Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Erbium: YAG laser treatment efficacy and association with histologic features for giant congenital melanocytic nevi management.

BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.

Genetic and phenotypic diversities of nevus spilus phenotypes: Case series and a proposed diagnostic algorithm.

Nevus spilus (NS) is composed of multiple types that characterized by a congenital hyperpigmented patch within variable even superimposed lesions originating from melanocytic lineage cells. The molecular mechanism and classification of diverse NS phenotypes remain unclear. Five children with a phenotype of NS were genotyped by the panel based on next-generation sequencing in this study. DNA from biopsies, blood samples and hair follicle were sequenced to confirm the presence of a somatic mutation. Sequencing results indicated somatic mutation in the gene of NRAS or HRAS in all biopsies from the nevi, and the pathogenic variants were not detected in the samples of blood and hair follicle. This study successfully identified the somatic mutation in five unrelated children with diverse NS phenotypes. Moreover, it provided typical images and differential diagnoses between variable NS phenotypes in clinical, pathological, and genetic features, and first proposed a clinical diagnostic algorithm that contributed to simplifying and optimizing the diagnoses and management of these overlapped diseases.

Ambiguous genitalia, giant congenital melanocytic nevus and subpulmonic outlet ventricular septal defect in an African child with Neurofibromatosis 1.

Neurofibromatosis type 1 is an autosomal dominant multisystemic disease caused by mutation of the neurofibromin (NF1) gene located on chromosome 17q11. We report a case of Neurofibromatosis 1 with ambiguous genitalia, giant congenital melanocytic nevus, and associated subpulmonic outlet ventricular septal defect, hitherto unreported in sub-Saharan Africa. In addition, a literature review of congenital heart diseases associated with Neurofibromatosis 1 is presented.

Dynamic evolution of a scalp congenital melanocytic nevus with poliosis and cutis verticis gyrata.

Cutis verticis gyrata (CVG), characterized by cerebriform overgrowth of the scalp, is rarely observed in congenital melanocytic nevi (CMN). We describe a 13-year-old male with autism and a large CMN of the scalp with numerous satellite nevi whose scalp nevus exhibited evolution with poliosis and CVG. Given the potential association of CVG (independent of CMN) with seizures, neuropsychiatric, and ophthalmologic disorders, and nevus-associated CVG (cerebriform intradermal nevus) with melanoma, multidisciplinary evaluation of CMN patients with CVG is important to guide management and treatment.

Impact of public exhibition on the perception of birthmarks.

BACKGROUND: The importance of photographs in social media, the steep rise in popularity of tattoos, and the prominence of individuals with visibly different skin in fashion are likely to be changing the landscape of self- and public perception of birthmarks. Study objectives were to assess the impact of a photoshoot and public exhibition on the self-perception of individuals with extensive birthmarks, and to explore the viewing public's reactions. METHODS: Thirty individuals with congenital melanocytic nevi (CMN) were recruited internationally. Each had a professional photoshoot portrait with their skin exposed, resulting in a public exhibition in London entitled "How do you C Me Now?" Participants/parents completed pre- and post-questionnaires relating to self-perception and the impact of their birthmarks on behavior. Over 8000 members of the public viewed the exhibition, 464 completing an on-site questionnaire on its effects. RESULTS: All participants/parents rated the experience as positive, valuable and helpful. Scores on self-appreciation and self-confidence were significantly higher after the photo shoot. Members of the general public overwhelmingly reported the exhibition increased their positive feelings towards people with birthmarks. The majority of public respondents also reported that the exhibition made them feel better about their own skin and about their looks in general. CONCLUSION: This unique exhibition and the associated research has provided a striking new perspective on potential psychological interventions for individuals with birthmarks.

Giant Congenital Melanocytic Nevus with Congenital Neurofibroma: A Case Report.

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is characterized by its large size and potential for transformation into melanoma. It can be associated with other neural cristopathies, including neurofibroma, however, it has not previously been described with a congenital neurofibroma. CASE REPORT: A newborn girl presented with a large congenital neurofibroma arising in a bathing trunk type of giant congenital melanocytic nevus. CONCLUSION: Congenital neurofibromas can be associated with (or a component of) a GCMN.

Non-multiple medium-sized congenital melanocytic nevi: to excise or to follow up?

Introduction: 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. Aim: 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. Material and methods: A total of 10 patients with non-multiple, medium-sized, congenital melanocytic nevus were included in this study. Lesions were removed using surgical procedures. Results: 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. Conclusions: 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.

Association of novel MUC16, MAP3K15 and ABCA1 mutation with giant congenital melanocytic nevus.

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN. METHODS: Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN). RESULTS: We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation. CONCLUSION: The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.

Spitzoid proliferative nodules arising in a congenital melanocytic naevus: A case report with clinical, dermoscopic and histologic correlation.

