OVERVIEW: What every practitioner needs to know

Are you sure your patient has neurocutaneous melanosis? What are the typical findings for this disease?

Neurocutaneous melanosis (NM) is a congenital disorder that includes melanocytic lesions of the skin and leptomeninges. Children with NM are at risk for developing malignant melanoma.

Congenital nevi are benign melanocytic lesions which are found in approximately 2% of infants at birth. A nevus is considered a large or giant congenital nevus when an individual lesion is greater than 20 cm in diameter in adults or when many smaller lesions are greater than 2% of total body surface area. Nevi are typically covered with hair, and thus the term hairy nevi is also used. Giant nevi are usually bilateral, and can appear anywhere on the body. There are frequently also satellite nevi present. The most typical pattern is described as a ‘bathing-trunk’ or ‘garment’ pattern because of the distribution over the lumbar area and sacrum. Giant congenital nevi found together with melanosis in the leptomeninges of the brain is considered neurocutaneous melanosis (NM).

NM is a disorder thought to be caused by abnormal differentiation of neural crest cells, which leads to increased numbers of melanocytes in the leptomeninges, along with cutaneous melanosis. Note that, by definition, metastatic melanoma is a distinct entity from NM. However, there is an increased risk of melanoma in patients with NM, thus criteria have been developed to help categorize NM so as to help distinguish metastatic melanoma separately from NM with melanoma or metastatic melanoma.

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Diagnostic criteria for NM (as revised by Kadanoaga and Frieden, 1991):

1. One large congenital nevus (20cm or more in adults; 9cm on the head or 6cm on the trunk of an infant) or 3 or more smaller congenital nevi, together with either melanoma or melanosis of the meninges.

2. No cutaneous melanoma except when examined areas of meningeal lesions are benign.

3. No melanoma of the meninges except when examined areas of the cutaneous lesions are histologically benign.

NM can be asymptomatic apart from the skin findings, with the melanosis in the CNS found only on screening imaging. Neurological manifestations of the disease are variable and depend on the location and extent of CNS melanosis. The size and locations of the nevi do not seem to correlate with the presence of CNS involvement, although this is debated.

Neurologic manifestations typically occur during the first year, most commonly with symptoms of increased intracranial pressure and/or hydrocephalus. Another frequent presenting symptom is seizures.

What other disease/condition shares some of these symptoms?

The clinical diagnosis of nevi is typically straightforward due to the characteristic appearance of the nevus or nevi. Skin biopsy can confirm the diagnosis. If CNS lesions consistent with melanosis can be seen magnetic resonance imaging (MRI), then the diagnosis of NM can be made if metastatic melanoma is not present. Otherwise, there are few skin lesions which mimic giant nevi.

What caused this disease to develop at this time?

NM is a sporadic disorder resulting from abnormal migration of melanocytes during embryologic development. Melanocytes are normally present in the leptomeninges, which are derived from neuroectodermal tissue, and are normally concentrated at the base of the brain and cervical spinal cord. But it is not known what causes the abnormal proliferation or migration of the melanocytic tissues.

There are no known risk factors or genetic predisposition for NM.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Skin biopsies to rule out melanoma should be obtained if otherwise benign appearing nevi undergo suspicious changes.

Would imaging studies be helpful? If so, which ones?

Imaging of the brain or spinal cord is necessary to make the diagnosis of NM. In patient with giant congenital nevus, an MRI with contrast should be obtained of the brain and the entire spinal cord. While melanocytosis can typically be seen on non-contrast T1 imaging as a hyperintensity, contrast administration is needed to detect for any malignant transformation, which can be more difficult to detect radiologically unless it is extensive.

The most common CNS abnormality associated with NM is Dandy-Walker malformation, found in approximately 10% of children with NM. Patients with Dandy-Walker malformation and NM tend to have the poorest prognosis, and tend to die in the first decade of life.

If you are able to confirm that the patient has neurocutaneous melanosis, what treatment should be initiated?

For cosmetic reasons and due to the risk of malignant transformation of cutaneous lesions, some experts advocate complete resection of the nevi. This is controversial given the often extensive surgery which would be necessary. In addition, in patients with NM, cutaneous resection does not alter the risk of malignant transformation in the CNS.

Treatment for neurological manifestations should be directed at the specific cause of symptoms. A ventriculoperitoneal shunt may be necessary if there is increased intracranial pressure resulting in hydrocephalus. Depending on the size and location of any melanosis or melanoma, surgical resection may alleviate other neurological symptoms such as spinal cord compression.

In children with NM who have no symptoms, regular imaging of the CNS is necessary to follow the melanosis, assess for progression as well as malignant transformation. However, there are no set guidelines for imaging frequency. Likewise, regular dermatological evaluation for the cutaneous lesions is imperative.

If melanoma is already present, there is no effective treatment, and prognosis is extremely poor.

What are the adverse effects associated with each treatment option?

The adverse effects of any the treatments for NM are those which are inherent in the procedure itself, i.e. the surgical risks and complications of a ventriculoperitoneal shunt, and the presence of NM does not necessarily pose any additional risks to these procedures.

What are the possible outcomes of neurocutaneous melanosis?

There is an increased risk of malignancy due to cutaneous melanosis alone (with or without NM), although estimates vary dramatically. The risk appears to increase with the size or extent of coverage of the nevi. Multiple small congenital nevi seem to have a lifetime risk of melanoma of ~1%, while those with large or giant nevi (>20cm) have a lifetime risk of ~5% (Price and Schaffer, 2010).

Apart from the risk of malignancy, the prognosis of NM is highly variable, and counseling parents can be difficult. Some children will remain asymptomatic, with diagnosis known only because of screening due to congenital nevi. Those who become symptomatic during infancy do poorly, with the worst prognosis associated with Dandy-Walker malformation, typically due to compression of the brainstem due to posterior fossa cyst. Most children with NM and Dandy-Walker malformation die during the first decade of life. However, survival rates in many cases can be dramatically improved with timely surgical intervention, with morbidity determined by the specific location and extent of CNS involvement.

What causes this disease and how frequent is it?

NM is a rare sporadic disorder, affecting mostly Caucasians, with no gender predilection. There are fewer than 200 cases reported in the literature. Giant congenital nevi (without NM) are present in 1 in 20,000 children, and the risk of a child with a giant nevus to develop NM is estimated to be between 2 and 10%.

How do these pathogens/genes/exposures cause the disease?


Other clinical manifestations that might help with diagnosis and management


What complications might you expect from the disease or treatment of the disease?


Are additional laboratory studies available; even some that are not widely available?


How can neurocutaneous melanosis be prevented?

At this time there is no known way to prevent a child from being born with NM.

What is the evidence?

Due to the highly variable presentation of NM, there is no systematic or formal study evaluating the efficacy of management and treatment decisions. Treatments for CNS melanosis are designed for palliation of specific symptoms, and are highly specific to the size and location of the melanosis.

Kadonaga, JN, Frieden, IJ. “Neurocutaneous melanosis: definition and review of the literature”. J Am Acad Dermatol. vol. 24. 1991 May. pp. 747-55. (A review of all cases in the english literature from 1861 to 1989, which revealed less than 50 cases of definitive NM. The authors provide modified diagnostic criteria for NM.)

Price, HN, Schaffer, JV. “Congenital melanocytic nevi – when to worry and how to treat: Facts and controversies”. Clin Dermatol. vol. 28. 2010 May-Jun. pp. 293-302. (A thorough review and discussion of the work-up and treatment of congenital nevi (with or without NM), with a short section specifically on NM.)

Ongoing controversies regarding etiology, diagnosis, treatment