Nancy Ryan

Null cell adenoma of the human pituitary

Among 343 surgically-removed pituitary adenomas, 56 tumors were unassociated clinically or biochemically with increased hormone secretion and contained no adenohypophysial hormones by the immunoperoxidase technique, except for 10 cases in which a few scattered cells showed positive immunostaining for β-TSH or β-FSH, β-EH, prolactin and/or α-subunit. These tumors were chromophobic adenomas with no PAS, lead hematoxylin or carmoisine positivity and electron microscopy failed to reveal their morphogenesis. The term null cell adenoma of the pituitary is proposed to designate this tumor type. This term recognizes the most obvious features of these tumors: the absence of markers which would permit the disclosure of their cellular origin. Null cells are also found in the nontumorous adeno-hypophysis, suggesting that null cell adenomas derive from preexisting nonneoplastic null cells. The question of whether pituitary null cells are hormonally inactive committed precursors, uncommitted stem cells or dedifferentiated cells remains to be elucidated.

Effects of Estrogen on the Human Pituitary: A Clinicopathologic Study

Pituitary glands obtained at autopsy of 67 men treated with diethylstilbestrol were examined for diffuse and nodular lactotrophic hyperplasia as well as prolactin cell tumorlets or adenomas. A control group consisted of 42 untreated patients with prostatic carcinoma and 209 other elderly men. Diffuse and nodular lactotrophic hyperplasia and the percentage of prolactin cells were greater in treated patients, but these differences were not statistically significant. The higher frequency of prolactin cell adenomas among treated patients (19%) than among control subjects (11%) also lacked statistical significance. An apparent low frequency of occurrence of adenoma in control patients with prostatic carcinoma remains unexplained. No correlation was noted between tumor number, size, morphologic features, or immunoreactivity and such factors as dose of estrogen therapy, associated diseases, ultimate cause of death, or patient age. A correlation was noted, however, between duration of estrogen therapy and the total number of pituitary adenomas, including those composed of prolactin cells. Relative proportions of other types of adenoma were similar within the study and control groups. We conclude that estrogen medication cannot be considered a major risk factor in the cause of prolactin-producing adenomas in older men.

Pituitary Prolactin Cell Hyperplasia

In female Long-Evans rats, development of prolactin cell adenomas is preceded by hyperplasia of prolactin cells, suggesting that factors affecting the endocrine function of prolactin cells might have an important role in the genesis of prolactin-producing pituitary tumors.

Calcium deposition in human pituitary adenomas studied by histology, electron microscopy, electron diffraction and X-ray spectrometry.

The incidence and morphogenesis of calcification were investigated by histology, electron microscopy, electron diffraction and X-ray spectrometry in 312 surgically removed human pituitary adenomas. By light microscopy the incidence of calcification was 9%. The calcium deposits were evident in several adenoma types, but were most frequent and extensive in prolactin-producing adenomas. Histologically calcium deposits represented amorphous precipitates and psammoma bodies staining with hematoxylin, the von Kossa technique and alizarin red. By electron microscopy, calcified deposits were noted in the cytoplasm of adenoma cells and extracellular space. Electron diffraction and X-ray spectrometry of intracellular precipitates as well as psammoma bodies showed the presence of phosphate, calcium and organically bound sulphur with a ratio of 3.5:5:2, indicating that they contained calcium hydroxyapatite. Present findings provide evidence that mitochondria with microcrystal deposition of calcium represent the primary sites of calcification.

Human Pituitary Growth Hormone Cells in Old Age

Pituitaries obtained at autopsy from 18 men and 17 women, over 80 years of age, who died of various acute illness, were investigated histologically by various staining procedures, including the immunoperoxidase technique. Compared with pituitaries of 10 male and 10 female subjects who died of short-lasting diseases between 20 and 56 years of age, no involution of growth hormone cells was found in pituitaries of the older group. Incidence, distribution, granulation and immunoreactivity of growth hormone cells showed no apparent differences related to age and sex. Lack of regression of growth hormone cells with advancing age indicates that the pituitary can produce growth hormone in old subjects.

Histologic, immunocytologic and subcellular changes in the rat adenohypophysis caused by prolactin, growth hormone and ACTH-producing transplanted pituitary tumors: a comparison with spontaneous prolactin-producing adenomas.

