Adenoma-like adenocarcinoma: clinicopathologic characterization of a newly recognized subtype of colorectal carcinoma

The 5th edition of the World Health Organization (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 is comparable with 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.Ninety-one cases were classified as adenoma-like adenocarcinoma, and 251 cases were classified as 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, whereas in the rest, the component of adenoma-like morphology was more than 50% but less than 100%, designated as mixed adenoma-like adenocarcinoma. Compared with adenocarcinoma, NOS, adenoma-like adenocarcinoma cases were significantly associated with the absence of tumor budding (P < 0.001), the absence of an immature/myxoid desmoplastic reaction (P < 0.001), the presence of intraepithelial tumor-infiltrating lymphocytes (P = 0.006), involvement of fewer lymph nodes ( P < 0.001), fewer tumor deposits (P = 0.042), lower pT stage (P = 0.047), lower pN stage (P < 0.001), and consequently the pTNM prognostic group (P < 0.001), as well as better recurrence-free survival (RFS), as per univariate analysis than adenocarcinoma, NOS cases (P = 0.026) but not as per multivariate analysis. However, mixed adenoma-like adenocarcinoma had a worse RFS than pure adenoma-like adenocarcinoma (hazard ratio = 1.639, 95% confidence interval = 0.494–5.437). Our findings not only support the importance of distinguishing this new subtype of colorectal adenocarcinoma but also raise 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 the WHO.