Melanoma in patients with Li-Fraumeni syndrome (Review)

Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of TP53, a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. Cumulative cancer incidence for LFS patients by the age of 70 years is 80-100%, mostly involving adrenocortical carcinoma, brain tumors, bone and soft tissue sarcomas, leukemia and female breast cancer from the age of 20 years. Dominant negative TP53 variant is correlated with an increased tumorigenesis risk in LFS. Sporadic TP53 mutations are related to almost half of global cancers since p53 in addition to p73 protein represent essential players in anticancer cellular protection. Epidemiological aspects concerning skin cancers, especially malignant melanoma (MM), in LFS are less clear. A low level of statistical evidence demonstrates LFS cases with pediatric MM, multiple MM, spitzoid MM, atypical presentations, mucosal and uveal MM. Retrospective cohorts indicate a higher cumulative risk than the general population by the age of 70 years for MM and basal cell carcinoma. Non-syndromic and syndromic TP53 mutations are a major pathway of metastasis, including MM. In LHS, an important level of awareness involves skin cancers despite not being a part of the typical malignancy-containing picture. Additional data are crucially needed. However, at least one dermatologic control is a step in the multidisciplinary panel of surveillance of these patients; but in cases with benign and pre-malign pigmentations, serial dermatoscopy and full body photography are recommended for early melanoma detection in order to improve the prognosis and to reduce the overall malignancy burden.