Neurocutaneous Melanosis Research Articles

Spinal Neurocutaneous Melanosis

Neurocutaneous melanosis is characterized by melanin-producing cells within the skin, leptomeninges, or brain parenchyma. It is a severe manifestation of congenital melanocytic nevus syndrome and can develop malignant melanomas. The disorder is commonly present in pediatric patients within the first two years of life and has a poor prognosis. We report a case of an 8-year-old male with epilepsy and cognitive deficit presenting spinal neurocutaneous melanosis.

Giant congenital melanocytic nevus in an 8-year-old female: a case report

Giant congenital melanocytic nevus are melanocytic lesions secondary to abnormal melanoblast migration during the embryogenesis. The incidence reported is in 1 case for every 20 000 newborns and it is present since birth. The importance of its detection relies on the associated complications, such as melanoma development or neurocutaneous melanosis, as well as the psychological and social impact they generate; patients will require a long-term multidisciplinary attention. There is no elective treatment, management is still controversial, it must be individualized according to the characteristics of the nevus and the age of the patient. We present the case of an 8-year-old patient where the diagnosis of giant congenital melanocytic nevus is determined for the first time.

Nevi - when to refer.

Congenital melanocytic nevi (CMN) and acquired nevi are prevalent in pediatric populations, with distinct characteristics and management considerations. This chapter aims to equip pediatricians with knowledge to discern between benign and high-risk nevi, facilitating appropriate referrals and management within primary care settings. Risk factors associated with malignant melanoma (MM) underscore the importance of vigilant monitoring and early referral to dermatology for suspicious lesions. Recent findings highlight the variability in CMN presentation and the evolving diagnostic strategies, emphasizing the need for multidisciplinary approaches to optimize patient outcomes. Management of CMN involves tailored surveillance and intervention strategies, with an emphasis on early identification of high-risk features for MM and neurocutaneous melanosis (NCM). Pediatricians play a crucial role in advocating for sun protection practices and facilitating timely referrals, thereby contributing to the overall well being of pediatric patients with nevi.

Perivascular Spaces: Neuroimaging, Microanatomy, Homeostasis, and Pathophysiologic Mechanisms of Disease

Perivascular spaces in the brain are microscopic pial-lined structures that surround small blood vessels and form the basis of the glymphatic system, which has a crucial role in fluid homeostasis and clearance of cellular waste byproducts. While often seen on MR imaging, enlarged perivascular spaces have been associated with multiple pathologies, such as neurodegenerative disorders, cerebral amyloid angiopathy, infectious or inflammatory diseases, and congenital conditions such as mucopolysaccharidoses. In addition, neoplasia can involve and spread via perivascular spaces, such as neurocutaneous melanosis. Lastly, congenital giant perivascular spaces are sometimes tumefactive and can be confused with neoplasia, leading to misdiagnosis. The morphologic characteristics, anatomic location, and burden of perivascular spaces may aid in differentiating the underlying etiology. Understanding the role of perivascular spaces in the brain and pathophysiologic mechanisms of disease that result in characteristic manifestations is essential for diagnostic interpretation.Learning Objective: To describe the normal anatomy and variable appearance of perivascular spaces and their role in the glymphatic system and to understand pathologic manifestations of perivascular spaces in various disease processes associated with glymphatic dysfunction, and their possible underlying mechanisms

Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis

Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

Giant Congenital Melanocytic Naevi in Newborns: A Case Series

Giant Congenital Melanocytic Naevi (GCMN) is a very rare condition that mostly occurs due to an oncogenic mutation involving the NRAS (neuroblastoma RAS viral oncogene homologue) gene. GCMNs can be clinically diagnosed due to their typical features, but histopathology confirms the diagnosis. GCMN has a high propensity for transforming into malignant melanoma and leptomeningeal melanocytosis, leading to neurological deficits such as epilepsy and neurofibromatosis. As it is associated with Central Nervous System (CNS) melanosis, Magnetic Resonance Imaging (MRI) of the brain and spine is crucial. Here, three cases are reported of the babies born with GCMN from August 2022 to July 2023 in a tertiary care hospital among a total of 11,915 live births, where the incidence is much higher than found in the literature. Present series describes three cases with GCMN, including clinical features, MRI findings, short-term outcomes, risk factors, and modalities of the management. All three cases showed extensive blackish pigmented patches involving most of the body surface and MRI evidence of Neurocutaneous Melanosis (NCM). The third baby succumbed to death due to fulminant sepsis on day 2 of life. Management of GCMN requires a multimodal approach, including medical, surgical, chemotherapeutic, palliative, and psychological support for patients as well as parents, and follow-up is necessary for the early detection of malignant transformation. Detailed knowledge of this very rare condition may enable us to develop newer treatment modalities to achieve better outcomes in the near future.

