, with an episode of afebrile status epilepticus. After initial stabilization, magnetic resonance imaging (MRI) brain showed significant communicating hydrocephalus. Further scans revealed multiple areas of cord compression with leptomeningeal enhancement along the cord at the levels of T1 and T6-7. Cerebrospinal fluid (CSF) cytology was suggestive of melanoma involvement. Biopsy taken from the soft tissue at T7 level uncovered a biphenotypic neoplasm comprising of melanoma and undifferentiated neuroblastoma, with pathogenic NRAS p.Gln61Arg mutation seen in melanoma.

The patient was further evaluated with a computed tomography (CT) scan of her chest, abdomen, and pelvis showing extensive metastases involving bilateral pulmonary nodules and retroperitoneal soft tissue infiltration. Her disease then progressed rapidly over the course of a few weeks with worsening hydrocephalus despite regular CSF tapping from her Rickham’s reservoir as well as a new development of cerebral venous sinus thrombosis. Repeat MRI spine showed worsening of nodular leptomeningeal enhancement of the entire cervical spine with complete effacement of the CSF in the cervical spinal canal and compression of almost the entire cord. A ventriculoperitoneal shunt was subsequently inserted and she was started on targeted therapy with Trametinib and Azacitidine. She is planned for reassessment scans after 2 weeks of treatment.

We presented a rare case of symptomatic NCM with subsequent malignant transformation and spinal metastasis with resultant neurological decline. To our knowledge, this is the only case in paediatric and adult literature with a biphenotypic neoplasm comprising melanoma and undifferentiated neuroblastoma. Neuroblastomas being a paediatric cancer originating from neural crest cells, has a distinct phenotype from melanocytic proliferations. The co-existence of both cancers has not been captured in literature likely due to their extreme rarity. Neurological symptoms largely depend on the site of the lesion, which include seizures, headaches, cranial neuropathies, hydrocephalus, cord compression, and developmental regression. Careful clinical and histopathological evaluations are necessary to distinguish between NCM versus malignancy. Although mortality due to severe raised intracranial pressure from NCM is possible, malignant transformation confers a worse prognosis with demise within 3 years of symptom onset. Multimodal therapy including surgical resection, irradiation, targeted therapy or immunotherapy have been utilised, most with little success. Further studies of patients with NCM and its malignant transformations would be useful to characterize this unique cohort.