Proliferative nodules (PNs) are benign nodular proliferation of melanocytes occurring within congenital melanocytic naevi (CMN). Differential diagnosis between PN and melanoma is challenging for clinicians and pathologists. We describe the case of a 9-month-old boy who developed multiple nodules arising in a medium-sized CMN. Clinically, pink papules were observed, with dotted vessels on dermoscopy, suggesting spitzoid PN. On histopathological examination, the dermoscopic findings correlated with the vertical vessels of a spitzoid PN. Dermoscopy could be a useful tool to differentiate PN from melanoma. However, further studies describing the dermoscopic features of the different PN subtypes are needed. Histopathology remains the gold standard for definitive diagnosis aided by ancillary molecular tests such as fluorescence in situ hybridization or comparative genomic hybridization.

Neonatal Curettage of Large to Giant Congenital Melanocytic Nevi Under Local Anesthetic: A Case Series With Long-Term Follow Up.

BACKGROUND: Neonatal curettage of large to giant congenital melanocytic nevi (L-GCMN) is a simple, minimally invasive procedure typically performed within the first 2 weeks of life. OBJECTIVES: To retrospectively review our experience with serial curettage of L-GCMN in the neonatal period performed under local anesthesia and their long-term outcomes. METHODS: Curettage was performed by a single pediatric dermatologist on nine neonates with L-GCMN under local anesthetic and with oral analgesia between 2002 and 2016 in Red Deer, Alberta, Canada. Patient charts were reviewed retrospectively to assess patient and procedure characteristics, tolerability, safety, cosmetic and functional outcomes, and malignant transformation. RESULTS: Patients were treated with an average of 6 curettage sessions (range 3 to 15) to remove the majority or entirety of the nevus. All patients tolerated local anesthesia well. The most common adverse event of the procedure was transient neutropenia. Two patients developed positive bacterial cultures without clinical signs of infection, treated with antibiotics. All curetted specimens demonstrated benign pathology. Patients were followed annually thereafter, for an average of 6 years. Eight patients with L-GCMN of the trunk had minimal to partial repigmentation with good cosmetic outcome. One patient had recurrence of a facial nevus. None of the patients developed cutaneous malignant melanoma. CONCLUSIONS: Curettage appears to be a safe and effective treatment option for select cases of L-GCMNs of the trunk. We do not recommend the procedure for face or scalp CMN. This procedure can be performed under local anesthesia with serial curettage to avoid potential risks of general anesthesia.

Diagnostic utility of PRAME in distinguishing proliferative nodules from melanoma in giant congenital melanocytic nevi.

We describe a case of a melanocytic proliferation arising in a giant congenital melanocytic nevus (CMN) and outline the potential utility of an immunohistochemical study with PReferentially expressed Antigen in MElanoma (PRAME) in distinguishing benign proliferative nodules (PN) from melanoma in this context. A 15-day-old girl presented with a fibrotic nodule clinically suspicious for melanoma within a giant CMN. Histopathological examination showed a predominantly intradermal melanocytic nevus with congenital features intermixing with an ill-defined proliferation of larger melanocytes demonstrating mild-to-moderate cytologic atypia and increased mitotic activity. Anti-PRAME was diffusely positive within the congenital nevus while negative within the larger proliferating cells. Chromosomal microarray analysis revealed whole chromosomal gains and losses only, consistent with a PN arising in a giant CMN. To our knowledge, PRAME expression in giant CMN, PN, and pediatric melanomas has not been previously described. Based on our experience with this case, we propose that differential patterns of PRAME expression may be present in these three lesions, allowing PRAME immunohistochemistry to potentially serve as a helpful adjunct diagnostic tool for laboratories that do not readily have access to molecular testing in rendering a diagnosis for atypical melanocytic proliferations arising in giant CMN.

An update on congenital melanocytic nevus syndrome: A case report and literature review.

Congenital melanocytic nevus syndrome (CMNS) is a rare condition characterized by pigmented skin lesions that are usually present at birth and are associated with an increased risk of neurological abnormalities and malignant melanoma. It mostly results from a post-zygotic NRAS mutation of neural-derived crest cells, leading to uncontrolled cell growth. Because of the increased knowledge of the genetics underlying CMNS, targeted therapy becomes a promising treatment option. We present a case of CMNS in a newborn. Physical examination at birth showed a giant congenital melanocytic nevus, extending from the occipital to the lower lumbar region. A magnetic resonance imaging scan revealed multiple cerebral and cerebellar parenchymal lesions. Genetic analysis of the cutaneous lesions showed the presence of an NRAS Q61R mutation. The patient was treated with dermabrasion to reduce the color intensity of the nevus. However, this was complicated by recurrent wound infections and laborious wound healing. At the age of 1 year, the patient had an age-appropriate psychomotor development, without neurological deficits.

