Congenital Nevi Research Articles

Perfil epidemiológico e clínico de crianças com nevo melanocítico congênito gigante em um serviço de dermatologia

OBJECTIVE: to describe five children with Congenital Giant Melanocytic Nevus (NMCG) at the Dermatology Service at the State University of Pará in Belém - PA, Brazil. CASE DESCRIPTION: patients aged 1 to 11 years, four of whom were female, all of them brown, in good nutritional status, prenatal without complications, and denied consanguinity. The five cases presented lesions on the trunk, with different distribution patterns: swimming trunks (1), body (1), back (1), and bolero (2), most with more than fifty satellite lesions containing hypertrichosis and pruritus. In the histopathological analysis, all of them were compatible with a nevus, one of the cases was associated with a neurofibroma, two with neurocutaneous melanosis and one with melanoma in the brain, evolving to death. COMMENTS: Congenital Giant Melanocytic Nevus is a rare condition, defined by the presence of a melanocytic lesion, measuring at least 20 cm, present since birth. It has its clinical relevance due to the association with serious complications such as melanoma and / or neurocutaneous melanosis. The registration of this series aims to contribute to greater knowledge about the disease, which has physical, psycho-emotional, social, and risk of malignancy implications.

A Newborn with a Giant Congenital Melanocytic Nevus and Hyperbilirubinemia: What to do Now

Giant congenital melanocytic nevi (GCMN) are rare skin lesions that affect approximately 1 in 20,000 live births. GCMN must be followed up closely because of its association with an increased risk of malignant degeneration. We report a newborn with a giant lession of 14 cm in diameter which was located on the chest and multiple satellite lesions were present on the body. The patient required phototherapy due to hyperbilirubinemia. Some studies suggest that phototherapy can increase the incidence of neonatalnevi, and melanocytic nevi is the most important risk factor for the occurrence of skin melanoma. Considering the risk of developing kernicterus, we concluded that the most appropriate solution for the patient was to cover the lesions and apply phototherapy in the prone position.

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

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. 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. A total of 10 patients with non-multiple, medium-sized, congenital melanocytic nevus were included in this study. Lesions were removed using surgical procedures. 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. 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.

Congenital Giant Melanocytic Nevus with Meningeal Melanocytosis in a Term Neonate- A Case Report

Congenital giant melanocytic nevus presenting in the neonatal period is a clinical diagnosis, but the extra dermatology manifestations require early recognition. Meningeal melanocytosis is one such association which increases the risk of epilepsy. We report a neonate with large congenital melanocytic nevus over the torso with satellite lesions presenting with meningeal melanocytotic in the right parietal and cerebellar region. We discuss the clinical course, management and review the literature on this condition.

Squamous Cell Carcinoma Arising in the Irradiated Field More than 60 Years after Radiotherapy for a Giant Congenital Melanocytic Nevus.

Squamous Cell Carcinoma Arising in the Irradiated Field More than 60 Years after Radiotherapy for a Giant Congenital Melanocytic Nevus.

Congenital Melanocytic Nevi of the Lower Limb: The Rule of Thumb for Surgical Excision in Children

Congenital melanocytic nevi (CMN) of the lower limb display the highest projected adult size. Surgical management includes simple excision and also more complex interventions with tissue expansion, skin graft, or flap, depending on the CMN size and patient age.

Bulky Perineal Naevocytoma with a Rare Variant of Giant Congenital Melanocytic Nevus in a Female Neonate

Bulky Perineal Naevocytoma with a Rare Variant of Giant Congenital Melanocytic Nevus in a Female Neonate

Spotlight in Plastic Surgery: January 2023.

Spotlight in Plastic Surgery: January 2023.

A Curious Case of an Accented Extra Nose.

There have been about 60 cases of supernumerary nostril reported. We encountered a 38 weeker, male child with supernumerary nostril and midline congenital nevus which was later locally excised. The uniqueness of our case is the presence of an entirely well-formed nostril perched on top on the normal nose.

