Dermoscopy aids in differentiating café-au-lait macules from congenital melanocytic nevi in patients with darker skin phototypes.

Dermoscopy aids in the diagnosis and management of pigmented growths and disorders of pigmentation in children. However, there is limited literature on the dermoscopic appearance of café-au-lait macules (CALMs) and congenital melanocytic nevi in patients with dark skin. We report two cases of young children with dark skin and many hyperpigmented patches in whom dermoscopy was utilized to accurately diagnose CALMs and facilitate testing for neurofibromatosis.

Eruptive Melanocytic Nevi in the Setting of Encorafenib, Cetuximab, and Binimetinib Combination Therapy: A Case Report.

Introduction: The development of new and changing melanocytic lesions has been increasingly reported as an adverse dermatologic toxicity of BRAF inhibitor therapy. Melanocytic lesions and melanomas induced by BRAF inhibitor therapy that lack BRAF V600E expression have been less commonly described. One mechanism that has been proposed for the development of BRAF inhibitor-induced melanocytic lesions, including those lacking BRAF V600E expression, is the paradoxical activation of the MAPK signaling pathway in BRAF wild-type (BRAFWT) cells. Case Presentation: Herein, we report a rare case of a 39-year-old woman who developed numerous BRAF V600E-negative eruptive melanocytic nevi following encorafenib, cetuximab, and binimetinib combination therapy, the current standard of care for the treatment of BRAF-mutant metastatic colorectal cancer. Conclusion: Patients treated with BRAF inhibitors, with or without related combination therapies, who develop BRAFWT melanocytic lesions are at risk for developing both dysplastic nevi and melanoma, thereby warranting baseline dermatoscopic evaluation prior to the initiation of therapy as well as regular follow-up during and after treatment.

Epidemiological characteristics and hospitalization burden analysis of pediatric inpatients with melanocytic nevi in China from 2016 to 2021: A nationwide retrospective study of 13,396 cases.

BACKGROUND: Melanocytic nevi typically appear in early childhood, and their removal is a common plastic surgery procedure performed on children. However, the epidemiological characteristics and hospitalization burden of children with melanocytic nevi have rarely been described in detail. METHODS: Medical records of pediatric inpatients with melanocytic nevi from January 1, 2016, to December 31, 2021, were collected from the Futang Research Center of Pediatric Development database in China. We then extracted and statistically analyzed the relevant information, including demographic characteristics, clinical information, hospitalization burden, and other basic information for each inpatient. RESULTS: Among the 13,396 inpatients with melanocytic nevi, the highest number of cases was found in East China, and most patients were residents of urban areas. Most hospitalized patients consisted of boys aged 7-12 years with melanocytic nevi. Lesion sites in the buttocks and lower limbs were most common among pediatric inpatients with melanocytic nevi. Compound nevi were the most common (38.50 %) histological subtype and the rate of conversion into melanoma was 1.02 % (137 inpatients) among pediatric inpatients with melanocytic nevi. The hospitalization burden for patients varied significantly based on factors such as the age of the patients undergoing surgery, year of hospitalization, site of the lesion, histological subtype, and surgical method. In general, if the patients' age was under 1 year, lesion site was located in face, and there was a need for excision combined with tissue expander can significantly increase the treatment fees for pediatric inpatients with melanocytic nevi. CONCLUSION: Given the increasing number and relatively large hospitalization burden among children with melanocytic nevi hospitalized in China, the government needs to pay more attention to this group and provide corresponding economic and policy support.

Spinal melanoma with optic neuropathy -rare manifestation of Neurocutaneous melanosis and PET-MRI findings.

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.

Study of Risk Factors for the Presence of Interdigital Nevi of the Feet. / Estudio de los factores de riesgo de la presencia de los nevus interdigitales de los pies.

BACKGROUND AND OBJECTIVES: No studies focused on counting the interdigital acquired melanocytic nevi (AMN) of the foot (IDNf) have ever been conducted. Therefore, our objective was to study the relationship between the presence of IDNf and the total number of AMN in the feet and the rest of the body, the racial phenotypic characteristics, and other risk factors for melanoma. MATERIAL AND METHODS: We conducted a cross-sectional observational study with 255 patients ≥18 years old who attended our Dermatology Unit from September 2020 through February 2021, and included all AMN ≥1mm from the feet and ≥2mm from the rest of the bod. The association between the variables was studied using univariate and multivariate logistic regression models. RESULTS: The presence of IDNf was significantly and independently associated with the presence of plantar AMN and body counts ≥50 AMN. However, no significant differences were observed regarding sex, age, personal history of melanoma, presence of nevi on the dorsum of the foot, history of sunburn or UV rays, or racial phenotypic characteristics. CONCLUSIONS: The presence of IDNf is associated with a higher count of plantar nevi and total AMN in the body, meaning that interdigital spaces of the foot-anatomical expansions of the sole and other possibly genetic causes-could be responsible for the number of AMN found in this location, as these regions are not photoexposed.

Bilateral Naevus of Ito and Ota With Palatal Involvement.

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.

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.

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.

