Are You Confident of the Diagnosis?

Neurocutaneous melanosis (NCM) is a rare congenital syndrome characterized by the presence of congenital melanocytic nevi and melanosis within the central nervous system, most commonly involving leptomeninges but in some cases involving the brain parenchyma. NCM is present at birth and is not the result of metastatic spread from a primary cutaneous melanoma. It may be asymptomatic or (in a minority of patients) cause neurologic signs and symptoms even resulting in death due to either malignant change (ie, melanoma) or space-occupying effects from the proliferation of “benign” melanocytes within the closed space of the central nervous system.

Characteristic findings on physical examination

The diagnosis of NCM should be considered in any neonate or child who has a large cutaneous melanocytic nevus (typically defined as one that is projected to be greater then 20 cm in largest diameter in adulthood: (Figure 1). NCM can also occur in the setting of multiple (>3) congenital melanocytic nevi without the presence of a large or giant nevus.

Figure 1.

Large or giant congenital melanocytic nevus.

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Clinical suspicion for NCM increases if there are multiple “satellite” nevi or if neurologic signs or symptoms are present in the setting of a large congenital melanocytic nevus. In most cases, the large melanocytic nevi involved in the setting of NCM are located in a “bathing trunk” or occipital/cervical, “cape-like” distribution (Figure 2) . Posterior axial location is an additional risk factor for NCM (Figure 3). An increased number of satellite nevi is more predictive of NCM risk than size or location (Figure 4, Figure 5) and multiple intermediate sized congenital nevi (>3) may convey higher risk then the presence of one large CMN (Figure 6).

Figure 2.

“Cape-like” large congenital melanocytic nevus.

Figure 3.

Large or giant congenital melanocytic nevus in the posterior axis.

Figure 4.

“Satellite” nevi associated with large congenital melanocytic nevi.

Figure 5.

Congenital nevi on the posterior lower legs. Number of “satellite” congenital melanocytic nevi are the greatest predictor of NCM.

Figure 6.

Multiple intermediate congenital melanocytic nevi.

The “melanosis” that occurs in NCM refers to an excess of melanotic cells in the meninges that may be nodular or diffuse. This melanosis occurs in the locations of the brain or spinal cord that may have macroscopic pigmentation normally. These sites include the convexities or base of the brain, ventral surfaces of the pons, medulla, and upper cervical or lumbosacral spinal cord. It is the extent of melanocytic infiltration by these normally quiescent melanocytic cells that is pathologic. Mass effects related to the proliferation of these cells can lead to the clinical complications of NCM.

Based on the presence or absence of clinical signs and/or symptoms, NCM can be divided into asymptomatic and symptomatic forms. The prognosis for symptomatic NCM is poor. The prognosis for asymptomatic patients (whose NCM is usually discovered through screening) is difficult to predict, but likely analogous to cutaneous disease in that only a minority of patients will go on to develop progressive CNS disease (eg, melanoma or proliferation leading to symptoms).

Neurologic symptoms are usually present within the first 5 years of life and most often occur before 2 years of age, with approximately 50% of patients who have central nervous system-related clinical manifestations presenting within the first year of life. Rarely symptoms can present in the second or even third decade of life.

Symptoms of NCM in infants are usually related to increased intracranial pressure due to mass effect on the ventricular flows, which can result in hydrocephalus, seizures, cranial nerve palsy (particularly related to cranial nerve VI). More general signs and symptoms of increased intracranial pressure include irritability, lethargy, headache, recurrent vomiting, generalized seizures, increased head circumference, bulging anterior fontanelle, photophobia, papilledema and neck stiffness. Physicians should monitor for changes head circumference or other signs/symptoms of increased intracranial pressure in NCM patients regularly in infancy and early childhood. More subtle presentations can occur as well, so patients who are found to have NCM when screening is done should have a baseline evaluation and regular follow up by neurology. In one study the authors described mild to minimal motor deficits, nerve dysfunction and impaired mental status in patients thought to be asymptomatic before thorough examination.

