title: Medullary carcinoma of the colon: can the undifferentiated be differentiated?
abstract: 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.
authors.affiliation: Department of Pathology, Rigshospitalet, Frederik V's Vej 11, 2100, Copenhagen, Denmark, miakanstrup@hotmail.com.
authors.forename: Anne-Marie Kanstrup
authors.initials: AM
authors.lastname: Fiehn
authors.forename: Morten
authors.initials: M
authors.lastname: Grauslund
authors.forename: Anders
authors.initials: A
authors.lastname: Glenthøj
authors.forename: Linea Cecilie
authors.initials: LC
authors.lastname: Melchior
authors.forename: Ben
authors.initials: B
authors.lastname: Vainer
authors.forename: Gro Linno
authors.initials: GL
authors.lastname: Willemoe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D015588:Observer Variation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C501486:MLH1 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins