Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases

Abstract

Histologic classification of ampullary carcinomas as intestinal versus pancreatobiliary is rapidly becoming a part of management algorithms, with immunohistochemical classification schemes also being devised using this classification scheme as their basis. However, data on the reproducibility and prognostic relevance of this classification system are limited. In this study, five observers independently evaluated 232 resected ampullary carcinomas with invasive component >3 mm. Overall interobserver agreement was 'fair' (κ 0.39; P<0.001) with complete agreement in 23%. Using agreement by 3/5 observers as 'consensus' 40% of cases were classified as 'mixed' pancreatobiliary and intestinal. When observers were asked to provide a final diagnosis based on the predominant pattern in cases initially classified as mixed, there was 'moderate' agreement (κ 0.44; P<0.0001) with 5/5 agreeing in 35%. Cases classified as pancreatobiliary by consensus (including those with pure-pancreatobiliary or mixed-predominantly pancreatobiliary features) had shorter overall (median 41 months) and 5-year survival (38%) than those classified as pure-intestinal/mixed-predominantly intestinal (80 months and 57%, respectively; P=0.026); however, on multivariate analysis this was not independent of established prognostic parameters. Interestingly, when compared with 476 cases of pancreatic ductal adenocarcinomas, the pancreatobiliary-type ampullary carcinomas had better survival (16 versus 41 months, P<0.001), even when matched by size and node status. In conclusion, presumably because of the various cell types comprising the region, ampullary carcinomas frequently show mixed phenotypes and intratumoral heterogeneity, which should be considered when devising management protocols. Caution is especially warranted when applying this histologic classification to biopsies and tissue microarrays. While ampullary carcinomas with more pancreatobiliary morphology have a worse prognosis than intestinal ones this does not appear to be an independent prognostic factor. However, pancreatobiliary-type ampullary carcinomas have a much better prognosis than their pancreatic counterparts.

Immunohistochemistry and special stains in gastrointestinal pathology practice

“…23 Unfortunately, the stains sometimes do not establish a clear line of differentiation. 24 Mucin stains may also be useful in separating gastric phenotype dysplasia from intestinal phenotype dysplasia of the upper gastrointestinal tract. Gastric pattern dysplasia is associated with different clinicopathological features.…”

Non-ampullary–duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas

“…The tubular group was subclassified into three categories: intestinal, gastro-pancreatobiliary, and mixed type (if the intestinal, pancreatobiliary, and/or gastric features were present in the same case). 8 Briefly, invasive carcinomas with more basophilic appearance and complex glands lined by pseudostratified columnar cells with cigar-shaped nuclei were classified as intestinal type; those with widely separated small tubular units lined by one or two layers of cuboidal cells were classified as pancreatobiliary type; and those with a tubular and papillary proliferation with foveolar-type or pyloric-type (Brunner gland) differentiation were classified as gastric type. 8 In this study, gastric and pancreatobiliary lineages were grouped together in accordance with recent concepts in pancreatic histology that favor the combined classification of these two lineages because of their close association, shared immunophenotype, and frequent co-occurrence.…”

“…8 Briefly, invasive carcinomas with more basophilic appearance and complex glands lined by pseudostratified columnar cells with cigar-shaped nuclei were classified as intestinal type; those with widely separated small tubular units lined by one or two layers of cuboidal cells were classified as pancreatobiliary type; and those with a tubular and papillary proliferation with foveolar-type or pyloric-type (Brunner gland) differentiation were classified as gastric type. 8 In this study, gastric and pancreatobiliary lineages were grouped together in accordance with recent concepts in pancreatic histology that favor the combined classification of these two lineages because of their close association, shared immunophenotype, and frequent co-occurrence. 8,9,10 Non tubule-forming carcinoma types (such as mucinous, medullary, poorly cohesive/poorly differentiated carcinoma, and adenosquamous carcinomas) were classified according to the World Health Organization 2010 Classification of Digestive Tumors.…”

Duodenal Epithelial Polyps: A Clinicopathologic Review

“…50 Adenocarcinoma arising in these polyps is either of gastric or mixed (gastric and intestinal) phenotype as supported by maintained coexpression of MUC6, MUC5AC, and CDX2 immunostains. 19,[59][60][61] The most frequent molecular abnormalities detected in duodenal pyloric gland adenomas include mutations in oncogenes KRAS (70%) and GNAS (50%), and less frequently, CTTNB1 and tumor suppressor genes SMAD4 and TP53. APC mutations are usually absent.…”