Histologic Grading of Invasive Lobular Carcinoma: Does Use of a Two-Tiered Nuclear Grading System Improve Interobserver Variability?
AL Adams, DC Chhieng, WC Bell, T Winokur, O Hameed. University of Alabama at Birmingham, Birmingham, AL
Background: The Nottingham histologic grade (NHG) is an established prognostic marker for infiltrating ductal carcinoma. Its usefulness in the case of invasive lobular carcinoma (ILC) has been less clear, given that two of the three parameters, tubule formation and mitotic activity, show little variation in ILC, thereby 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 two-tiered nuclear grading system. Given the inherent potential for interobserver variability with any grading system, the goal of the current study is to compare the degree of interobserver variability in the grading of ILC utilizing a two-tiered nuclear grade versus the NHG.
Design: Representative sections from 38 cases of ILC were graded independently by 5 pathologists using NHG criteria for tubule formation, nuclear pleomorphism, and mitotic activity. In addition to the NHG, tumors were categorized by a two-tiered nuclear grading system as low grade (grade 1 nuclei) or high grade (grades 2-3 nuclei). Pair-wise kappa values and interobserver agreement rates were calculated for both the NHG and the nuclear grade, and results were compared using the paired t-test.
Results: Results are summarized in the table. Overall, mean kappa values demonstrated only fair (NHG) to moderate (nuclear grade) agreement. A statistically significant difference was observed between kappa values for NHG compared to those for nuclear grade. Interobserver agreement rates also showed improvement with use of the nuclear grading system as compared to NHG.
|NHG||Nuclear Grade||P Value|
|Kappa||0.0828 to 0.572 (mean 0.3228)||0.304 to 0.695 (mean 0.4738)||0.0021|
|Interobserver Agreement Rate||53-79% (mean 70%)||68-92% (mean 83%)||<0.0001|
Conclusions: Interobserver variability is to be expected with any histologic grading system. Given that histologic grade has prognostic implications for breast cancer patients which may guide treatment choices, accurate reporting of histologic grade is paramount. In the case of ILC, where use of the traditional NHG places substantial weight on the criterion of nuclear pleomorphism, a two-tiered nuclear grading system may reduce interobserver variability yet still provide useful prognostic information.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 5, Tuesday Afternoon