Coexistent carcinoma in congenital dilatation of the bile duct and anomalous arrangement of the pancreatico-bile duct: Carcinogenesis of coexistent gall bladder carcinoma

Sameshima, Yasuhiko; Uchimura, Masayuki; Muto, Yoshihiro; Maeda, Junpei; Tsuchiyama, Hideo

doi:10.1002/1097-0142(19871015)60:8<1883::aid-cncr2820600835>3.0.co;2-x

Cited by 41 publications

(25 citation statements)

References 6 publications

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“…Intestinal metaplasia of the common bile duct and gallbladder was seen in 20% of the cases, and the severity of the epithelial changes was proportional to the duration of the experiment (9). In humans, an increased incidence of carcinoma has been shown in patients with an anomalous choledochopancreatic junction that is associated with intestinal metaplasia (10). In this study, however, we were unable to find foci of dysplasia in the metaplastic areas; therefore, the possibility that the tumor induced the metaplastic changes cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Metaplastic Lesions of the Extrahepatic Bile Ducts: A Morphologic and Immunohistochemical Study

et al. 2001

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Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic study of these lesions has not been done. We examined the bile duct mucosa in 42 pancreaticoduodenectomy specimens, 32 with neoplastic lesions and ten with inflammatory lesions of the extrahepatic bile ducts, to assess the prevalence and type of metaplastic lesions. For comparison, the common bile ducts from 10 autopsy cases were reviewed. Twenty of the 42 total cases (48%), 13 of the 32 neoplastic cases (40%), and 7 of the 10 inflammatory cases (70%) had metaplastic changes. Pyloric gland metaplasia was the most common type (16/20 cases; 80%), whereas intestinal metaplasia was seen in 1/20 cases (5%). A combination of pyloric gland and intestinal metaplasia occurred in 2/20 cases (10%), and squamous metaplasia plus the abovementioned two types of metaplasia was seen in 1/20 cases (5%). None of the normal common bile ducts obtained from ten autopsies had metaplastic changes. Endocrine cells were identified in nine (56%) of 17 metaplastic lesions. In contrast, endocrine cells within the intramural glands were seen in only 2 of the 10 normal common bile ducts. Although a significant proportion of carcinomas (6/13 cases) was in close proximity to areas of metaplasia, we were unable to find dysplastic foci within the metaplastic glands or the metaplastic surface epithelium. Reactive atypical cells involved the surface biliary epithelium and intramural glands and were associated with inflammation and metaplastic changes. The presence of goblet, mucinous, squamous, and reactive atypical cells in association with hyperplasia of intramural glands in frozen sections or small biopsy specimens may be mistaken for malignancy; hence, recognition of these lesions is of diagnostic importance. KEY WORDS: Extrahepatic bile duct, Intestinal metaplasia, Metaplasia, Pyloric gland metaplasia, Squamous metaplasia. Mod Pathol 2001;14(11):1119 -1125Intestinal and pyloric metaplasia are common metaplastic changes in chronic cholecystitis and cholelithiasis (1, 2). Similar changes may occur in association with inflammation and neoplasms of the extrahepatic bile ducts, but detailed morphologic and immunohistochemical studies of these lesions have not been done. Although metaplastic changes of the extrahepatic bile ducts have been described adjacent to areas of dysplasia and carcinoma, very little information is available on the subject (3). In fact, we were unable to find a single publication on metaplastic lesions of the extrahepatic bile ducts in the American medical literature. Reactive surface biliary cells and metaplastic cells often coexist in inflammatory lesions of the extrahepatic bile ducts. Their recognition in bile duct brushings, frozen sections, or small biopsy specimens may be problematic, and a diagnosis of malignancy can be rendered erroneously. In this study, we examined the nonneoplastic bile duct mucosa of forty-two pancreaticoduodenectomy specimens with either neoplastic or inflammatory processes of the extrahepatic bile duct...