In a patient with known NCM, any new onset neurologic sign or symptom must be investigated thoroughly. Evaluations should include repeat magnetic resonance imaging (MRI) with contrast (contrast is not usually necessary for baseline studies to establish the diagnosis but is to evaluate new symptoms), and evaluation of cerebrospinal fluid (CSF) fluid via lumbar puncture. Findings in the CSF in this setting typically include an elevated protein level with normal glucose and a sterile leukocytosis. A yellow discoloration of the CSF may occur secondary to melanin granules; and the CSF in patients with NCM may even reveal melanoctyes of a benign, or in the setting of NCM related melanoma, malignant nature.

Structural abnormalities of the central nervous system (CNS) can also be associated NCM and can even be detected on prenatal ultrasound. Several patients with NCM have been reported to have the Dandy Walker complex. Other associated malformations of the CNS are discussed below. Patients manifesting structural abnormalities in association with NCM are more likely to become symptomatic.

A subset of NCM patients becomes symptomatic later in childhood. Often this occurs around 7-10 years of age or early in puberty. This subset of patients often tend to have symptoms and signs associated with intracranial mass lesions and spinal cord compression; they may exhibit psychiatric symptoms, expressive aphasia, dysarthria, focal seizures, paraplegia or localizing sensorimotor changes. Physicians should screen for these symptoms in older NCM patients as well, as there are rare reports of patients who do not manifest NCM related symptoms until the second or third decades

The onset of neurologic symptoms can also serve as a “red flag” indicating the development of CNS melanoma, which underlies approximately half of cases of overtly symptomatic NCM. In this setting, the clinician should consider also consider the possibility of metastasis from a primary cutaneous melanoma. Any worrisome skin findings; in particular new, firm subcutaneous nodules or ulcerated papules or nodules within CMN; should be biopsied for histologic evaluation.

However, the weight of evidence suggests that, in patients with LCMN and NCM, symptomatic CNS disease stemming from NCM in the brain is a much more common morbidity then the development of primary cutaneous melanomas. Cutaneous melanoma is rare even in large or giant CMN. It is exceedingly rare in small or intermediate congenital melanocytic nevi. Most melanomas that manifest within this setting occur within the LCMN (not in satellites) and at an early age (in one retrospective study 89% of melanomas in LCMN occurred before the age of 30)

Expected results of diagnostic studies

The diagnosis of NCM in a patient with CMN is typically made via MRI of the brain and spinal cord (Figure 7).

Figure 7.

MRI imaging. Left image: Arrows show high T1 signal in the amygdala bilaterally Right image: Arrows show high T1 signal along the surface of the cerebellum and in the pons.

When screening for NCM in an asymptomatic patient, the study can be done without contrast for evaluation of the brain and spinal cord. However, in older patients whose brain have undergone myelinization (occurs around 4-5 months), contrast may help visualize areas of melanosis. The most characteristic findings of NCM on MR imaging are focal T1 or T2 shortening that correlates with increased melanization. It is thought that the presence of melanin elicits paramagnetic effects, shortening the T1 or T2 relaxation times.

The most common locations for this leptomeningeal melanosis include the anterior temporal lobes in the region of the amygdala, the base of the brain, the interpeduncular fossa, the ventral surface of the pons, the medulla and the cerebellum, the upper cervical spinal cord and the ventral lumbosacral cord . Involvement of the spinal meninges in NCM has been reported in as many as 20% of cases. A rare presentation is that of diffuse leptomeningeal enhancement in postgadolinium T1-weighted MR imaging of the convexities of the cerebral and cerebellar hemispheres, posterior surface of the brainstem, and quadrigeminal and superior vermian cisterns that may also be seen.

When evaluating a symptomatic known or suspected NCM patients with symptoms, contrast should be administered. Vasogenic edema and areas of hemorrhage or necrosis may indicate malignancy. Electroencephalographic studies often demonstrate either focal or generalized abnormalities. Various other imaging techniques such as computed tomography with contrast can show leptomeningeal involvement. However, it is generally agreed that MR imaging is the most sensitive modality to detect neural melanosis as well as intra-cerebral and extra-cerebral tumors in NCM. It is also the diagnostic procedure of choice in the evaluation of hydrocephalus.

