TRIPLE PRIMARY MALIGNANT NEOPLASMS INCLUDING A MALIGNANT BRAIN-TUMOR - REPORT OF 2 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 ge netic alterations in triple or more PMN, including malignant brain tum ors are discussed with intensive review of the literature. RESULTS The first patient, a 77-year-old male, suffered metachronously from tubul ar adenocarcinoma of the stomach, transitional cell carcinoma of the b ladder, and glioblastoma in the brain. This glioblastoma had loss of h eterozygosity 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 demons trated 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 th e other hand, neither of these hereditary cancer syndromes were contai ned 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 m ight play an important role in tumorigenesis of PMN in the younger gro up, whereas epigenetic factors would be more important in the older gr oup. Characteristic organ association and factors influencing carcinog enesis, such as aging, environmental carcinogens, and underlying genet ic alterations in these tumors are further discussed.