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Section: Discussionmentioning

confidence: 99%

Metaplastic Lesions of the Extrahepatic Bile Ducts: A Morphologic and Immunohistochemical Study

et al. 2001

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“…The early changes in the gallbladder mucosa of patients with AAPBD leading to carcinogenesis are unclear. Major histopathologic findings in several studies of this Tokiwa et al: Cell proliferation in pancreaticobiliary anomaly anomaly included coexistent metaplastic changes of the gallbladder mucosa 6,22,23. These changes were found not only in cancerous but also in noncancerous areas.…”

Section: Early Changes In Gallbladder Epitheliummentioning

confidence: 95%

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct

Tokiwa

Ono

Iwai

1999

Journal of Hepato-Biliary-Pancreatic Surgery

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Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is an anatomical maljunction of the bile duct and the pancreatic duct that is frequently associated with gallbladder carcinoma. In patients with AAPBD, it has been postulated that pancreatic juice regurgitates into the biliary tree, and the mixture of refluxed pancreatic juice and stagnant bile juice acts as an irritant factor to the biliary tract epithelium, leading to chronic inflammation and metaplasia. Eventually these mucosal changes may progress to invasive carcinoma. We reviewed clinicopathologic studies on epithelial changes of the gallbladder in patients with AAPBD to clarify the implications relevant to carcinogenesis. Conventional histological studies have shown that the most characteristic change observed in the gallbladder of children with this anomaly was epithelial hyperplasia. Furthermore, the incidence of mucosal hyperplasia was significantly increased in the gallbladder of children in whom the pancreatic duct joined the common bile duct (P-C type) compared with the incidence in children in whom the common bile duct joined the pancreatic duct (C-P type). In addition, cell kinetic studies have demonstrated increased cellular proliferative activity of the gallbladder in children with AAPBD. Cell proliferative activity was significantly elevated in children with the P-C type of AAPBD compared with that in children with the C-P type of anomaly. In conclusion, AAPBD may yield increased cell proliferation in the gallbladder of patients with this anomaly in early childhood, resulting in epithelial hyperplasia. Although it remains unknown which agents are responsible for promoting the activation of cellular function, it seems that bile acids and refluxed pancreatic proteases are likely play a role in such promotion. Further investigations are needed to elucidate the mechanism of increased cellular function.

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“…Gallbladder carcinoma is associated with AJPBD in approximately 10% of patients. In this regard, several investigations revealed that among AJPBD patients without a dilatation of common bile duct, the incidence of gallbladder carcinoma is higher than in those with choledochal cyst, a cystic dilatation of common bile duct [35,36,37].…”

Section: Anomalous Junction Of the Pancreaticobiliary Ductmentioning

confidence: 99%

Carcinogenesis of malignant lesions of the gall bladder

Tazuma

Kajiyama

2001

Langenbeck's Arch Surg

110

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Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established risk factor for gallbladder carcinoma, and the risk seems to correlate with stone size. Metaplastic changes of the gallbladder epithelium present in chronic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladder carcinoma when their characteristics are echopenic, sessile, and high cell density. Endoscopic ultrasound is the most useful technique to detect the early changes of malignancy in polyps. Anomalous junction of pancreaticobiliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder is an additional risk factor for gallbladder malignancy. At the molecular level, it has been proposed that chronic inflammation of the gallbladder may lead to the loss of p53 gene heterozygosity and excessive expression of p53 protein. Furthermore, a proposed mechanism underlying the high risk of gallbladder carcinoma in patients with AJPBD is that chronic reflux of pancreatic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras. In contrast, the causal relationship between porcelain gallbladder and malignancy is yet to be established. In this article, recognition of risk factors for gallbladder carcinoma was summarized with special attention to gallstones and chronic inflammation.

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Coexistent carcinoma in congenital dilatation of the bile duct and anomalous arrangement of the pancreatico-bile duct: Carcinogenesis of coexistent gall bladder carcinoma

Cited by 41 publications

References 6 publications

Metaplastic Lesions of the Extrahepatic Bile Ducts: A Morphologic and Immunohistochemical Study

Metaplastic Lesions of the Extrahepatic Bile Ducts: A Morphologic and Immunohistochemical Study

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct

Carcinogenesis of malignant lesions of the gall bladder

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