Histologically, the cutaneous lesions in NCM are no different than other congenital melanocytic nevi. Most are intradermal melanocytic nevi with about a third showing features of compound nevi. The nevus cells often extend into the reticular dermis and occasionally into the subcutis with nevus present between collagen bundles, around appendages, nerves and blood vessels. As discussed below in the “Systemic Complications and Implications” section, there are some histologic features of the CNS lesions that make it difficult to determine whether melanocytes in the CNS are benign or malignant; but several distinguishing features do exist. If feasible, biopsy of CNS melanocytic tumors, or histologic examination of melanocytes culled from the CSF can help determine the biologic behavior of new or symptomatic tumors.

The issue of how, whe, and which patients should be screened for NCM is a controversial one, discussed further in the “Management” section of this chapter. The main rationale for this type of screening is to try to provide patients and families with prognostic information. While it is appropriate to alert families to the possibility that a child with large or multiple congenital nevi might have CNS or spinal cord melanosis, it is important to reassure them that the association is actually quite rare. Also, it is important to convey that though the outcome in patients with symptomatic NCM is very poor, most patients with MRI-documented NCM are asymptomatic and remain so.

Who is at Risk for Developing this Disease?

Patients with large congenital nevi (LCMN) are at risk for neurocutaneous melanosis. A “large” congenital nevus is a nevus that is estimated to become (by adulthood) equal to or greater than 20 cm in its largest diameter. Neurocutaneous melanosis seems to occur in about 2.5-7% of patients with LCMN overall, but the exact risk of NCM in patients with LCMN is really unknown at this time. Patients are at increased risk if they have LCMN with multiple satellite lesions, or in posterior axial locations.

Multiple nevi are also important. Perhaps a third of cases of NCM occur in a setting of multiple small or intermediate sized nevi in the absence of any LCMN. NCM has almost never been reported in patients with less then three CMN. It appears that in patients with LCMN, the risk of NCM increases as the number of satellites increase. This is in contrast to the risk of cutaneous melanoma, which increases with the size of the CMN but is not related to the number of satellites.

The risk of NCM in patients with large cutaneous melanocytic nevi (LCMN) may actually be greater then the risk that these patients will develop cutaneous melanomas. In patients with large congenital melanocytic nevi that involve the posterior axis and have multiple satellite nevi, studies have shown that approximately 20-30% of these “high risk” patients will have asymptomatic NCM when screened with MRI.

Neurocutaneous melanosis is not a hereditary condition. It is sporadic and occurs equally between the sexes. It is thought to be more common in Caucasians than African-Americans, but detailed studies on the ethnic distribution of this disease are not available at this time.

What is the Cause of the Disease?

During embryogenesis, melanoblasts normally migrate from the neural crest, along the leptomeninges and then to the skin. It is thought that aberrant migration of these cells results in the deposition of melanocytes within and along the leptomeninges. The benign proliferation of melanocytes in and around the leptomeninges can result in increased intracranial pressure leading to neurologic signs and symptoms. The malignant proliferation of these melanocytes can result in primary melanoma occurring within the central nervous system.


The reason for the aberrant migration of early melanotic cells is not well understood. However, some studies indicate that alteration of Met receptor signaling in neural crest -derived melanocytes may be involved. Hepatocyte growth factor/scatter factor (HGF/SF) binding to Met receptors is intimately involved in proliferation, motility and melanin synthesis in vitro. A mouse model with overexpression of HGF/SF exhibits both pigmented nevi and leptomeningeal melanocytosis.

Systemic Implications and Complications

Patients manifesting asymptomatic NCM by definition do not have systemic complications and do quite well. On the other hand, the prognosis for patients with symptomatic NCM is quite poor. Median survival time after the onset of symptoms has been estimated at around 6.5 months. Due to the young age at which most NCM patients present with clinical symptoms, the median age of death is approximately 4.5 years old.

Death can occur from a variety of complications; most commonly, increased intracranial pressure, hydrocephephalus, and brainstem compression. For symptomatic patients, an honest and forthright discussion of prognosis is an important aspect of management; particularly in the case of infants. That being said, there are patients with symptomatic NCM whose symptoms can be controlled or at least mitigated with anti-seizure medications, surgical or other interventions for many years.

