Congenital Nevi Research Articles

Cicatricial eyebrow restoration using the follicular unit extraction technique.

Cicatricial eyebrow loss that occurs after trauma or burns considerably reduces a person's self-confidence. Several methods, either surgical or nonsurgical, have been defined to reconstruct eyebrows. This study focused on eyebrow restoration using the atraumatic follicular unit extraction (FUE) technique in patients and emphasized certain details that should be considered during the treatment process. In this study, we discussed the management of 18 cases using this technique and their outcomes with respect to published literature. This study examined eyebrow restoration performed using a modified FUE technique in 18 patients who had cicatricial eyebrow loss due to trauma, excised congenital giant nevus, or burns. Moreover, special methods, including platelet-rich plasma, microneedling, steroid injections, and fat grafting, were used in each patient to increase the odds of graft survival. Aesthetically and functionally satisfactory outcomes were observed along with the appropriate orientation and symmetry of the eyebrows in all patients' follow-ups. Moreover, patients exhibited increased self-confidence, and the quality of skin, particularly in the transplantation area, was improved. There was no complication either in the recipient or in the donor site. Eyebrow restoration using the atraumatic FUE technique should be considered as the first treatment option in cases with cicatricial eyebrow loss as long as an appropriate evaluation and treatment method is followed for each patient.

Identification of a recurrent mosaic KRAS variant in brain tissue from an individual with nevus sebaceous syndrome.

Nevus sebaceous syndrome (NSS) is a rare, multisystem neurocutaneous disorder, characterized by a congenital nevus, and may include brain malformations such as hemimegalencephaly or focal cortical dysplasia, ocular, and skeletal features. It has been associated with several eponyms including Schimmelpenning and Jadassohn. The isolated skin lesion, nevus sebaceous, is associated with postzygotic variants in HRAS or KRAS in all individuals studied. The RAS proteins encode a family of GTPases that form part of the RAS/MAPK signaling pathway, which is critical for cell cycle regulation and differentiation during development. We studied an individual with nevus sebaceous syndrome with an extensive nevus sebaceous, epilepsy, intellectual disability, and hippocampal sclerosis without pathological evidence of a brain malformation. We used high-depth gene panel sequencing and droplet digital polymerase chain reaction (PCR) to detect and quantify RAS/MAPK gene variants in nevus sebaceous and temporal lobe tissue collected during plastic and epilepsy surgery, respectively. A mosaic KRAS c.34G > T; p.(Gly12Cys) variant, also known as G12C, was detected in nevus sebaceous tissue at 25% variant allele fraction (VAF), at the residue most commonly substituted in KRAS. Targeted droplet digital PCR validated the variant and quantified the mosaicism in other tissues. The variant was detected at 33% in temporal lobe tissue but was absent from blood and healthy skin. We provide molecular confirmation of the clinical diagnosis of NSS. Our data extends the histopathological spectrum of KRAS G12C mosaicism beyond nevus sebaceous to involve brain tissue and, more specifically, hippocampal sclerosis.

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.

A Neonate Born with Natural Garment

A Neonate Born with Natural Garment

Congenital Pigmentary Anomalies in the Newborn

Congenital pigmentary anomalies may be evident at birth or soon after, with some birthmarks becoming apparent later in infancy or early childhood. It is important to recognize various pigmentary anomalies in the neonate, most of which are benign but a subset of which are associated with cutaneous morbidity or systemic ramifications and require further evaluation. This review will focus on pigmentary mosaicism, congenital melanocytic nevi, nevus spilus, dermal melanocytosis, and pigmentary anomalies associated with neurofibromatosis type 1 (café au lait spots, freckling, plexiform neurofibromas, nevus anemicus), tuberous sclerosis (hypomelanotic macules), and incontinentia pigmenti.

