Neurocutaneous Melanosis Research Articles

Neurocutaneous melanosis concurrent with a posterior cranial fossa cyst (Dandy–Walker complex) and an intradural arachnoid cyst of the spinal canal

The paper describes a female patient with neurocutaneous melanosis (NCM) concurrent with Dandy–Walker malformation and a spinal arachnoid cyst, who has been treated in the A.Ya. Kozhevnikov Clinic of Nervous System Diseases. Over the course of one year, the patient had progressive neurological symptoms as central lower paraparesis and coordination disorders; her medical treatment was ineffective. Neuroimaging revealed Dandy–Walker malformation and a spinal arachnoid cyst. Surgical intervention (fenestration of the upper and lower poles of the arachnoid cyst at the C VI-VII and T IX-X level) was performed. After one month, reoperation (commissure resection in the arachnoid cyst cavity at the T V-VI level; implantation of a cystoperitoneal shunt) was made because of the absence of a clinical result. Reversal of neurological disorders was noted postoperatively. The described clinical case is unique, since NCM is an extremely rare abnormality, especially when concurrent with Dandy–Walker malformation and an arachnoid cyst. In addition, it is of interest that the manifestation of neurological symptoms and verification of the diagnosis occurred just in adulthood, although NCM is most commonly diagnosed in children. The present case shows that an operation aimed at improving cerebrospinal fluid dynamics in patients with arachnoid cysts and Dandy–Walker complex in the presence of NCM can lead to a significant reversal of neurological symptoms and improvement in the quality of life despite gross brain structural changes detected by magnetic resonance imaging.

Neurocutaneous Melanosis: Cutaneous and Neuroimaging Findings

Neurocutaneous Melanosis: Cutaneous and Neuroimaging Findings

Primary pigmented meningeal melanocytoma originating in Meckel cave in a patient with carney complex

Rationale:Primary melanin-producing tumors are rare extra-axial neoplasms OPEN of the central nervous system. In the literature, few case reports have discussed neoplasms involving the cavernous sinus; of these, only 4 have reported on neoplasms originating in Meckel cave. The diagnostic approach, including clinical and radiological analysis, is challenging, and cytopathological assessment with a molecular basis is the best approach to discriminate between these lesions. Herein, we discuss the pathophysiology, diagnostic approach, intraoperative features, and postoperative management in a unique case of primary pigmented meningeal melanocytoma originating in Meckel cave in a patient who was diagnosed with Carney complex (CCx) and sickle cell disease (SCD).Patient concerns:A 23-year-old man diagnosed with SCD had also been diagnosed previously with CCx, without any familial history or neurocutaneous melanosis. He had experienced headaches accompanied by left facial pain and paresthesia for 2 months.Diagnosis:The initial computed tomography scan and magnetic resonance imaging (MRI) revealed a mass arising from the left Meckel cave. On MRI, it followed the signal intensity of melanin. He underwent subtotal resection of the mass. Considering the patient's history of CCx, melanocytic schwannoma was the most relevant diagnosis. A postoperative histopathological examination was suggestive of benign pigmented meningeal melanocytoma.Interventions:The patient underwent an uneventful subtotal resection of the mass through a left temporal linear incision.Outcomes:The patient showed progressive improvement of neurologic deficits, and after 2 years of follow-up, he did not present with any new complaints.Lessons:To the best of our knowledge, this is the first report of the unusual presentation of both SCD, as well as of primary pigmented meningeal melanocytoma in a patient with CCx. Complete surgical resection can be curative in most cases of melanocytoma. The presence of CCx with SCD suggests potential shared genetic contributions that will require further exploration.

Letter to the Editor: Neurocutaneous Melanosis in Infancy: Always a Dismal Prognosis?

Letter to the Editor: Neurocutaneous Melanosis in Infancy: Always a Dismal Prognosis?

