Adult-type hepatocellular carcinoma in the center of a fibrolamellar hepatocellular carcinoma

A large hepatic tumor was detected in the noncirrhotic liver of a 27-year-old female patient. The tumor was radiologically characterized by a peripheral mass encircling a central ovoid tumor, and was resected by an extended right hemihepatectomy. Histologic examination revealed that the peripheral and major component of the tumor represented a fibrolamellar hepatocellular carcinoma, whereas the central, well-demarcated tumor was a less well-differentiated adult-type hepatocellular carcinoma completely encircled by the former. Cells of the peripheral tumor mass abundantly expressed cytokeratin-7, typically present in the fibrolamellar variant, whereas no cytokeratin-7 immunoreactivity was found in the central tumor. To our knowledge, this is the first reported case of a not admixed but clearly separated evolution of these 2 histologic patterns within the same tumor, and suggests that the 2 types of hepatocellular carcinoma may share a common pathogenic pathway.     

Alpha-fetoprotein producing renal cell carcinoma: a case report.

We report a case of alpha-fetoprotein (AFP) producing renal cell carcinoma. A 53-year-old man with fever was found to have a left renal mass on computed tomography. No mass was detected in the liver. Serum AFP was 1,460 ng/ml. Radical nephrectomy showed a 10 cm mass in the upper half. A half of the tumor was whitish yellow and firm whereas another half was soft and bright yellow with hemorrhagic and necrotic areas. Histologically, the two areas were different. The lower part consisted of the clear cell renal cell carcinoma and the upper part consisted of granular cells. On immunohistochemistry, the granular tumor cells only were positive for AFP. Serum AFP level dropped abruptly to 383 ng/ml on the 6th postoperative day and gradually returned to normal during the 6 months. Multiple metastatic nodules were found in the lungs, liver and bone in 9th postoperative month and the AFP was less than 1 ng/ml. This suggest metastatic lesions are non-AFP producing clear cell type. It can be concluded that serum AFP elevation was due to synthesis by the renal cell carcinoma in the absence of liver neoplasm. Although AFP producing renal cell carcinoma is a rare entity, serum AFP can be a useful marker for the detection of the tumor.     

Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FLM) is a rare tumour that typically presents in young adults. It occurs in non-cirrhotic liver and is usually associated with normal serum alpha-fetoprotein. It is defined by a triad of morphological features: polygonal tumour cells with eosinophilic cytoplasm, prominent macronucleoli and lamellar fibrosis. A central scar can be present. The principal differential diagnosis is conventional hepatocellular carcinoma (HCC), especially the scirrhous variant. Acinar differentiation and focal mucin production are common and can be confused with adenocarcinoma. Focal neuroendocrine differentiation can occur and can be mistaken for neuroendocrine tumours. FLM also shows distinctive features at the molecular level; many of the commonly observed abnormalities in conventional HCC like p53 and β-catenin mutations are not observed in FLM. The extent of cytogenetic changes and CpG island methylation is low in FLM compared to conventional HCC. FLM is an aggressive neoplasm with 5-year survival of around 50%. Although the outcome in FLM has been considered more favourable compared to conventional HCC, this is likely to be related to absence of cirrhosis rather than unique morphological features of the tumour.     

Sarcoidosis-associated hepatocellular carcinoma

Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis.     

Pedunculated hepatocellular carcinoma

A case of this rare exception to the common gross types of hepatocellular carcinoma is reported. The main clinico-pathological findings of this variant are summarized in the light of a review of the relevant literature. Emphasis is placed on the usefulness of the latest diagnostic procedures including echography and CT scans for an increased accuracy of the preoperative clinical diagnosis.     

Ground-glass cells in hepatocellular carcinoma

Hematoxylin and eosin-stained sections representing ten cases of hepatocellular carcinoma showed many tumor cells with ground-glass cytoplasm identical to that found in hepatocytes containing hepatitis B surface antigen (HBsAg). However, the aldehyde fuchsin stain was negative, as were the were the immunoperoxisidase stains for HBsAg and core antigen (HBcAg). Electron microscopically, the ground-glass appearance corresponded to the presence of non-membrane-bound amorphous or fibrillar inclusions. Immunohistochemically, the ground-glass material reacted with antiserum to human fibrinogen, suggesting synthesis of this protein by the carcinoma cells. Although the ground-glass appearance in hepatocellular carcinomas may sometimes be associated with HBsAg, special stains or technics are necessary to confirm its presence.     

