Cases reported "Precancerous Conditions"

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1/8. Premalignant lesions and hepatocellular carcinoma in a non-cirrhotic alcoholic patient with iron overload and normal transferrin saturation.

    A 66-year-old white man had a hepatic resection for a 6-cm well-differentiated hepatocellular carcinoma which had developed in a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking and heterozygosity for the C282Y mutation of the HFE gene. The liver was mildly fibrotic and overloaded with iron. It also contained numerous iron-free hepatocellular lesions from <1 to 10 mm, suggesting a premalignant change. These lesions were of three types: (i) iron-free foci, (ii) hyperplastic nodules and (iii) dysplastic nodules with severe dysplasia or even foci of well-differentiated grade I hepatocellular carcinoma. This observation suggests the possibility of malignant transformation of the liver in the newly-described syndrome of iron overload and normal transferrin saturation. It also illustrates the multistep process of carcinogenesis in the non-cirrhotic liver.
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keywords = carcinogenesis
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2/8. Endoscopic and histological reversibility of gastric adenoma after eradication of helicobacter pylori.

    Although epidemiological studies strongly suggest an association between helicobacter pylori infection and gastric carcinogenesis via a multistage process, a causal link between them has not been demonstrated. We evaluated the endoscopic and histological changes of gastric adenoma, which is considered a premalignant condition, after eradication of H. pylori. Thirty-five H. pylori-infected patients with gastric adenoma were treated with triple therapy (lansoprazole 30mg/day, clarithromycin 400mg/day, and amoxicillin 1500 mg/day) for 1 week. Of these 35 patients, 30 (86%) exhibited no H. pylori by culture or histology after the therapy. Of the 30 gastric adenomas, 7 decreased in size endoscopically; three gastric adenomas especially showed apparent remission, although histological cure in these three patients was not apparent. Our results suggest that removal of H. pylori infection may only mask a gastric adenoma endoscopically owing to the change around the gastric mucosa.
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keywords = carcinogenesis
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3/8. Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas.

    BACKGROUND/AIMS: The multistep development of overt hepatocellular carcinoma from very well-differentiated early hepatocellular carcinoma, and of early hepatocellular carcinoma from adenomatous hyperplasia has been strongly suggested. The clinicopathologic and immunohistochemical characteristics of solitary minute hepatocellular carcinomas smaller than 1 cm in size have yet to be clarified. METHODOLOGY: Fourteen minute hepatocellular carcinomas were divided into 2 groups consisting of: 1) hepatocellular carcinoma of hepatitis B surface antigen positive patients (B-HCC) (n = 5), and 2) hepatocellular carcinoma of hepatitis c virus antibody positive patients (C-HCC) (n = 9), then they were all analyzed histopathologically and clinicopathologically. Immunohistochemical studies were also performed using the antibodies against p53 protein. RESULTS: Six of the 14 minute hepatocellular carcinoma were demonstrated to be moderately or poorly differentiated tumors. Among the 8 well-differentiated minute hepatocellular carcinomas, 2 tumors already contained less differentiated components. B-HCC tended to be less differentiated than C-HCC (P < 0.05). Adenomatous hyperplasia was detected in only 2 cases of C-HCC. Small cell liver dysplasia was detected significantly more frequently in C-HCC than in B-HCC (P < 0.05). The prognosis of the 14 minute hepatocellular carcinomas varied considerably. Immunohistochemically, some tumor cells were positive for p53 in 3 cases. CONCLUSIONS: Our study suggests that 1) the multistep carcinogenesis through adenomatous hyperplasia may not be so frequent, 2) De novo carcinogenesis from not only well-differentiated hepatocellular carcinoma, but also from less differentiated hepatocellular carcinoma, especially B-HCC, may be present, 3) the carcinogenesis in the B-HCC cases may behave differently from that in C-HCC cases, and 4) minute hepatocellular carcinomas demonstrate varying prognoses after hepatectomy.
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ranking = 3
keywords = carcinogenesis
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4/8. Cowden disease or multiple hamartoma syndrome--cutaneous clue to internal malignancy.

