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.

Giant Congenital Melanocytic Nevus in an Afghan Child

We report an 8-year-old Afghan female with giant congenital melanocytic nevus (GCMN) which covered the entire back. The GCMN extended to anterolateral parts of the trunk surrounded by multiple satellite melanocytic nevi.

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.

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.