A clinical and biologic review of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway caused by postzygotic somatic mutations. The estimated incidence of newborns with CMN is 1%-2%. The main complications of CMN include proliferative nodules, melanomas, and neurocutaneous melanosis, and the latter two are the most troublesome issues to address. Treatments are primarily taken into account for aesthetic purposes and the reduction of melanoma risk. Due to the much lower incidence of malignant transformation observed in recent studies than in previous data, clinical management paradigms for CMN patients have gradually shifted towards conservative observation and close monitoring. Surgery and lasers are still the main treatments, and targeted therapy may be a promising strategy to help manage complications. With the increase in awareness of mental health, increasing focus has been placed on the quality of life (QoL) and psychological issues of both CMN patients and their parents. Recent studies have revealed that families coping with CMN might endure intense pressure, a major loss in QoL, and psychological problems after diagnosis and during treatment. Here, we sought to present an overview of genetic basis, complications, treatments, and psychological issues related to CMN and hope to provide better management for patients with CMN.

NIMG-77. EARLY DIAGNOSIS OF NEUROCUTANEOUS MELANOSIS MASQUERADING AS SUBARACHNOID HEMORRHAGE

Abstract A 50-year-old male presented to the emergency room with a sudden onset right upper limb facial numbness and dysphasia, soon followed by full-recovery. Brain computed tomography revealed hyperdense lesions within the left frontal sulcus, highly suspicious of subarachnoid hemorrhage. T1-weighted magnetic resonance imaging showed multiple leptomeningeal enhancement in the left frontal area.The digital subtraction angiography indicated an absence of vascular lesions. One-month after, the lesions progressed in the occipital area, when left sixth nerve palsy developed. Multiple giant nevus over the legs, trunk, and scalp had attracted attention. Owing to the suspicious symptomatic leptomeningeal lesions, open biopsy was performed. Surprisingly, diffuse, thick, black-colored tissue infiltration of the subarachnoid space, involving prominent cortical vessels, was noted. Pathology confirmed meningeal melanocytosis. Neurocutaneous melanosis is characterized by giant congenital or multiple satellite nevi and melanocytic tumors of the leptomeninges. Early disease diagnosis is crucial. Once the patient develops neurological symptoms, prognosis could quickly worsen.

Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Congenital Melanocytic Nevus: An Unusual Presentation

The overgrowth of melanocytes produces congenital melanocytic nevus. They are commonly present since birth, and the common terms used to describe them are called 'bathing trunk,' 'coat-sleeve,' or 'stocking naevi,' and they are usually found over thighs and back. The giant congenital nevus of size larger than twenty centimeters is highly pigmented and usually hairy. It is more commonly found in females compared to males. It is well recognized that the lesion's displeasing nature might have psychological and social ramifications, negatively affecting the patient's self-esteem, particularly females. Although congenital melanocytic nevus is mostly clinically diagnosed, the histological investigation is required to confirm the diagnosis and rule out malignant changes. The likelihood of transforming the giant nevus to malignant melanoma accounts for approximately five percent; fifty percent of melanomas develop before age two, and eighty percent develop before age seven. The risk of transformation to malignant melanoma is early in giant melanocytic nevus cases and adolescence in small and medium-sized nevi cases. Other complications like transformation to neurocutaneous melanosis consisting of the spread of melanoma to the central nervous system and leptomeninges are also dreadful. Hence, early removal is recommended. Here, we have reported a rare case of a six-year-old patient with a medium-sized nevus on their face with hairy tufts in between. On biopsy, the diagnosis was made as a junctional nevus. After which, the patient was managed with subsequent lesion excision and split skin grafting with an uneventful postoperative period. Our case report aims to report a rare case of congenital melanocytic nevus and to determine the importance of timely diagnosis and intervention. Keywords: , , , ,

