Discussion: Neurocutaneous melanocytosis (NCM) refers to a dysplasia of melanin producing neural crest-derived cells. This disease is a spectrum from proliferation of benign nevus cells to frank leptomeningeal melanoma. Melanoblasts arise in the neural crest and migrate to skin, ocular structures, inner ear, and leptomeninges.(1) Leptomeningeal melanocytosis probably arises from a proliferation of these cells. Of patients with leptomeningeal melanocytosis approximately 40-50% develop primary meningeal melanomas.(2)

NCM is usually sporadic, although autosomal dominant cases have been reported.(3) Leptomeningeal melanocytosis is described primarily in children while primary leptomeningeal presents in older age groups. In 220 cases reviewed by Allcut, the peak age of leptomeningeal melanoma was in the 4th decade.(4)

The proliferating cells in leptomeningeal melanocytosis may disrupt CSF flow dynamics and lead to hydrocephalus, particularly in children. Consequently presenting symptoms are often those of increased intracranial pressure including headache, vomiting, visual changes, and lethargy. Encasement of cranial nerves may produce multiple cranial neuropathies. As in metastatic melanoma, intra-tumoral hemorrhage is common.

As with most leptomeningeal processes MRI is the diagnostic imaging modality of choice.(5) MRI may be normal but often demonstrates meningeal thickening, studding, or meningeal-based mass lesions. The meningeal disease may have a characteristic increased signal intensity on uncontrasted T1-weighted images or decreased signal intensity on T2-weighted sequences reflecting the paramagnetic properties of mature melanin. In the case presented(Fig. 2), abnormal decreased T2 signal is visualized in the parietal lobe parenchyma. This is most likely due to paramagnetic effects of melanin in the adjacent pial infiltration. The lesions enhance following gadolinium administration.(6)

Although CSF samples may reveal elevated levels of 5-S-cysteinyldopa definitive diagnosis usually requires meningeal biopsy.(7) Histologic material reveals proliferation of pigmented cells.(4) Immunohistochemistry may be useful. The melanotic cells reveal cytoplasmic reactivity to melanoma specific antigen HMB45, neuron-specific enolase, and S-100.4.

The natural history of NCM is not well understood, in part due to the relative rarity of the disorder. In addition, as mentioned above, the disorder is a spectrum of melanocytic proliferative disease. Whereas diffuse leptomeningeal melanoma is probably rapidly fatal, it is unclear whether there are cases of leptomeningeal melanocytosis that are more indolent. In Allcuts series of eight children with leptomeningeal melanoma, survival times ranged from one to 54 months. Kiel reported a mean survival of 5 months.(4,8)

References:
1. Balmaceda CM et al. Nevus of ota and leptomeningeal melanocytic lesions.
Neurology 1993; 43:381-386.

2. Fox H. Neurocutaneous melanosis. In: Handbook of Clinical Neurology, Vinken PJ,
Brwyn EW (eds). New York: Elsevier 14(1972):414-428.

3. Rubenstein LJ. Neurocutaneous melanosis and primary meningeal melanomas, in
AFIP. Rubenstein LS (ed): Tumors of the Central Nervous System. 1972, 309-311.

4. Allcut D, Michowiz S, Weitzman S, et al. Primary leptomeningeal melanoma: An unusually aggressive tumor in
childhood. Neurosurg 1993; 44:175-176.

5. Fukui MB, Moltze CC, Kanal E, et al. MR imaging of the meninges. Part II.
Neoplastic Disease. Radiology 1996;201:605-612.

6. Poe et al. Neurocutaneous melanosis presenting as an intradural mass of the cervical
canal:Magnetic resonance features and the presence of melanin as a clue to diagnosis:
Case report. Neurosurg 1994; 35:741-743.

7. Kamu S et al. Measurement and cytologic demonstration of 5-5-cysteinyldopa for the
clinical diagnosis of primary leptomeningeal melanoma. Neurology 1994; 44:175-176.

8. Kiel FW et al. Primary melanoma of the spinal cord. J Neurosurg 1961;18:616-620.

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