Características de nevos melanocíticos congénitos gigantes: presentación de 8 casos

IntroductionGiant congenital melanocytic nevi (GCMN) are benign proliferations of melanocytes present at birth or until the first 2-3 years of life. They could measure at least 20cm in their largest diameter in adulthood. Although rare they do affect the quality of life, as well as being associated with melanoma and neurocutaneous melanosis (NCM), for which certain clinical features are risk markers. MethodologyAn observational retrospective study was performed using the clinical records and photographic files of the GCMN diagnosed from November 2009 to March 2018 in the Paediatric Dermatology Unit of the Pereira Rossell Hospital in Montevideo-Uruguay. Using the information gathered, a descriptive analysis was performed on the clinical features and their association with melanoma and NCM. ResultsOut of the 8 GCMN diagnosed (5 boys), 5 were located on the back, 2 in the extremities, and 1 in head/neck region. Five showed satellite nevi, 7 with roughness and hair, 4 with colour heterogeneity, and 2 developed proliferative nodules. Five patients were evaluated with brain and spinal magnetic resonance imaging, and 3 with transfontanelle and spinal ultrasound. One showed NCM compatible findings. None showed neurological symptoms, and none of them had developed melanoma. ConclusionsIn a period of 8.3 years, 8 GCMN were diagnosed, mainly in boys, and on the back. Most of them showed hypertrichosis, roughness, and satellite nevi. The largest 2GCMN were located in the posterior midline, and showed nodules and> 20 satellite nevi. These have been associated with a greater risk of NCM, but were present in only one of these patients.

Giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (GCMN) are melanocytic lesions secondary to the abnormal migration of melanoblasts during the embryogenesis, affecting approximately one in 20,000 live births. They are usually present since birth and are distinguished by changing their morphological characteristics within time, and increasing their size parallel to the growth of the child, reaching a diameter ≥ 20 cm in adulthood. The importance of the GCMN lies in the complications associated to them; mainly the development of melanoma or neurocutaneous melanosis, in addition to the psychological or social impact that generates in most of the cases. Therefore, individuals with GCMN will require a multidisciplinary long-term follow-up. Currently, the management of children with GCMN is still controversial since there is no treatment of choice. Consequently, the treatment must be individualized according to the characteristics of the nevus and the specific needs of each patient.

Protocol for the development of core set of domains of the core outcome set for patients with congenital melanocytic naevi (OCOMEN project).

Having large congenital melanocytic naevi (CMN) is associated with a psychosocial burden on patients and their parents because of its remarkable appearance and the extra care it may require. Large CMN also pose an increased risk of malignant melanoma or neurocutaneous melanosis. There is a lack of international consensus on what important outcome domains to measure in relation to treatment. This makes it difficult to compare options, to properly inform patients and their parents, and to set up treatment policy for CMN. Therefore, we aim to develop a core outcome set (COS), i.e. the minimum set of outcomes that are recommended to be measured and reported in all clinical trials of a specific health condition. This COS can be used in the follow-up of CMN patients with or without treatment, in clinical research and practice. In the Outcomes for Congenital Melanocytic Nevi (OCOMEN) projects, we follow the recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Cochrane Skin Core Outcomes Set Initiative (CS-COUSIN). This project entails the following: (i) a systematic review to identify the previous reported outcomes in literature; (ii) focus groups with national and international patients and parents to identify patient-important outcomes; (iii) classification of outcomes into outcome domains; (iv) e-Delphi surveys in which stakeholders (patients/parents and professionals) can rate the importance of domains and outcomes; and (v) an online consensus meeting to finalize the core outcome domains of the COS. The results will be disseminated by means of publication in a leading journal and presentations in international meetings or conferences. We engage international experts in CMN, both patients and professionals, to ensure the international utility and applicability of the COS.

