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Enucleation combined with hepatic vascular exclusion is a safe and effective alternative to hepatic resection for liver cell adenoma.

Liver cell adenomas are benign, rare tumors that occur primarily in women with a history of oral contraceptive use. Surgical treatment is recommended to reduce the risk of sudden, unpredictable hemorrhage or malignant transformation, but mortality rates of 5 to 8 per cent are reported for major hepatic resections. This report summarizes an experience of eight patients with liver cell adenoma treated by enucleation or resection, alone or combined with hepatic vascular exclusion (HVE). The latter technique, originally described in the mid-1960s, markedly reduces operative blood loss associated with hepatic resection. All eight patients were women of child-bearing age, and seven reported previous oral contraceptive use. The majority of patients were asymptomatic at the time of presentation. Six patients (75%) had a single adenoma and the remaining two had multiple lesions. HVE was used successfully in four patients with no perioperative mortality and reduced by nearly 50 per cent the intraoperative blood loss compared to conventional hepatic resection (1635 mL versus 3875 mL, respectively). Six evaluable patients were followed for an average of 65 months, with no evidence of liver dysfunction or adenoma recurrence. Enucleation of liver cell adenoma appears to be a safe alternative to formal hepatic resection and provides excellent long-term results. HVE markedly reduces operative blood loss, has no adverse effect on metabolic function, decreases the potential health risk associated with transfusion, and should be used whenever possible.

Adenoma, Liver Cell↗

Rupture of liver cell adenoma with fatal massive hemoperitoneum resulting from minor road accident.

Blunt abdominal trauma can cause rapid death resulting from serious injuries of internal organs. The liver is commonly involved and may show tearing, usually in its upper surface, resulting in hemoperitoneum eventually leading to death. Minor trauma implies serious liver damage only when previous pathologic changes causing enlargement of the organ are present. The case of a 25-year-old woman who died as a consequence of a minor road accident is reported. At autopsy, the body showed no external injuries, the only relevant finding being a massive hemoperitoneum from the rupture of an unusually large liver cell adenoma. Liver cell adenomas carry a serious risk of spontaneous rupture, which may result in the death of the patient. The occurrence of the rupture after a minor blunt abdominal trauma is highly unusual.

Accidents, Traffic↗

Hepatocellular carcinoma in a liver-cell adenoma within a non-cirrhotic liver.

Liver-cell adenomas are benign lesions of the liver occurring predominantly in young women. Hepatocellular carcinomas in most of the cases arise in a cirrhotic liver during the fifth or sixth decade. We describe the case of a 40-year-old woman in whom work-up for epigastric pain revealed a peptic ulcer and a large hepatic mass. Tests for chronic liver diseases were negative. Imaging findings and biopsy specimens of the tumour were inconclusive. The tumour was surgically removed and a hepatocellular carcinoma arising within a liver-cell adenoma in a non-cirrhotic liver was found. Malignant transformation of liver-cell adenoma has only been reported in a few case reports. Mechanisms of transformation remain unclear. The imaging findings as well as histological features are presented in detail and the literature is discussed.

Adenoma, Liver Cell↗

Ultrastructure of sinusoidal cells in a benign liver cell adenoma.

A typical benign liver cell adenoma was removed from a 25-year-old female taking an oral contraceptive. The biopsy was perfusion-fixed, allowing good visualization of sinusoids and sinusoidal cells. Kupffer cells were seldom seen. Endothelial cells were of irregular thickness; most of them had few fenestrae and were attached to each other by well visible junctions. Normal perisinusoidal cells (PSC) were not seen but were replaced by myofibroblast-like cells with thick subendothelial processes. A basement membrane often underlaid endothelial cells and the processes of PSC. The enlarged Disse space with a flattened sinusoidal hepatocyte membrane contained occasional red blood cells and an abundant extracellular matrix but few collagen fibers. These sinusoidal abnormalities leading to the capillarization of sinusoids, either the cause or the consequence of the disease, indicated a loss of normal hepatocyte homeostasis.

Adenoma↗

[Liver resection and liver transplantation in liver cell adenoma, hepatocellular carcinoma and fibrolamellar liver carcinoma].

Hepatocellular adenomas are rare benign conditions but represent an indication for resection due to their risk of rupture and malignant mutation. Surgical resection should include a safety margin according to oncologic principles. Surgical resection does represent the optimal treatment modality for hepatocellular carcinoma without accompanied cirrhosis of the liver. The rare fibrolamellar carcinoma has the best prognosis. Liver transplantation is usually not performed in HCC without cirrhosis. In case of HCC with cirrhosis in stage I and II the relapse free 5-year-survival rate is more than 50% after liver transplantation. In the UICC-stages III and IV the results of liver transplantation are worse, which points to the impact of exact preoperative staging. Liver resection in HCC and cirrhosis is indicated in stage I and II in case of good liver function. In case of liver resection the survival rates are worse with significantly higher relapses compared to liver transplantation. For small, functionally irresectable hepatocellular carcinoma in cirrhosis liver transplantation is the treatment of choice today.

Adenoma, Liver Cell↗

Hemoperitoneum from spontaneous rupture of a liver cell adenoma in a male with hyperthyroidism.

Spontaneous liver rupture is uncommon, is difficult to diagnose, and carries a high mortality. Liver cell adenoma is a rare benign liver tumor with increasing incidence in women on oral contraceptive pills, and they have been reported to rupture spontaneously. In men such a phenomenon is an extreme rarity. In animal experiments thyroid hormone is proven to play a role in the growth of liver cell-derived neoplasms as they do in normal hepatocyte proliferation. An association of liver cell adenoma and hyperthyroidism in humans has not been previously reported. We present the successful management of an unusual case of spontaneous hemoperitoneum from rupture of a liver cell adenoma in a young man with hyperthyroidism.

Adenoma, Liver Cell↗

Liver cell adenoma with concomitant hepatocellular carcinoma: report of two cases.

Malignant transformation of liver cell adenoma and unequivocal hepatocellular carcinoma in resected liver cell adenomas are rare. We report two cases of liver cell adenoma with concomitant hepatocellular carcinoma. The first occurred in a 19-year-old male with an asymptomatic liver mass and was discovered incidentally. He had a history of nephrotic syndrome treated with oral prednisolone for 15 years. The second occurred in a 46-year-old female who was admitted due to right tubo-ovarian abscess. Computerized tomography scanning incidentally found a 10-cm liver mass in the right lobe. There was no history of oral contraceptive use. Both patients were negative for serum hepatitis B surface antigen and anti-hepatitis C virus antibody. Neither had cirrhosis. These two cases imply that malignant transformation of liver cell adenoma does occur, and that liver cell adenomas should be excised when malignant transformation is suspected.

Adenoma, Liver Cell↗

Simultaneous resection of liver cell adenomas and an intrahepatic portosystemic venous shunt with elevation of serum PIVKA-II level.

A 27-year-old woman with no history of liver disease or oral contraceptive use presented with sudden abdominal pain. Laboratory data showed mild liver dysfunction with jaundice. Computed tomography and angiography revealed centrally located large liver cell adenomas (LCAs) and an intrahepatic portosystemic venous shunt (IHPSS) in the left lobe. The serum des-gamma-carboxy prothrombin (known as "protein induced by a lack of vitamin K or antagonist II," PIVKA-II) level was extremely high (6,647 mAU/ml), indicating malignant transformation of the tumors. Under the diagnosis of LCAs and IHPSS, the patient underwent simultaneous resection of the four liver tumors and portovenous shunt, and the hepatic vascular abnormality was resolved. The pathological diagnosis was LCAs without hepatocellular carcinoma. Immunohistochemical analysis with an anti-PIVKA-II monoclonal antibody showed positive staining of the adenoma cells. This case shows that LCA without malignant transformation can produce PIVKA-II, leading to high serum levels of PIVKA-II. Simultaneous resection of multiple tumors and closure of the portosystemic shunt are strongly recommended in a patient with LCA associated with IHPSS.

