Neurocutaneous melanosis (NCM) is a nonfamilial congenital neurocutaneous syndrome characterized by melanocytic nevi and excessive proliferation of melanocytes within the CNS (5). This rare condition, estimated to occur in less than 1 in 20,000 newborns, is believed to be an embryologic defect in the migration of melanoblasts from the neural crest to the leptomeninges and the skin (5). Since its first description by Rokitansky in 1861 (7), about 100 patients have been reported (6). NCM can be associated with a large spectrum of neurologic symptoms, which vary with age (5, 6). The most common initial clinical signs and symptoms are related to increased intracranial pressure, including seizures (48%), vomiting (40%), headache (35%), cranial nerve palsies (26%, papilledema (10%), and meningeal signs (3%). Some children also develop signs of spinal cord and root involvement and myelopathy. Conversely, patients with later onset usually show localized sensorimotor deficits, difficulties with speech, or psychiatric symptoms (5, 6). CNS melanoma develops in about 50%.
The diagnosis of NCM should be strongly suspected in patients with large pigmented nevi or small multiple hairy dark nevi, usually over the neck, trunk, or the back (5). The main differential diagnosis is with metastatic melanoma of the skin with brain metastases, primary malignant leptomeningeal melanoma, benign melanotic neuroectodermal tumors, melanocytic nerve sheath tumor (nevus of Ota), and melanotic nevus of Scheiden (5, 6). Neuroimaging is of great importance for a correct diagnosis. In fact, as melanin pigment is inherently paramagnetic, the typical NCM lesions usually exhibit high intensity on T1-weighted MR images and low intensity to isointensity on T2-weighted images (2). This pattern of parenchymal melanosis is most evident and frequent at the uncus and adjacent temporal cortex.
Our patient had a clinical diagnosis of drug-resistant temporal lobe epilepsy caused by histologically proven NCM. Such cases, are rarely reported in literature (1, 4, 8) and NCM should be therefore listed among the possible causes of chronic partial epilepsy. In this patient, the post-surgery pathological study revealed that the lesion was composed of melanin-containing polygonal cells arranged in solid alveolar or multiple lobular patterns. The histological and immunohistochemical features of the cells are consistent with those of melanocytes (3). The perivascular infiltrations of the Virchow-Robin spaces of brain tissue with melanocytes are also a typical histological hallmark of NCM (5, 6). Although distinguishing between benign proliferative melanosis and invasive malignant melanoma can be difficult, a confirmation of benign noninvasive disease in our patient is supported by lack of necrosis, cellular atypia, or excessive mitotic activity. Furthermore, melanoma can be differentiated from melanocytosis by immunohistochemical labelling of proliferation-associated antigens such as Ki-67 (3, 6). Finally, the absence of dysmorphic neurons is consistent with the view that etiologically the lesion represents a developmental malformation involving neural crest-derived and neuroepithelial cells (6).
The prognosis of NCM is variable but usually poor, sometimes even in absence of malignancy. More than 50% of patients die within 3 years after the neurologic presentation, generally due to increased intracranial pressure. In particular, the association of Dandy-Walker syndrome has an extremely bleak prognosis (5, 6). Chemotherapy and radiotherapy have little effect on the disease course in case of malignant leptomeningeal involvement. The efficacy of prophylactic resection of dermal lesions to reduce the risk of malignancy is uncertain (6). Our patient showed surgically successful removal of the epileptogenic lesion, confirm that resection should be seriously considered for treatment of this type of lesion.
Contributed by Pasquale Striano, Alessandro Consales , Mariasavina Severino, Giulia Prato, Corrado Occella, Andrea Rossi, Armando Cama, Paolo Nozza , Maria Giuseppina Baglietto