Neurocutaneous melanosis

Neurocutaneous melanosis is a rare fatal neurological ailment characterised by cutaneous nevi with leptomeningeal melanosis.Though there is no effective treatment but able to diagnose and take care of symptoms and complications will help in the palliative care of these patients and would further help in counselling the relatives as per the prognosis of this disease. 12yr old boy rt.handed presented with left partial seizures in clusters followed with left sided weakness. He had episode of right partial status epilepticus 6 months back and 3 months back. On examination he was drowsy with power 0 in left UL & LL with increased salivation, neck stiffness. Skin examination showed giant melanocytic naevi on limbs, face, torso and back. MRI Brain showed parafalcine hypointense meninges on T2, hyperintense meninges on T1 images with nodular leptomeningeal enhancement with hydrocephalus. CSF study showed 1 lymphocyte, proteins 14mg/dl, sugar 56mg/dl. CSF cytology showed abnormal cells which were stained with May Grunwald Giemsa showing prominent nucleoli. CT chest and abdomen was normal.EEG showed generalised slowing with no epileptiform activity. His seizures were controlled with LVT, LAC, OXZ, CLZ. He was also started on diamox, mannitol for hydrocephalus. He had intermittent fever which was controlled with antibiotics. He had residual left hemiplegia and had to be fed through rhyles tube. He did continue to have intermittent seizures for which antiepileptic drugs were adjusted. Our subject had all the risk factors for NCM reported as presence of a GCMN, male sex, satellite nevi or multiple CMN, and head, neck, or posterior midline location.

Association of Dandy-Walker Malformation and Neurocutaneous Melanosis in a Newborn: A Case Report

Background: This case report presents a very rare Dandy-Walker malformation (DWM) in association with a sporadic condition characterized by congenital melanocytic nevi and melanocytic thickening of the leptomeninges called Neurocutaneous melanosis (NCM). The DWM is a rare congenital disorder characterized by enlarged posterior fossa and a cystic enlargement of the fourth ventricle with cerebellar vermis dysgenesis. This association is a very rare complex, and this is another rare case to be reported in the literature. Case report: A full-term newborn was presented with tachypnea at birth whose hydrocephalous was reported prenatally. The magnetic resonance imaging and cerebrospinal fluid immunohistochemistry confirmed leptomeningeal melanosis. After documenting findings by skin biopsy, we decided to report this case. Diagnosis and treatment for such disease entity are discussed in this report. Conclusion: Even without malignant transformation, the prognosis is poor after symptomatic progression of the NCM resulting from either mass effect in the central nervous system or hydrocephalus. We reported this case in order to increase the knowledge of pediatric physicians to diagnose this combined situation.

Melanoma primario del sistema nervioso central asociado a melanosis neurocutánea

Los melanomas primarios de Sistema Nervioso Central son inusuales y se asocian hasta en un 40-60% de los casos a melanosis neurocutánea. Se presenta el caso de una paciente adulta con melanosis neurocutánea asociada a melanoma primario de sistema nervioso central con evolución clínica desfavorable.

Melanoma arising in a Giant congenital melanocytic nevus: two case reports

BackgroundA giant congenital melanocytic nevus (GCMN) is found in 0.1% of live-born infants. If present, the lesion has a chance of about 6% to develop into malignant melanoma. Both children and adults can be affected by malignant melanoma arising in a giant congenital nevus. Up to 95% of GCMNs harbor NRAS mutations, and mutations in the BRAF, MC1R, TP53, and GNAQ genes have also been described. The individualization of therapy is required, but diagnostic and prognostic criteria remain controversial.Case presentationsWe report two cases: 1) melanoma arising in a giant congenital nevus during the first month of life complicated with neurocutaneous melanosis (NCM), and 2) melanoma arising in a giant congenital nevus during the first 6 months of life. Pathology, immunohistochemistry, and genetic analyses of tumor tissue were performed. The first case revealed only a non-pathogenic P72R polymorphism of the TP53 gene in the homozygote condition. For the second case, a Q61K mutation was detected in the NRAS gene.ConclusionMalignant melanoma associated with GCMN is rare and therefore poorly understood. Outcomes have been linked to the stage at diagnosis, but no additional pathological prognostic factors have been identified. The most frequent genetic event in giant CMNs is NRAS mutations, which was discovered in one of our cases. To accumulate evidence to improve disease prognosis and outcomes, children with congenital melanocytic nevus should be included in a systemic follow-up study from birth.

Neurocutaneous Melanosis in Association With Large Congenital Melanocytic Nevi in Children: A Report of 2 Cases With Clinical, Radiological, and Pathogenetic Evaluation.

