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
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
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DOI：
10.1038/modpathol.2016.124
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发表时间：
2016-12-01
期刊：
影响因子：
7.5
通讯作者：
Adsay, Volkan
中科院分区：
文献类型：
--
作者：
Reid, Michelle D.;Balci, Serdar;Adsay, Volkan
壶腹癌作为肠与胰胆的组织学分类正在迅速成为管理算法的一部分，免疫组织化学分类方案也正在设计使用这种分类方案作为其基础。然而，这种分类系统的可重复性和预后相关性的数据是有限的。在这项研究中，5名观察者独立评估了232例浸润性成分>3 mm的壶腹癌切除术。总体观察者间一致性为“一般”（kappa 0.39; P< 0.001），完全一致性为23%。使用3/5观察者的一致性作为“共识”，40%的病例被归类为“混合型”胰胆管和肠道。当观察者被要求根据最初分类为混合型病例的主要模式提供最终诊断时，有5/5的人同意35%，达到“中度”一致（kappa 0.44; P< 0.0001）。一致认为归类为胰胆管疾病的病例（包括具有单纯胰胆管或混合胰胆管特征的患者）总体上较短（中位41个月）和5年生存率（38%）高于纯肠道/混合肠道为主的患者（分别为80个月和57%; P= 0.026）;然而，在多变量分析中，这并不独立于既定的预后参数。有趣的是，与476例胰腺导管腺癌相比，胰胆型壶腹癌的生存率更高（16个月对41个月，P< 0.001），即使在大小和淋巴结状态匹配时也是如此。总之，大概是因为不同的细胞类型组成的区域，壶腹癌经常表现出混合的表型和瘤内异质性，这应该考虑到设计管理协议时。当将这种组织学分类应用于活检和组织微阵列时，尤其需要谨慎。虽然壶腹癌有更多的胰胆管形态比肠的预后差，这似乎不是一个独立的预后因素。然而，胰胆型壶腹癌的预后比胰腺癌好得多。
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' (kappa 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 (kappa 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 adenocarcinornas, 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.