The 5 edition of the WHO Classification of Tumours (Digestive System) recognizes a new subtype of colorectal adenocarcinoma, called adenoma-like adenocarcinoma. In this study we sought to determine its clinicopathologic associations, and how it compares to adenocarcinoma, of no special type (NOS). We retrospectively reviewed all available archival slides of stage I-III colonic adenocarcinoma resection specimens at our institution from 2013 to 2016. 91 cases were classified as adenoma-like adenocarcinoma, and 251 cases were adenocarcinoma, NOS. Of the adenoma-like adenocarcinoma cases, a majority (65 cases, 71%) were composed exclusively of adenoma-like features, designated as pure adenoma-like adenocarcinoma, while in the rest, the component of adenoma-like morphology was more than 50% but less than 100%, designated as mixed adenoma-like adenocarcinoma. Compared to adenocarcinoma, NOS, adenoma-like adenocarcinoma cases were significantly associated with the absence of tumor budding (p<0.001), absence of an immature/myxoid desmoplastic reaction (p<0.001), presence of intraepithelial tumor associated lymphocytes (iTILs) (p=0.006), fewer lymph nodes involved (p<0.001), fewer tumor deposits (p=0.042), lower pT stage (p=0.047), lower pN-stage (p<0.001), and consequently pTNM prognostic group (p<0.001), as well as better recurrence-free survival (RFS) on univariate analysis compared to adenocarcinoma, NOS cases (p=0.026) but not on multivariate analysis. However, mixed adenoma-like adenocarcinoma had a worse RFS compared to pure adenoma-like adenocarcinoma (HR: 1.639, 95%CI: 0.494-5.437). Our findings support the importance of distinguishing this new subtype of colorectal adenocarcinoma, but also raises the question whether mixed adenoma-like adenocarcinoma cases should be included in this category, and if so, whether 50% is an appropriate cutoff, as currently defined by WHO.
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