Mitosis counts: reproducibility and significance in grading of malignancy

The interindividual and intraindividual reproducibility of mitosis counts was investigated in 10 cases of malignant non-Hodgkin's lymphoma. With thickness of histologic sections, staining, and the area measured kept constant, the degree of reproducibility was found to be dependent largely on the experience of the investigator. For investigators at similar levels of experience, the mitosis rates obtained were of the same order of magnitude. However, defined mitosis counts do not allow unrestricted grading of malignancy, even after elimination of methodologic pitfalls. Proliferation rates of malignant tumors cannot be expected to be constant due to biologic conditions, such as varying metabolic activity or tumor cell heterogeneity.