Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

Publication date: Available online 26 December 2016
Source:Human Pathology
Author(s): Lik Hang Lee, Rhonda K. Yantiss, Eran Sadot, Bing Ren, Marcela Santos Calvacanti, Jaclyn F. Hechtman, Sinisa Ivelja, Be Huynh, Yue Xue, Tatiana Shitilbans, Hamza Guend, Zsofia K. Stadler, Martin R. Weiser, Efsevia Vakiani, Mithat Gonen, David S. Klimstra, Jinru Shia
Colorectal medullary carcinoma, recognized by the World-Health-Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as-yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from "classic medullary histology" to non-medullary poorly-differentiated histologies and demonstrated significant overlapping between categories. By assessing a selected subset (n=30) that represented the spectrum of histologies, we showed that the inter-observer agreement for diagnosing medullary carcinoma by using 2010 World-Health-Organization criteria was poor; the Kappa value among 5 gastrointestinal pathologists was only 0.157 (95% confidence-interval, 0.127–0.263; P=.001). When we arbitrarily classified the entire cohort into "classic" and "indeterminate" medullary tumors (group 1, n=19; group 2, n=26, respectively) and non-medullary poorly-differentiated tumors (group 3, n=35), groups 1 and 2 were more likely to exhibit mismatch-repair-protein-deficiency than group 3 (P<.001); however, improved survival could not be detected in neither group compared to group 3. Our findings suggest that the diagnosis of medullary carcinoma, as currently applied, may only serve as a morphological descriptor indicating an increased likelihood of mismatch-repair-deficiency. Additional evidence including more objective classification system is needed before medullary carcinoma can be regarded as a distinct entity with prognostic relevance. Until such evidence becomes available, caution should be exercised when making this diagnosis, and when comparing results across different studies.



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