Neoplasms of the ampulla of vater with concurrent pancreatic intraductal neoplasia: a histological and molecular study.
Adenoma and adenocarcinoma of the ampulla of Vater are uncommon neoplasms of the gastrointestinal tract. Only one report has analyzed the relationship between ampullary adenocarcinoma and pancreatic intraductal neoplasia (PanIN), the precursor lesion of pancreatic adenocarcinoma. An association between PanIN and ampullary adenoma has not been reported previously. Case reports have documented the progression of PanIN to invasive pancreatic adenocarcinoma. We reviewed five resected ampullary adenoma and 17 ampullary adenocarcinoma cases and evaluated the pancreas for PanIN. Pancreatic sections from 35 autopsies were reviewed as a control group. Immunohistochemistry for overexpression of p53 and COX-2 proteins was performed in selected cases, as was PCR analysis for K-ras mutations. Follow-up clinical data were obtained. All 22 ampullary neoplasms were associated with PanIN, which was high grade in two (40%) adenoma cases and seven (41%) adenocarcinoma cases. In 16 (73%) evaluable cases, PanIN extended to the pancreatic resection margin; two of which had high grade PanIN. Among the autopsy controls eight (23%) had low-grade PanIN. Seven of the 22 ampullary cases but none of the autopsy controls had coexistent pancreatitis. A smoking history was present in two of four autopsy cases in which this history was available. Overexpression of the p53 and COX-2 proteins was present in only one case of high-grade PanIN. K-ras mutations were present in four of four of the PanIN lesions evaluated, including one autopsy case. Clinical follow-up revealed no progression of PanIN to invasive carcinoma in the remnant pancreas, although the follow-up period was too short to adequately assess that risk (an average of 3.8 y for adenoma cases and 2.5 y for adenocarcinoma cases). We conclude that adenomas and carcinomas of the ampulla are associated with PanIN, and often high-grade PanIN. Although its malignant potential has not been fully established, PanIN is underreported and often unrecognized. PanIN may be analogous to colorectal adenoma in that both are prevalent in the older adult population, but few progress to carcinoma.
Agoff
S N
SN
Department of Pathology, University of Washington Medical Center/Harborview Medical Center, Seattle, Washington 98104-2499, USA. agoff@u.washington.edu
Crispin
D A
DA
Bronner
M P
MP
Dail
D H
DH
Hawes
S E
SE
Haggitt
R C
RC
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology*; D003138:Common Bile Duct Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D051546:Cyclooxygenase 2; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000473:pathology*; D010183:Pancreatic Ducts / Q000737:chemistry / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D004273:DNA, Neoplasm; D007527:Isoenzymes; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases