Localization of prolactin in chromophobe pituitary adenomas: study of human necropsy material by immunoperoxidase technique

In order to identify prolactin-producing tumours in human pituitary glands, 45 chromophobe adenomas, obtained from unselected necropsies, have been studied by various staining procedures including the immunoperoxidase technique for the demonstration of prolactin. The presence of immunoreactive prolactin was revealed in the cytoplasm of the tumour cells in six cases (13%), indicating that the occurrence of prolactin-producing adenomas is not rare. No correlations were established between tumours and clinical history. Two adenomas were detected in female and four in male patients. The age of the patients at necropsy ranged from 28 to 75 years. Three adenomas were associated with disseminated carcinoma, two with fatal liver disease, and one with diabetes mellitus, atherosclerosis, and pyelonephritis. Manifest endocrine symptoms were not disclosed, and endocrine investigations, including measurements of blood prolactin levels, were not undertaken. Thus, direct evidence is lacking as to whether or not these tumours were actively secreting prolactin. In the non-tumorous parts of the anterior lobes the number of prolactin cells was decreased in two cases, suggesting that prolactin released from the adenoma cells suppressed prolactin production in the non-tumorous pituitary. However, the number of prolactin cells of the non-tumorous adenohypophysis seemed to be unchanged in two and increased in another two cases. The present findings conclusively proved the existence of the prolactin-producing adenomas as a distinct entity. These tumours do not stain with acid or basic dyes, they are PAS or thionin negative, and do not contain immunoreactive growth hormone. Thus, by conventional staining procedures they are indistinguishable from other chromophobe adenoma types. Herlant's erythrosin and Brookes' carmoisine methods, claimed spedifically to stain prolactin cells, failed to provide reliable results, hence their use cannot be recommended in tumour identification. Immunoperoxidase staining of prolactin is the only technique which conclusively reveals the presence of immunoreactive prolactin in the cytoplasm of the tumour cells and permits diagnosis. It is proposed that this technique be introduced in pituitary morphological studies. Its application may lead to a better understanding of problems related to prolactin-producing tumours and their secretory activity.