Adenoma, Liver Cell↗

Liver cell adenoma in a young man with elevated serum PIVKA-II level.

A 21-year-old man was referred to our hospital because of a liver mass lesion detected by abdominal ultrasonography. He had received no hormonal treatment. Physical examinations revealed no abnormalities, and laboratory data, including hepatic function test results, were within normal ranges, with the exception of elevated levels of serum protein induced by vitamin K absence or antagonist (PIVKA)-II (2.2 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass lesion measuring 10 x 10 cm, with hypoechoic areas located in the right posterior segment of the liver. A low-density area and a hypervascular area were detected in the right posterior segment of the liver by computed tomography and celiac angiography, respectively. As hepatocellular carcinoma could not be completely excluded, the tumor was resected. The tissue consisted of sheets of tumor cells with eosinophilic cytoplasm and round nuclei showing a thin trabecular pattern, and these histological findings indicated liver cell adenoma. After resection of the tumor, serum PIVKA-II returned to the normal level.

Adenoma, Liver Cell↗

Association of multiple liver cell adenomas with spontaneous intrahepatic portohepatic shunt.

The association of multiple liver cell adenomas containing foci of focal nodular hyperplasia with a spontaneous intrahepatic portohepatic venous shunt is reported in a 13-year-old male patient. At least eight nodules less than 10 cm in diameter were recognized and proved by means of surgical resection or surgical biopsies. These lesions were heterogeneous and hypodense on precontrast computed tomographic (CT) scans, and were slightly enhanced after injection of contrast medium. At magnetic resonance (MR) imaging, the signal intensity of these nodules varied. It was either hyperintense or hypointense on T1-weighted SE images. Sonography and angiography demonstrated a portohepatic venous shunt and hepatic arterialization was observed. These findings emphasize the hypothesis that hepatic arterialization may cause the development of liver cell adenomas. Moreover, it is suggested that liver cell adenoma and focal nodular hyperplasia have a common pathogenesis.

Adenoma, Liver Cell↗

Two case reports of childhood liver cell adenomas harboring beta-catenin abnormalities.

The benign epithelial neoplasm liver cell adenoma is rare, especially in childhood. We report 2 such cases, 1 of which was associated with Prader-Willi syndrome. Differential diagnosis of the liver cell adenomas on the basis of histopathologic findings proved difficult and was based on the absence of cellular and nuclear atypia, mitotic activity, and invasive growth. In both cases, immunohistochemical staining demonstrated the nuclear accumulation of beta-catenin, and in 1 case, the tumor cells carried a mutation of the beta-catenin gene. Recently, disregulation of the Wnt/beta-catenin pathway, attributable to abnormalities of the beta-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas. Our report may be the first to describe the beta-catenin abnormalities in childhood liver cell adenoma. These findings imply that abnormalities of beta-catenin can be an early initiating event in human liver tumorigenesis.

Adenoma, Liver Cell↗

Disappearance of liver cell adenoma: CT and MR imaging.

We report the disappearance of liver cell adenoma, documented by computed tomography (CT) and magnetic resonance (MR) imaging. A 42-year-old woman with a diagnosis of hepatic adenoma was followed up by CT and MR imaging after cessation of oral contraceptive use. At the time of diagnosis, the adenoma was 4 cm in diameter and appeared hypervascular on CT. At MR imaging, the lesion was hypointense on T1-weighted sequences, and hyperintense on T2-weighted sequences. The lesion disappeared 4 years after cessation of oral contraceptive use. We conclude that in nonoperated patients CT scans and MR imaging are useful for following the evolution, and documenting the regression, of liver cell adenomas.

Adenoma, Liver Cell↗

The malignant transformation of liver cell adenomas.

