Congenital Nevi Research Articles

Giant Congenital Melanocytic Nevus associated with Neurofibromatosis Type 1 in a young Indian girl – A Rare Presentation

Giant congenital melanocytic nevi are pigmented lesions, with an incidence of 1 in 20,000 new-borns. Neurofibromatosis 1 is an autosomal dominant disorder with an incidence of 1 in 3500 individuals. The coexistence of both these conditions is a rare entity, with few cases reported in the medical literature. Here we report these two diseases in a 13-year-old girl in India.

The congenital melanocytic nevus: a rare clinical image.

Congenital melanocytic nevus affects around 1% of newborns. Facial melanocytic nevus may be linked to an increased risk of pediatric cancer. Furthermore, because the lesions reveal hair and dark pigmentation, the cosmetic and emotional impacts might be substantial. A 6-year-old female was brought to the outpatient department with complaints of black discoloration of the left side of the face and excessive hair growth on a particular site. After detailed history collection and physical examination, it reveals that the black discoloration is since birth. The physician diagnosed her with congenital melanocytic nevus and hence referred them to the dermatology department for further management.

Alibert and His Contribution to Dermatology (1768-1837).

Jean Louis Marc Alibert, 1786-1837, France, is considered one of the founders of modern dermatology, he was able to organize the Hôpital Saint Louis in Paris and developed a school, among other contributions he wrote at least two books, he described the tumoral stage of mycosis fungoides, congenital nevus, keloids, and proposed The Tree of Dermatoses as his concept for the understanding of skin diseases.

A Congenital Melanocytic Hairy Nevus of the Face and Conjunctival Nevus

A Congenital Melanocytic Hairy Nevus of the Face and Conjunctival Nevus

Front Cover

The cover image is based on the Case Report Giant Congenital Melanocytic Nevus in an Afghan Child by Arash Nemat and Nahid Raufi ., https://doi.org/10.1002/ccr3.5258.

The one-two punch of giant congenital melanocytic nevus in a child

The one-two punch of giant congenital melanocytic nevus in a child

Imaging and Clinical Features of Neurocutaneous Melanosis in the Pediatric Population.

Neurocutaneous Melanosis (NCM) is a rare nonfamilial phakomatosis characterized by the presence of congenital melanocytic nevi and abnormal melanocyte infiltration of the leptomeninges. This paper shows the importance of early diagnosis and the most important imaging features of the disease on CT and MR scans. PubMed database was searched from January 1972 to September 2020. Papers including imaging findings of NCM, clinical, follow-up, and treatment features were collected, selecting only 89 studies. NCM is a term used for the first time by van Bogaert in 1948. It refers to a condition caused by an error during morphogenesis and migration leading to leptomeningeal melanocytic accumulation. Although histological findings are the gold standard for diagnosis confirmation, neuroimaging and clinical features strongly support the suspect of NCM. Localization and extension of the lesions are predictive of neurological manifestations related to increased intracranial pressure, mass lesions, or spinal cord compression. CT demonstrates sites of increased density in the anterior temporal lobe, mainly the amygdala, thalami, cerebellum, and frontal lobes base. However, MRI is the best imaging method to diagnose central nervous system lesions, often appearing as T1-short signal areas of the cerebral parenchyma, indicative of central nervous system melanosis. MRI can also reveal associated intracranial and intraspinal abnormalities. Early imaging, when available, is helpful if NCM suspect is raised and may be of guidance in comparing later studies. NCM requires a multidisciplinary approach since it is a multisystem disease with a genetic component.

Risk of Malignant Transformation Arising From Giant Congenital Melanocytic Nevi: A 20-year Single-center Study.

Although giant congenital melanocytic nevus (GCMN) is regarded as premalignant, the incidence and risk factors of malignant transformation are controversial. This study aimed to share the authors' surgical experience with GCMNs and provide data on their demographics, malignant transformation, and prognosis. This single-center, consecutive study included 152 patients with GCMN who visited this center from March 2000 to February 2020. Their medical documentation was reviewed retrospectively, and the nevi were classified according to the size as follows: Group 1, 10 to 19.9 cm (n = 45); Group 2, 20 to 39.9 cm (n = 62); and Group 3, ≥40 cm (n = 45). Seven malignancies were found (4.6%; 4 melanomas, 2 rhabdomyosarcomas [RMS], and 1 malignant peripheral nerve sheath tumor [MPNST]). The risk increased according to the nevus size (2.2% in Group 1, 3.2% in Group 2, and 8.9% in Group 3) but the difference was not statistically significant (p = .3305). Malignant transformation from GCMN cannot be ignored. It can include transformation into melanoma, RMS, and MPNST. Early surgical resection and regular follow-up should be performed in patients with nevi ≥10 cm.