Dandy-Walker complex and other CNS structural abnormalities, such as posterior fossae cysts, syringomyelia, arachnoid cysts, intraspinal lipomas, and defects of the vertebrae or skull have been described in patients with NCM and likely portend a greater likelihood of developing symptomatic NCM. The pathogenic mechanism of this association is unknown but may be related to defective ectodermal-mesodermal interactions secondary to excessive meningeal melanosis, leading to maldevelopment. In cases of children with symptomatic NCM and an associated Dandy Walker complex, the majority of reported patients have died before the age of 4 and the prognosis is even worse then that of symptomatic NCM alone.

Hydrocephalus is the most common complication of NCM and affects approximately two-thirds of symptomatic patients. Many patients die due to complications secondary to increased intracranial pressure. Most often the hydrocephalus is of the “communicating” type; which occurs when the accumulation of melanotic cells at the basal subarachnoid cisterns obstructs CSF flow and decreases the reabsorption of CSF in the arachnoid villi. A smaller proportion of NCM related hydrocephalus is of the “noncommunicating” type related to the obstruction of outflow foramina or aquaductal stenosis by melanotic cells.

Leptomeningeal melanoma, occurring most frequently in the frontal and temporal lobes, is a feared complication of NCM and occurs in approximately half of all patients with symptomatic NCM. However, it may also be an overdiagnosed entity in NCM patients. In the setting of NCM; it is difficult to differentiate benign from malignant lesions due to the marked cellular pleomorphism, tendency towards nesting and the appearance of invasion due to close approximation into endothelial spaces that characterizes the “benign” melanotic cells found in the meninges of NCM patients.

Histologic features that help identify leptomeningeal melanoma include: (1) necrosis and hemorrhage (2) invasion of the actual basal lamina of the endothelium (3) increased degree of cellular atypia and mitotic activity (4) the presence of annulate lamellae (concentric lamellar structures thought to represent modified melanosomes). If biopsy of nodules suspicious for malignant degeneration proves impossible or undesirable to the patient due to risk of neurologic damage, postitron emissions tomography may be useful in assessing the potential biologic behavior of new or changing CNS lesions.

Unfortunately, the differentiation between benign and malignant leptomeningeal tumors may be of more academic than prognostic value. The outcomes for symptomatic neurocutaneous melanosis with and without the complication of leptomeningeal melanoma are similarly bleak although some studies do show worse prognosis in the presence of leptomeningeal melanoma.

Treatment Options

Treatment options are summarized in Table I.

Table I.
Medical Management Surgical Interventions Physical Modalities
Chemotherapy- for secondary melanoma Shunt placement- to relieve hydrocephalus Radiation- for secondary melanoma
Psychologic or psychosocial counseling or support Surgical excision neurologic lesions- if possible  
  Surgical excision cutaneous lesions  

Optimal Therapeutic Approach for this Disease

Treatment of asymptomatic neurocutaneous melanosis is generally not undertaken unless there are MRI findings indicative of a pathologic process, such as hydrocephalus that is likely to lead to symptoms in the future. In this situation preemptive measures like ventricular shunt placement may be appropriate. However, we do not recommend attempts at surgical resection or other means of removal or destruction of asymptomatic CNS melanosis prior to the development of symptoms.

Treatment options for symptomatic NCM are limited and generally the outcomes with various modalities have been unsatisfactory even in the absence of melanoma. Once symptoms appear, a large proportion (perhaps upwards of 90%) of patients will die of complications related to their NCM; with half dying within 3 years and 70% within 10 years. Therapeutic options for NCM patients are usually palliative and limited to surgery, radiotherapy, chemotherapy, or ventricular shunt placement. Surgical debulking may be a temporizing measure that improves symptoms and delays death by months. The most effective palliative treatment in children with NCM and hydrocephalus is the placement of a shunt with a filter to prevent dissemination and seeding of melanoma throughout the peritoneal cavity.

The treatment of NCM may be difficult; however, as Drs. Khakoo and Margohoob point out in a letter to the editor in the Journal of Clinical Oncology: “ It is important to acknowledge that occasionally the symptoms of NCM may be temporary, while at other times they may be controllable with anti-seizure medications, removal of surgically resectable mass lesions, or placement of ventriculoperitoneal shunt. Although the long-term prognosis for patients with symptomatic disease remains guarded, it is not uncommon to encounter patients living relatively normal lives many years after their symptoms first appeared.”

