Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases

Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection. All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs. From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.