Features of skinfold thickness in men with benign nevi

Nevi, although benign neoplasms of the skin, but have a certain tendency to malignancy, which is influenced by various external and internal human factors. Predicting the risk of benign nevi against this background is an important topic for experimental research. The aim of the study was to establish the features of the skinfold thickness (SFT) in men of the first adult age with benign nevi. SFT was determined according to the Bunak scheme for men (aged 22-35 years) with melanocyte benign simple nevi (n=34), melanocyte benign dysplastic nevi (n=27), melanocyte benign congenital nevi (n=14) and non-melanocyte benign (n=17). The control group – SFT of 82 practically healthy men of the same age group was selected from the data bank of the Research Center of National Pirogov Memorial Medical University, Vinnytsya. Statistical processing of the results was performed in the license package “Statistica 5.5” using non-parametric evaluation methods. It was found that in practically healthy men higher than in patients – SFT on the anterior and posterior surfaces of the shoulder and thigh (in all groups of patients); SFT on the forearm, at the lower angle of the scapula, chest and shin (only in patients with melanocyte benign dysplastic nevi). Also in healthy men are found lower than in patients – SFT on the side (in all groups of patients); SFT in the abdomen (in patients with melanocyte benign simple and non-melanocyte benign nevi). When comparing SFT between patients with benign nevi, in most cases, lower values of SFT found in patients with melanocyte benign dysplastic nevi. The obtained results indicate the initial manifestations of abdominal (android) type of fat deposition in the body in patients with benign nevi (most pronounced in patients with melanocyte benign simple nevi).

A rare association of giant congenital melanocytic nevus (bathing trunk nevus) with cryptorchidism and inguinal hernia: Case report

Giant Congenital Melanocytic Nevus (GCMN) are rare cutaneous lesions occurring in 2,00,000 - 5,00,000 births. We are reporting a child who had left undescended testis and inguinal hernia along with GCMN. Along with orchidopexy and hernia repair, a test patch dermabrasion of nevus was done. We review our experience with this rare entity.

Transcriptome Analysis of Large to Giant Congenital Melanocytic Nevus Reveals Cell Cycle Arrest and Immune Evasion: Identifying Potential Targets for Treatment.

Large to giant congenital melanocytic nevus (lgCMN) is a benign cutaneous tumor that develops during embryogenesis. A large number of lgCMN patients are ineligible for surgical treatment; hence, there is an urgent need to develop pharmacological treatments. Clinically, tumorigenesis and progression essentially halt after birth, resulting in the homeostasis of growth arrest and survival. Numerous studies have employed whole-genome or whole-exome sequencing to clarify the etiology of lgCMN; however, transcriptome sequencing of lgCMN is still lacking. Through comprehensive transcriptome analysis, this study elucidated the ongoing regulation and homeostasis of lgCMN and identified potential targets for treatment. Transcriptome sequencing, identification of differentially expressed genes and hub genes, protein–protein network construction, functional enrichment, pathway analysis, and gene annotations were performed in this study. Immunohistochemistry, real-time quantitative PCR, immunocytofluorescence, and cell cycle assays were employed for further validation. The results revealed several intriguing phenomena in lgCMN, including P16-induced cell cycle arrest, antiapoptotic activity, and immune evasion caused by malfunction of tumor antigen processing. The arrested cell cycle in lgCMN is consistent with its phenotype and rare malignant transformation. Antiapoptotic activity and immune evasion might explain how such heterogeneous cells have avoided elimination. Major histocompatibility complex (MHC) class I-mediated tumor antigen processing was the hub pathway that was significantly downregulated in lgCMN, and ITCH, FBXW7, HECW2, and WWP1 were identified as candidate hub genes. In conclusion, our research provides new perspectives for immunotherapy and targeted therapy.

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.

Congenital melanocytic nevus becoming evident at puberty.