Attempts at treating childhood leptomeningeal melanoma with various antineoplastic regimens involving radiation and chemotherapy have not seemed to improve survival times significantly. However, a recent case report detailed a good response and 6 months without recurrence after a regimen including radiation therapy, cyclophosphamide, sorafenib, and temozolomide.

Patient Management

Once neurocutaneous melanosis is identified, the options for management are limited and generally interventions do not improve long-term outcomes significantly. Symptomatic NCM should primarily be managed by neurologists, neurosurgeons and oncologists. The more common clinical scenario where dermatologists are likely to be involved is in managing patients with giant or multiple nevi with asymptomatic NCM. In this setting education regarding prognosis, worrisome signs and symptoms and providing support for the stigmatizing aspects of cutaneous disease are central to management. Education regarding patient support groups i.e. Nevus Outreach can be particularly helpful.

The literature available does not unequivocally answer the question of how to screen and monitor these patients. However, based on the data available we believe there is a rationale for screening certain children with specific risk factors for neurocutaneous melanosis of the brain and spine. The questions then become: which children to screen, when to screen them and with what screening approach?

We currently recommend MRI of the brain in those patients at risk (based on risk factors as discussed above). These are patients who exhibit large to giant nevi in posterior axial location or multiple (>3) intermediate, large or giant CMN. In patients with large or giant congenital nevi, the number of “satellite nevi” is the single greatest predictor of whether a patient will have associated neuromelanosis. The issues of performing MRI scans of the spine are somewhat more controversial but in our view, the study is worth considering when the majority of the nevus is overlying the spine, particularly the lumbosacral skin. Consideration should also be given to imaging the spine should be imaged if and when there are many satellite nevi (>20).

Decisions regarding repeating these studies should be individualized. In patients with no or very small and focal melanin deposits, repeating the studies may not be necessary. However if large amounts of melanosis are present, repeating scans periodically (eg, annually to biannually) may be indicated. With moderate involvement, we usually repeat scan around the second peak of symptom onset (8-10 years old). Patients with a large burden of melanosis should be evaluated and followed by a neurologist, who can help decide how often to repeat imaging based on even subtle changes in the neurologic exam. If the initial MRI is negative, we do not repeat the study and to our knowledge no cases have been reported wherein an initially negative MRI has become positive on subsequent imaging.

Interestingly patients with multiple small and intermediate sized CMN (>3), without a large or giant CMN, account for approximately one-third of all cases of symptomatic NCM reported in the literature. Given the rarity of this clinical presentation, this group of patients seems to be at an even higher risk then the classically described patient with large or giant nevi and suggests that satellites, rather than the giant nevus itself, may be central to NCM risk.

Along those lines, recent studies suggest that NCM risk is related to number of satellites. A recent series found that when there are more then 20 satellite lesions, there is a five-fold increase over patients with giant melanocytic nevi and less then 20 satellite nevi. It is therefore reasonable to deduce that increasing numbers of satellite, mean increasing risk of neuromelanosis, but whether this relationship is linear, exponential or other is uncertain. Determining whether to screen patients with just a few multiple small or intermediate CMN or a large CMN with just a few satellites involves balancing the risk of the MRI procedure vs the benefit of the prognostic information garnered. This determination should be made by the clinician and patient’s family together.

The location of the large or giant CMN is often cited as an important risk factor for NCM. Some studies have found that dorsal axial location was the greatest predictor of NCM. However, multivariate analysis and other studies have revealed that is is much less important then number of satellite lesions.

To summarize- it seems that the two types of patients with congenital melanocytic nevi that deserve imaging are:

1. Patients with large or giant congenital nevi that are truncal in location and involve the posterior midline axis. The more satellite lesions these patients have, the more likely they are to have neural involvement and the more a clinician may want to push for imaging in order to obtain information pertaining to prognosis.

2. Patients with multiple small or intermediate-sized CMN. If they have greater than 20, then we would recommend imaging if the parents desire. If they have less then 20, they deserve a frank discussion with their parents regarding the risks of imaging versus the risks of NCM. However, emphasis should be placed on the fact that imaging will only provide prognostic information and that NCM is a difficult to treat disorder whether CNS lesions are identified before or after the patient shows symptoms.

