Congenital melanocytic nevi (CMN) exhibit various clinical presentations. Dermoscopy and confocal microscopy only assess the superficial dermis. Magnetic resonance imaging cannot evaluate skin layers comprehensively. High-frequency Doppler ultrasound (HFUS) can define the extent of melanocytic lesions and suggest patterns of potential complications. The objective of the study is to evaluate HFUS characteristics of patients with CMN and, secondarily, to study the utility of HFUS in evaluating proliferative nodules and enlarged lymph nodes. A prospective study of patients with multiple and non-small CMN between January 2016 and June 2021 was conducted. Clinical imaging and HFUS were routinely used to follow up on distinctive areas. A retrospective analysis of HFUS images and correlation with presentation was performed. Seventy-one patients with CMN, 149 HFUS scans. Median age: 14 years (IQR: 8 months-79 years), 59% female. Large/giant nevi n = 44 (61.9%). CMN affected the epidermis/dermis in 51 (71.8%), hypodermis in 17 (24%), and muscle in 3 (4.2%). Thirteen patients (18.3%) had nodular lesions; 1 showed atypical vessels on HFUS, which was confirmed histologically as an atypical proliferative nodule. Heterogeneity of patients and retrospective analysis. HFUS allows the characterization of non-small CMN by assessing depth and diagnosing complications such as melanomas and enlarged lymph nodes.

Among nevus-associated melanomas, which overall account for 20%-30% of all melanomas, those arising specifically in congenital melanocytic nevi are infrequent, but can be disproportionately frequent in childhood and adolescence. Congenital melanocytic nevi (CMNi) are common benign melanocytic tumors that are present at birth or become apparent in early childhood. They are classified based on the projected adult size. Small and medium-sized CMNi are frequent, whereas large/giant CMNi (over 20 cm in diameter) are rare, but can be associated with high morbidity due to marked aesthetic impairment and the risk of neurocutaneous syndrome or melanoma development. In this setting, melanomas can appear in early childhood and are very aggressive, while the risk of small-medium CMNi of developing melanoma is low and similar to non-congenital melanocytic nevi. Histologically, most melanomas on CMNi initiate their growth at the epidermal-dermal junction, but in large/giant CMNi they can develop entirely in the dermis, in deeper tissues, or in extracutaneous sites (especially in the central nervous system). Most CMNi harbour an NRAS mutation, but other genes are rarely involved, and gene translocations have recently been described. However, no prognostic implications have been associated with the CMN genotype. Melanomas developed on CMNi harbour additional molecular alterations to which the aggressive clinical course of these tumors has been attributed. This review covers the distinctive clinical and pathological aspects of melanomas on CMNi, and includes the epidemiology, etiopathogenesis, clinical and dermoscopic presentation, histological and molecular characteristics, as well as tumour behaviour.

Treatment indications of congenital melanocytic naevi (CMN) have shifted from the prevention of malignant transformation more towards the improvement of appearance and psychosocial health. Surgical excision is often preferred, but its safety and effectiveness remain unclear. To assess the outcomes of surgical excision of medium-to-giant CMN. safety (complications). effectiveness (satisfaction and CMN core outcomes). PubMed, EMBASE, and CENTRAL were searched for studies on the excision of medium-to-giant CMN and/or CMN requiring reconstruction or serial excision. Meta-analyses of safety per patient were conducted, and pooled outcomes of safety and effectiveness were presented in summary-of-findings tables. A total of 1444 studies were found, of which 22 were included, evaluating 643 eligible patients. Study quality varied, and reporting of baseline characteristics and outcomes was heterogeneous. Pooled proportions were overall 9.8% for major wound-related complications, 1.2% for minor wound-related complications, 1.2% for scar-related complications, and 4.3% for anatomical deformities. For large/giant CMN, complication rates were, respectively, 23.1%, 2.9%, 12.9%, and 2.4%; and for CMN with eyelid involvement, 0.5%, 3.3%, 0.4%, and 54.2%. Patients rated their satisfaction with the cosmetic outcome as 24.4% excellent, 71.0% good, and 4.6% poor/moderate. Physicians rated this as 18.3% excellent, 70.1% good, and 11.7% poor/moderate. Thirty-five other outcomes of effectiveness were summarized. However, many were rarely reported. Surgical excision of CMN appears to be safe and effective in many cases, depending on CMN size and location. Major wound-related complications and scar-related complications occurred more frequently with large/giant CMN, whereas anatomical deformities occurred with the majority of CMN with eyelid involvement.

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.

The nevogenesis of large/giant congenital melanocytic nevus (lgCMN) is a complex biological process including several integral prenatal stages. Limited by ethical concerns, the debate of whether lgCMN develops from the epidermis to the dermis or in the opposite direction remains controversial. With the present study of the accompanying satellite nevi, we tend to support that lgCMN develops from epidermis to dermis. The satellite nevi were divided into 3 groups: big (diameter >10 mm), medium (>5 mm but ≤10 mm), and small (≤5 mm). Hematoxylin and eosin and immunohistochemical staining (SOX10, Ki67, and p16) were performed to compare the nevocyte infiltration depth as well as the positively stained rates among these satellite nevi. Compared to big satellite nevi, less deeply the nevocytes infiltrated the dermis, as well as more cells expressed SOX10 and Ki67 in the epidermis and fewer cells expressed p16 in the dermis of small satellite nevi. Additionally, two specimens were obtained from each of 4 patients who underwent serial resections of lgCMN at an average interval of 1.75 years to examine the histopathological changes. In the present study, satellite nevi of different sizes represent different stages of lgCMN from early to late, deepening our comprehension of the sequential stages of lgCMN nevogenesis. Initially, abnormal nevocytes seeded, proliferated, and spread along the epidermis. At rete ridges that protrude from the papillary dermis within the epidermis, some nevocytes formed nests and gradually penetrated into the dermis. Eventually, the nevocytes infiltrated the dermis and entered a homeostatic state. This study provides new evidence supporting the theory of epidermal-to-dermal nevogenesis in lgCMN.