Problems in histological grading of malignancy and its clinical significance in patients with operable breast cancer

Although the histological grading of malignancy in patients with operable breast cancer, typically consisting of three factors: tubular formation, mitotic counts, and nuclear atypia, plays an important role in identifying patients at high risk of recurrence, the most effective combination of factors is still not completely clear. In assessing prognosis, the problems of clinical application of the grade of malignancy are not only related to the assemblage of the factors employed, but also to the heterogeneity within the tumor and interobserver variations. In a review of the correlation between the histological grading system for malignancy in operable breast cancer patients and the recurrence rate, only the grade of nuclear atypia statistically correlated with the rate of recurrence. Furthermore, a grading system consisting of mitotic counts and nuclear atypia was more significantly correlated to the risk of recurrence than was the system based on the three factors described above. Concerning the heterogeneity of histologic features within the primary tumor, a system based on the grade of mitotic counts or nuclear atypia showed a high degree of heterogeneity, but a system based on the grade of tubular formation showed low heterogeneity and bimodal distribution.