Computer-Assisted Microscope Analysis of Feulgen-Stained Nuclei in Gonadotroph Adenomas and Null-Cell Adenomas of the Pituitary Gland

Abstract

The current classification of clinically nonfunctioning pituitary adenomas is based on immunocytochemical and ultrastructural studies. However, a number of cases have less distinctive features that cannot be easily conformed with the prevailing morphologic classifications. The diagnostic information contributed by the determination of the nuclear DNA content (DNA ploidy level) and quantitative chromatic pattern description as opposed to the morphofunctional diagnosis in clinically nonfunctioning adenomas was consequently investigated in a series of 71 pituitary adenomas, including 31 null-cell adenomas, 35 gonadotropin adenomas, and 5 nonfunctioning adenomas that were not examined by electron microscopy. DNA ploidy level (8 variables) and quantitative chromatin pattern description (30 variables) were carried out by means of the computer-assisted microscope analysis of 80-1600 Feulgen-stained nuclei analyzed/case. The diagnostic information contributed by the 38 quantitative variables was determined by multifactorial statistical analysis (i.e., Discriminant Analysis). This computer-assisted classification significantly differentiated nulLcell adenomas from gonadotropin adenomas (p = 0.0025). In addition, it was able to differentiate three major subtypes of nonfunctioning adenomas on the basis of their immunohistochemical profiles. These were the immunonegative adenomas, the follicle-stimulating hormone (FSH)-positive adenomas, and the a-subunit (a) and/or luteiwizing hormone (LH)-positive adenomas (p < 0.0001 to p < 0.001). We thus suggest that the cytometric image analysis of Feulgen-stained nuclei can contribute on the discrimination of subtypes of clinically nonfunctioning pituitary adenomas.