Background: Melanocytic nevi present at birth, or within the first few months of life, are defined as congenital melanocytic nevi (CMN). Neurocutaneous melanosis (NCM) is a rare disorder, represents pigment cell tumors of the leptomeninges, and occurs in association with large or multiple CMN. NCM carries an extremely poor prognosis. NRAS and BRAFV600E genetic mutations were reported in CMN. Our aim was to report 2 rare cases of NCM associated with large-sized CMN.Materials and Methods: Two cases were enrolled, a 19-month-old boy with multiple satellite and giant CMN (GCMN); and a 57-month-old girl with large CMN (LCMN). Both patients had central nervous system (CNS) symptoms, and therefore, were studied from clinical, radiological, and immunohistopathological aspects. Cytogenetic study was done for one of them.Results: Both patients had CMN located in the head/neck, with no cutaneous melanoma. MRI was the most reliable method for early detection of NCM. NCM was proved in the 2 studied cases by immunohistopathology performed after surgery. The boy with GCMN carried NRAS mutation at codon 61, in addition to the characteristic facial features relevant to RASopathies. Both patients died despite surgical intervention.Conclusion: Our report highlights the need for pediatricians to be alert to the risk of NCM in association with CMN, especially when a CMN lesion is large, or there are multiple satellite lesions, or the nevus location is at the head or neck. Moreover, in the setting of CMN, the absence of skin melanoma does not exclude the presence of NCM.

Giant congenital melanocytic nevus with neurocutaneous melanosis

Giant congenital melanocytic nevus with neurocutaneous melanosis

Neurocutaneous melanosis with pulmonary metastasis: looking beyond the skin

Neurocutaneous melanosis are neuroectodermal disorders characterized by giant congenital melanocytic nevus or multiple (≥3) nevus’s associated with melanocytic leptomeningeal tumour. Central nervous system tumour can be benign or malignant and usually presents at an early age. The neurological manifestation includes raised intracranial pressure, seizures and spinal cord compression. The dissemination of malignant nevomelanocytes to the peritoneal cavity has been observed with ventriculoperitoneal shunt placement in neurocutaneous melanosis. We report an infant of neurocutaneous melanosis with primary central nervous system melanoma and its metastasis to the lung in view of rarity.

Two neonates with characteristic MRI findings of neurocutaneous melanosis

Two neonates with characteristic MRI findings of neurocutaneous melanosis

NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called “forme fruste” of neurocutaneous melanosis

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.

New insights into neurocutaneous melanosis.

Neurocutaneous melanosis is a rare disorder in which children with large cutaneous melanotic nevi have associated melanosis in the brain. Although many affected children have structurally normal brains, some have associated developmental disorders or brain anomalies. To determine the range of extent of brain melanosis as assessed by magnetic resonance imaging (MRI) and to investigate the frequency and types of associated brain anomalies. We retrospectively reviewed brain and spine MRIs of 80 patients with congenital melanocytic nevi (range: 1 day to 22 years of age) affiliated with Nevus Outreach Inc. from 1998 to 2017. Central nervous system (CNS) melanosis was diagnosed when a mass with abnormal parenchymal T1 hyperintensity was seen. The locations of abnormal signal, associated malformations, the presence of contrast enhancement and, in patients with more than one MRI, changes over time were recorded. Associations among findings were analyzed using chi-square test or Fisher exact test. Brain abnormalities were identified in 33 patients. The most common finding was melanosis in the amygdala, which was found in 31 patients (an isolated finding in 14 patients). Nineteen patients had melanosis in the brainstem, cerebellum, cerebral cortex or thalamus. Cerebral and/or spinal leptomeningeal enhancement was uncommon (five patients). Hindbrain melanosis was associated with cerebellar and pontine hypoplasia (P=0.012). Brain melanosis was most easily seen on T1 images prior to myelination; reduced/loss of visibility was noted as the CNS matured. Brain melanosis is a common manifestation in children with large cutaneous melanotic nevi, most commonly found in the anterior temporal lobes (amygdala), brainstem, cerebellum and cerebral cortex. Hindbrain melanosis is associated with hypoplasia of the affected structures. Early imaging is optimal to provide the greatest sensitivity for diagnosis and to guide proper management.

