Interlaboratory Variability in the Histologic Grading of Colorectal Adenocarcinomas in a Nationwide Cohort

Differentiation grade of colorectal adenocarcinoma (CRC) is a prognostic factor and important for therapy selection. In patients with stage II colon cancer, poor differentiation is an indication for adjuvant chemotherapy. The variability in daily practice in the grading of CRC was assessed in a nationwide cohort. Using the Dutch Pathology Registry (PALGA), all synoptically reported CRC resections from 2010 to 2013 were identified. Proportions of poorly differentiated (PD) adenocarcinomas were determined and compared between 35 laboratories by univariable and multivariable logistic regression analyses. In total, 11,719 resections of 11,681 patients were included, of which 1427 (12.2%) were PD (range between 35 laboratories: 5.0% to 33.2%). After adjustment for case mix, 4 (11%) laboratories still reported a significantly lower (n=2) or higher (n=2) proportion of PD adenocarcinoma compared with the reference laboratory. Seven of 8 investigated laboratories showed considerable intralaboratory variation between pathologists as well. In a subgroup of 2812 patients (2813 tumors) who could have been eligible for adjuvant chemotherapy solely on the basis of the differentiation grade (stage II colon cancer patients without other high-risk factors [ie, T4, <10 lymph nodes evaluated, perforation, ileus, or angioinvasion]), 258 (9.2%) were PD (range between laboratories: 0% to 22.7%). In this subgroup, 4 laboratories still diagnosed significantly more PD adenocarcinomas after multivariable logistic regression analysis, increasing the number of colon cancer patients eligible for adjuvant therapy. In conclusion, this large nationwide cohort demonstrates considerable interlaboratory and intralaboratory variation in differentiation grading of CRC. Better standardization of grading criteria is needed for optimal determination of prognosis and treatment selection.