From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Endoglin and CD-34 immunoreactivity in the assessment of microvessel density in normal pituitary and adenoma subtypes.

UNLABELLED: Vascularization is a prerequisite of tumor growth, invasion and metastasis. In the present work, microvessel density was assessed by quantitating using two different endothelial cell biomarkers, endoglin (CD-105) and CD-34. Fifty endocrinologically active and 36 clinically nonfunctioning pituitary adenomas, all surgically resected, as well as 10 autopsy-derived normal adenohypophyses were investigated by immunohistochemistry. The results showed that in every pituitary adenoma type endoglin, an assumed biomarker of proliferating endothelial cells, immunostained fewer vessels than CD-34 which revealed immunopositivity in all capillaries. Differences in endoglin versus CD-34 immunoexpression indicate varying degrees of vascularity in pituitary adenoma subtypes. The low levels of endoglin immunoexpression in pituitary tumors exposed to long-acting somatostatin analogs and dopamine agonists are consistent with the view that these agents inhibit angiogenesis. KEYWORDS: immunohistochemistry, endoglin, CD34, microvascular density, angiogenesis, pituitary.

Severe lymphocytic adenohypophysitis with selective disappearance of prolactin cells: a histologic, ultrastructural and immunoelectron microscopic study.

We report the first documented example (case 1) of lymphocytic adenohypophysitis (LAH) associated with selective destruction of prolactin cells. The morphologic data are compared to those obtained in another, more typical case (case 2). Case 1 was a 35-year-old woman with remote history of pregnancy who presented with headache, oligomenorrhea and visual disturbances. The blood prolactin level was nearly undetectable, but no deficiency of other pituitary hormones was evident. A sellar and parasellar mass compressing the optic chiasm was removed transsphenoidally. Histology demonstrated massive infiltration with lymphocytes, plasma cells and macrophages causing marked destruction of pituitary acini. Part of the gland was fibrotic. Immunocytochemistry documented all pituitary hormones, but only few cells, probably mammosomatotrophs, were immunoreactive for prolactin. Electron microscopy and immunoelectron microscopy using double gold labeling for growth hormone and prolactin detected no prolactin cells. A striking ultrastructural finding was the prominence of folliculostellate cells in areas of active cell destruction supporting the presumed immune role of these cells. LAH in case 2 (24-year-old woman) became manifest during late pregnancy, causing pituitary enlargement and visual field defects. Pituitary tests showed no major hormonal deficits. Moderate hyperprolactinemia was appropriate for her pregnancy status. A sellar mass, thought to be adenoma, was removed. Histology demonstrated multifocal LAH without major destruction of acinar structures. Immunocytochemistry and electron microscopy documented all pituitary cell types including the marked abundance of prolactin-producing cells, resultant of gestational prolactin cell hyperplasia. In addition to prolactin cells and growth hormone cells, immunoelectron microscopy showed several bihormonal mammosomatotrophs, also appropriate for pregnancy.

Double adenoma of the pituitary: a somatotroph adenoma colliding with a gonadotroph adenoma.

Pituitary collision tumors are rare. They may create difficult diagnostic problems and their histogenesis is not clear. We report here an unusual case of a somatotroph adenoma colliding with a gonadotroph adenoma.The 64-year-old man had clinical acromegaly. His blood growth hormone level was elevated and magnetic resonance imaging demonstrated a pituitary tumor. The surgically removed sellar mass was investigated by histology, immunocytochemistry and electron microscopy. Morphologic study revealed a collision tumor; one was a somatotroph adenoma, the other a gonadotroph adenoma. Authors call attention to the difficulties in clinical, imaging and pathological diagnosis. Detailed morphologic studies are needed to establish the presence of two distinct tumors composed of two different cell types.

Ultrastructural and immunoelectron microscopic study of three unusual plurihormonal pituitary adenomas.

Monomorphous pituitary adenomas expressing several hormones by immunocytochemistry are common, whereas adenomas displaying multiple immunoreactivities and consisting of more than one morphologic cell types are rare. Three such unusual pituitary adenomas, surgically removed from two patients with acromegaly and one patient with hyperprolactinemia, were investigated by histology, immunocytochemistry, transmission electron microscopy, as well as immunoelectron microscopy using double immunogold labeling. Immunocytochemistry revealed variable degrees of immunoreactivities for growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (beta-TSH), and alpha-subunit of glycoprotein hormones in all three tumors. The three adenomas consisted of phenotypically diverse cell populations as documented by transmission electron microscopy. In addition to monohormonal GH cells, immunoelectron microscopy demonstrated numerous cells colocalizing GH and PRL or GH and beta-TSH, and rarely PRL and beta-TSH in tumors of acromegalics. The adenoma causing hyperprolactinemia consisted chiefly of mammosomatotrophs colocalizing PRL and GH, whereas beta-TSH labeling was scant. The three tumors in the study were selected from a cluster of five plurimorphous plurihormonal adenomas received from the same locale where they accounted for an unprecedented 21% of adenomas producing GH and/or PRL. The enhanced susceptibility to develop plurimorphous adenomas of the acidophil cell line may have a genetic basis in the stable population the patients came from.