Histologic grading of invasive lobular carcinoma: does use of a 2-tiered nuclear grading system improve interobserver variability?☆

Abstract 

The Nottingham histologic grade (NHG) is a prognostic marker for infiltrating ductal carcinoma. Its usefulness for invasive lobular carcinoma (ILC) has been less clear, given that 2 of the 3 parameters, tubule formation and mitotic activity, show little variation in ILC, placing much of the emphasis on nuclear grade. We have previously reported a trend for improved overall and relapse-free survival in patients with ILC of low nuclear grade, as classified by a 2-tiered nuclear grading system. Given the inherent potential for interobserver variability with any grading system, the goal of this study is to compare interobserver variability in the grading of ILC using a 2-tiered nuclear grade vs the NHG. Thirty-eight cases of ILC were graded independently by 5 pathologists using NHG criteria. Tumors were also categorized by a nuclear grading system as low grade (grade 1 nuclei) or high grade (grades 2-3 nuclei). Pairwise κ values and interobserver agreement rates were calculated for both NHG and nuclear grade. Results were compared using the paired t test. Mean interobserver agreement rates and κ values improved with use of the nuclear grading system as compared to NHG (83% vs 70%, 0.4738 vs 0.3228, respectively). The differences between the 2 were statistically significant. Because histologic grade has significant prognostic implications for patients with breast cancer, accurate reporting is paramount. For ILC, where use of the NHG places substantial weight on nuclear pleomorphism, a 2-tiered nuclear grading system may reduce interobserver variability yet still provide useful prognostic information.

Keywords: Breast cancer, Nottingham grade, Lobular carcinoma, Interobserver variability