In resource-poor environments, obtaining an MRI on at-risk patients may not be feasible. Alternatively some parents may feel that the risk of general anesthesia typically needed for an MRI in a young child is not worth performing as it will likely only provide prognostic information and only rarely affect clinical outcomes. If the decision to obtain MRI is made, it is ideal to obtain the study before the brain is fully myelinated. It is more difficult to detect melanosis with MRI in a fully myelinated brain. Some experienced radiologists feel that contrast may help to reveal melanosis in this setting (personal communication, AJ Barkovich, Neuroradiology- UCSF ). Apart from this, contrast is not needed for screening of the asymptomatic patient. It is always recommended to assess patients with new symptoms.

If MRI without anesthesia can be accomplished in a very young infant (ie, with feeding and bundling) then this is worth trying to do soon after birth. Maximal myelinization of the central nervous system occurs around age 4-6 months. Risk of general anesthesia to infants is thought to decrease to near the risk of older children around the age of 3-6 months. Therefore, we generally recommend 3-6 month of age as time of greatest MRI sensitivity with least risk (secondary to general anesthesia) to the infant. The earlier the scan is done, the less likely that melanosis will be obscured by myelinization. The risk of the particular patient for NCM should be weighed against the risk of anesthesia in order to make a determination with regard to the timing of MR. These recommendations do not apply to symptomatic children who should proceed with imaging regardless of age.

Once NCM is diagnosed, the management of asymptomatic and symptomatic patients with NCM is entirely different. In the case of the asymptomatic patient with image-proven NCM, the above algorithm applies. In asymptomatic patients with NCM, the issues surrounding prophylactic skin surgery are the same that surround any child with congenital melanocytic nevi. We don’t believe that asymptomatic NCM precludes skin surgery unless the MR findings are severe and judged likely to lead to symptoms. However, some might argue that there may be a rationale for postponing surgery till after the age of two since this is the median age of the onset of neurologic symptoms. We believe this is probably not advisable since many cutaneous melanomas in large congenital melanocytic nevi occur before the age of 2. However, our practice is also not to aggressively remove CMN to decrease melanoma risk. This is further discussed in the CDS: Dermatology chapter devoted to congenital melanocytic nevi.

Surveillance for cutaneous melanoma within the nevi is also similar, with the risk of melanoma being higher in large congenital nevi than small or medium sized nevi and highest in truncal lesions. These cutaneous melanomas often (about half) occur before the age of 5 years old and almost always before puberty. The melanomas that occur in skin of patients with NCM have almost never been reported to occur in satellite nevi.

Once the patient is symptomatic their prognostic category and changes the approach to management significantly. A multispecialty approach should be undertaken and these patients managed primarily by neurologists, neurosurgeons, and oncologists with occasional follow up by dermatology perhaps annually or semi-annually. In one review of symptomatic NCM patients the median age of onset of symptoms was 1.5 yrs. Presenting signs and symptoms are discussed above. It seems clear that there is little to no rationale for prophylactic skin surgery in children with symptomatic NCM.

Unusual Clinical Scenarios to Consider in Patient Management

Rarely, neurocutaneous melanosis has presented in the setting of phakomatosis pigmentovascularis and nevus of Ota without associated congenital melanoctyic nevi. Another unusual presentation of neurocutaneous melanosis is within the setting of SCALP syndrome. This recently described entity describes the constellation of: Sebaceous nevus syndrome, CNS malformations, Aplasia cutis congenital, Limbal dermoid, Pigmented giant congenital melanocytic with neurocutaneous melanosis. Some unusual associations have been reported with neurocutaneous melanosis.

Other associations reported with NCM may be coincidental in nature. In the following there is at least a theoretical pathogenic link:

For instance, a child with neurocutaneous melanosis was also reported to have Hirschsprungs’s disease. This is interesting in light of biologic studies suggesting that the pathogenesis of intestinal aganglionosis is related to developmental failure of vagal neural crest-derived cells; perhaps in similar way that neurocutaneous melanosis may occur due to some abnormality of neural crest derived cell migration.