Among the stimuli capable of causing nevi and influencing the production of melanin there are, in addition to genetic factors, phototype, immune suppression, sun radiation, even hormonal factors (1). Clinical evidence of this is the exceptional occurrence of melanoma before puberty, the increase in moles and melanic production in conjunction with puberty and pregnancy, and the regression of many moles in the last decades of life (4). However, there are also experimental studies that demonstrate the role of hormones and in particular of estrogens in the appearance of benign and malignant melanocytic lesions. Prior to the discovery of estrogen receptors (ER) beta, studies with ER alpha had not demonstrated a role of estrogen on the pathophysiology of benign and malignant melanocytic lesions (8). After the discovery of ER beta, it was found that these receptors are present in all melanocytic lesions, both benign and malignant (6). As regards benign melanocytic lesions, ER beta are particularly present in congenital (2) and in Spitz-Reed nevi (7). The vulvar melanocytic nevus of the actual report is probably a poorly pigmented congenital junc-tional nevus, also due to the non-photo-exposed site, which has suddenly become visible due to the effect of peripuberal hormonal stimuli. There is another very similar example in clinical practice, namely the congenital melanocytic nevus not evident at birth (3). Melanocytic nevi that appear in the first year of life are usually thought to be congenital (5). However, many of these nevi are really present at birth, but not visible because they are junctional and non-pigmented (3). The accuracy of this hypothesis is demonstrated by the fact that at their first appearance these nevi already have many times a diameter greater than one centimeter and that after becoming evident due to the pigmentation generally induced by the first sun exposures they never show autonomous growth.

Measuring the success of treatments for congenital melanocytic naevi (birthmarks)

Congenital melanocytic naevi (CMN) are birthmarks that can have a great impact on the lives of patients because of the unusual appearance of CMN and the risk of developing skin cancer (melanoma) or brain and spine problems. Larger CMN (more than 20 cm) are relatively rare and affect one in every 20,000 newborns. At the moment, different studies looking at CMN often measure different outcomes and this makes it difficult to compare studies.

Prospective Analysis of Etiologies of Nose Defects in a Tertiary Care Referral Centre

The purpose of the study was to analyze the various causes of nasal defects seen in practice by plastic surgeons in the Department of Plastic Surgery, in a tertiary care North Indian Hospital. The study included all patients of any age and sex presenting to the outpatient department or emergency department with nose defects. The patients were enquired about the cause and history of their nasal defects. The most common etiologies of nasal defects seen were skin tumors of the nose, the most common one being the basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC), and congenital naevus. Both the malignancies BCC and SCC were seen in older age. While BCC was significantly more common in males, a specific gender preference could not be concluded in SCC. Trauma was the next most common cause and included road traffic accidents, assaults, and animal bites. These were more commonly seen in the youth and less commonly in geriatric or pediatric populations. Other less common causes of nasal defects included postburn lesions.

Cerebriform congenital melanocytic nevus of scalp and its management using tissue expansion

Congenital melanocytic nevi are benign proliferations of cutaneous nevomelanocytes. Usually, they manifest at birth or become apparent within the first few years of life. The nevi show variable surface morphology (papular, rugose, verrucous, or cerebriform). Congenital melanocytic nevus showing cerebriform morphology is a rarity. Early diagnosis and surgical excision are usually recommended in congenital melanocytic nevus to prevent the future risk of malignant transformation which is higher in larger lesions, especially in giant forms (>20 cm in size). An excision of the lesion also helps to avoid the social and psychological consequences arising out of significant cosmetic deformity. We report a 21-year-old patient who presented with a cerebriform congenital melanocytic nevus measuring 10 cm × 7 cm × 2 cm in the right parietal region. Early-onset, pigmented lesion with a cerebriform surface, and the histopathology features of congenital melanocytic nevus were the points that favored the diagnosis of cerebriform congenital melanocytic nevus in our patient. He was treated with excision of the lesion and defect coverage with tissue expansion in two stages. Two rectangular tissue expanders were placed beneath the galea aponeurotica (one with a capacity of 300 cc in the left parietal region and another with 500 cc in the occipital region). Both the expanders were inflated twice to their capacity. Second stage surgery was performed after about 3 months in which the tissue expanders were removed and the pre-expanded scalp skin was used to drape the scalp defect that resulted from the excision of the lesion. An excision and a two staged reconstruction of the scalp using tissue expanders, may ensure a good aesthetic outcome in the management of intermediate to large sized congenital melanocytic nevus.

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.