Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications Academic Article uri icon


MeSH Major

  • Carcinoma, Medullary
  • Colorectal Neoplasms


  • 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.

publication date

  • April 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5392420

Digital Object Identifier (DOI)

  • 10.1016/j.humpath.2016.12.013

PubMed ID

  • 28034727

Additional Document Info

start page

  • 74

end page

  • 82


  • 62