Serosal surfaces, mucin pools, and deposits, oh my: challenges in staging colorectal carcinoma

Colorectal carcinoma is the third most common cancer in the United States. Proper and standardized pathologic staging is vital for prognostic assessment and impacts therapeutic decisions. The Tumor Node Metastasis (TNM) staging system was developed by the American Joint Committee on Cancer (AJCC) to be a data-driven, evidence-based staging system providing an accurate prediction of outcome. The AJCC 7th edition (2010) included several changes clarifying some issues and leading to new controversies. We aim to address selected challenging issues in tumor T staging, neoadjuvant treatment effects in rectal cancer, and definition of lymph node vs tumor deposit. Serosal involvement in colorectal cancer is staged as T4, which is associated with decreased survival and may impact additional therapy decisions. Although careful sampling and sectioning are helpful, challenges remain in interpretation of tumor within 1 mm of serosal surface with a reaction. Elastic stain as a surrogate marker for serosal invasion has been studied, but its usefulness remains unclear. Some unique issues in rectal cancer include the presence of serosa in proximal but not in distal tumors and post-neoadjuvant effects. Tumor should be staged based on tumor cells rather than acellular mucin pools. Additionally, tumor response should be graded only in primary tumor but not in lymph nodes or metastatic sites. The distinction between tumor deposits and lymph nodes has been modified in AJCC TNM from using size in the 5th edition, to the round contour in the 6th edition, to only features of residual lymph node architecture in the 7th edition. Interobserver variability remains but tumor deposits should be documented when present. The number of deposits should not be added to the total number of positive lymph nodes, and the N1c designation should only be used in cases without any positive lymph nodes. Future clarification will likely evolve as more data become available.