Calvin Ezrin

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.

Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity.

Abstract A pituitary adenoma removed by surgery from a 43 year old man was studied by various morphologic technics, including different staining procedures, immunocytology and electron microscopy. Clinically and biochemically, the patient was eucorticoid, and laboratory tests showed that the pituitary adrenal axis responded normally to stimulation. By histology, the tumor was a densely granulated basophilic cell adenoma, exhibiting intense cytoplasmic staining with aniline blue, periodic-acid Schiff or lead hematoxylin. Presence of immunoreactive ACTH was demonstrated in the cytoplasm of some adenoma cells by the immunoperoxidase technic. No immunostaining was obtained when anti 1–24 ACTH was replaced by antibodies raised against human growth hormone, prolactin, TSH, FSH or LH. By electron microscopy, the adenoma was found to consist of corticotroph cells characterized by large secretory granules varying in electron density, presence of bundles of type I microfilaments, lysosomal accumulation as well as crinophagy. The morphologic findings can be interpreted as indicating a defect in the release of secretory granules and their intracellular lysosomal disposal. It remains to be determined, in cases of silent pituitary adenomas, how often this proposed mechanism can account for the absence of endocrine hyperactivity. The accumulation of lysosomes, crinophagy, plus the presence of immunoreactive ACTH in a corticotroph cell adenoma unassociated with enhanced hormone discharge, appears to constitute a distinct Clinicopathologic entity.

Regression of pituitary tumors, a possible effect of bromergocryptine☆

With the advent of the prolactin radioimmunoassay and more sensitive methods of roentgenologic examination, prolactin-secreting pituitary tumors are now being diagnosed with much greater frequency. Definitive treatment has been considered to involve transphenoidal hypophysectomy. The symptoms of hyperprolactinemia including amenorrhea, galactorrhea and infertility can usually be controlled without difficulty by bromergocryptine therapy, but little is known regarding continued tumor growth. Bromergocryptine and other ergot alkaloids have been shown to decrease the production of prolactin and to inhibit the rate of pituitary tumor growth in animal studies. In man, evidence for a similar effect is not as clear. The present study demonstrates tumor regression associated with bromergocryptine therapy in two patients.

Pituitary chromophobe adenomas consisting of prolactin cells

Morphologic studies of pituitary neoplasms removed by surgery from 36 human patients revealed 8 chromophobe adenomas which differed clearly from the remaining tumors. The cytoplasm of the adenoma cells failed to stain with PAS, aniline blue, aldehyde fuchsin, aldehyde thionin, orange G or light green, but positively stained granules were found by using erythrosine or carmoisine. Immunoperoxidase technique disclosed the presence of prolactin in the cytoplasm of some adenoma cells. The adenoma cells exhibited distinct ultrastructural features such as well developed rough surfaced endoplasmic reticulum with Nebenkern formation, prominence of Golgi apparatus, presence of misplaced exocytosis as well as pleomorphism of secretory granules with a considerable variation of size ranging from 130 to 500 nm in diameter. Thus, by electron microscopy the adenoma cells showed a close resemblance to prolactin cells of the non-tumorous pituitary glands except for the reduced size and number of secretory granules. These chromophobe adenomas are regarded as representing a distinct pathological entity clearly distinguishable from other forms of pituitary neoplasms. In view of the morphologic findings and the elevation of blood prolactin level (measured in 3 patients) the term, “sparsely granulated prolactin producing pituitary adenoma”, appears to be the most appropriate one to designate these tumors.

Effect of Starvation on Pituitary Growth Hormone Cells and Blood Growth Hormone and Prolactin Levels in the Rat

Growth hormone (GH) cells of rats were studied on days, 2, 4 and 7 of starvation. Immunoperoxidase staining for light microscopy confirmed the presence of GH in the pituitaries of all groups of animals. Electron microscopy revealed crinophagy in the cytoplasm of GH cells on days 4 and 7. By ultrastructural morphometry, volume density and the diameter of secretory granules in the cytoplasm of GH cells remained unchanged. Blood GH determinations showed a significant decrease on day 4 of the starvation period. On day 7 most of the values were in the range of the controls. Blood prolactin levels fell significantly on day 7. It appears that the pituitary is capable of secreting GH even in rats completely deprived of exogenous nutrients.

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.

Pituitary Adenomas in Old Age

Pituitaries obtained at unselected autopsies of 152 men and women over 80 years of age, dying of different diseases, have been investigated histologically by using various staining procedures, including the immunoperoxidase technique. In 20 pituitaries, 22 adenomas were found providing evidence that these tumors are common in aging subjects. In 9 adenomas out of 17 cases, the immunoperoxidase technique revealed the presence of prolactin, indicating that prolactin-producing adenomas constitute the most frequently occurring pituitary tumor type in old age. The presence of growth hormone was demonstrated in one adenoma which also contained prolactin. No storage of ACTH, FSH, LH or TSH was found in the tumors. The biologic behavior of pituitary adenomas disclosed as incidental findings in old age remains to be elucidated. These neoplasms may have a slower growth rate, but more work is required to establish whether they differ from those found in younger age groups.