Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin

Abstract

BackgroundPeriampullary adenocarcinomas comprise pancreatic, distal bile duct, ampullary and duodenal adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. With steadily increasing numbers of pancreatoduodenectomies over the last decades, pathologists, surgeons and oncologists are more often confronted with the diagnosis of “other than pancreatic” periampullary cancers. The intestinal subtype of ampullary cancer has been shown to correlate with better prognosis.MethodsHistological subtype and immunohistochemical staining pattern for CK7, CK20 and CDX2 were assessed for n = 198 cases of pancreatic ductal, distal bile duct, ampullary and duodenal adenocarcinoma with clinical follow-up. Routine pathological parameters were included in survival analysis performed with SPSS 20.ResultsIn univariate analysis, intestinal subtype was associated with better survival in ampullary, pancreatic ductal and duodenal adenocarcinoma. The intestinal type of pancreatic ductal adenocarcinoma was not associated with intraductal papillary mucinous neoplasm and could not be reliably diagnosed by immunohistochemical staining pattern alone. Intestinal differentiation and lymph node ratio, but not tumor location were independent predictors of survival when all significant predictor variables from univariate analysis (grade, TNM stage, presence of precursor lesions, surgical margin status, perineural, vascular and lymphatic vessel invasion, CK7 and CDX2 staining pattern) were included in a Cox proportional hazards model.ConclusionsIntestinal type differentiation and lymph node ratio but not tumor location are independent prognostic factors in pooled analysis of periampullary adenocarcinomas. We conclude that differentiation is more important than tumor location for prognostic stratification in periampullary adenocarcinomas.

Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification

“…As reported in previous morphological studies[9,10], we observed overlap with the pancreatobiliary type also at the immunohistochemical level. As depicted in Fig 4A, tumors of the intestinal type co-expressed pancreatobiliary markers, such as CK7, CK17, MUC1, and MUC5AC, although to a lesser extent.…”

“…Due to the intrinsic limitations in interobserver agreement linked to the assessment of hematoxylin-eosin stained slides, the current lack of reliable diagnostic criteria, especially when tumors show mixed or intermediate histological features[10,35,36], and to minimize design bias to predefined categories, a pure histomorphological classification based on hematoxylin-eosin staining was not addressed.…”

“…Previous studies have pursued the immunohistochemical distinction between the intestinal and pancreatobiliary type[10,38]. However, they tested only a small number of predefined markers and this could explain the lower discriminant power yielded by their diagnostic algorithms.…”

“…However, studying these tumors for possible phenotypic diversity may reveal differences of potential prognostic and therapeutic relevance. Attempts at classifying periampullary carcinomas have already introduced two histological types of differentiation: pancreatobiliary and intestinal[9,10]. Evidence supports that ampullary carcinomas of the intestinal type have a more favorable prognosis than those of the "classical" pancreatobiliary type.…”

Patterns of care and treatment outcomes in older patients with biliary tract cancer.

“…Disease characteristics included site of primary (intrahepatic, hilar, distal bile duct, and gallbladder carcinoma) and disease stage according to the 7 th edition of the American Joint Committee (AJCC) on cancer staging system. Patients with carcinoma of the ampulla of Vater were excluded, as these are thought to behave differently to other cancers of the biliary tract [36]. Treatment modalities collected included surgery with curative intent (R0 [negative margins]/ R1 [microscopic positive margins]), chemotherapy or best supportive care.…”