OBJECTIVE: To investigate clinical experience with the apparent malignant transformation of benign liver cell adenomas. DESIGN: Retrospective review of personal experience and literature. SETTING: University hospital and affilated community hospitals. PATIENTS: All patients diagnosed with liver cell adenomas over a 30-year period. INTERVENTIONS: Liver resection and/or tumor biopsy. MAIN OUTCOME MEASURES: Gender, age, drug associations, alpha-fetoprotein levels, response to treatment, and survival. RESULTS: Thirteen patients from personal experience and 26 patients from the reports of others had liver cell adenomas that were not resected. Five of these patients subsequently developed hepatocellular carcinoma. CONCLUSIONS: Malignant transformation of a liver cell adenoma is a rare phenomenon, but it does occur. Alpha-fetoprotein levels may be more helpful in diagnosis than expected from previous reports. Solitary benign adenomas should be resected whenever possible. Patients with diffuse multiple tumors should be observed closely over a long period.

Adenoma↗

Are oral contraceptive-associated liver cell adenomas premalignant?

From January 1977 to June 1990, 1,670 patients with a liver mass or masses underwent transabdominal fine needle aspiration biopsy of the liver. Of those cases, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." Among the 99 patients with hepatocellular carcinoma, 3 were users of oral contraceptives. The nine patients with liver cell adenoma were all users of oral contraceptives. Of them, two developed foci or areas of liver cell dysplasia within the adenomas. The mean periods of oral contraceptive use among these three groups of patients were different. It appeared that patients started to develop liver cell adenoma after five years of oral contraceptive use (mean, 6.3 years). Foci or areas of liver cell dysplasia began to arise within liver cell adenomas after 8 years of oral contraceptive use (mean, 9 years), and the patients started to develop hepatocellular carcinoma after 10 years of contraceptive use (mean, 11 years). The cytologic features of liver cell dysplasia strikingly mimicked those of hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas foci or areas of liver cell dysplasia within the adenomas are irreversible, premalignant changes and may transform into hepatocellular carcinoma.

Adult↗

Hepatic tumors and oral contraceptives: surgical management.

The clinical and pathological features of 14 patients with benign liver tumors are reviewed. There were two males and 12 females in this series of cases. All but one of the females had been on contraceptive steroid therapy for an average of 7.8 years. Abdominal pain was the presenting complaint in 75% of cases, a palpable abdominal mass was present in 22%, while 12.5% of the patients presented with acute hemorrhagic shock due to rupture of a liver cell adenoma. Liver cell adenomas (LCA) were found in 87.5% of the cases and a diagnosis of focal nodular hyperplasia (FNA) was made at histologic examination of the resected tumors in 12.5% of cases. Surgical resection of the liver tumors was performed successfully in 89% of the cases. Hepatic lobectomy was accomplished in four patients, hepatic segmentectomy was possible in three cases, while local wedge resection or focal excision were indicated on seven occasions. There was no operative mortality in this series, but one patient required reoperation for drainage of a complicating subphrenic abscess.

Adult↗

INK4a-ARF alterations in liver cell adenoma.

BACKGROUND: The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS: To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS: After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivation by DNA sequence analysis, methylation specific polymerase chain reaction, restriction enzyme related-polymerase chain reaction (RE-PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INK4a) were assessed by differential PCR. RESULTS: Methylation of p14(ARF) was found in 3/25 cases (12%) and alterations in p16(INK4a) occurred in 6/25 liver cell adenomas (24%) which correlated with loss of mRNA transcription. We failed to detect microdeletions or specific mutations of both exons. p16(INK4a) methylation appeared in the context of an unmethylated p14(ARF) promoter in six cases. In normal liver tissue, p14(ARF) or p16(INK4a) alterations were not observed. CONCLUSIONS: Our data suggest that p14(ARF) methylation occurs independently of p16(INK4a) alterations in liver cell adenomas. Furthermore, methylation of p14(ARF) and p16(INK4a) may be a result of cell cycle deregulation and does not seem to be a prerequisite of malignancy.

Adenoma, Liver Cell↗