Treatment of maxillofacial congenital melanocytic nevus with percutaneous radiofrequency thermal ablation: A case series study.

When congenital melanocytic nevus (CMN) is in the maxillofacial region, a safer, more effective and fewer side-effects treatment is needed for patients with high requirement for appearance. The objective of this study was to investigate the effectiveness of radiofrequency thermal ablation (RFA) for CMN in the maxillofacial region. We reviewed 21 patients treated with RFA for CMN followed by a blinded retrospective analysis of serial photographs taken during the course of their therapy. Questionnaires were used to evaluate perceived therapeutic response and complications of this treatment. Most CMNs stopped growing, faded in color and became smaller. Reduction in size of 90% to 100% was obtained in two patients (10%), 75% to 90% in six patients (29%), 50% to 75% in two patients (10%), <50% in eight patients (38%), and three had no reduction (13%). Clear effect of clinical response score was obtained in two patients (10%), excellent in four patients (19%), good in 14 patients (67%), and fair in one patient (4%). No serious complication, severe hypertrophic scarring, and evidence of recurrence was observed in any case. Percutaneous RFA, as a minimally invasive and safe treatment, may provide an alternative treatment for maxillofacial CMN.

Cutaneous Melanoma Arising in Congenital Melanocytic Nevus: A Retrospective Observational Study.

BACKGROUND: Congenital melanocytic nevi (CMN) are benign proliferations of melanocytes usually present at birth. The magnitude of the melanoma risk for CMN is controversial, generating an ongoing debate on the best approach to manage these lesions. OBJECTIVE: To perform a retrospective, observational study with the aim to evaluate the prevalence of CMN-associated melanomas in tertiary referral centers, as well as the eventual correlation between clinical, dermoscopic, and histological features of CMN-associated melanomas. METHODS: A single-center retrospective observational study was performed on all clinical and dermoscopic images of histologically confirmed melanomas arising on CMN over a 14-year period (January 2005 to March 2019). RESULTS: Our database included 2,159 melanomas in the considered period. Of those, 27 (1.3%) were CMN-associated melanomas. The mean age of patients with CMN-associated melanoma was 33 years (range, 11-70 years). The mean diameter of CMN-associated melanoma was 18 mm (range, 6 mm to 20 cm), and 56% were located on the back. Twenty-one (77.8%) of CMN-associated melanomas arose on small CMN (<1.5 cm), 5 (18.5%) on medium-sized CMN (1.5-19.9 cm), and 1 (3.7%) on a large/giant type (≥20 cm). The majority of CMN-associated melanomas (63%) exhibited a globular dermoscopic pattern in their benign part, while a blue-white veil and irregular blotches were the most frequent dermoscopic features in the malignant part. About three quarters of melanomas occupied 10-50% of the nevus surface. Breslow thickness was higher in melanomas involving less than 10% of nevus surface (mean thickness, 1 mm) than in those affecting 10-50 and >50% of the nevus surface (0.8 and 0.7 mm, respectively). CONCLUSIONS: In our series, small CMN was the most frequent type of CMN-associated melanoma. Although the risk of melanoma is increasing by the increasing size of CMN, our finding is definitely related to the much higher prevalence of small CMN in the general population as compared to the prevalence of intermediate-sized and large CMN. LIMITATIONS: Small sample size, single-center experience, retrospective design.

Case report of a challenging medium-sized congenital melanocytic nevus (CMN): Highlighting a role for reflectance confocal microscopy (RCM) for evaluating changing CMN in children.

A 3.5-month-old boy presented with a changing medium-sized congenital melanocytic nevus on his leg. Due to atypical features on dermoscopy and reflectance confocal microscopy (RCM), an excision of the area of concern was performed. Histopathology showed many of the pathological features usually associated with a diagnosis of melanoma in situ in older patients, but due to the young age of the patient, absence of mitoses, and the degree of atypia, a diagnosis of a dysplastic compound nevus arising in a congenital compound (predominantly dermal) nevus was favored. In our case, RCM corresponded to histopathology helped target the area of concern and map the clinical and subclinical components to facilitate an optimal biopsy.

Congenital Melanocytic Nevus: Considerations for Neonatal Clinicians and a Parent Perspective.

Congenital melanocytic nevus (CMN) or nevi, also known as dark moles, are present at birth. While small CMN are quite common, large and giant nevi are rare and can be associated with significant psychological distress and the potential for further clinical sequelae. Neonatal clinicians can offer anticipatory guidance to families through distribution of resources and navigation to additional consultants.

Congenital Melanocytic Nevus with Scrotal Mass: A Diagnostic Dilemma.

Congenital melanocytic nevus is deposition of pigment producing cells of melanocytic lineage in the dermis. We present an extremely rare case of congenital melanocytic nevus with a scrotal mass associated with deposition of melanin in the brain. The mass may mimic like a testicular tumour on clinical presentation.