Photo gallery. Rare dermatoses. Part I

Orphan dermatoses are caused by both genetic causes and a number of autoimmune, inflammatory and infectious processes in the body. Congenital giant nevus is associated with serious complications: malignant melanoma, CNS lesions (neurocutaneous melanosis). Multiple epidermoid cysts are often a component of Gardner's syndrome. Angiolymphoid hyperplasia with eosinophilia, a vascular tumor formation with proliferation of histiocytoid endothelial cells, with severe lymphocytic and eosinophilic infiltration, recurs in 1/3 of cases. Morbigan's disease is persistent erythema and swelling of the middle third and upper part of the face. Skin mastocytosis in children is prone to spontaneous resolution during puberty. Squamous cell skin cancer accounts for 20% of all skin cancers and has a high risk of recurrence, metastasis, and death. Buschke's scleroderma is a scleroderma-like disease that causes progressive fibrous-mucinous thickening of the skin affecting the neck, shoulders, proximal upper extremities, and face. Fulminant (lightning) acne is a sharply exacerbated form of acne vulgaris, characterized by an acute onset and the appearance of confluent abscesses. Cases of acne fulminans have been observed during treatment with isotretinoin. Norwegian (crustose) scabies is associated with a compromised immune response, which allows the mites to multiply and can number in the millions. Pretibial myxedema (thyroid dermopathy) is a rare extrathyroid manifestation of Graves' disease along with thyrotoxicosis, thyroid hypertrophy, ophthalmopathy, and acropachy. Porokeratosis Mibelli predisposing factors of development are immunosuppressive conditions, malignancy is possible. Osteomas are formations from bone tissue in the dermis or subcutaneous fat as a result of metaplasia of fibroblasts into osteoblasts, or differentiation of primitive mesenchymal cells into osteoblasts and their migration to an ectopic site. Sarcoidosis of the skin is characterized by a variety of clinical forms, rarely observed before 40 years. Xanthomas with histiocytosis X ― a violation of lipid metabolism. The rural type of leishmaniasis (acute necrotizing) has a short incubation period, a significant spread of rashes and healing with the formation of scar tissue. The giant condyloma of BuschkeLevenshtein is characterized by progressive growth, large size and recurrent course, it can transform into squamous cell carcinoma. Degos disease ― malignant atrophic papulosis ― a rare disease caused by blockage of the arteries and veins.

Нейрошкірний меланоз (хвороба Рокітанського) як рідкісна причина епілептичних нападів у педіатричній практиці

Neurocutaneous melanosis is a rare disease belonging to the group of phakomatoses, characterized by the presence of giant melanocytic nevi on the skin and melanocytic infiltration of the parenchyma and meninges, as well as a high risk of neurological complications and malignancy. Purpose - to analyze the information of modern specialized literature on the etiology, pathogenesis, approaches to diagnosis and treatment of a rare orphan disease - neurocutaneous melanosis (Rokitansky's disease) and to describe clinical cases of this disease. A review of the scientific literature and a personal case of diagnosis and treatment of two patients are given. In the first case, the clinical history of a boy aged 1 year and 4 months is presented with neurocutaneous melanosis and Dandy-Walker anomaly, complicated by frequent drug-resistant epileptic seizures. In the second case, a description of the medical history of a 14-year-old boy with newly diagnosed neurocutaneous melanosis complicated by progressive obstructive hydrocephalus and generalized tonic-clonic seizures is presented. MRI features deserve special attention, namely specific changes in the T2-weighted mode, which reveals typical areas of hyperintense signal in the brain parenchyma and from the dura mater (leptomelanosis). It is the neuroimaging data with a high probability that gives reason to assume the correct diagnosis, reducing time and costs for additional examinations. There is no pathogenetic treatment for this disease. For the symptomatic treatment of obstructive hydrocephalus, surgical intervention is used, and in the presence of epileptic seizures, anticonvulsant therapy is used. Conclusions. The given clinical observation confirms the complexity of the diagnostic search for orphan diseases of the nervous system. Objective examination data and neuroimaging methods (CT and MRI of the brain and spinal cord) play a key role in the diagnosis of neurocutaneous melanosis. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

A Case Report of Neurocutaneous Melanosis with Associated Dandy-Walker Complex

Background: Neurocutaneous melanosis (NCM) and Dandy-Walker malformation (DWM) are two forms of rare congenital neurodysplasia. NCM is a rare dysmorphogenesis characterized by single or multiple giants pigmented cutaneous nevi and the involvement of benign and/or malignant melanocytic tumors of the leptomeninges. DWM is a rare congenital malformation of the brain. Cystic enlargement of the fourth ventricle is its characteristic that communicates with an enlarged posterior fossa, cerebellar dysgenesis, high tentorial insertion, and hydrocephalus. However, these two conditions are rare, and NCM associated with DWC is even more unusual.
 Case Report: Here, we report a male newborn with macrocephaly and multiple pigmented nevi over his whole body with regular borders and normal weight, height, and spine. He was finally diagnosed as NCM in association with DWC.
 Conclusion: After diagnosing NCM in association with DWC, appropriate follow-up is recommended; however, there is no particular treatment to prevent the malignant change.