Giant congenital melanocytic nevus in a Cameroonian child: a case report

BackgroundGiant congenital melanocytic nevus is a very rare condition characterized by a large skin lesion and an increased risk of complications like neurocutaneous melanosis and malignant transformation. Reports of giant congenital melanocytic nevus are scarce in the sub-Saharan African literature and here we present a case of this disease in a Cameroonian adolescent.Case presentationA 12-year-old Cameroonian girl from the "Baka" ethnic group, with no relevant family and medical histories presented with a progressively extensive brownish-black nodular hypertrophic skin lesion of approximately 45 cm, which she had had since she was 2-days old. The lesion covered her entire back giving an appearance of “turtle child”, which was highly suggestive of a giant congenital melanocytic nevus. She was booked in for a surgical intervention organized by a health campaign within her community. Meanwhile she was provided with psychological support and her family was counseled on warning signs of complications which would warrant an urgent consultation.ConclusionsHere we presented a case of giant congenital melanocytic nevus, apparently the first in the Cameroonian literature. In view of the potential severe complications as well as psychological trauma of this pathology, we draw clinicians’ attention to this extremely rare but real pathology in our country, for a timely diagnosis and management.

Neurocutaneous melanosis presenting with hydrocephalus and malignant transformation: case-based update

IntroductionNeurocutaneous melanosis (NCM) is a sporadic condition characterised by congenital melanocytic nevi and melanocytic thickening of the leptomeninges. It is believed to result from congenital dysplasia of melanin-producing cells within the skin and leptomeninges. The management of cutaneous manifestations remains controversial; for neurological manifestations, outcome remains poor even with the use of radiotherapy and chemotherapy.Patients and methodsWe describe the case of a 5-month-old boy who presented with giant congenital melanocytic nevus and hydrocephalus. MR imaging and CSF immunohistochemistry confirmed leptomeningeal melanosis. We discuss the diagnosis, treatment and prognosis of this rare disorder in the light of recent published literature.ResultsPatient required placement of right-sided ventriculoperitoneal shunt to control hydrocephalus. The patient tolerated the procedure well and was discharged home with normal neurological function. A presumptive diagnosis of NCM was made based on the MR characteristics, CSF cytology and clinical presentation. He received trametinib, a MAPK/Erk kinase inhibitor for 7 months. At 30 months of age, he developed left-sided weakness and status epilepticus requiring paediatric intensive care unit admission and ventilator support. The patient eventually succumbed to malignant transformation of leptomeningeal disease.ConclusionCutaneous manifestations of NCM are usually congenital, and neurological manifestations develop early in life. Patients with large or multiple congenital nevi should therefore be investigated early to facilitate treatment. MR imaging is the investigation of choice which can further assist in performing biopsy. Symptomatic NCM is refractory to radiotherapy and chemotherapy and has a poor prognosis. A multidisciplinary approach is necessary in the management of NCM patients.

Symptomatic neurocutaneous melanosis with unusual benign course: A case report and review

Neurocutaneous melanosis (NCM) is a rare, congenital, noninherited neurocutaneous syndrome characterized by the presence of “multiple or large congenital nevi” with central nervous system melanocytic deposits. Majority of cases are asymptomatic. Symptomatic cases present with hydrocephalus and signs and symptoms of increased intracranial pressure. The latter is associated with poor prognosis. We herein report an asymptomatic patient with giant congenital melanocytic nevi. He had a screening magnetic resonance imaging study at the age of 2 months that showed T1 hyperintensities in the region of amygdala of both temporal lobes. He was asymptomatic until the age of 4 years when he presented with seizure activity. A diagnosis of NCM was made. He was discharged on emergency antiepileptic medication. On regular follow-up, he remained seizure free for 1 year after the first episode of seizure. Unlike other cases reported in literature, this, to the best of our knowledge, is the first report of nonprogressive symptomatic NCM.