[A rare form of benign tumor of the liver possibly related to the use of oral contraceptives: focal pediculated nodular hyperplasia]

Abstract

Following a recent case, the authors review the literature of hepatic nodular hyperplasia. The incidence of this condition increases regularly with the consumption of oestrogens. They attempt to define the methods of detection for patients at highest risk. Without exaggerating the incidence of this complication of oral contraceptives, the authors believe that it will become increasingly more common than the vascular complications which, although frequently discussed, are relatively rare.

PIP: This article describes a case of focal pedunculated nodular hyperplasia, a rare form of benign liver tumor, and reviews the literature on focal nodular hyperplasia (FNH) and hepatocellular adenoma. Focal pedunculated nodular hyperplasia is the rarest form of FNH and accounts for fewer than 20% of cases. Hepatocellular adenoma is usually a single encapsulated tumor ranging in size from 1-30 cm in diameter. FNH is usually also a single tumor which is always polylobed and multinodular. The size is variable and it is well defined although not encapsulated. Microscopically neither FNH nor hepatocellular adenoma has normal portal spaces or centrolobular veins. A peliose (intratumoral pseudomicrocysts) is often observed in oral contraceptive (OC) users in both cases. Atypical, dysplasic, or neoplasic cells are observed in about 10% of cases of hepatocellular adenoma but have never been reported in FNH. Considerable hypervascularization is found in hepatocellular adenoma but not in FNH, although in FNH large vascular pedicel may be observed at the periphery. Both tumors are most frequently seen in fertile aged women. Over 1/3 of cases of hepatocellular adenoma are discovered due to intraperitoneal bleeding. FNH is asymptomatic in 73.5% of cases and hemoperitoneum is very rare. The case reported was that of a 40-year-old woman with no significant medical history who had used a combined OC containing ethinyl estradiol and norgestrel for 6 years until 2 years previously, when she terminated use due to subsequently controlled hypertension. A 6-month history of menorrhagia was uncontrolled despite use of an OC containing levonorgestrel only. The liver tumor was discovered in the course of a total hysterectomy performed because of a large polymyomatous uterus associated with significant menorrhagia. The FNH was surgically removed 2 months later. The tumor was highly vascularized and connected to segment 4 by a voluminous pedicel containing numerous thick vascular elements. The postoperative course was smooth. The relationship between OC use and benign hepatic tumors is now well established. Their overall frequency has been estimated at 4.9/million women aged 15-45. The duration of exposure to OCs seems to be a determining factor. The risk is negligible at durations of OC use under 1 year but is multiplied by 7 for FNH and by 5 for hepatocellular adenoma after 5 years. EE, mestranol, and 19 norsteroids all seem to play etiologic roles. 58% of hepatocellular adenomas in OC users are discovered because of hemoperitoneum following rupture. Bleeding is usually massive and the mortality rate is about 6%. FNH is revealed by bleeding in 15% of cases in OC users and is asymptomatic in 49% of users. Tumor development depends on whether OC use is continued. It is not currently known whether the tumors tend in the long run to degenerate into hepatic carcinoma, and whether OC use plays a role. The occurrence of liver cancer in OC users does not seem to be greater than in the general population, but OC users are younger at diagnosis, their survival time is longer, and alpha fetoprotein levels are not elevated. Surveillance of OC users is difficult because FNH is so often asymptomatic. Periodic sonograms after 5 years of OC use may be indicated.