Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.

Naevus of Ito and naevus of Ota are benign dermal melanocytoses with similar pathogenic mechanisms of failure in the melanocyte migration to typical locations within the basal layer from neural crest cells and differ in distribution. Bilateral and oral mucosal involvement of naevus of Ota can occur but is infrequent. Naevus of Ito is seldom associated with naevus of Ota and extracutaneous manifestations. A review of the English literature showed 14 cases of naevus of Ota with palatal involvement. None showed bilateral involvement of both naevi with oral involvement. Here we report the case of bilateral naevus of Ito and bilateral naevus of Ota with palatal involvement. A 32-year-old male came to us with naevus of Ito on both sides of his back and naevus of Ota on both sides of his face involving the sclera of both eyes with a bluish lesion along the midline of the hard palate.

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UNASSIGNED: Congenital melanocytic nevi (CMN) are benign lesions composed of clonal proliferations of melanocytes. Although medium-sized CMN are common and generally remain benign throughout a person\'s lifetime, they may be precursors of melanoma. There is a limited number of studies focused on the risk of melanoma in solitary, medium-sized, congenital melanocytic nevus; therefore, the incidence of malignant transformation and guidelines for treatment are not well established.
UNASSIGNED: Prompted by the limited data, we conducted this study to gather more information about medium-sized CMN, to optimize clinical care. We share our analysis of surgically removed medium-sized CMN.
UNASSIGNED: A total of 10 patients with non-multiple, medium-sized, congenital melanocytic nevus were included in this study. Lesions were removed using surgical procedures.
UNASSIGNED: In most of the cases the reason for excision of the medium-sized CMN was evolution of the lesion or aesthetic considerations reported by the patients. In 2 cases, due to the large size of the lesions, serial excisions were performed, while other CMN were removed surgically using simple excision technique. Eight of 10 medium-sized CMN were histologically described as benign, and 2 cases of malignant transformations were reported.
UNASSIGNED: According to our clinical experience and knowledge, we recommend managing patients on an individual basis, taking into consideration multiple clinical attributes. In our opinion, long-lasting observation is the management of choice, and if there is need of surgery, we recommend total simple or staged excision depending on nevus size.

Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.

This study assessed self-reported health-related quality of life and psychological adjustment in 43 adolescents and young adults (ages in years: 14-24, M = 17.6, SD = 2.2) with congenital melanocytic nevi (CMN) and examined associations with sociodemographic variables, characteristics of the CMN, perceived social reactions, and cognitive emotion regulation strategies. Outcome measures included the Pediatric Quality of Life Inventory™ 4.0 and the Strengths and Difficulties Questionnaire. Findings suggest impaired psychosocial health and psychological adjustment in youth with CMN compared to community norms. Impairments were associated with higher age of participants, lower socioeconomic status, visibility of the skin lesion, perceived stigmatization, poorer perceived social support, and maladaptive cognitive emotion regulation strategies (self-blame, rumination, and catastrophizing), but not with sex of participants, extent of the skin lesion, and surgical removal of the nevus. Implications for clinical practice and future research are discussed.

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BACKGROUND: Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of NRAS and BRAF genes in resection specimens from large or giant CMN in a group of Polish patients.
METHODS: The formalin-fixed, paraffin-embedded resection specimens from 18 patients, fixed in the years of 2006 to 2017, were included in the study. The regions containing the highest load of melanocytes were macrodissected prior to DNA isolation. The NRAS and BRAF mutation status was evaluated using qPCR.
RESULTS: We detected activating mutations in NRAS gene (codons: 12 and 61) in 7 out of the 18 (38.9%) patients. No BRAF mutations were found.
CONCLUSIONS: Our study, the first molecular analysis of large/giant CMN in Polish patients, supports the hypothesis that NRAS mutation in codon 61 are frequent, recurrent mutations in large/giant CMN. Moreover, we show, for the first time, that NRAS mutations in codon 12 (p.Gly12Asp) can be also detected in giant CMN. The exact role of these genetic alterations in CMN formation remains to be elucidated.

Neurocutaneous melanosis (NCM; MIM # 249400; ORPHA: 2481], first reported by the Bohemian pathologist Rokitansky in 1861, and now more precisely defined as neurocutaneous melanocytosis, is a rare, congenital syndrome characterised by the association of (1) congenital melanocytic nevi (CMN) of the skin with overlying hypertrichosis, presenting as (a) large (LCMN) or giant and/or multiple (MCMN) melanocytic lesions (or both; sometimes associated with smaller \"satellite\" nevi) or (b) as proliferative melanocytic nodules; and (2) melanocytosis (with infiltration) of the brain parenchyma and/or leptomeninges. CMN of the skin and leptomeningeal/nervous system infiltration are usually benign, more rarely may progress to melanoma or non-malignant melanosis of the brain. Approximately 12% of individuals with LCMN will develop NCM: wide extension and/or dorsal axial distribution of LCMN increases the risk of NCM. The CMN are recognised at birth and are distributed over the skin according to 6 or more patterns (6B patterns) in line with the archetypical patterns of distribution of mosaic skin disorders. Neurological manifestations can appear acutely in infancy, or more frequently later in childhood or adult life, and include signs/symptoms of intracranial hypertension, seizures/epilepsy, cranial nerve palsies, motor/sensory deficits, cognitive/behavioural abnormalities, sleep cycle anomalies, and eventually neurological deterioration. NMC patients may be symptomatic or asymptomatic, with or without evidence of the typical nervous system changes at MRI. Associated brain and spinal cord malformations include the Dandy-Walker malformation (DWM) complex, hemimegalencephaly, cortical dysplasia, arachnoid cysts, Chiari I and II malformations, syringomyelia, meningoceles, occult spinal dysraphism, and CNS lipoma/lipomatosis. There is no systemic involvement, or only rarely. Pathogenically, single postzygotic mutations in the NRAS (neuroblastoma RAS viral oncogene homologue; MIM # 164790; at 1p13.2) proto-oncogene explain the occurrence of single/multiple CMNs and melanocytic and non-melanocytic nervous system lesions in NCM: these disrupt the RAS/ERK/mTOR/PI3K/akt pathways. Diagnostic/surveillance work-ups require physical examination, ophthalmoscopy, brain/spinal cord magnetic resonance imaging (MRI) and angiography (MRA), positron emission tomography (PET), and video-EEG and IQ testing. Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL).

Proliferative nodules arising within congenital melanocytic nevi often present a diagnostic challenge given a close resemblance to melanoma. Several morphologic variants have been characterized. In difficult cases, ancillary molecular tests can be used to better exclude the possibility of malignant degeneration. Herein, we report a case of an unusual proliferative nodule with overlapping features of angiomatoid Spitz tumor and ancient melanocytic nevus, which demonstrated normal findings on both chromosomal microarray and a gene expression profiling assay.