Contribution of immunohistochemistry, electron microscopy, and cell culture to the characterization of nonfunctioning pituitary adenomas: A study of 40 cases

We studied 40 endocrinologically inactive pituitary adenomas by immunohistochemistry, electron microscopy, and cell culture in order to determine the incidence of gonadotropic adenomas and to classify nonfunctioning adenomas. Immunohistochemical studies using a large panel of monoclonal and polyclonal antibodies identified the following nonfunctioning adenomas: 20 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and 15 nonsecreting adenomas. Among nonsecreting adenomas, ultrastructural study of 13 cases identified seven null cell adenomas and six oncocytomas. Silent corticotropic adenomas were classified into subtypes I, II, and III according to Kovacs and Horvath. Most often, gonadotropic adenomas displayed a varying number of oncocytic cells, characteristic secretory granules, and a prominent Golgi apparatus. Postembedding immunoelectron microscopy was performed on eight gonadotropic or nonsecreting adenomas, but this technique did not provide any additional information. Six gonadotropic adenomas and 10 so-called nonsecreting adenomas were studied in primary cell cultures. The six gonadotropic adenomas and seven of the 10 nonsecreting adenomas released gonadotropins in the culture medium. The use of in vitro results as a supplementary diagnostic criterion allowed classification of the 40 nonfunctioning adenomas as follows: 27 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and eight nonsecreting adenomas. These results demonstrate a high proportion of gonadotropic adenomas among nonfunctioning adenomas (67.5%) and the usefulness of several techniques in characterizing this type of pituitary adenoma.