Richard J. Perrin
I. NORMAL ANATOMY AND HISTOLOGY. The pituitary gland (hypophysis or “undergrowth”) is located at the base of the brain, beneath the hypothalamus, within the sella turcica of the sphenoid bone. The smaller, posterior lobe of the pituitary contains the neurohypophysis (pars nervosa), which is connected to the hypothalamus via the pituitary stalk, or infundibulum (“little funnel”). Associated with the pituitary stalk is the infundibular portion (pars tuberalis) of the adenohypophysis. The other portions of the adenohypophysis form the anterior lobe (pars distalis) and vestigial intermediate lobe (pars intermedia); the latter contains remnants of Rathke’s cleft cyst (glandlike cystic spaces).
Histologically, on H&E-stained sections, normal adenohypophysis (e-Fig. 27.1)* is composed of three different cell types: acidophils (producing growth hormone [GH] or prolactin [PRL]), basophils (producing adrenocorticotrophic hormone [ACTH], thyroid-stimulating hormone [TSH], luteinizing hormone [LH], and follicle-stimulating hormone [FSH]), and chromophobes (hypogranulated acidophils and basophils); all are arranged in an acinar pattern. The acini are demarcated by a delicate fibrovascular stroma best visualized on reticulin stains. Although each acinus contains a mixed population of these cell types, the composition varies regionally. Acidophils dominate the lateral portions, basophils (ACTH and TSH) dominate the medial portions, and basophilic gonadotrophs (LH and FSH) are distributed uniformly. Occasionally with aging, basophils extend into the neurohypophysis; this phenomenon, termed “basophilic invasion,” should not be misinterpreted as an infiltrating neoplasm. The posterior pituitary is composed of axons, axon terminals, and sometimes axonal swellings (spheroids) called Herring bodies which contain vasopressin and oxytocin. Specialized glial cells (true “pituicytes”) accompany the axons; these are generally considered to be the cells of origin for the rare and related benign tumors pituicytoma and choristoma (granular cell tumor [GCT]). Ectopic pituitary tissue can be found in the nasal cavity, sphenoid sinus, or rarely, within ovarian teratomas.
II. INTRAOPERATIVE EVALUATION AND TISSUE HANDLING. Intraoperative evaluations are frequently requested for pituitary neoplasms, most often to confirm the clinical diagnosis of pituitary adenoma. Although frozen sections usually provide adequate information to make an intraoperative diagnosis, a small (1 mm3) amount of tissue should be used for cytologic examination. Intraoperative cytologic smears or “touch preps” lack freezing artifacts that obscure nuclear details (e-Fig. 27.2) and thus provide extremely valuable complementary information at the time of frozen section. Likewise, ample tissue should be reserved for paraffin embedding, free from freezing artifacts, to preserve antigenicity and morphologic features that might otherwise be compromised. This point is particularly important in the evaluation of a smaller microadenoma, which can easily be exhausted through cavalier intraoperative processing. Finally, a small (1 mm3) amount of tissue should be reserved for ultrastructural examination; tissue fixed directly in 3% glutaraldehyde and embedded in plastic will retain fine structural features that cannot be recovered from formalin-fixed, paraffin-embedded tissue.
III. NONNEOPLASTIC LESIONS
A. Pituitary hyperplasia. Diffuse expansion of pituitary acini, best evaluated on reticulin stained sections, is the histologic hallmark of pituitary hyperplasia. However, this diagnosis is often difficult to render with certainty. Nodular expansion of acini with one single hormonal cell type is noted in a variety of clinical scenarios, including pregnancy and estrogen therapy. One must also be cognizant of the naturally heterogeneous composition of the anterior pituitary, which favors acidophils laterally and basophils medially.
B. Pituitary apoplexy (e-Fig. 27.3). Spontaneous hemorrhage and infarction of nonneoplastic or neoplastic pituitary may represent a surgical emergency (in the setting of increased intracranial pressure, subarachnoid hemorrhage, or visual disturbance). For diagnosis of an underlying tumor in a partially necrotic specimen, a reticulin stain may prove more reliable than immunohistochemistry; immunohistochemistry should usually be performed but is often difficult to interpret in this setting.
C. Lymphocytic hypophysitis is a rare autoimmune disorder of the adenohypophysis that progressively destroys the gland, resulting in panhypopituitarism. The posterior hypophysis may also be affected, resulting in diabetes insipidus. Lymphocytic hypophysitis occurs with greater frequency in pregnant or postpartum women. Subsets of patients also have other associated autoimmune disorders. Microscopically, the anterior pituitary demonstrates lymphoplasmacytic infiltrates without granuloma formation. The resulting glucocorticoid deficiency is often fatal if untreated.
D. Granulomatous hypophysitis. This rare autoimmune disorder expands and selectively destroys the anterior pituitary with well-formed, noncaseating granulomas and a mild lymphocytic infiltrate. Radiologically, this condition may mimic adenoma, but it also often involves the thyroid, adrenal glands, and testes. Unlike lymphocytic hypophysitis, it shows no association with pregnancy.
E. Rathke’s cleft cyst (e-Fig. 27.4) is a developmental abnormality that arises between the anterior and the posterior lobes or in the infundibular stalk. Smaller examples are often detected incidentally. Lesions>1 cm are usually symptomatic (e.g., cause hypopituitarism or visual disturbances related to compression of the optic chiasm). The cyst is lined by cuboidal to columnar epithelium that may or may not be ciliated and may or may not contain goblet cells. Focally, the epithelium may show flattening and/or squamous metaplasia. The cyst contents are variably serous or mucoid. Xanthogranulomatous inflammation may be present in cysts that have undergone prior hemorrhage. Surgical resection is curative.
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