    Cowden disease (CD) #158350, also known as multiple hamartoma syndrome, is a multisystemic cancer predisposition disorder, inherited in an autosomal dominant pattern. Mucocutaneous lesions are the most constant features: facial papules, acral keratoses and oral papillomatosis. The most common associated cancers are breast, thyroid and endometrial carcinomas. The CD gene locus has been mapped to chromosome 10q22-23. Subsequently the tumor suppressor gene PTEN was located to this chromosomal region and soon after germline mutations in the PTEN gene were demonstrated in CD patients. Somatic PTEN mutations have been found in a variety of sporadic cancers. So CD is an important clinical and genetic model for carcinogenesis. We recently observed four cases of CD and reviewed the literature on CD over the last 40 years, in particular the clinical and histopathological features, genetics, and diagnostic criteria. Based on these data we propose a possible management of CD patients. With increased knowledge and awareness of the typical mucocutaneous lesions an earlier diagnosis and an appropriate cancer surveillance of these patients might be possible.
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keywords = carcinogenesis
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5/8. Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules.

    We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis b virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.
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ranking = 2
keywords = carcinogenesis
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6/8. Enzyme pattern and marker antigens in nodular "regenerative" hyperplasia of the liver.

    Characteristic alterations of marker enzymes and tumor-associated antigens have been detected in the preneoplastic lesions of experimental hepatocarcinogenesis. An identical pattern of enzyme activity (increased gammaglutamyl transferase, loss of glucose-6-phosphatase, and canalicular adenosine triphosphatase) was demonstrated in a case of nodular "regenerative" hyperplasia of liver. The lack of marker antigens (alphafetoprotein, carcinoembryonic antigen, alpha 1-antitrypsin) in the hyperplastic nodules in this patient may be related to the discontinuation of oral contraceptive steroids four years earlier. The phenotypic changes of enzyme activity suggest that nodular "regenerative" hyperplasia of the liver in man is preneoplastic.
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keywords = carcinogenesis
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7/8. Congenital bile duct cyst: a premalignant lesion of the biliary tract associated with adenocarcinoma--a case report.

    The incidence of carcinoma arising in the wall of a congenital bile duct cyst is high and there is no doubt that these lesions represent a precancerous state of the biliary tract. In almost all cases congenital bile duct cysts are related to anomalous arrangements of the pancreaticobiliary duct system which seems to play a crucial role in the development of cystic bile ducts and biliary carcinogenesis. Bile stasis together with reflux of pancreatic juice causing longstanding inflammation and activation of bile acids might be the factors in carcinogenesis of the exposed bile duct epithelium in the cystic wall. In the case of primary or secondary extrahepatic bile duct cysts, primary excision is mandatory because of the high risk to develop biliary cancer with even nowadays poor prognosis despite advantages in biliary surgery during the last years. We report a case of a young woman in which bile duct cancer was found arising in the wall of a congenital bile duct cyst. Despite radical surgery the outcome was poor proving the high malignant potential of bile duct cancer. The question of possible tumor seeding in hepatobiliary surgery is discussed as a way of inducing hepatobiliary metastatic tumors.
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ranking = 2
keywords = carcinogenesis
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8/8. An endodermal sinus tumor arising from a mature cystic teratoma in the retroperitoneum in a child: is a mature teratoma a premalignant condition?

    We herein report an 18-month-old girl who presented with a retroperitoneal mature teratoma that later developed into an endodermal sinus tumor. Her symptoms included an expanding abdominal girth. The serum levels of alpha-fetoprotein were moderately elevated. The excised specimen was a benign mature cystic retroperitoneal teratoma measuring 18 x 11 x 8 cm in size. A hemorrhagic focus measuring 4 cm in diameter was present, which proved to be the focus of an endodermal sinus tumor histologically. The retroperitoneal mature teratoma observed in this case showed malignant germ-cell differentiation. The above case is thought to be extremely rare, but these findings also suggest the possibility of a mature teratoma presenting as a premalignant condition. The sequence of "mature teratoma--germ-cell malignancy" is thus considered to represent a new potential pattern of early phase of carcinogenesis in teratomas.
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ranking = 1
keywords = carcinogenesis
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