Diagnosis and Management of Pituitary Tumors

106 SCHEITHAUER ET AL.Figure 7-18 Normal gonadotroph cells occur singly and lie uniformly distributed in the pituitary gland. LH immunostain × 400.developed membranous organelles, several lysosomes, and smallsecretory granules.Gonadotroph Cells These represent an estimated 15–20%of adenohypophysial cells. The middle-sized or large, ovoid, PASpositiveand FSH-LH immunoreactive cells are quite evenly scatteredthroughout the pars distalis (Figure 18). They exhibit a largeinterface with the basal lamina. Their ultrastructure is characterizedby a spherical, euchromatic nucleus, cytoplasm of low electrondensity containing slightly dilated RER, a large ring-shapedGolgi complex, and 200- to 500-nm secretory granules variable inshape, texture, and electron density (Figure 19).Prolonged stimulation owing to primary hypogonadism or surgicalablation of the gonads results in the development of “castration”or “gonadectomy” cells. The alteration is characterized by agradual increase in cell size, progressive proliferation and dilationof RER, and prominence of the Golgi complex (Figure 20). Withadvancement of changes, secretory granule numbers tend todecrease and dilation of RER increases, the result being formationof so-called signet ring cells.Physiologic suppression of gonadotrophs is observed duringadvanced stages of pregnancy (83). As estrogen levels surgearound term, immunoreactivity for FSH and LH may no longer bedetectable in gonadotrophs. The ultrastructural aspects of suppressionare only poorly documented in rare cases of hypogonadotrophichypogonadism (Kallmann’s syndrome) and in the nontumorousadenohypophysis around gonadotroph adenomas. Suppressedcells are small and feature a heterochromatic nucleus, numerouscytoplasmic lysosomal bodies, and few small secretory granules.Null Cells Cells with ultrastructural features resemblingthose of null adenoma (see below) occur in the normal pituitary(Figure 21). Their origin, nature, and relation to other cell types,as well as to null cell adenomas for that matter, is unclear.Stellate Cells In addition to the functionally distinctive celltypes noted above, cells termed “stellate” or “folliculostellate”also occur within the normal pituitary. Immunoreactive for S-100protein (Figure 22) and glial fibrillary acidic protein (GFAP), stellatecells lack secretory granules as well as hormone secretion andare characterized by processes that either surround pituitary acinior insinuate themselves between adenohypophysial cells (Figure 23).The physiologic role of stellate cells is uncertain. They are thoughtto be supporting or sustentacular in nature and have been found tocontain growth factors and cytokines. Furthermore, they arethought to be implicated in paracrine regulation (81,84,85). Todate, no convincing evidence of neoplastic transformation of stellatecells has been reported.A common feature of the normal anterior pituitary is folliclescomposed of adenohypophysial cells (Figure 24). These structuresare often filled with an eosinophilic, proteinaceous substance.ACTH cells frequently contribute to follicle formation. On immunohistochemistry,the cell apices of the follicles are epithelialmembrane antigen- (EMA) immunoreactive (Figure 24). At theultrastructural level, the cell apices are linked by junctional complexes(Figure 25).Rathke’s Cleft Remnants (Figure 26) At the interface of theanterior and posterior pituitary lobes, remnants of Rathke’s cleftmay be encountered as glands or cleft-like spaces composed ofcuboidal, columnar, mucin-producing, or ciliated epithelium.Occasional pituitary hormone-producing cells may also beencountered. Accumulation of secretions within the cyst gives riseto small cysts, a frequent incidental autopsy findings (86). Symptomaticcysts are far less common.Miscellaneous Cells Squamous metaplasia of adenohypophysialcells is a common occurrence in the pars tuberalis (87)(Figure 27),in the surrounding of healed pituitary infarcts, and so forth.