背景:在0.1%的活产婴儿中发现巨大的先天性黑素细胞痣(GCMN)。如果存在,病变有约6%的机会发展为恶性黑色素瘤。儿童和成人都可能受到巨大先天性痣中产生的恶性黑色素瘤的影响。高达95%的GCMNs有NRAS突变,和BRAF的突变,MC1R,TP53和GNAQ基因也已被描述。需要个体化治疗,但诊断和预后标准仍存在争议.
方法:我们报告了两例:1)在出生后的第一个月内发生在巨大的先天性痣中的黑色素瘤并发神经皮肤黑变病(NCM),和2)在生命的前6个月中出现在巨大的先天性痣中的黑色素瘤。病理学,免疫组织化学,并对肿瘤组织进行遗传分析。第一例仅揭示了纯合子条件下TP53基因的非致病性P72R多态性。对于第二种情况,在NRAS基因中检测到Q61K突变。
结论:与GCMN相关的恶性黑色素瘤很少见,因此知之甚少。结果与诊断阶段有关,但尚未发现其他病理预后因素。巨型CMNs中最常见的遗传事件是NRAS突变,这是在我们的一个案例中发现的。积累改善疾病预后和预后的证据,患有先天性黑素细胞痣的儿童应从出生开始纳入系统随访研究.
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.
METHODS: 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.
CONCLUSIONS: 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.