Malignant and benign tumors associated to multiple primary melanomas: just the starting block for the involvement of MITF, PTEN and CDKN2A in multiple cancerogenesis?

Background: Multiple primary melanomas (MPMs) could represent an interesting field of investigation for possible linkage between multiple cancer phenotypes and genetic background. In this setting, the co-existence of MPMs and malignant/benign neoplasms in a group of MPMs patients has been highlighted and the corresponding germ-line mutations have been traced. Methods: The study evaluated the prevalence of benign and malignant neoplasms in a group of 49 MPMs patients and compared the data with 49 age- and gender-matched single primary melanoma (SPM) controls. Genetic testing was performed when a germ-line mutation was suspected. Results: A statistically significant prevalence (P<0.0001) of benign and malignant neoplasms were found among MPMs patients. Of 27 diagnosed malignancies, basal cell carcinoma was the most frequent (n=10, 37.1%), followed by colorectal adenocarcinoma (n=4, 14.8%), prostate adenocarcinoma (n=3, 11.1%), breast adenocarcinoma (n=2, 7.4%), papillary thyroid carcinoma (n=2, 7.4%), pancreas adenocarcinoma (n=2, 7.4%), renal cell carcinoma (n=2, 7,4%), oral squamous carcinoma (n=1, 3.7%), liver adenocarcinoma (n=1, 3.7%), large B lymphoma (n=1, 3.7%), multiple myeloma (n=1, 3.7%), urinary bladder carcinoma (n=1, 3.7%), stomach carcinoma (n=1, 3.7%). Ten different benign neoplasms arising in various organs were also reported. Germline mutations involving PTEN, MITF E318K, CDKN2A, MC1R were detected. Conclusions: Close cancer surveillance should be recommended in MPMs patients. Clinicians should select the appropriate population for genetic testing and refer those patients for genetic counseling. Tailored clinical and instrumental screenings and follow-up strategies have to be based on the patient’s mutation status.