Medullary carcinoma of the colon: can the undifferentiated be differentiated?
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Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without knowledge of the original diagnosis and subgrouped the tumors into the two entities. Agreement was reached in 31 of 45 cases (69 %) with kappa = 0.32. An extensive immunohistochemical panel was performed, and KRAS, NRAS, and BRAF mutational status was assessed. Of the 31 cases with diagnostic agreement, the expression of only MLH-1 along with corresponding expression of PMS-2 differed significantly (p = 0.04). A high rate of BRAF mutations was detected in both subgroups without significant differences. Expression of MLH-1 was superior in dividing the tumors into two separate entities with significant differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether these morphological subtypes should be maintained or whether an alternative classification of poorly differentiated colorectal adenocarcinomas based on MLH-1 status rather than morphology should be suggested.
KeywordsMedullary carcinoma Immunohistochemical profile Molecular profile Interobserver agreement MLH-1
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Conflicts of interest
No conflicts to be declared.
- 1.Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11.[Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available at: http://globocan.iarc.fr. Accessed 1 July 2014.
- 2.Thirunavukarasu P, Sathaiah M, Singla S et al (2010) Medullary carcinoma of the large intestine: a population based analysis. Int J Oncol 37(4)Google Scholar
- 3.Danish Colorectal Cancer Group, Annual Report 2012. Available at: http://dccg.dk. Accessed 1 July 2014
- 4.Hamilton SR, Bosman FT, Boffeta P et al (2010) Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH et al, eds. WHO Classification of Tumours of the Digestive System. Lyon: International Agency for Research on Cancer; 131–182Google Scholar
- 15.Hansen TP (2002) Immunohistochemical tumor markers in colorectal cancer: a methodological and prognostic study. University of Southern Denmark, OdenseGoogle Scholar
- 19.Chetty R, Govender D (2013) Gene of the month: KRAS. J Clin Pathol 1–3Google Scholar
- 27.Bertagnolli MM, Niedzwiecki D, Compton CC et al (2009) Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol 27:1814–1821PubMedCentralPubMedCrossRefGoogle Scholar
- 29.Jacquemier J, Reis-Filho JS, Lakhani SR et al (2012) Carcinomas with medullary features. In: Lakhani SR, Ellis IO, Schnitt SJ et al, eds. WHO Classification of Tumours of the Breast. Lyon: International Agency for Research on Cancer; 46–47Google Scholar