Summary The effects of three transplanted pituitary adenomas on the intrasellar nontumorous adenohypophysis of rats hosting these tumors were investigated by histology, immunocytochemistry and electron microscopy. The first two tumors, designated MtT. W5 and MtT. W10 secreted prolactin and growth hormone, while the third, MtT. F4 produced prolactin and ACTH. The intrasellar pituitaries appeared smaller, immunocytochemistry demonstrated a reduction in prolactin positivity in the anterior pituitaries of rats hosting MtT. W10 and MtT. F4 tumors. A similar reduction was noted for growth hormone in the adenohypophysis of rats bearing MtT. W5 and MtT. W10 tumor implants. Ultrastructural investigation revealed an apparent decrease in secretory granule size associated with a reduction in cell volume in the mammotrophs, somatotrophs and corticotrophs exposed to hypersecretion of their respective hormones. The number of cytoplasmic organelles appeared to be diminished. It was apparent that in rats with transplanted pituitary tumors, a feedback mechanism exists, altering the morphology of the respective nontumorous adenohypophysial cells and presumably inhibiting their secretory activity. These changes were compared with a prolactin-secreting adenoma arising spontaneously in the pituitaries of aging Long-Evans rats. In these animals, the pituitaries were enlarged and the number of immunoreactive mammotrophs in the nontumorous portions of the adenohypophysis was markedly increased. The fine structural morphology of the nontumorous mammotrophs differed from those in the previous three groups, and was consistent with increased secretory activity similar to that found in normal lactating rats. These findings support the assumption that the morphologic features of these mammotrophs were not affected by prolactin secretion of the tumor.

An immunohistochemical and ultrastructural comparison of the effects of 2-bromo-α-ergocryptine on intrasellar and transplanted rat pituitaries

Following 2 weeks of administration of 2-bromo-α-ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo-α-ergocryptine-treated rats.

Enhanced Responsiveness of Lactotrophs in Ectopic Pituitaries to Bromocryptine and Estrone Acetate

Intrasellar and transplanted pituitaries removed from the same rats were studied using light microscopy, immunocytology, electron microscopy and ultrastructural morphometry following treatment with bromocryptine and/or estrone acetate. Ectopic lactotrophs of rats treated with bromocryptine showed an increase in storage granule size and number, which was not observed in the lactotrophs of corresponding intrasellar pituitaries. In lactotrophs of intrasellar and ectopic pituitaries, treatment with estrone acetate caused a decrease of storage granule size, while rough endoplasmic reticulum (RER) and Golgi region volume density increased. When rats were treated with a combination of bromocryptine and estrone acetate, intrasellar lactotrophs exhibited increased volume density and diameter size in forming granules as well as increased RER volume density. In ectopic lactotrophs, combined treatment led to a decrease in RER, volume densities of Golgi region and forming granules, as well as increased storage granule size. It can be concluded that ectopic lactotrophs were more sensitive to the inhibiting effects of bromocryptine treatment than intrasellar lactotrophs. Intrasellar lactotrophs were more susceptible to estrone acetate than bromocryptine treatment. As a result, the increased responsiveness of ectopic lactotrophs to estrone acetate was less conspicuous.

Autolytic changes in the rat adenohypophysis: A histologic, immunocytologic and electron microscopic study

Thirty-nine adult female Long Evans rats were decapitated and the heads stored at room temperature. The pituitaries were removed at intervals from 30 minutes to seven days, fixed, embedded and studied by histology, immunocytology and electron microscopy. Histologically, changes were noticeable after two hours postmortem. Immunoperoxidase staining showed postivity for growth hormone, prolactin, FSH, LH and TSH up to seven days after sacrifice, appearing even stronger in the advanced stages of autolysis. Fine structural alterations were evident at 30 minutes and more conspicuous later. Changes included dilation, partial degranulation and whorl formation of RER, swelling of Golgi complexes and mitochondria, chromatin clumping, lysis, rhexis and pyknosis of nuclei, cytosegresome formation and disruption of cell membranes. Secretory granules remained well preserved throughout, although some exhibited fusion or reduced electron density. Dilation of capillaries with accumulation of erythrocytes, platelets and fibrin fibers were prominent findings. The severity of changes varied considerably from cell to cell indicating that the rate of autolysis is not the same among different cell types and is possibly affected by the actual functional state of the cell. It appears that increased membrane permeability and disruption of plasmalemma represent important steps in the autolytic process.

Staining of human pituitary glands with lead hematoxylin in comparison with other histochemical procedures, including the immunoenzyme technique

Human pituitary glands and pituitary adenomas, obtained by surgery or at autopsy, have been stained with lead hematoxylin and the results were compared with those of other histochemical procedures, including the immunoperoxidase technique. Lead hematoxylin positivity was found in the cytoplasm of melanocorticotroph, thyrotroph as well as gonadotroph cells, indicating that lead hematoxylin has no selective affinity for melanocorticotroph cells. Lead hematoxylin positive cells also stained with the PAS technique. Lead hematoxylin positivity was not revealed in growth hormone cells or in prolactin cells. Basophilic adenomas, composed of melanocorticotroph cells and associated with Cushings disease or with Nelsons syndrome or unaccompanied by hormonal hypersecretion, showed intense lead hematoxylin positivity. Thus, no correlation was evident between lead hematoxylin positivity and secretory activity. Acidophilic or chromophobic adenomas consisting of growth hormone cells, prolactin cells, stem cells, undifferentiated cells or oncocytes, however, were negative. It can be concluded that the lead hematoxylin staining techniques a reliable, easy and reproducible histochemical method, and its use can be recommended in studies related to adenohypophysial cytology.