Large Congenital Melanocytic Nevi Research Articles

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.

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.

RARE-10. Neurocutaneous melanocytosis-associated hydrocephalus: the MSK experience from 2001-2022

OBJECTIVE: We hypothesize that patients with neurocutaneous melanocytosis-associated melanoma and ventriculoperitoneal shunts are at risk of developing intraperitoneal spread of melanoma. BACKGROUND: Neurocutaneous melanocytosis, a rare condition characterized by excessive proliferation and deposition of melanocytes in the leptomeninges and brain parenchyma, typically occurs in children with large congenital melanocytic nevi and multiple smaller congenital nevi. These patients are at heightened risk for developing NRAS+ melanomas in the central nervous system, which in turn may lead to symptomatic hydrocephalus requiring cerebrospinal fluid diversion for symptom relief. METHODS: Retrospective single-institution study of patients with histologically or radiographically confirmed NCM evaluated at Memorial Sloan Kettering Cancer Center (MSKCC) from 2001-2022. RESULTS: Of the 47 patients with a diagnosis of NCM, 44 patients had symptomatic neurological complications. Eleven patients developed hydrocephalus, 10 had CNS melanoma, and required ventriculoperitoneal shunt placement. Nine of the 10 patients ultimately died of their disease. Three patients were diagnosed with intraperitoneal melanoma, though data are unavailable for the remaining eight. CONCLUSIONS: All (n=11) patients with NCM-associated CNS melanoma required VP shunts for symptomatic relief. Ten of these patients died within 4.3 years of VP shunt placement, with a range of 1 month to 13.5 years prior to succumbing to their disease. While the intraperitoneal pathology remains unknown for 7 of the cases, 3 had confirmed intraperitoneal melanoma, suggesting that VP shunts provided the conduit to CNS melanoma seeding of the peritoneum. Obtaining baseline abdominal imaging studies prior to VP shunt placement may be helpful in the follow-up of these patients.

Quality of Life in Chinese Patients With Large Congenital Melanocytic Nevi

BackgroundLarge congenital melanocytic nevus (LCMN) is a rare skin disease that deeply affects an individual's appearance, may influence patients' self-evaluation and social relationships, and further affects their quality of life (QoL). The Skindex-29 and 36-Item Short Form Survey (SF-36) are valid instruments used to evaluate QoL specifically. It is necessary to assess the QoL of patients with LCMN and summarize potentially impactful factors to help people understand LCMN patients and assist doctors in offering professional advice.MethodsTwenty-five patients were recruited from Shanghai Ninth People's Hospital from July 1st, 2019, to March 31st, 2021. Both males and females were included, and the age groups were divided into infants (0–6 y), children (7–12 y), teenagers (13–17 y) and youths (18–45 y). The Skindex-29 and SF-36 were applied as questionnaires for the assessment of QoL. Clinical information was acquired by physical examination.ResultsQoL in patients with LCMN was diminished, especially in the emotional aspect. However, different genders, ages and distribution patterns of LCMN did not significantly influence QoL, but the patterns of “Bonce” and “Body” affected QoL the most and the severest. The results of Skindex-29 and SF-36 were consistent in that LCMN mainly reduced QoL from an emotional perspective.ConclusionsThis research shows that LCMN has the strongest impact on patients' emotional wellbeing but weakly influences the whole fettle of QoL. The gender, age and distribution patterns of lesions all have no direct effect on QoL, although a larger proportion of LCMNs probably insinuates worse QoL. Even though patients with LCMN show better QoL than those with other visible skin conditions, their general mental health still requires ample attention from surroundings and professional doctors.

Care of Congenital Melanocytic Nevi in Newborns and Infants: Review and Management Recommendations.

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines.

The retrospective molecular analysis of large or giant congenital melanocytic nevi in a group of Polish children.

BackgroundLarge and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of NRAS and BRAF genes in resection specimens from large or giant CMN in a group of Polish patients.Material and methodsThe formalin-fixed, paraffin-embedded resection specimens from 18 patients, fixed in the years of 2006 to 2017, were included in the study. The regions containing the highest load of melanocytes were macrodissected prior to DNA isolation. The NRAS and BRAF mutation status was evaluated using qPCR.ResultsWe detected activating mutations in NRAS gene (codons: 12 and 61) in 7 out of the 18 (38.9%) patients. No BRAF mutations were found.ConclusionOur study, the first molecular analysis of large/giant CMN in Polish patients, supports the hypothesis that NRAS mutation in codon 61 are frequent, recurrent mutations in large/giant CMN. Moreover, we show, for the first time, that NRAS mutations in codon 12 (p.Gly12Asp) can be also detected in giant CMN. The exact role of these genetic alterations in CMN formation remains to be elucidated.

