TY - JOUR

T1 - Medullary carcinoma of the colon

T2 - can the undifferentiated be differentiated?

AU - Fiehn, Anne-Marie Kanstrup

AU - Grauslund, Morten

AU - Glenthøj, Anders

AU - Melchior, Linea Cecilie

AU - Vainer, Ben

AU - Willemoe, Gro Linno

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

KW - Adaptor Proteins, Signal Transducing

KW - Adenocarcinoma

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Carcinoma, Medullary

KW - Colonic Neoplasms

KW - Diagnosis, Differential

KW - Female

KW - GTP Phosphohydrolases

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Membrane Proteins

KW - Middle Aged

KW - Molecular Diagnostic Techniques

KW - Mutation

KW - Nuclear Proteins

KW - Observer Variation

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins B-raf

KW - ras Proteins

U2 - 10.1007/s00428-014-1675-6

DO - 10.1007/s00428-014-1675-6

M3 - Journal article

C2 - 25339302

VL - 466

SP - 13

EP - 20

JO - Virchows Archiv

JF - Virchows Archiv

SN - 0945-6317

IS - 1

ER -