Am J Surg Pathol. 2023 Jun 15.
Depth of invasion through the intestinal wall, categorized as primary tumor stage (pT), is an important prognostic factor in colorectal cancer. However, additional variables that may affect clinical behavior among tumors involving the muscularis propria (pT2) have not been examined at length. We evaluated 109 patients with pT2 colonic adenocarcinomas (median age: 71 y, interquartile range: 59 to 79 y) along various clinicopathologic parameters, including invasion depth, regional lymph node involvement, and disease progression after resection. Tumors extending to the outer muscularis propria (termed pT2b) were associated in multivariate analysis with older patient age (P=0.04), larger tumor size (P<0.001), higher likelihood of lymphovascular invasion (LVI; P=0.03) and higher lymph node stage (pN; P=0.04), compared with tumors limited to the inner muscle layer (pT2a), and LVI was the single most important variable predicting regional lymph node metastasis at resection in these tumors (P=0.001). The Kaplan-Meier analysis during a median clinical follow-up of 59.7 months (interquartile range: 31.5 to 91.2) revealed that disease progression was more likely in pT2 tumors that exhibited, at the time of staging: size >2.5 cm (P=0.039), perineural invasion (PNI; P=0.047), high-grade tumor budding (P=0.036), higher pN stage (P=0.002), and distant metastasis (P<0.001). Proportional hazards (Cox) regression identified high-grade tumor budding (P=0.02) as independently predicting shorter progression-free survival in pT2 tumors. Finally, among cases that would not ordinarily be candidates for adjuvant treatment (ie, pT2N0M0), the presence of high-grade tumor budding was significantly associated with disease progression (P=0.04). These data suggest that, during the diagnosis of pT2 tumors, pathologists may wish to pay particular attention and ensure adequate reporting of certain variables such as tumor size, depth of invasion within the muscularis propria (ie, pT2a vs. pT2b), LVI, PNI, and, especially, tumor budding, as these may affect clinical treatment decisions and proper patient prognostication.