Quantitative analysis of nucleolar margination in diagnostic cytopathology

The diagnostic value of nucleolar margination, defined as the percentage of nucleoli touching the nuclear membrane, was investigated in 359 cytological preparations of benign and malignant lesions of the thyroid, breast, prostate and central nervous system. Premalignant lesions of the uterine cervix and non-invasive papillary carcinomas of the bladder were also examined. It was observed that the percentages in benign lesions were, in general, lower than in the malignant and that the values increased progressively with increasing grade in the cervix and bladder. When the overlap index was calculated, this gave exact information on the usefulness of nucleolar margination in distinguishing benign from malignant lesions, particularly in the prostate and thyroid and, to a lesser extent, in the breast and central nervous system. As for lesions of different grades, the calculation of the index allowed the identification of two subgroups, one corresponding to low grades (mild cervical dysplasia or urothelial papillary carcinoma of grade 1), the other subgroup to high grades (severe cervical dysplasia and carcinoma in situ, or papillary carcinoma of grade 3). Moderate dysplasia cases and grade 2 papillary carcinomas do not appear as separate intermediate categories but rather show values falling into the range of either the higher or lower grades. The margination values obtained from the cytological preparations corresponded well to those in the histological slides obtained from the resected specimens. In conclusion, nucleolar margination appears to be a feature which is easy to evaluate in a reproducible way and useful in cytological diagnosis.