Novel Classification System and Surgical Algorithm for Facial Congenital Melanocytic Nevi

Background Congenital melanocytic nevus (CMN) is characterized by pigmented skin patches. Large CMN affects 1 in 20,000 newborns globally and runs the risk of melanoma transformation. A classification system for CMN patterns has been previously established for the trunk and extremities. However, there is no classification system for facial CMN to date. This study proposes a facial CMN classification scheme that can help guide management decisions. Methods Facial CMN images were retrieved from public repositories. The outline of the facial CMNs were extracted and transposed onto a standardized 3D model. To identify distinct patterns, the CMN images of anatomic sub-regions of the face were clustered and heat-maps were generated. The clinical features of the CMNs were standardized based on previously published criteria. Results The study identified 291 images of facial CMNs. The CMNs could be categorized into seven distinct patterns based on anatomic distribution. Each CMN could be further characterized according to estimated size category, color heterogeneity, rugosity, nodularity, and degree of hypertrichosis. Discussion The study proposes a novel classification scheme for facial CMN to characterize the variability in the anatomic distribution. Researchers further aim to test the validity of their scheme on a CMN image dataset from collaborating institutions. Conclusion A better understanding of the patterns of facial CMNs can glean insights into the embryonic pathways of melanocytic migration on the face. Grouping of facial CMNs by patterns may guide the development of treatment strategies to best preserve the esthetics and functionality of a child's face. Congenital melanocytic nevus (CMN) is characterized by pigmented skin patches. Large CMN affects 1 in 20,000 newborns globally and runs the risk of melanoma transformation. A classification system for CMN patterns has been previously established for the trunk and extremities. However, there is no classification system for facial CMN to date. This study proposes a facial CMN classification scheme that can help guide management decisions. Facial CMN images were retrieved from public repositories. The outline of the facial CMNs were extracted and transposed onto a standardized 3D model. To identify distinct patterns, the CMN images of anatomic sub-regions of the face were clustered and heat-maps were generated. The clinical features of the CMNs were standardized based on previously published criteria. The study identified 291 images of facial CMNs. The CMNs could be categorized into seven distinct patterns based on anatomic distribution. Each CMN could be further characterized according to estimated size category, color heterogeneity, rugosity, nodularity, and degree of hypertrichosis. The study proposes a novel classification scheme for facial CMN to characterize the variability in the anatomic distribution. Researchers further aim to test the validity of their scheme on a CMN image dataset from collaborating institutions. A better understanding of the patterns of facial CMNs can glean insights into the embryonic pathways of melanocytic migration on the face. Grouping of facial CMNs by patterns may guide the development of treatment strategies to best preserve the esthetics and functionality of a child's face.

An Unusual Pigmented Plaque in a Newborn.

An Unusual Pigmented Plaque in a Newborn.

The Bork-Baykal Phenomenon in Congenital Melanocytic Nevus.

The Bork-Baykal phenomenon is a new entity that was first reported in large congenital melanocytic nevus 2015 and classified as a specific variant of congenital melanocytic nevus (CMN). Afterward, this rare feature was reported in other skin disorders reflecting the different embryologic developmental periods of the nipple-areola complex (NAC) with the surrounding skin. Preserving of the NAC appears to bowl over the clinicians both in congenital and acquired skin disorders.

Distribution Patterns (7B Rule) and Characteristics of Large Congenital Melanocytic Nevi: A Retrospective Cohort Study in China.

Large congenital melanocytic nevus has a high risk of malignancy. However, few studies have summarized its characteristics, treatments, outcomes and malignancy incidence in Chinese patients. This paper reviews a retrospective cohort study evaluating 1,171 patients from Shanghai Ninth People's Hospital between 1 January 1989 and 31 August 2019 using electronic medical records and phone calls to collect clinical and pathological data in which 133 patients were diagnosed with a large congenital melanocytic nevus. Three patients relapsed, and none developed melanoma among the qualified patients. Besides, a new “7B” rule for distribution patterns of large congenital melanocytic nevi was proposed, including bonce, bolero, back, bathing trunk, breast/belly, body extremity, and body. The most common distribution pattern of large congenital melanocytic nevi was bonce, and all blue nevi distributed as bonce. Statistical analysis showed a significant difference (P = 0.0249) in the “7B” patterns between the melanocytic nevus and the neuronevus. In conclusion, the malignancy rate of large congenital melanocytic nevi is much lower in China than in other regions and people of other races. The pathology of large congenital melanocytic nevus may decide its “7B” distribution pattern.

