title: Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas.
abstract: Literature on non-ampullary-duodenal carcinomas is limited. We analyzed 47 resected non-ampullary-duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of 'gastro-pancreatobiliary markers' (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas 'intestinal markers' were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like). An adenoma component common in ampullary-duodenal cancers was noted in only about a third. Most had plaque-like or ulcerating growth. Mismatch repair protein alterations were detected in 13% (all with plaque-like growth and pushing-border infiltration). When compared with ampullary (n=355) and pancreatic ductal (n=227) carcinomas, non-ampullary-duodenal carcinomas had intermediary pathologic features with mean invasive size of 2.9 cm (vs 1.9, and 3.3) and 59% nodal metastasis (vs 45, and 77%). Its survival (3-, 5-year rates of 57 and 57%) was similar to that of ampullary-duodenal carcinomas (59 and 52%; P=0.78), but was significantly better than the ampullary ductal (41 and 29%, P<0.001) and pancreatic (28 and 18%, P<0.001) carcinomas. In conclusion, non-ampullary-duodenal carcinomas are more histologically heterogeneous than previously appreciated. Their morphologic versatility (commonly showing gastro-pancreatobiliary lineage and hitherto unrecognized patterns), frequent plaque-like growth minus an adenoma component, and frequent expression of gastro-pancreatobiliary markers suggest that many non-ampullary-duodenal carcinomas may arise from Brunner glands or gastric metaplasia or heterotopic pancreatobiliary epithelium. The clinical behavior of non-ampullary-duodenal carcinoma is closer to that of ampullary-duodenal subset of ampullary carcinomas, but is significantly better than that of ampullary ductal and pancreatic cancers. The frequency of mismatch repair protein alterations suggest that routine testing should be considered, especially in the non-ampullary-duodenal carcinomas with plaque-like growth and pushing-border infiltration.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Molecular Medicine, San Matteo Hospital, University of Pavia, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Serdar
authors.identifier: 0000-0002-7852-3851
authors.initials: S
authors.lastname: Balci
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Reid
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Saka
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Pelin
authors.initials: P
authors.lastname: Bagci
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Bahar
authors.initials: B
authors.lastname: Memis
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: Hyejeong
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Nobuyike
authors.initials: N
authors.lastname: Ohike
authors.affiliation: Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Muraki
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Quigley
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Walid
authors.initials: W
authors.lastname: Shaib
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kooby
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Sarmiento
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Knight
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014670:Ampulla of Vater / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003138:Common Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology*; D004379:Duodenal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D009077:Mucins