Neurocutaneous Melanosis

Fernando Burstein M.D., Hisham Seify M.D., Luis Zapiach M.D.

From the center for craniofacial disorders at the Scottish Rite Children’s Medical Center

and the division of Plastic and reconstructive Surgery Emory University.

Abstract:

 Neurocutaneous melanosis (NCM) is a rare phakomatosis characterized by a focal or

diffuse proliferation of melanin-producing cells in both the skin and the leptomeninges.

This syndrome is believed to result from an error in the morphogenesis of embryonal

neuroectoderm. Two-thirds of patients with NCM have giant congenital melanocytic

nevi, and the remaining one-third have numerous lesions but no giant lesions. Most

patients present with neurological manifestations early in life, which can be secondary to

intracranial hemorrhages, impairment of cerebrospinal fluid circulation, or malignant

transformation of the melanocytes.

The prognosis of patients with symptomatic neurocutaneous melanosis is extremely poor,

even in the absence of malignancy. Chemotherapy has been ineffective in the few

patients in whom it has been tried.

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Introduction:

Neurocutaneous melanosis (NCM) is a rare phakomatosis (Greek for "birthmark" or "spot”) characterized

by pigmented nevi that are large or multiple or both, and leptomeningeal melanosis or melanoma, without

evidence of malignancy in the skin lesions, and without involvement of nonmeningeal organs. Most cases

are sporadic, and no sex or racial predilection is evident.

In 1861, Rokitansky first described the condition in a 14-year-old girl, which was characterized by the

presence of a large congenital melanocytic nevi and benign melanotic tumors of the leptomeninges. Van

Bogaert first coined the term neurocutaneous melanosis in 1948. (1, 2)

First Fox in 1972(3) and later Kadonaga and Frieden in 1991(1) proposed criteria for the diagnosis of this

lesion:

1-The presence of large or multiple congenital melanocytic nevi (one of which is at least 20-cm in

diameter) with benign (melanosis) or malignant (melanoma) CNS tumors.

2-The absence of malignant melanoma in any organ (including skin) other than CNS.

The disease may be associated with another neurocutaneous syndrome such as Sturge-Weber or von

Recklinghausen’s disease. Associations were also reported with the Dandy-Walker complex, spinal

lipoma, and arachnoid cyst. (4, 5)

Embryology:

Although the origin of the meninges is debated, they are thought to develop from

mesenchyme derived from mesoderm and/or mesectoderm. These tissues are derived

from the neural crest and contribute to the pia mater of the occipital part of the hindbrain.

Because melanocytes of both skin and leptomeninges are thought to be derived from

multipotential precursor cells of the neural crest, neurocutaneous melanosis is postulated

to represent a congenital error in the morphogenesis of the embryonic neuroectoderm.

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Histopathology:

Neuropathological examination shows that leptomeningeal melanosis predominates over the convexities,

the base of the brain, the anterior surface of the brainstem, and the upper cervical and lumbosacral spinal

cord. These areas may have macroscopic pigmentation in physiological conditions. Associated

developmental CNS malformations, such as arachnoid cysts, intraspinal lipoma, syringohydromyelia,

and vertebral deficits, have been reported in association with neurocutaneous melanosis.

Histopathologic examination of the lesion shows accumulation of melanotic cells in the basal arachnoidea

and pia mater of the ventral surface of the mesencephalon, pons, medulla, cerebellum, upper cervical

and/or lumbosacral spinal chord, resulting in leptomeningeal melanosis. Presence of melanocytosis in CSF

makes leptomeningeal involvement likely. Parenchymal melanin deposits probably represent melanocytes

in the perivascular spaces. The anterior temporal lobes, and particularly the amygdala, seem to be the most

frequent locations for parenchymal melanocytic accumulation. Other preferential sites include the

cerebellum, thalami, and the base of the frontal lobe .(6,7,8,9)

Clinical Manifestations:

CNS involvement may be suspected in patients with lethargy, seizures, vomiting, or signs suggestive of

raised intracranial pressure secondary to hydrocephalus. Moreover, cranial nerve palsies are frequently

associated. Further, syringomyelia, spinal arachnoiditis, and subdural and/or parenchymal hemorrhages

complicate the clinical presentation . Hydrocephalus occurs in the majority of patients, secondary to

meningeal thickening from CSF outflow obstruction or decreased CSF resorption. (10, 11,12)

Imaging:

The characteristic finding in the diagnosis of leptomeningeal melanosis or parenchymal melanin deposits

is T1 shortening on MRI. This is often ascribed to the paramagnetic metal scavenging of melanoma

cells resulting in a spontaneous high signal of melanin on T1-weighted images. Other authors attribute

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T1 shortening to paramagnetic free radicals known to occur in melanin. Leptomeningeal en-

hancement in cases of absent T1 shortening also indicates leptomeningeal melanosis . According

to Barkovich, the absence of meningeal enhancement does not exclude the diagnosis of neurocutaneous

melanosis . (13)

There are reports of MR-revealed neurocutaneous melanosis without detectable leptomeningeal

melanosis but with temporal lobe malignant melanoma . Eaves et al (14) suggests that primary

brain melanoma without diffuse leptomeningeal involvement in patients with giant intradermal nevi

is a variant of neurocutaneous melanosis. The development of hydrocephalus, however, makes

leptomeningeal involvement probable. Differentiation between benign and malignant parenchymal

melanocytosis on MR is difficult. Necrosis, edema, and hemorrhage are suggestive of malignancy, but can

be absent in malignant melanomas. Leptomeningeal enhancement is not pathognomonic for

leptomeningeal melanosis, and can be seen in infectious or malignant processes of the CNS. Again, it is

not possible to differentiate benign from malignant leptomeningeal melanosis with MR imaging.

Subsequently, follow-up with serial neurologic examination and imaging studies is advised. Surgical

intervention must be considered only if evidence of progression is documented. Ultimately, the prognosis

is poor once CNS symptoms occur. (15,16,17,18)

Prognosis:

The risk for patients with LCMN of developing manifest NCM is not known but patients

with such nevi located on the head, posterior neck, and/or paravertebral area seem to have

the highest risk. DeDavid et al (11) reviewed 289 cases of LCMN and found that 33

(12%) had developed manifest NCM. CNS melanomas occurred in 21 of the 33 patients

(64%) with manifest NCM. Furthermore, all 33 patients with NCM had their large nevi in

axial locations (cephalic, posterior cervical, and paravertebral), and of the 31 patients for

whom the presence or absence of satellites was known, all had satellite nevi.Neurologic

signs and symptoms usually develop by age 5, rarely in late adulthood. Neurologic

symptoms are indicator of poor prognosis …thin 3 years of onset neurological

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References:

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nevi, neurocutaneous melanosis and neurological alterations. Dermatology. 1997;195:125-128

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