RARE-24. LARGE CONGENITAL MELANOCYTIC NEVI AND NEUROCUTANEOUS MELANOCYTOSIS: A RETROSPECTIVE CASE SERIES

Neurocutaneous melanocytosis (NCM) is a rare disease characterized by excessive proliferation and deposition of melanocytes in the leptomeninges and brain parenchyma, occurring in children with large congenital melanocytic nevi (LCMN). Manifestations of NCM range from asymptomatic CNS melanin deposition to cranial neuropathies, seizures, and hydrocephalus. Patients with NCM are at risk for malignant melanoma. We conducted a retrospective, single-institution study of patients with LCMN evaluated at Memorial Sloan Kettering Cancer Center from June 2000 to January 2020. Of 55 patients studied, 15 had no radiographic NCM, and 40 had radiographic NCM at initial evaluation. MRI findings included: focal melanocytosis (33), diffuse leptomeningeal disease (4), solid melanoma (3). Malformations were identified in 13, including arachnoid cyst (4), congenital hydrocephalus (4), Dandy-Walker malformation (3), and tethered cord (1). Twenty-one patients completed imaging once and were followed clinically. Seventeen with serial imaging (10 with focal melanocytosis, 7 with normal MRI) remained stable over a median 24-month follow up (range: 1–124). Six had suspected radiographic progression of NCM without melanoma. Malignant melanoma developed in 11 patients, 5 with focal melanocytosis on initial imaging. Median time from focal melanocytosis identification to melanoma diagnosis was 80 months (range: 18–200). Median age at melanoma diagnosis was 9.9 years (range: 1.1–25.3). Median survival from melanoma diagnosis was 9.1 months (range: 1–60.4). Focal NCM on neuroaxis imaging does not predict time to transformation to malignant melanoma. Serial imaging is not indicated in absence of disease-modifying treatment. Clinical follow up of at-risk individuals is essential in early identification of complications.

NCOG-60. MALIGNANT MELANOMA IN NEUROCUTANEOUS MELANOCYTOSIS: A RETROSPECTIVE CASE SERIES (2000-2020)

Abstract Neurocutaneous melanocytosis (NCM) is a rare neurocutaneous syndrome which typically develops in children with large congenital melanocytic nevi (LCMN) and excessive melanocyte proliferation in the leptomeninges and brain parenchyma. Malignant melanoma develops in an estimated 2.3% of patients with LCMN and 40-60% of patients with NCM. NCM-associated melanomas frequently harbor NRAS mutations with no well-established role for targeted therapy. In a retrospective, single-institution study, we reviewed eleven patients with NCM-associated CNS melanoma evaluated at Memorial Sloan Kettering Cancer Center from June 2000 to January 2020. Five patients had previously identified focal melanocytosis prior to developing melanoma. In this subgroup, the median time from identification of focal melanocytosis to melanoma diagnosis was 80 months (range: 18-200). Median age at melanoma diagnosis was 9.9 years (range: 1.1-25.3). Presentation at the time of diagnosis with CNS melanoma included headache (45%), focal deficits (45%), and seizure (18%). Eight patients had hydrocephalus (73%). Five patients presented with a focal mass (45%) and six patients had focal or diffuse leptomeningeal disease without a mass (55%). Leptomeningeal spread eventually developed in all patients. Where molecular testing was available, three melanomas had NRAS mutations and none were associated with BRAF mutations. Seven patients were treated with cancer-directed therapy including temozolomide, trametinib, ipilimumab, and nivolumab, with each therapy being administered to two patients. Radiation therapy was used in three patients, including whole brain radiation therapy and stereotactic radiosurgery. Median survival from melanoma diagnosis was 9.1 months (range: 1-60.4). The longest surviving patient was initially diagnosed with cutaneous melanoma, surviving 60.4 months after diagnosis with cutaneous melanoma and 22.7 months after diagnosis with CNS melanoma. Prognosis remains guarded in patients with NCM-associated melanoma, and further investigation is warranted to identify effective management strategies.

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.

Congenital melanocytic nevi.

