Newborn Skin: Part II. Birthmarks.

Birthmarks in newborns can be classified as vascular, melanocytic or pigmented, or markers of underlying developmental abnormalities of the nervous system. A nevus simplex is a benign capillary malformation. Newborns with a nevus flammeus can be safely treated before one year of age with a pulsed dye laser to reduce the visibility of lesions. Infantile hemangiomas should be treated with systemic beta blockers if there is a risk of life-threatening complications, functional impairment, ulceration, underlying abnormalities, permanent scarring, or alteration of anatomic landmarks. Dermal melanocytosis is a benign finding that is easily recognized and does not warrant further evaluation. A solitary congenital melanocytic nevus that is less than 20 cm in diameter may be observed in primary care; children with larger or multiple nevi should be referred to pediatric dermatology due to the risk of melanoma. Newborns with skin markers of occult spinal dysraphism (other than a simple, solitary dimple) should have lumbar spine imaging using ultrasonography or magnetic resonance imaging.

Neonatal Paratesticular Scrotal Mass: A Rare Case of Atypical Neurofibromatous Neoplasm with Uncertain Biologic Potential.

ABSTRACT: Atypical neurofibromatous neoplasm with uncertain biologic potential presenting as a paratesticular scrotal mass in a neonate with congenital giant melanocytic nevus is rare. Only one such case of neonatal scrotal neurofibroma has been reported earlier. We report an additional case and its management.

Thickness of melanocytes in giant congenital melanocytic nevus for complete surgical excision: clinicopathological evaluation of 117 lesions according to the area and size.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion. METHODS: Overall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness. RESULTS: The thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20-29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size. CONCLUSION: GCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN. In the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.

What are congenital melanocytic nevi?

Congenital melanocytic nevi (CMN) are special types of moles. CMN happen when extra pigment-making cells (melanocytes) grow in a baby's skin while the baby is forming before birth. They are not caused by anything their parent did or didn't do during pregnancy. These moles are there when the baby is born, stay on the skin for life, and grow as the child grows.

Clinical study on the role of platelet-rich plasma in human acellular dermal matrix with razor autologous skin graft repair of giant congenital pigmented nevus in children.

BACKGROUND: NA OBJECTIVE: Evaluate the safety and feasibility of platelet-rich plasma (PRP) in the treatment of giant congenital melanocytic nevi (GCMN) in children with human acellular dermal matrix (HADM) transplantation. PATIENTS AND METHODS: A total of 22 children with GCMN were included in the study. They were divided into an experimental and a control group. The experimental group used the method of HADM with Razor Autologous Skin Graft combined with PRP to repair skin and soft tissue defects after giant nevus resection (Group A, n = 11). The control group was treated with HADM with Razor Autologous Skin Graft (Group B, n = 11) only. To compare the survival rate of skin grafts, we used the Vancouver Scar Scale (VSS) for the postoperative skin graft area and the Patient and Observer Scar Assessment Scale (POSAS) to compare the two groups of patients. RESULTS: There was no statistically significant difference in age, gender, location of giant nevi, and pathological classification between Group A and Group (P > 0.05). The survival rate of skin grafting and the VSS and POSAS scores of scar tissue in group A were superior to those of group B (P < 0.05). CONCLUSIONS: PRP has improved the survival rate of composite skin grafting in children with GCMN, and long-term satisfactory prognosis of scar healing. Therefore, we consider this treatment method a valuable contribution to clinical practice.

Metabolomic analysis reveals the biological characteristics of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (GCMN) is a congenital cutaneous developmental deformity tumor that usually occurs at birth or in the first few weeks after birth, but its pathogenesis is still unclear. In this study, nuclear magnetic resonance-based metabolomics strategy was employed to evaluate the metabolic variations in serum and urine of the GCMN patients in order to understand its underlying biochemical mechanism and provide a potential intervention idea. Twenty-nine metabolites were observed to change significantly in serum and urine metabolomes, which are mainly involved in a variety of metabolic pathways including glyoxylate and dicarboxylate metabolism, TCA cycle and metabolisms of amino acids. The substantial cores of all the disturbed metabolic pathways are related to amino acid metabolism and carbohydrate metabolism and regulate the physiological state of the GCMN patients. Our results provide the physiological basis and physiological responses of GCMN and will be helpful for better understanding the molecular mechanisms of GCMN in future research.

Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition.

Among children with multiple congenital melanocytic nevi, 25% have no established genetic cause, of whom many develop a hyperproliferative and severely pruritic phenotype resistant to treatment. Gene fusions have been reported in individual cases of congenital melanocytic nevi. We studied 169 patients with congenital melanocytic nevi in this study, 38 of whom were double wild type for pathogenic NRAS/BRAF variants. Nineteen of these 38 patients had sufficient tissue to undergo RNA sequencing, which revealed mosaic BRAF fusions in 11 of 19 patients and mosaic RAF1 fusions in 1 of 19. Recurrently, fusions involved the loss of the 5´ regulatory domain of BRAF or RAF1 but preserved the kinase domain. We validated all cases and detected the fusions in two separate nevi in 5 of 12 patients, confirming clonality. The absence of the fusion in blood in 8 of 12 patients indicated mosaicism. Primary culture of BRAF-fusion nevus cells from 3 of 12 patients demonstrated highly increased MAPK activation, despite only mildly increased BRAF expression, suggesting additional mechanisms of kinase activation. Trametinib quenched MAPK hyperactivation in vitro, and treatment of two patients caused rapid improvement in bulk tissue, improving bodily movement and reducing inflammation and severe pruritus. These findings offer a genetic diagnosis to an additional group of patients and trametinib as a treatment option for the severe associated phenotypes.

Resurfacing of Sleeve-Like Circumferential Giant Congenital Melanocytic Nevi on the Upper Extremity With Pre-Expanded Pedicled Flap.

As the relative shortage of healthy tissue obviates the option of local soft tissue coverage, reconstruction of circumferential giant congenital melanocytic nevi (GCMN) on the upper extremity remains particularly challenging. Here the authors report a 3-stage procedure involving pre-expanded pedicled flap from the torso for the reconstruction of upper extremity after circumferential GCMN excision in pediatric patients. The giant nevus was completely removed and the size of the excised nevus was 31 × 14.5 cm. The donor site was primarily closed. No major complication was encountered. Reconstruction with expanded pedicled flap achieved satisfactory results, both functionally and cosmetically.

Vitamin D status in children with congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are rare, pigmented birthmarks that can predispose patients to melanoma of the central nervous system and skin. Data from non-CMN melanoma cohorts suggest that vitamin D levels may be connected to outcome, prompting this study of 25-hydroxyvitamin D levels in plasma samples from 40 children with CMN. While 27% were insufficient and 13% deficient, this was representative of European populations, and UK supplementation guidelines are already in place. Our data support routine vitamin D supplementation for all CMN patients during winter months, without routine serum measurement.

Histopathological characteristics analysis of giant melanocytic naevi in children.

BACKGROUND: The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis. AIMS: This study aimed to investigate the pathological features of GCMN, including its satellite lesions. PATIENTS/METHODS: Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed. RESULTS: In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus. CONCLUSIONS: We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.

Congenital melanocytic naevus (CMN) through the lens: Using photo-elicitation interviews to explore adjustment in adolescents with a rare birthmark condition.

