Multiple primary malignancies in Spanish patients with hepatocellular carcinoma: Analysis of a hospital-based tumor registry

Background and Aim: Little is known about the etiological associations and clinical features of extrahepatic primary malignant (EHPM) neoplasms in subjects with hepatocellular carcinoma (HCC). The aim of this study was to characterize this phenomenon in a consecutive series of Spanish patients in order to define its natural history and influence on survival. Methods: A retrospective analysis of 245 patients with HCC during the period 1999-2003 was performed. Subjects identified with a second primary malignancy elsewhere constituted the EHPM group and were compared to patients with HCC alone. Results: Eighteen patients (7.3%) had one or two associated extrahepatic malignancies (mean age 67.7 +/- 9.7 years); of these, 17 had double cancer and one patient, triple. Nine of the 19 EHPM occurred before HCC diagnosis. The associated cancers included five cases of colorectal carcinoma, four cases of head and neck carcinoma, three cases of genitourinary cancer, two cases of lymphoproliferative disorder, one lung carcinoma, one skin melanoma, one breast carcinoma, and two cancers of unknown origin. Age and sex distribution, etiology of underlying hepatopathy, and liver function tests did not differ significantly between both groups. There was no difference between the overall survival rates. Conclusions: EHPM is not rare among Spanish patients with HCC, although no specific clinicopathological features were detected in this population. Our results suggest that the association of another primary tumor with HCC does not imply a worse prognosis. The possibility of development of EHPM should be kept in mind when deciding on therapy and follow-up of HCC.