Features of total and longitudinal body sizes in men with benign nevi

The use of anthropometric markers to predict the onset or severity of the disease is key to solving the problem of preventive medicine and can be an indispensable tool in preventive examinations in schools, universities and industries. The purpose of the study was to establish total and longitudinal body sizes in men of the first mature age with benign nevi. Anthropometry (determination of total and longitudinal body sizes) was performed according to Bunak’s scheme for men (aged 22-35 years) patients with melanocytic benign simple nevi (n=34), melanocytic benign dysplastic nevi (n=27), melanocytic benign congenital nevi (n=14) and non-melanocytic benign nevi (n=17). As a control from the data bank of the research center of National Pirogov Memorial Medical University, Vinnytsya selected total and longitudinal body sizes of 82 practically healthy men of the same age group. Statistical processing of the obtained results was performed in the license package “Statistica 5.5” using non-parametric evaluation methods. It was found that the mass and surface area of the body in healthy men is lower than in patients (except for dysplastic nevi), and in patients with dysplastic nevi – lower than in patients with non-melanocytic nevi; the height of the suprathoracic, acromial and finger anthropometric points in healthy men is lower than in patients with nevi (except for the acromial point height in patients with dysplastic nevi), and the height of the pubic and acetabular anthropometric points – in healthy men is greater than in patients with simple (only pubic point) and dysplastic nevi; in addition, the height of the pubic and acetabular anthropometric points in patients with simple nevi is lower than in patients with non-melanocytic nevi and congenital nevi (only for the acetabulum height). Given the height of anthropometric points and the fact that body length between healthy and sick men has no significant or tendency differences, in sick men we observe a longer torso and shorter lower extremities (most pronounced in patients with simple and dysplastic nevi), which is a manifestation of “subpathological” constitutional types, which indicate a longer torso and shorter lower extremities.

Psychosocial Experiences in Children With Congenital Melanocytic Nevus on the Face and Their Parents Throughout the Tissue Expansion Treatment.

Large congenial melanocytic nevus (LCMN) on the head and face can have negative psychological effects on children and possibly also parents. Patients and their families experience prolonged periods of stress during tissue expansion treatment. The purpose of this study was to evaluate the psychological impact of LCMN on children and parents and explore their fluctuations of psychological status during treatment. Psychosocial status was evaluated in 30 children with LCMN on the head and face and a control group of 56 sex- and age-matched children using the Child Behavior Checklist and the inventory of Subjective Life Quality for Child and Adolescents. The parents of both groups were also evaluated using the Symptom Checklist-90, the Hospital Anxiety and Depression Scale, and the Perceived Stress Scale. Psychological assessments were performed before expander implantation, before lesion resection, and after operation. Results indicated that children with LCMN were more prone to social problems, withdrawal, and aggressive behavior. Furthermore, their psychological problems increased after entering to school. Parents of children with LCMN had high levels of emotional problems and stress. Continuous expansion resulted in the psychosocial status of both children and parents to reach the worst levels during the period before lesion resection. Six months after surgery, most of these psychosocial effects reduced to levels lower than before surgery. Additionally, we identified several risk factors, namely sex, number of operations, being in education, employment status of mother, and family pressures. Large congenial melanocytic nevus on head and face have considerable psychological impact on children and their parents throughout the tissue expansion treatment. This study demonstrates the need for appropriate psychological screening and interventions.

Treatment of malignant melanoma - a review of the literature

Melanoma is caused by genetic mutations in melanocytes, pigment-producing cells found in the skin, eye, inner ear, and soft meninges. Sun exposure, atypical nevi, previous history of melanoma, and the presence of multiple (≥40) common nevi were found to be associated with an increased risk of melanoma detection (OR: 1. 3; 95% CI: 1. 1-1. 6). Its prevalence is highest among light-skinned populations and in regions of lower latitudes. Significance of family history of melanoma and presence of congenital nevi were excluded. For localized primary melanoma, the dominant prognostic factors for survival are lesion thickness, ulceration, and lymph node involvement Understanding the pathogenesis of melanoma has been crucial in developing new therapeutic approaches. The characterization of oncogenic signaling pathways and interactions has made it possible to identify new targets for clinically effective therapies, such as pathway inhibitors and antibodies to immune checkpoints or the use of phototherapy. In this article we describe the main signaling pathways which are deregulated in melanoma. We also mention how it has become a viable and crucial strategy for melanoma therapy and then thoroughly review the safety, clinical efficacy and progress regarding PDT- promising alternative therapy and the immunotherapies of melanoma in especially advanced metastatic stage basing on published clinical data and registered clinical trials, most of which are in phase III.

An Unusual Pigmented Plaque in a Newborn.

An Unusual Pigmented Plaque in a Newborn.

Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype

PurposeMuch of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach. MethodsWhole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplications in PPP2R3B were investigated using immunohistochemistry, transcriptomics, and stable inducible cellular models, themselves characterized using RNAseq, quantitative real-time polymerase chain reaction (qRT-PCR), reverse phase protein arrays, immunoblotting, RNA interference, immunocytochemistry, proliferation, and migration assays. ResultsWe identify here a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. This encodes PR70, a regulatory unit of critical phosphatase PP2A. Duplications increase expression of PR70 in human nevus, and increased expression in melanoma tissue correlates with survival via a nonimmunological mechanism. PPP2R3B overexpression induces pigment cell switching toward proliferation and away from migration. Importantly, this is independent of the known microphthalmia-associated transcription factor (MITF)-controlled switch, instead driven by C21orf91. Finally, C21orf91 is demonstrated to be downstream of MITF as well as PR70. ConclusionThis work confirms the power of a rare disease approach, identifying a previously unreported copy-number change predisposing to melanocytic neoplasia, and discovers C21orf91 as a potentially targetable hub in the control of phenotype switching.