Adolescents with the rare birthmarks congenital melanocytic naevi (CMN) experience physical and psychosocial challenges, many of which stem from looking different from the 'norm'. However, some adjust and have positive experiences. Understanding the lived experiences of adolescents who have adjusted to CMN can provide a holistic picture of adjustment and inform the development of support and interventions for others with the condition. Open, participant-driven photo-elicitation interviews were conducted with four White females (15-17 years) who self-identified as having adjusted to CMN. Participants chose five photographs which were used to guide the interviews (47-80 min). Interpretative phenomenological analysis (IPA) was used to analyse the transcribed interview data. Three superordinate themes were identified: 'Accepting My 'True' Self' (1), 'I am Not Alone in This' (2), and 'Developing as a Person' (3). The themes related to accepting CMN as part of their identity, developing a positive body image (e.g., body appreciation, broad conceptualisations of beauty, body image flexibility), feeling supported and accepted by family, friends, and others with CMN, and developing adaptive coping skills. Findings suggest positive body image may be important for adjustment and can be determined by an individual. The benefits of using photo-elicitation within appearance research are discussed.

Treatments of palpebral congenital melanocytic nevus: a systematic review.

PURPOSE: Palpebral congenital melanocytic nevi (PCMN) is a rare congenital skin lesion affecting the eyelids that can lead to cosmetic and psychological concerns and potential health risks such as malignancy. Several authors have analyzed therapeutical strategies to treat PCMN. However, there was no consensus in the literature. This systematic review aimed to evaluate the effectiveness, safety, and success of treatments of PCMN. METHODS: We conducted a systematic review following PRISMA guidelines from October 2022 to April 2023. We included all types of study designs that described or compared PCMN treatments and interventions, as well as histology, recurrence, adverse events, patient satisfaction, and malignant transformation. The search strategy was based on specific search words through the following databases: PubMed, Embase, Latin American and Caribbean Health Sciences Literature (Lilacs), Web of Science, and Scopus. Ongoing studies and gray literature studies were included. RESULTS: We analyzed 25 case reports with 148 participants. The effectiveness, success, and satisfaction with various treatments for PCMN depend on the specific treatment method and the individual patient's case. CONCLUSIONS: Most of the studies showed that surgical procedures (exeresis) are able to treat PCMN in the eyelid. The variability in outcomes emphasizes the importance of further research to better understand the most effective and safe approaches for treating congenital melanocytic nevi.

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.

Transformed Giant Congenital Melanocytic Nevus on 18 F-FDG PET/CT.

ABSTRACT: A 50-year-old man experienced cough and bloody sputum for 1 month. CT detected a mass in the right lung. Staging 18 F-FDG PET/CT revealed multiple hypermetabolic lesions in the lung, mediastinum, liver, and bones. Further physical examination revealed black patches in the skin covering most parts of the body, which presented at his birth and were growing very slowly, consistent with giant congenital melanocytic nevus. Pathology examination after biopsy of the lung demonstrated metastatic melanoma.

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.

PRAME Immunohistochemical Expression and TERT Promoter Mutational Analysis as Ancillary Diagnostic Tools for Differentiating Proliferative Nodules From Melanoma Arising in Congenital Nevi.

ABSTRACT: Proliferative nodules (PNs) are benign melanocytic proliferations that typically develop within congenital melanocytic nevi. These tumors have overlapping histological features with melanoma. Ancillary immunohistochemistry and genomic sequencing are often used in diagnostically challenging cases. To assess the utility of preferentially expressed antigen in melanoma (PRAME) immunoreactivity and telomerase reverse transcriptase (TERT) promoter mutation analysis in distinguishing PNs from melanoma arising in congenital nevi cases. Twenty-one PNs and 2 melanomas arising in congenital nevi were immunohistochemically stained with PRAME. Cases with adequate tissue were also assessed for TERT promoter mutations through sequencing studies. The positivity rates in the PN cases were compared with those of the melanomas. Two of 21 PN cases were diffusely positive for PRAME (≥75% of the tumor cells positive). Two of 2 melanomas arising in congenital nevus cases were also diffusely PRAME positive. The difference was statistically significant using a Fisher exact test. None of the tumors harbored TERT promoter mutations. PRAME immunohistochemical marker may have diagnostic value in distinguishing diagnostically challenging PNs from melanoma, but diffuse expression is not specific for melanoma.