To update pediatric providers on new developments in our understanding of the clinical presentation, genetics, and systemic risks associated with congenital melanocytic nevi (CMN). CMN are primarily caused by sporadic postzygotic somatic mutations, most frequently in NRAS, and studies of the genetic underpinnings of CMN have demonstrated a diverse array of genetic drivers. The primary complications of large and giant CMN include neurocutaneous melanocytosis and malignant melanoma. Abnormalities in CNS MRI may predict a worse clinical course for patients and increased risk of melanoma. Targeted therapies of the MEK pathway have begun to be studied for the treatment of CMN and prevention of associated complications. Patients with large and giant CMN should be managed by an interdisciplinary care team for the monitoring of dermatologic, neurologic, and psychosocial concerns. Ongoing research is underway to better characterize the genetic drivers of CMN and to better guide development of targeted therapeutics.

Congenital Melanocytic Hairy Nevi in a Child from North-Western Nigeria

Aim: To present the first report of a large congenital melanocytic nevus with satellite nevi in an apparently healthy child from Sokoto, North-Western Nigeria.&#x0D; Presentation of Case: A three year old girl was brought to the paediatric out-patient clinic of Paediatrics department of Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto with complaints of darkened skin colour on the left side of the face and scalp, the left arm, lower back, buttocks, and thighs, and excessive hair growth over the same side of the face since birth. There were no neurological symptoms Physical examination findings revealed a well-nourished, not ill looking child. She had a hyper pigmented patch on the left side of the face extending from the lower jaw to the scalp, measuring 21 cm in its longest length, with hypertrichosis on the same site, and two distinct, firm, painless nodular lesions on the left temporal region measuring 3 mm and 4mm respectively. On the lower one-third of the left arm was a hairy, velvety area of hyperpigmentation measuring 2X3 cm in diameter. Other affected sites were the lower back, the gluteal region and the thighs. Her neurologic and other systemic examinations were normal. A diagnosis of large congenital facial melanocytic hairy nevus with multiple satellite nevi was made.&#x0D; Discussion: Congenital melanocytic nevi are benign proliferations of melanocytic cells said to be present at birth or in the first two years of life. Large lesions are rare, they measure 20 cm or more and are said to occur more commonly on the trunk and thighs. The exact pathogenesis of congenital melanocytic nevi is yet, unknown. It is thought to occur as a result of a morphological error in the neuroectoderm during embryogenesis. Treatment of patients with large congenital melanocytic nevus may include surgical or non-surgical procedures as well as psychological interventions. Large lesions, multiple satellite lesions or paravertebral and axial locations are sometimes associated with the risk of neurological complications and malignant transformation.&#x0D; Conclusion: Large congenital melanocytic nevi are uncommon skin lesions that can occur in apparently healthy children. Individualization of the patients with regards to treatment options and long term monitoring are imperative.

530 Local inhibition of MEK/AKT prevents cellular growth in human congenital melanocytic nevi

Large congenital melanocytic nevi (lCMN) management is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of MAPK and AKT pathways when compared to primary melanocytes. MEK and AKT inhibitors reduced nevosphere diameter in sphere-forming assays, as well as nevocyte cell viability and proliferation in in vitro assays. Standardized lCMN explants were then cultured ex vivo with the same inhibitors which induced a decrease in MelanA+ and Sox10+ cells in both epidermis and dermis. A similar reduction in melanocyte cell numbers was not observed in control normal skin explants. Finally, intradermal injections of these inhibitors were performed within standardized lCMN xenografts in Rag2-/- mice. They induced a dramatic decrease in nevocytes in treated lCMN xenografts which persisted 30 days after the end of treatment. Melanocytes in control normal skin xenografts were not affected by a similar treatment. Using nevus explant and xenograft preclinical models, we demonstrated that intradermal MEK/AKT inhibition might serve as neo-adjuvant therapy for the treatment of NRAS-mutated CMN to avoid iterative surgeries.

Neurocutaneous Melanosis in Association With Large Congenital Melanocytic Nevi in Children: A Report of 2 Cases With Clinical, Radiological, and Pathogenetic Evaluation.