Melanomas in children and adolescents: Clinicopathologic features and survival outcomes

Melanoma in the first two decades of life is uncommon and poorly understood. To assess clinicopathologic features and survival of children (≤11 years) and adolescents (12-19years) diagnosed with melanoma. A pooled cohort of 514 patients was analyzed (397 Dutch, 117 Australian; 62 children, 452 adolescents). Pathology reports were re-evaluated to determine melanoma subtypes. Multivariable Cox models were generated for recurrence-free survival (RFS) and overall survival (OS). Melanoma subtypes were conventional melanoma (superficial spreading, nodular, desmoplastic, acral lentiginous), spitzoid melanoma, and melanoma associated with a congenital nevus in 428, 78, and 8 patients, respectively. Ten-year RFS was 91.5% (95%CI 82.4-100%) in children and 86.4% (95%CI 82.7-90.3%) in adolescents (p=0.32). Ten-year OS was 100% in children and 92.7% (95%CI 89.8-95.8%) in adolescents (p=0.09). On multivariable analysis possible only for the adolescent cohort due to the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status and melanoma subtype were not. Breslow thickness >4mm was associated with worse RFS. Retrospective study. Survival rates for children and adolescents with melanomas were high. Ulceration, head or neck location and Breslow thickness >4mm predicted worse survival in adolescents.

Histopathological and Immunohistochemical Features of Small to Big Satellite Nevus Uncover the Nevogenesis of Large/Giant Congenital Melanocytic Nevus.

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.

NRAS p.Q61R/K allele load is correlated to different phenotypes of congenital melanocytic naevi.

Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined. To determine the correlation of variants allele load and different phenotypes of CMN. A panel of genes in the Ras/Raf/MAPK signalling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes, including anatomical localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, colour variation and hypertrichosis, were analysed. In addition to the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS (p.G13R and p.M72fs), BRAF (p.D22N) and MAP2K1 (p.I107fs, p.F209fs, p.Q354H and p.G91_L92insHDQARRLVGDLEHHKPSG). Furthermore, a higher allele load of NRAS p.Q61R/K was found in the trunk and limbs of CMN. It was also found in CMN with larger size, higher colour variation and more significant hypertrichosis, surface rugosity and asymmetry. We discovered more genetic variants of NRAS, BRAF and MAP2K1 and established a correlation between the allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitate a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics used in clinical practice.

Defining patient-centered research priorities in pediatric dermatology.

Patient and caregiver perspectives are critical in understanding dermatologic disease impact, presentation, and management in children. The Pediatric Dermatology Research Alliance (PeDRA) Patient Advisory Committee (PtAC), a group of patient representatives and parents of children with cutaneous disease, pursued a multistep, iterative, consensus-building process to identify comprehensive, high-priority research needs. Building on discussions at the 2020 PeDRA Annual Conference, a research prioritization survey was developed and completed by PtAC members. Survey themes were aggregated and workshopped by the PtAC through a series of facilitated calls. Emerging priorities were refined in collaboration with additional PeDRA patient community members at the 2021 PeDRA Annual Conference. Subsequently, a final actionable list was agreed upon. Fourteen PtAC members (86.7% female) representing patients with alopecia areata, atopic dermatitis, vascular birthmarks, congenital melanocytic nevi, ectodermal dysplasias, epidermolysis bullosa, Gorlin syndrome, hidradenitis suppurativa, ichthyosis, pemphigus, psoriasis, Sturge-Weber syndrome, and pachyonychia congenita completed the survey. Following serial PtAC meetings, 60 research needs were identified from five domains: psychosocial challenges, health care navigation/disease management, causes/triggers, treatments to preserve or save life, and treatments to preserve or save quality of life. Many pediatric dermatology research priorities align across affected communities and may drive meaningful, patient-centric initiatives and investigations.

Deficiencies in mismatch DNA repair: providing the soil for large-to-giant congenital melanocytic naevus development.

Deficiencies in mismatch DNA repair: providing the soil for large-to-giant congenital melanocytic naevus development.

260 Mosaic BRAF fusions are a recurrent cause of multiple congenital melanocytic naevi

Congenital melanocytic naevi (CMN) are moles present at birth, and when multiple or very extensive can involve other organ systems as well as predisposing to melanoma. Some CMN develop a highly proliferative phenotype whose progression is poorly understood. Genotypically, CMN are caused by mosaic NRAS missense mutations in 67% of cases and BRAF missense mutations in 7% of cases. Single cases of mosaic gene fusions have been previously described. To investigate the remaining 25%, skin biopsies from 19 patients shown to be double wildtype for NRAS/BRAF underwent transcriptome-wide paired-end RNA sequencing to detect gene fusion transcripts.

Reflectance confocal microscopy in paediatric patients: Applications and limits.

Reflectance confocal microscopy (RCM) is a non-invasive diagnostic tool extensively studied for adult patients. In this retrospective case series conducted at the Dermatology Unit of the University of Campania, Naples, Italy, all patients under 19 years old who were submitted to RCM from January 2011 to December 2021 where evaluated. The aim of the study was to review the most usual indications and possible benefits that it might add for children. Data collection included 215 patients (86 males and 129 females, mean age: 12). Most of the exams (n=85; 39.5%) were performed for lesions clinically compatible with Spitz nevi, congenital nevi (n=50 23,2%) and atypical melanocytic lesions (n=46; 21%) among which two melanomas were detected. RCM can be an useful instrument when evaluating paediatric patients and may help avoid unnecessary biopsy in most cases, representing an additional instrument to improve diagnostic accuracy.