Giant congenital melanocytic nevi (garment variety): a case report

Giant congenital melanocytic nevi (GCMN) are large brown-to-black skin lesions caused due to genetic mutations which lead to defective proliferation, differentiation and migration of melanoblasts which are precursor cells of melanocytes. There is a mutation in the NRAS gene causing abnormal proliferation of embryonic melanoblasts. Congenital melanocytic nevus is primarily a clinical diagnosis. The malignant melanoma and neurocutaneous melanosis are the two major complications associated with GCMN. The risk of transformation of GCMN to malignant melanoma varies between 0 and 3.8%. About 1% of live births presents with a CMN. The incidence of GCMN is estimated at less than 1: 20,000 newborns. The variety ‘garment-like’ of GCMN is even scarcer, 1: 5,00,000. GCMN has got major psychosocial impact on the patient and his family due to its unsightly appearance. Treatment includes surgical and non-surgical procedures, psychological intervention and clinical follow-up, with special attention to changes in color, texture on the surface of the lesion. We presented a case of 1-day-old female neonate born with GCMN in our hospital.

RASGRF2 gene fusions identified in a variety of melanocytic lesions with distinct morphological features

The WHO classification identifies nine classes of melanocytic proliferations according to location, UV exposure, histological, and genetic features. Only a minority of lesions remain unclassified. We describe five cases that harbored either an ERBIN-RASGRF2 or an ATP2B4-RASGRF2 in-frame fusion transcript. These lesions were collected from different studies, unified only by the lack of identifiable known mutations, with a highly variable phenotype. One case was a large abdominal congenital nevus, three were slowly growing pigmented nodules, and the last was an ulcerated nodule arising on the site of a preexisting small nevus, known since childhood. The latter was diagnosed as a 4mm thick melanoma with loss of BAP1 expression. The four other cases were compound, melanocytic proliferations with an unusual deep pattern of small dense nests of bland melanocytes encased in a fibrous background. The RASGRF2 fusion was confirmed by a break-apart FISH technique. Array CGH performed in three cases found non-recurrent secondary copy number alterations. Follow-up was uneventful. In silico analysis identified a single RASGRF2 fusion in the TCGA pan-cancer database, whereas RASGRF2 variants were stochastically distributed in all cancer subtypes.

Neurocutaneous Melanocytosis: Cytological, Clinical and Radiological Assessment in a Patient Presented with Congenital Melanocytic Nevi and Seizure Disorder: Case Report and Review of the Literature

Neurocutaneous Melanocytosis (NCM) is a rare congenital disorder characterized by multiple melanocytic nevi scattered all over the body, in addition to leptomeninges. It is suggested that NCM is developed due to abnormal proliferation of melanin-producing cells following dysmorphogenesis in the embryology life. The clinical symptoms of NCM depend on the size and site of the lesion. One of the most common sites is the anterior temporal lobe. Management options are limited in such patient and the prognosis is generally poor. Clinical, radiological, along with CSF cytology can establish the diagnosis of NCM. Surgical intervention carries temporary better results than adjuvant therapy in patients with NCM.

25959 Clinical and histopathologic evolution of inflammatory linear verrucous epidermal nevus in a pediatric patient

An 11-year-old girl presented with lines of “pink bumps” down her right arm, which first appeared 2 years prior and had worsened over the preceding 2-3 months. The lesions were intensely pruritic. She denied exposures or trauma to the area. She reported a history of asthma, seasonal allergies, and eczema. Physical examination revealed 50 4- to 9-mm pink-brown, flat-topped erythematous and scaly papules arranged linearly following a Blaschkoid distribution along the right dorsolateral arm, forearm, and wrist. Punch biopsy demonstrated superficial and deep perivascular and perieccrine lymphocytic inflammation, suggestive of lichen striatus (LS), which correlated with the initial clinical presentation. The patient was counseled regarding the self-limited nature of LS; however, she remained symptomatic for 2 more years with minimal response to topical or intralesional steroids. The papules became more verrucous and inflammatory, and this change, coupled with the lack of expected resolution, led to rebiopsy. Histopathology revealed areas of parakeratosis overlying an absent granular layer alternating with orthokeratosis overlying a thickened granular layer, a pattern indicative of inflammatory linear verrucous epidermal nevus (ILVEN). ILVEN is a rare form of congenital epidermal nevus that, unlike LS, may be characterized by a chronic, progressive course. Early ILVEN can mimic LS and linear hyperkeratotic lesions including linear psoriasis, linear lichen planus, and linear verruca. This case highlights the clinical and histopathological evolution of ILVEN and emphasizes the importance of subsequent biopsies for definitive diagnosis in refractory cases. Recognition of ILVEN points clinicians toward alternative treatments, including laser therapy, which is currently under consideration.

