Ultrastructural features of apoptosis in human pituitary adenomas

Although several recent studies deal with various molecular aspects of apop tosis, or programmed cell death, very little information is available on th e ultrastructural changes associated with apoptosis in the adenohypophysis and its role in the regulation of pituitary adenoma growth and progression. This paper describes the distinct ultrastructural sequences that develop d uring the various phases of the apoptotic process. The study is based on th e ultrastructural investigation of more than 8,000 surgically removed pitui tary biopsies, which were examined by histology and immunocytochemistry for diagnostic purposes. No apoptosis was found in normal adenohypophysis and it is also a rare event in pituitary adenomas. When present, adenomatous ad enohypophysial cells exhibit common and characteristic apoptotic changes. T he ultrastructural alterations of membraneous organelles associated with ap optosis are similar to those previously reported in other tissues. It is no teworthy that apoptosis is clearly distinguishable from the ubiquitous dark cells denoting the common way of cell death. The findings suggest that apo ptosis in pituitary adenomas is not a random event. Practically every speci men containing multiple apoptotic cells represents corticotroph adenoma. Oc casional examples occur in lactotroph or gonadotroph adenomas. Although ele ctron microscopic specimens are admittedly small, the large number of inves tigated cases gives credence to the observations.