Melanoma arising in a Giant congenital melanocytic nevus: two case reports

Abstract

Background A giant congenital melanocytic nevus (GCMN) is found in 0.1% of live-born infants. If present, the lesion has a chance of about 6% to develop into malignant melanoma. Both children and adults can be affected by malignant melanoma arising in a giant congenital nevus. Up to 95% of GCMNs harbor NRAS mutations, and mutations in the BRAF , MC1R , TP53 , and GNAQ genes have also been described. The individualization of therapy is required, but diagnostic and prognostic criteria remain controversial. Case presentations We report two cases: 1) melanoma arising in a giant congenital nevus during the first month of life complicated with neurocutaneous melanosis (NCM), and 2) melanoma arising in a giant congenital nevus during the first 6 months of life. Pathology, immunohistochemistry, and genetic analyses of tumor tissue were performed. The first case revealed only a non-pathogenic P72R polymorphism of the TP53 gene in the homozygote condition. For the second case, a Q61K mutation was detected in the NRAS gene. Conclusion Malignant melanoma associated with GCMN is rare and therefore poorly understood. Outcomes have been linked to the stage at diagnosis, but no additional pathological prognostic factors have been identified. The most frequent genetic event in giant CMNs is NRAS mutations, which was discovered in one of our cases. To accumulate evidence to improve disease prognosis and outcomes, children with congenital melanocytic nevus should be included in a systemic follow-up study from birth.

Analysis of TP53 gene in uterine myomas: No mutations but P72R polymorphism is associated with myoma development

“…Recently, melanoma arising in a giant congenital nevus during the first month of life complicated with neurocutaneous melanosis was found to be associated with only a non-pathogenic P72R polymorphism of the TP53 gene in the homozygote condition. 31 Additionally, P72R polymorphisms were suggested to be associated with an increased plasma cell myeloma risk 32 as well as chronic lymphocytic leukemia. 33 A possible trend towards worse overall survival among patients with P72R polymorphism was mentioned in patients with acute myeloid leukemia.…”

“…A connection between P72R polymorphism and various cancers was reported in current literature. Recently, melanoma arising in a giant congenital nevus during the first month of life complicated with neurocutaneous melanosis was found to be associated with only a non‐pathogenic P72R polymorphism of the TP53 gene in the homozygote condition . Additionally, P72R polymorphisms were suggested to be associated with an increased plasma cell myeloma risk as well as chronic lymphocytic leukemia .…”

Treatment of giant congenital melanocytic nevi with cultured epithelial autografts: Clinical and histopathological analysis

“…Larger CMNs are associated with an increased risk of malignant transformation to melanoma. It has been reported that malignant transformation presents before puberty or in childhood [ 11 , 12 ]. Therefore, treatment is targeted at effective removal of as many melanocytes as possible at an early age to decrease the risk of malignant transformation [ 13 ].…”

Melanoma arising in a giant congenital melanocytic nevus with neuroblastoma RAS mutation

“…Alternate treatment options include combinations lasers (diode, fractional carbon dioxide and q-switched Nd-YAG lasers) and curettage. 4,6,7 Compared to adults, pediatric melanomas have more atypical features, thicker lesions at diagnosis, higher frequency of nodular histotype and more aggressive course [Table 1]. 1 A mutational analysis concluded that sun-induced pediatric melanomas exhibit a UV-induced mutational spectrum similar to its adult counterpart (telomerase reverse transcriptase-promoter (TERT-p), BRAF V600 and phosphatase and tensin homolog (PTEN) mutations).…”

“…Giant congenital melanocytic nevus is characterized by a diameter exceeding 20 cm by adulthood and is associated with 5-40% life-time risk of developing melanoma at the lesional site, most occurring within the first 5 years of life. 3,4 Neuromelanosis and melanoma are more likely with size >40 cm, number >20 or multiple satellite lesions and a truncal location. A gadoliniumenhanced screening magnetic resonance imaging (MRI) of the brain and whole spine is recommended <1 year age in a child presenting with this condition.…”