A Rare Case of Giant Congenital Melanocytic Nevi: A Case Report

Background: Giant congenital melanocytic nevi are often characterised as melanocytic lesions present at birth. It is thought that it affects 1 in 20,000 births. The lesion is significant because it may be associated with serious consequences, such as malignant melanoma, and may also result in neurological deficits, such as neurocutaneous melanocytosis. This study aimed to present the case of giant congenital melanocytic nevus as a rare case.
 Case presentation: This study reported a 14-year-old female reported with large blackish rough spots on the trunk that were neither itchy or painful since birth. The patient had no previous history of convulsions, headaches, or vomiting. Plaque hyperpigmentation, macula hyperpigmentation, and hypertrichosis were found on the trunk. Dermoscopy show reveals brown-black homogeneity. Histopathology examination reveals brown-pigmented nevus cells distributed diffusely, with some nevus cells surrounding adnexa skin.
 Conclusion: Regular examination is essential to monitor the possibility of neurocutaneous melanosis and malignant melanoma development.

396 - Neurocutaneous melanosis and nevus of ota: a case report

396 - Neurocutaneous melanosis and nevus of ota: a case report

Newborn Wearing an Ascot Cap

This report describes a newborn with a congenital melanocytic nevus (CMN) over the scalp, which gave a striking appearance of an Ascot cap. Though CMN are common, their location gives a unique look and associated findings (dermatological lesions like satellite lesions, café-au-lait spots, Mongolian spots, etc.) are often underappreciated in clinical practice. Through this report, we also wish to convey a message that clinicians should decide the need for investigations (MRI brain to rule out neurocutaneous melanosis) in these benign conditions are based on individual risks rather than merely the presence of CMN.

PERFIL EPIDEMIOLÓGICO E CLÍNICO DE CRIANÇAS COM NEVO MELANOCÍTICO CONGÊNITO GIGANTE EM UM SERVIÇO DE DERMATOLOGIA

ABSTRACT: Objective: to describe five children with Congenital Giant Melanocytic Nevus (NMCG) at the Dermatology Service at the State University of Pará in Belém - PA, Brazil. Case description: patients aged 1 to 11 years, four of whom were female, all of them brown, in good nutritional status, prenatal without complications, and denied consanguinity. The five cases presented lesions on the trunk, with different distribution patterns: swimming trunks (1), body (1), back (1), and bolero (2), most with more than fifty satellite lesions containing hypertrichosis and pruritus. In the histopathological analysis, all of them were compatible with a nevus, one of the cases was associated with a neurofibroma, two with neurocutaneous melanosis and one with melanoma in the brain, evolving to death. Comments: Congenital Giant Melanocytic Nevus is a rare condition, defined by the presence of a melanocytic lesion, measuring at least 20 cm, present since birth. It has its clinical relevance due to the association with serious complications such as melanoma and / or neurocutaneous melanosis. The registration of this series aims to contribute to greater knowledge about the disease, which has physical, psycho-emotional, social, and risk of malignancy implications.

Perfil epidemiológico e clínico de crianças com nevo melanocítico congênito gigante em um serviço de dermatologia

OBJECTIVE: to describe five children with Congenital Giant Melanocytic Nevus (NMCG) at the Dermatology Service at the State University of Pará in Belém - PA, Brazil. CASE DESCRIPTION: patients aged 1 to 11 years, four of whom were female, all of them brown, in good nutritional status, prenatal without complications, and denied consanguinity. The five cases presented lesions on the trunk, with different distribution patterns: swimming trunks (1), body (1), back (1), and bolero (2), most with more than fifty satellite lesions containing hypertrichosis and pruritus. In the histopathological analysis, all of them were compatible with a nevus, one of the cases was associated with a neurofibroma, two with neurocutaneous melanosis and one with melanoma in the brain, evolving to death. COMMENTS: Congenital Giant Melanocytic Nevus is a rare condition, defined by the presence of a melanocytic lesion, measuring at least 20 cm, present since birth. It has its clinical relevance due to the association with serious complications such as melanoma and / or neurocutaneous melanosis. The registration of this series aims to contribute to greater knowledge about the disease, which has physical, psycho-emotional, social, and risk of malignancy implications.

Neurocutaneous Melanosis: A Diagnostic Challenge

Neurocutaneous Melanosis (NCM) is a rare congenital syndrome presenting as a large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumours of the leptomeninges. The syndrome is defined as an error in the morphogenesis of the embryonal neuroectoderm. It is one of the rare phakomatoses seen in childhood and shows variable presentations. The authors hereby presents a case report of a 15-year-old male patient with NCM, who presented with recurrent episodes of seizures and difficulty in walking. On physical examination, the patient had multiple congenital cutaneous nevi on the trunk, back, and hands. Immunohistochemistry(IHC) with Haematoxylin & Eosin (H&E) staining confirmed the diagnosis of leptomeningeal diffuse melanocytosis was made.

Large café-au-lait spots on a 5-year-old boy

Large café-au-lait spots on a 5-year-old boy