Sporadic versus hereditary gastrinomas of the duodenum and pancreas: Distinct clinico-pathological and epidemiological features

Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal re?ux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zürich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished fromtumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1- associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1- associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1- associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.

Extrahepatic intraductal ectopic hepatocellular carcinoma:bile duct filling defect

BACKGROUND:Obstructive jaundice caused by an intraductal hepatocellular carcinoma is a rare initial symptom.We report a rare case of an extrahepatic icteric type hepatocellular carcinoma.METHODS:A 75-year-old patient was admitted to our hospital because of obstructive jaundice 3 months after resection of multilocular hepatocellular carcinoma.A postoperative bile leakage was treated by placement of a decompressing stent in the common bile duct.Endoscopic retrograde choledochoscopy showed extended blood clots filling the bile duct system and computed tomography revealed a local swelling in the common extrahepatic bile duct.The level of alpha-fetoprotein(AFP)was only slightly elevated but that of CA19-9 was dramatically increased.Cholangiography showed an intraductal filling defect typical of a cholangiocellular carcinoma.RESULTS:Bile duct brushing cytology showed no cholangiocellular carcinoma but hepatocellular carcinoma cells in the extrahepatic bile duct.An extrahepatic bile duct resection was performed.Histological examination confirmed the diagnosis of extrahepatic intraductal growth of hepatocellular carcinoma.CONCLUSION:Ectopic hepatocellular carcinoma is a rare but important differentially diagnosed of extrahepatic bile duct filling defect.

Intrahepatic cholestasis without jaundice

BACKGROUND:Cholangiocarcinoma(CC),the most common biliary tract malignancy,is frequently seen in advanced unresectable stages and is typically localized extrahepatically.Early diagnosis is unusual because of nonspecific symptoms.Painless jaundice is usually the first sign of tumor. METHOD:We present a patient with a CC(Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS:A 67-year-old woman presented with persisting elevation of liver parameters.Diagnostic tests showed a Klatskin tumor typeⅡ.A curative right hepatic trisegmentectomy was performed after liver volume augmentation by preoperative vein embolization. CONCLUSIONS:A direct drainage of the right posterior bile duct into the common bile duct as an aberrant hepatic duct is a rare variation and is present in less than 5%of the population.In case of persistently perturbed liver function tests,an aberrant bile duct can cover up severe intrahepatic cholestasis and even obscure the diagnosis of a Klatskin tumor.Up to now it has not been described in the literature.