Deficient mismatch repair is detected in large-to-giant congenital melanocytic naevi: providing new insight into aetiology and diagnosis.

The aetiologies of large-to-giant congenital melanocytic naevi (LGCMN) remain ambiguous. A previous study discovered signatures associated with deficient mismatch repair (dMMR) in patients with LGCMN. However, a screening diagnostic immunohistochemistry (IHC) panel of dMMR in patients with LGCMN has not been performed to date. To identify the MMR status and aetiologies of LGCMN. A total of 110 patients with CMN, including 30 giant CMN, 30 large CMN, 30 medium CMN and 20 small CMN, underwent diagnostic IHC (for MSH6, MSH2, PMS2 and MLH1) screening of dMMR. The control group comprised normal skin samples from 20 healthy people. MMR proteins with little effect (MSH3 and PMS1) on the MMR system were stained in all samples. The surgical procedures conducted on each patient were noted because they might alter the behaviour of CMN and confound the results. Binary logistic regression analyses were performed between the phenotypic data and MMR status to identify associations. Whole-exome sequencing was performed on the main naevi, satellite naevi and normal skin tissues of four patients to detect variants. Mutational signature analyses were conducted to explore the aetiologies of LGCMN. dMMR was detected in 37% (11 of 30) of giant, 23% (7 of 30) of large and 7% (2 of 30) of medium CMNs, but were not identified in small CMNs or normal skin tissues. Moreover, multiple LGCMNs had a much higher dMMR rate than did single LGCMNs. The regression analyses showed that MMR status was significantly associated with CMN size and the presence of satellites, but was not correlated with age, sex, location, satellite diversity or tissue expansion. Notably, the pattern of protein loss in LGCMN mainly consisted of PMS2 loss. Mutational signature analyses detected dMMR-related signatures in patients with LGCMN. Additionally, rare deleterious germline mutations in DNA repair genes were detected in LGCMN, mainly in MSH6, ATM, RAD50, BRCA1 and ERCC8. These germline mutations were single-patient variants with unknown significance. dMMR is one of the aetiologies underlying LGCMN, particularly in patients with giant main lesions and multiple satellite lesions. Further studies are necessary to investigate the role of the DNA repair system, particularly MMR, in LGCMN.

Surgical therapy of congenital nevi using power-stretching technique on the forehead.

Surgical therapy of congenital nevi using power-stretching technique on the forehead.

PRAME is a useful marker for the differential diagnosis of melanocytic tumours and histological mimics.

Although the morphological assessment of melanoma is generally straightforward, diagnosis can be especially difficult when the significant morphological and immunohistochemical results overlap with those of benign and malignant melanocytic tumours and histological mimics. This study assessed the potential diagnostic utility of measuring PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemically in naevi, melanomas and clear cell sarcomas (CCSs) in Chinese patients. We examined the immunohistochemical expression of PRAME in 317 melanocytic naevi, 178 primary melanomas, 72 metastatic melanomas and 19 CCSs and compared the sensitivity and specificity of PRAME immunohistochemistry (IHC) in the differential diagnosis of melanocytic tumours and histological mimics. Of the 317 melanocytic naevi, 98.1%were completely negative for PRAME; six cases showed focal PRAME immunoreactivity in a minor population of lesional melanocytes. Diffuse nuclear immunoreactivity for PRAME was found in 89.9% of primary melanomas and 93.1% of metastatic melanomas. Regarding melanoma subtypes, PRAME was expressed in 100% of superficial spreading melanomas, 100% of melanomas arise in congenital naevus, 91.4% of nodular melanomas, 87.8% of acral lentigo melanomas, 80.0% of lentigo malignant melanomas, 60.0% of Spitz melanomas, 96.2% of mucosal melanomas and 80.0% of uveal melanomas. None of the two desmoplastic melanomas expressed PRAME. Of the 19 CCS cases, 89.5% were negative for PRAME and 10.5% showed focal weak PRAME immunoreactivity in a minor population of tumour cells. Our findings indicate that PRAME may be a useful marker to support a suspected diagnosis of melanoma. In addition, lack of PRAME expression is a valuable hint to CCS in a suspected case, and then molecular confirmation of the presence of EWSR1 rearrangement is necessary.

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.