Unbiased stereologic techniques for practical use in diagnostic histopathology

Grading of malignancy by the examination of morphologic and cytologic details in histologic sections from malignant neoplasms is based exclusively on qualitative features, associated with significant subjectivity, and thus rather poor reproducibility. The traditional way of malignancy grading may therefore not be optimal regarding the scientific and clinical value in selecting specific therapy and making prognostic forecast for the individual patient with a solid cancer. A lot of examples in the international literature document the urgent need for replacing morphologically based techniques by introducing quantitative techniques in the histopathologic discipline of malignancy grading. Unbiased stereologic methods, especially based on measurements of nuclear three-dimensional mean size, have during the last decade proved their value in this regard. In this survey, the methods are reviewed regarding the basic technique involved, sampling, efficiency, and reproducibility. Various types of cancers, where stereologic grading of malignancy has been used, are reviewed and discussed with regard to the development of a new objective and reproducible basis for carrying out prognosis-related malignancy grading of solid tumors. This new, unbiased attitude to malignancy grading is associated with excellent virtues, which ultimately may help the clinician in the choice of optimal treatment of the individual patient suffering from cancer. Stereologic methods are not solely applicable to the field of malignancy grading. Surgical pathologists can use a wide range of these techniques in the routine of diagnostic and scientific work. It is not the intention, however, to give an extensive review of the methodology, but two other techniques will be covered: Unbiased estimation of volume of, and total tumor cell number within, solid neoplasms. Three-dimensional tumor size may be of relevance in staging cancer, whereas total tumor cell number may be of interest in the scientific work with malignancies and treatment of cancer.