Triple primary malignant neoplasms including a malignant brain tumor: Report of two cases and review of the literature

BACKGROUND Two rare cases of triple primary malignant neoplasms (PMN), including malignant brain tumors, which were glioblastoma multiformes, are described. METHODS The clinical characteristics and underlying genetic alterations in triple or more PMN, including malignant brain tumors are discussed with intensive review of the literature. RESULTS The first patient, a 77-year-old male, suffered metachronously from tubular adenocarcinoma of the stomach, transitional cell carcinoma of the bladder, and glioblastoma in the brain. This glioblastoma had loss of heterozygosity in exons 7-8 in p53 gene. The second patient, a 68-year-old, developed papillary adenocarcinoma of the lung, adenocarcinoma of the rectum, and glioblastoma in the brain during a period of 7 years. In 42 such cases described in the literature, age distribution demonstrated two characteristic peaks, one in the third decade and the other over 50 years of age. The younger group consisted mainly of Turcot's syndrome, and of a case of Li-Fraumeni familial cancer syndrome. On the other hand, neither of these hereditary cancer syndromes were contained in the elder group. Regarding the site of PMN, colorectal cancers were-associated most frequently with malignant brain tumors, followed by stomach cancers,and thyroid cancers. Malignant brain tumors, mostly glioblastoma multiforme, tend to occur as the last tumor of triple or more PMN. CONCLUSIONS These results suggest that genetic background might play an important role in tumorigenesis of PMN in the younger group, whereas epigenetic factors would be more important in the older group. Characteristic organ association and factors influencing carcinogenesis, such as aging, environmental carcinogens, and underlying genetic alterations in these tumors are further discussed.