Background: Melanocytic nevi present at birth, or within the first few months of life, are defined as congenital melanocytic nevi (CMN). Neurocutaneous melanosis (NCM) is a rare disorder, represents pigment cell tumors of the leptomeninges, and occurs in association with large or multiple CMN. NCM carries an extremely poor prognosis. NRAS and BRAFV600E genetic mutations were reported in CMN. Our aim was to report 2 rare cases of NCM associated with large-sized CMN.Materials and Methods: Two cases were enrolled, a 19-month-old boy with multiple satellite and giant CMN (GCMN); and a 57-month-old girl with large CMN (LCMN). Both patients had central nervous system (CNS) symptoms, and therefore, were studied from clinical, radiological, and immunohistopathological aspects. Cytogenetic study was done for one of them.Results: Both patients had CMN located in the head/neck, with no cutaneous melanoma. MRI was the most reliable method for early detection of NCM. NCM was proved in the 2 studied cases by immunohistopathology performed after surgery. The boy with GCMN carried NRAS mutation at codon 61, in addition to the characteristic facial features relevant to RASopathies. Both patients died despite surgical intervention.Conclusion: Our report highlights the need for pediatricians to be alert to the risk of NCM in association with CMN, especially when a CMN lesion is large, or there are multiple satellite lesions, or the nevus location is at the head or neck. Moreover, in the setting of CMN, the absence of skin melanoma does not exclude the presence of NCM.

A prospective study of patients with large congenital melanocytic nevi and the risk of melanoma.

BackgroundLarge congenital melanocytic nevus (LCMN) is considered a risk factor for melanoma, although the magnitude of this risk is controversial.ObjectiveTo evaluate the risk of melanoma development in patients with LCMN seen at a dermatology referral center in Brazil during a twelve-year period. To the best of our knowledge, there are no published similar studies on large congenital melanocytic nevus in South America.MethodsOur prospective cohort included only patients with congenital nevi ≥20cm. The cumulative risk of developing melanoma and the standardized morbidity ratio were calculated for patients followed up prospectively for at least 1 month.ResultsSixty-three patients were enrolled in this study. One patient who developed melanoma prior to enrollment was excluded, and five were eliminated because of insufficient follow-up time. Mean follow-up for the remaining 57 patients was 5.5 years (median 5.2 years). Median age of entry into the study was 2.6 years. Most patients (75.4%) underwent only clinical observation. Melanomas occurred in 2 (3.5%) patients. Five-year cumulative risk for melanoma was 4.8% (95% CI: 1.9-11.5%). Standardized morbidity ratio was 1584 (95% CI: 266-5232, p<0.001).Study limitationsThe small sample size reduces the accuracy of risk estimates.ConclusionsThis study analyzed prospectively for the first time data from South America demonstrating that patients with LCMN have a higher risk of developing melanoma than the general population (p<0.001).

Congenital melanocytic nevi in young children: Histopathologic features and clinical outcomes

Although only large congenital melanocytic nevi (CMN) are associated with a significantly high risk for malignant transformation, CMN of all sizes are prone to changes in clinical appearance in early childhood and thus are often biopsied or excised. While CMNs typically exhibit benign behavior, atypical histopathologic findings might be common and may prompt additional unnecessary procedures. To assess the prevalence and associated clinical outcomes of atypical histopathologic features in CMN in children. A single center retrospective study was conducted with patients 0-35months of age with CMN diagnosed by histopathology between 1993-2013. One hundred seventy-nine patients with a total of 197 CMNs were identified. Cytologic atypia, architectural disorder, or pagetoid spread were present in 73% of CMN. With a mean follow up of 7.3years, no cases of melanoma or CMN-related deaths were identified. Our findings were based on a largely Caucasian population and might not apply to darker skin types. Our findings might not apply to older children or adults with CMN. Atypical histopathologic features of cytologic atypia, architectural disorder, and pagetoid spread are common in benign CMN of young children.

Reduced H3K27me3 Expression Is Common in Nodular Melanomas of Childhood Associated With Congenital Melanocytic Nevi But Not in Proliferative Nodules.

The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about possible melanoma. Most new nodular growths that develop during childhood, however, are benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for diagnosis. Although the application of molecular methods has revealed new insights into the mutational and genomic landscape of childhood melanomas, little is known about epigenetic events that may drive the growth of a melanoma or PN in a CMN. In this study we compared the expression of H3K27me3, a key regulator in chromatin remodelling-controlled transcription, in PNs and pediatric nodular melanomas arising within medium-sized to large CMN by immunohistochemistry. Significant loss of H3K27me3 expression was seen in 4 of 5 melanomas, but not in any of the 20 PNs. This observation suggests that epigenetic events likely play a role in the pathogenesis of melanoma developing in the dermis or subcutis of CMN. Furthermore, assessing for H3K27me3 expression by immunohistochemistry may be diagnostically useful for problematic cases.