Pale bodies in hepatocellular carcinoma

Histochemical, immunohistochemical and ultrastructural studies were performed on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was observed in 3 (5.5%) of 55 consecutively resected HCC cases. Histologically, a large number of hepatocytes displayed pale or eosinophilic staining of the cytoplasm, resulting in ground-glass appearance. They were aggregated in nodular pattern, or diffusely intermixed with other malignant hepatocytes. PBs were negative for periodic-acid Schiff and Masson's trichrome staining. The inclusions showed a strong positive reaction for fibrinogen and some of them were weakly positive for albumin but negative for hepatitis B surface antigen, hepatitis B core antigen, alpha-fetoprotein and alpha-1-antitrypsin. Ultrastructurally, PBs were membrane-bound and contained granular materials of moderate electron density, and were closely related to dilated rough endoplasmic reticulum. These findings support that PBs are secretory fibrinogen accumulated in cystic ER and that such intracellular accumulation possibly reflects a defective transport of fibrinogen.     

Biological markers in hepatocellular carcinoma

Primary cancer of the liver, especially common in inter-tropical Africa and South-East Asia, still remains inaccessible to a really effective therapy, except for a rapid surgical excision. Improvement of its particularly poor prognosis requires therefore early screening based on reliable biological markers. Following alpha-feto-protein, various parameters have been proposed: enzyme, ferritin, desialylated serum protein, decarboxylated prothrombin... However, alpha-feto-protein remains, in practice, the reference diagnostic test, in spite of a moderate specificity below 500 ng/ml and the fact that it is frequently missing in early cancers. Its diagnostic score may be improved either by the use of monoclonal antibodies, or by determining the ratio of fucosylated form, or by concomitant use of other markers: alpha-L-fucosidase, decarboxy-prothrombin.     

Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma

Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), α-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.     

Alpha-fetoprotein producing uterine corpus carcinoma: A hepatoid adenocarcinoma of the endometrium

A case of alpha-fetoprotein (AFP) producing endometrial carcinoma in a 60-year-old Japanese woman is presented. The patient complained of abnormal vaginal bleeding of 10 days' duration. On admission a uterine corpus mass and high serum AFP concentration (31950 ng/mL) was noted. There was no tumorous lesion in any other organ radiographically and endoscopically. Histologically, the biopsy specimen taken from the uterine mass showed a poorly differentiated endometrial carcinoma and a radical hysterectomy was subsequently performed. The postoperative serum AFP value transiently decreased with chemotherapy, however, lung metastases were found and the patient died 12 months following surgery. The resected uterus had a necrotic tumor, 6 x 5 x 4 cm in size, filling the endometrial cavity, characterized by exophytic growth with infiltration in the myometrium. Histologically, the tumor was composed of the main medullary carcinoma area with microcysts and admixed small areas of well-differentiated endometrioid adenocarcinoma, accompanied by a smooth transition with one another. In both the areas, the tumor cells had immunoreactive AFP, alpha-1-antitripsin, albumin, transferrin, carcinoembryonic antigen, CA19-9, and epithelial membrane antigen. There was no histologic evidence for a germ cell tumor. Based on these findings, this uterine corpus tumor was regarded as hepatoid variant of endometrial carcinoma. Although the histogenesis remains controversial, we assume the hypothesis that the tumor may arise in the endometrium per se in association with abnormal differentiation of muellerian duct elements.     

microRNA与肝癌

肝癌是世界上最常见的恶性肿瘤之一,其发病率和病死率极高。microRNA(miRNA)是一类单链的非编码RNA,通常在转录后水平调控基因的表达。最近多项研究表明miRNA在肝癌中发挥着重要作用,已经成为肝癌诊断、治疗中的一个靶标。     

Cytology of hepatocellular carcinoma

Twenty-five cases of cytologically and histologically confirmed hepatocellular carcinoma (HCC) were cytomorphologically analyzed using May-Grünwald-Giemsa (MGG)-stained aspiration smears and supplemented with special stains. The cell types were categorized as well differentiated (18 cases), vacuolated (four cases), giant cell (one case), and poorly differentiated (two cases). Glycogen staining was positive in 80% of the cases and hence served as a reliable parameter of diagnostic importance in HCC. Cytoplasmic hyaline bodies (14.6%) and bile pigment (17%), when present, were other important features supporting the diagnosis of HCC. Vacuolation of the cell cytoplasm (80%) was possibly related to glycogen accumulation. The cause of nuclear vacuolation (60%) and the significance of nuclear argyrophilia as markers of abnormal cell growth remain to be studied.