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Semin Liver Dis. 1984 May;4(2):147-57.

Hepatic tumors induced by sex steroids.


Our study of more than 250 women with hepatic tumors, accessioned in our tumor registry at the University of Louisville, disclosed three types of tumor: FNH , HCA, and HCC. The ingestion of sundry kinds of sex steroids by the majority of these women, chiefly for purposes of preventing conception, warrants the suspicion that such hormones induced these different types of hepatic tumors. Publications by others reporting similar hepatic tumors in men using male sex steroids lends support to this hypothesis. Rupture of the hepatic tumor and consequent hemorrhage, producing hemoperitoneum, is a major risk factor. Other presenting symptoms are pain and palpable mass. Symptomatic women using OCs should be subjected to a CT or technetium hepatic scan as an initial screening assessment. Because of the imminent possibility of rupture, large turgid vascular tumors should be resected without biopsy. Biopsy-proved HCC should also be removed surgically. All other tumors, including small multiple tumors, will usually regress when exogenous sex steroids are withdrawn and pregnancy avoided. Other significant hepatic changes observed in this study are peliosis hepatis, periportal sinusoidal dilation, and vascular lesions. The branches of the hepatic artery and the tributaries of the portal vein show combinations of intimal and smooth muscle proliferation, vascular thickening, occlusive intimal thickening, and, at times, obstructing thrombosis. Similar smooth muscle proliferation in the afferent vessels of the livers of animals treated with sex steroids suggests that there is a cause and effect relationship in women using OCs.


Previous reports describing the oncogenic capacity of estrogens and endrogens and reports suggesting a relationship between primary liver tumors and oral contraceptives (OCs) prompted a meticulous evaluation of the lifestyle and medication usage of each patient accessioned by the registry at the University of Louisville School of Medicine. More than 250 cases of hepatocyte tumors in young women, not all steroid related, have been collected since 1973. The data are sufficient for analysis in 201 patients. The intention was to assess etiological factors and critically classify the histologic features. 3 separate tumors were distinguishable: hepatocelluar adenoma (HCA), focal nodular hyperplasia (FNH), and hepatocellular carcinoma (HCC). In 9 tumors a histologic classification could not be made, generally because of massive hemorrhage and infarction of the tumor. 1 tumor was removed several weeks after hepatic artery ligation was done to stop hemorrhage from the ruptured tumor. Only dense scar tissue remained. Currently, none of the patients in the unclassified group has developed a recurrence nor have any developed metastases. None have died. HCA is relatively soft and usually solitary. The usual description of HCA stresses encapsulation. This is true of 5 tumors in the registry; in these cases the HCA occurred in women not exposed to exogenous reproductive steroids. In contrast, in women ingesting sex steroids the HCA were frequently not encapsulated. Nonencapsulation was characteristic of multiple small tumors in the group taking OCs. The typical FNH has a central scar with radiating septa and a coarsely nodular appearance. In contrast to HCA, necrosis and hemorrhage are less frequently encountered. The presence of bile duct epithelium is the single most distinguishing characteristic differentiating FNH from CHA. In women taking exogenous sex steroids, HCA and FNH may be related lesions or may be different histologic manifestations of a stimulus affecting mesenchymal and entodermal elements of the liver in variable degrees. HCC is grossly indistinguishable from FNH, having a well formed central scar, fibrous septa, and coarse nodulation. Despite the fact that all HCCs were fairly well differentiated tumors, there were no longterm survivors. There is no conclusive evidence that a cause and effect relationship exists between primary tumors of the liver and OCs. A history of prolonged sex steroid administration, usually OCs, was present in the majority of the cases studied. Similar smooth muscle proliferation in the afferent vessels of the livers of animals, treated with sex steroids suggests that there is a cause and effect relationship in women using OCs.

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