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      Carcinoid tumors of the extrahepatic bile ducts: a study of seven cases.

      The American Journal of Surgical Pathology
      Adult, Aged, Bile Duct Neoplasms, genetics, metabolism, pathology, surgery, Bile Ducts, Extrahepatic, Carcinoid Tumor, Chromogranins, Cytoplasmic Granules, ultrastructure, DNA, Neoplasm, analysis, DNA-Binding Proteins, Female, Follow-Up Studies, Gastrins, Humans, Immunoenzyme Techniques, Loss of Heterozygosity, Lymph Nodes, Lymphatic Metastasis, Microsatellite Repeats, Middle Aged, Neurosecretory Systems, Pancreatic Polypeptide, Pancreaticoduodenectomy, Serotonin, Smad4 Protein, Somatostatin, Synaptophysin, Trans-Activators, Treatment Outcome

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          Abstract

          The authors report seven patients with carcinoid tumors of the extrahepatic bile ducts (EHBDs). All patients were women, with an average age at diagnosis of 49.8 years (range, 37-67 yrs). The most common presenting symptom was painless jaundice with or without pruritus. Although one patient had peptic ulcer disease before the onset of obstructive jaundice, none had systemic endocrine manifestations. These neoplasms were most often located in the common bile duct. Grossly, the carcinoid tumors were usually nodular and poorly demarcated, and ranged from 1.1 to 2.7 cm in size. Only one of the neoplasms was polypoid. Microscopically, the tumors had a trabecular or nesting pattern with occasional tubule formation, and were composed of relatively small cells with granular chromatin. All of the neoplasms expressed chromogranin and two expressed synaptophysin. Three expressed serotonin and two of the three were also immunoreactive for pancreatic polypeptide or somatostatin. Two tumors were focally positive for gastrin and one of these two tumors was also positive for serotonin and pancreatic polypeptide. All seven carcinoid tumors showed no immunoreactivity for p53, and assays for p53 loss of heterozygosity analysis were negative in two, suggesting that p53 mutations do not play a role in the pathogenesis of EHBD carcinoids. A mutation in codon 12 of K-ras was found in one carcinoid tumor whereas two of two showed immunoreactivity for Dpc4 protein. In view of the small number of carcinoids studied, the importance of these findings in the pathogenesis of these tumors is unclear. Ultrastructural examination of three of the tumors revealed numerous membrane-bound, round neurosecretory granules. Clinically, these lesions had an indolent course. Even in the presence of lymph node metastases (noted in two patients), all of the patients remained disease free 2 to 11 years (average follow up, 6.6 yrs) after segmental resection or pancreaticoduodenectomy (Whipple's procedure). Because carcinoid tumors of the EHBD are of low malignant potential, they should be separated from the more common adenocarcinomas in this location.

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