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.