26856 Proliferative nodule resembling angiomatoid Spitz with pronounced degenerative atypia arising within a giant congenital nevus

Proliferative nodules arising within congenital melanocytic nevi present a diagnostic challenge for dematopathologists given their close resemblance to melanoma. In difficult cases, ancillary molecular tests can be used to better exclude the possibility of malignancy. We report case of a biopsy and subsequent excision of an unusual proliferative nodule with overlapping features of angiomatoid Spitz tumor and ancient melanocytic nevus which demonstrated normal findings on both chromosomal microarray and a gene expression profiling assay.

Consensus on outcomes for research and care of patients with congenital melanocytic naevi

Consensus on outcomes for research and care of patients with congenital melanocytic naevi

Cutaneous Melanomas Arising during Childhood: An Overview of the Main Entities.

Cutaneous melanomas are exceptional in children and represent a variety of clinical situations, each with a different prognosis. In congenital nevi, the risk of transformation is correlated with the size of the nevus. The most frequent type is lateral transformation, extremely rare before puberty, reminiscent of a superficial spreading melanoma (SSM) ex-nevus. Deep nodular transformation is much rarer, can occur before puberty, and must be distinguished from benign proliferative nodules. Superficial spreading melanoma can also arise within small nevi, which were not visible at birth, usually after puberty, and can reveal a cancer predisposition syndrome (CDKN2A or CDK4 germline mutations). Prognosis is correlated with classical histoprognostic features (mainly Breslow thickness). Spitz tumors are frequent in adolescents and encompass benign (Spitz nevus), intermediate (atypical Spitz tumor), and malignant forms (malignant Spitz tumor). The whole spectrum is characterized by specific morphology with spindled and epithelioid cells, genetic features, and an overall favorable outcome even if a regional lymph node is involved. Nevoid melanomas are rare and difficult to diagnose clinically and histologically. They can arise in late adolescence. Their prognosis is currently not very well ascertained. A small group of melanomas remains unclassified after histological and molecular assessment.

Cultured epithelial autografts for the treatment of large-to-giant congenital melanocytic nevus in 31 patients.

IntroductionGiant congenital melanocytic nevus (GCMN) is a large melanocytic nevus, and its full-thickness removal is usually difficult due to the lack of skin available for reconstruction. Curettage is an alternative approach in cases of GCMN to remove the superficial dermis above the cleavage plane with a curette in the neonatal period, and its major complications include repigmentation, retarded epithelization, and hypertrophic scar formation. In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for the treatment of congenital melanocytic nevus (CMN) that is difficult to treat with conventional methods in 2016. We have used CEA for wounds after curettage in the neonatal period or following ablation after the neonatal period in combination with laser therapies to reduce the above-mentioned complications.MethodsIn this study, we summarized all consecutive CMN patients treated using CEA from December 2016 to April 2019 and evaluated the duration required for epithelialization, incidence of hypertrophic scar, and color change in the target nevus by comparing the L∗ values one year later between the Curettage group, the non-Curettage group with initial treatment or the subsequent group.ResultsNo significant differences were seen in the epithelization period or incidence of hypertrophic scars among the groups, but the color of the target nevus was improved significantly in the Curettage group (p < 0.01) and non-Curettage group with initial treatment (p < 0.01).ConclusionsIn conclusion, CEA seems to accelerate epithelization after curettage or ablation of CMN, and this treatment could improve the color of CMN when applied initially.

Medium-Sized Congenital Melanocytic Nevus with Halo Phenomenon: A Report of Two Cases

Congenital melanocytic nevi with halo phenomenon in children is a rare clinical finding. We report two cases of children who developed depigmentation within medium-size congenital melanocytic nevi. Clinicians should be suspicious when confronted with this phenomenon due to the risk of development into malignant melanoma. Herein, we review these rare cases of medium-sized halo congenital melanocytic nevi with and without associated vitiligo, with emphasis that depigmentation does not necessarily indicate malignant growth.