Neurocutaneous melanosis has also been reported in association with acute disseminated encephalitis in a 10-year-old. It was postulated that autoantigens form the invaded melanocytes led to tolerance breakdown of the immune system and a self-reactive encephalitogenic T-cell response against cells of the central nervous system. In, perhaps, a similar phenomena, there has been a case reported involving a 12-year-old boy with neurocutaneous melanosis, a CNS melanoma and new onset, type 1 diabetes mellitus. The diabetes totally resolved and the antiglutamic acid decarboxylase antibodies, which are felt to be important in the development of autoimmune diabetes mellitus, also went away after treatment of central nervous system melanoma. It was thought that the antibodies, which are expressed in neurons and islet cells of the pancreas may have been a paraneoplastic phenomenon related to his CNS tumor.

What is the Evidence?

Kadonaga, JN, Frieden, IJ. “Neurocutaneous melanosis: definition and review of the literature”. J Am Acad Dermatol. vol. 24. 1991 May. pp. 747-55. (This seminal article revises and more clearly defines criteria for neurocutaneous melanosis. It also reviews 39 cases, providing invaluable data regarding the timeline and nature of symptoms in patients with NCM.)

Makkar, HS, Frieden, IJ. “Neurocutaneous melanosis”. Semin Cutan Med Surg. vol. 23. 2004 Jun. pp. 138-44. (This article succinctly reviews and summarizes the epidemiology; pathogenesis; clinical cutaneous and neurologic features; risk factors for; histopathology and neuropathology; prognosis; management; and treatment of neurocutaneous melanosis. It provides clear recommendations for management based on a synthesis of available data to that point.)

Lovett, A, Maari, C, Decarie, JC, Marcoux, D, McCuaig, C, Hatami, A, Savard, P, Powell, J. “Large congenital melanocytic nevi and neurocutaneous melanocytosis: one pediatric center's experience”. J Am Acad Dermatol. vol. 61. 2009 Nov. pp. 766-74. (This article emphasized the importance of satellite nevi as a risk factor for NCM; reinforcing that the number of satellite nevi is even more predictive than posterior axial location of the presence of CNS involvement.)

Pavlidou, E, Hagel, C, Papavasilliou, A, Giouroukos, S, Panteliadis, C. “Neurocutaneous melanosis: report of three cases and up-to-date review”. J Child Neurol. vol. 23. 2008 Dec. pp. 1382-91. (A succinct and up-to-date review and synthesis of the available data regarding neurocutaneous melanosis along with three representative cases that nicely demonstrate the issues involved with diagnosis and management of NCM.)

Zhang, W, Miao, J, Li, Q, Liu, R, Li, Z. “Neurocutaneous melanosis in an adult patient with diffuse leptomeningeal melanosis and a rapidly deteriorating course: case report and review of the literature”. Clin Neurol Neurosurg. vol. 110. 2008 Jun. pp. 609-13. (A reminder that NCM can present in adulthood and the asympomatic child with positive signs of NCM in imaging is never totally out of the woods.”)

Cabanillas, M, Ginarte, M, Monteagudo, B, Toribio, J. “Role of positron emission tomography in the management of neurocutaneous melanocytosis”. Pediatr Dermatol. vol. 26. 2009 May-Jun. pp. 351-2. (An interesting discussion of how positron emission tomography may play a role in the the work-up of patients with NCM to help determine if malignant transformation has occurred in CNS lesions.)

Shah, KN. “The risk of melanoma and neurocutaneous melanosis associated with congenital melanocytic nevi”. Semin Cutan Med Surg. vol. 29. 2010 Sep. pp. 159-64. (This article evaluates the risk of melanoma and of neurocutaneous melanosis associated with congenital melanoctytic nevi. It provides a nice summary how and when each entity presents and the factors increasing the risk of each.)

Khakoo, Y, Marghoob, A. “Neurocutaneous melanocytosis: outcome not uniformly fatal”. J Clin Oncol. vol. 27. 2009 Oct 1. pp. e136(This editorial points out that NCM is not uniformly fatal. It suggests that palliative measures can be quite effective for long periods to decrease symptoms and improve quality of life. It also provides advice for families and patients on support groups that exist related to NCM.)