[Therapeutic management of a kissing nevus of the eyelid]. / Therapeutisches Management eines "kissing nevus" des Augenlids.

Congenital divided melanocytic nevi of the upper and lower eyelid are rare pigmented changes of the eyelids. These processes are also known as "kissing nevi," "panda nevi," and "split ocular nevi," and were first described by Fuchs in 1919. About 120 cases have been described in the literature so far. Congenital melanocytic nevi are either present at birth (small nevi are already found in about 1% of neonates) or manifest predominantly during the first decade of life. These rare melanocytic changes of the eyelids should be controlled regularly, as malignant transformation can occur. The actual incidence of malignant transformation is highly variable in the literature, ranging from 2 to 40% depending on the duration of follow-up, with an average of 14% for the whole lifetime. Moreover, nevi of the eyelids may be considered cosmetically disturbing and cause functional problems. Therapeutic removal (dermabrasion, cryotherapy, laser therapy, and surgical excision with ophthalmoplastic reconstruction) is rarely medically indicated due to the low risk of malignant transformation. Removal can be performed in cases of secondary amblyopia in ptosis, compression of the lacrimal point, epiphora, or cosmetic desire. Treatment becomes necessary not only in case of suspicious manifestation or impairment of eyelid function, but it also helps to avoid possible bullying at school among children and is recommended at age 4 to 6 (before school age).

Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).

We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.

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.

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.

An Observational Study Comparing the Number, the Localization and the Dermoscopic Patterns of Melanocytic Nevi in Cutaneous Melanoma and Basal Cell Carcinoma Patients.

Context: Number of nevi is a risk factor for melanoma and basal cell carcinoma. Studies suggest that the dermoscopic pattern of nevi of melanoma patients may differ from healthy individuals. Similar data in patients with basal cell carcinoma is missing. Aims: The purpose of the study was to determine the number, anatomic distribution and dermoscopic pattern of nevi in melanoma and basal cell carcinoma patients. Settings and Design: An observational prospective study was conducted. Materials and Methods: Total body mole maps of 26 melanoma and 33 basal cell carcinoma patients were analysed. Statistical Analysis Used: Statistical analysis was done using the "IBM SPSS for Windows Version 22.0" package programme. Results: Number of nevi both on head and forearm were found significantly higher in the melanoma group (P = 0.015 and P = 0.031). Most frequent dermoscopic pattern was the complex pattern which was observed in 50.67% of melanoma and in 53.41% of basal cell carcinoma groups. Percentage of nevi with homogenous pattern located on the trunk and percentage of nevi with complex pattern located on the forearm was significantly higher in the melanoma group (P = 0.030 and P = 0.042). Conclusions: Higher number of nevi on the head and forearms; and more nevi showing homogenous pattern on the trunk and complex pattern on the forearms were the hallmarks of nevi in melanoma patients in comparison to basal cell carcinoma patients.

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.

Differentiating between early melanomas and melanocytic nevi: A state-of-the-art review.

Clinicians and dermatologists are challenged by accurate diagnosis of melanocytic lesions, due to melanoma's resemblance to benign skin conditions. Several methodologies have been proposed to diagnose melanoma, and to differentiate between a cancerous and a benign skin condition. First, the ABCD rule and Menzies method use skin lesion characteristics to interpret the condition. The 7-point checklist, 3-point checklist, and CASH algorithm are score-based methods. Each of these methods attributes a score point to the features found on the skin lesion. Furthermore, reflectance confocal microscopy (RCM), an integrated clinical and dermoscopic risk scoring system (iDscore), and a deep convoluted neural network (DCNN) also aids in diagnosis. RCM optically sections live tissues to reveal morphological and cellular structures. The skin lesion's clinical parameters determine iDscore's score point system. The DCNN model is based on a detailed learning algorithm. Therefore, we discuss the conventional and new methodologies for the identification of skin diseases. Moreover, our review attempts to provide clinicians with a comprehensible summary of the wide range of techniques that can help differentiate between early melanomas and melanocytic nevi.

Eosinophils in metastatic melanoma.

The potential significance of tissue eosinophils melanomas is unknown. We strove to determine a potential association between the presence of tissue eosinophils and prognosis of patients with metastatic melanoma (MM). A retrospective electronic data base was queried to identify patients (age ≥18 years) evaluated January 1, 2011-October 1, 2022 (inclusive) at our multi-site medical center, who had metastatic melanoma and at least 1 biopsy of melanoma or a melanocytic nevus that was reported to show eosinophils. Patient demographics, histopathological tumor features, AJCC classification parameters, and peripheral blood eosinophilia (PBE) obtained during the patients' routine care were recorded. Seven patients met inclusion criteria had checkpoint inhibitor therapy for MM; 4/7 had prominent eosinophil infiltrates among their melanocytic nevi or/and melanomas, and all had absent or less than predicted tumor progression. In our small cohort of patients undergoing immunotherapy for metastatic melanoma, the presence of tissue eosinophils among nevi or melanomas was associated with a favorable response. While lymphocytes have been considered key in the host response to melanoma, the role of eosinophils may be underappreciated.