MRI shows a sella turcica mass with left cavernous sinus invasion.

Sagittal MRI shows the mass centered in the sella turcica consistent with a macroadenoma.

Monotonous uniform polygonal cells are arranged in broad cords or sheets.

Salt and pepper chromatin can be appreciated. The cell clusters are separated by a delicate fibrovascular stroma.

A reticulin stain highlights the network around the acini. In normal pituitary, the reticulin network is uniform and surrounds similarly sized acini. In hyperplasia, the reticulin network is also intact but the acini are larger. In an adenoma, the network is disrupted.

Pituitary adenomas express low molecular weight keratin as demonstrated by CAM 5.2 positivity.

Chromogranin is positive.

Synaptophysin is also strongly positive.

Pituitary adenomas are divided into secretory and nonsecretory adenomas. Small nonsecretory adenomas can slowly enlarge and cause local compression symptoms (i.e. visual defects) or compromise normal pituitary gland function (i.e. hypopituitarism).

Functioning (secretory) adenomas are less likely to cause compressive symptoms, but produce hormones and lead to endocrine symptoms. Secretory adenomas can be further subclassified into the hormone that it produces. Various hormone deficiencies can also occur if the growth destroys normal pituitary parenchyma. About 25-30% pituitary adenomas are nonfunctioning, 25% produce PRL, 20% produce GH, and 10% produce ACTH (Khan, Fletcher).

Adenomas smaller than 1cm are microadenomas and those between 1cm and 4 cm are macroadenomas. Giant adenomas >4cm are rare. Larger adenomas are more likely to be invasive. Adenomas tend to grow expansively with a pushing border, or invade adjacent structures such as sphenoid sinus, cavernous sinus or brain.

A variety of growth patterns are seen including trabecular, papillary and alveolar (nested) patterns. The tumor cells are monotonous and polygonal with a centrally placed round nuclei. A speckled salt-and-pepper chromatin is typical. The tinctorial quality of the cytoplasm depends on whether the chromophil cell is acidophilic or basophilic. Acidophils are comprised of somatotrophs and mammotrophs whereas basophils are comprised of gonadotrophs, thryotrophs and corticotrophs (Fletcher).

The histologic features such as pleomorphism, nuclear atypia and mitotic activity do not correlate with the invasiveness of the tumor. A clear progression from pituitary adenomas to invasive adenomas to pituitary carcinomas has not been demonstrated. Pituitary carcinomas, defined as pituitary neoplasm demonstratining systemic or craniospinal metastases, comprise less than 1% of pituitary tumors. Most pituitary carcinomas are functioning tumors secreting PRL or ACTH.

Two cytogenetic lesions of interest have been studied in pituitary adenomas:

• MEN type I: These patients have abnormalities of the parathyroid, pituitary and pancreas. Approximately 20% of patients with MENI syndrome develop a pituitary adenoma, usually a prolactinoma . MEN type I patients have germline mutations of the MENI gene, which is a tumor suppressor gene located on 11q13. This mutation is uncommon in sporadic tumors, however.
• GNAS1 mutation (gsp oncogene): A mutation of alpha subunit of a stimulatory G protein (GNASI) leads to constitutive activation of a G-protein pathway involving uncontrolled generation of c-AMP and cellular proliferation. This mutation of GNASI is also designated as gsp oncogene because of its role in oncogenesis. GNASI mutations are seen in 40% of GH-secreting adenomas. This mutation is not seen in adenomas making other hormones since their actions do not depend on a c-AMP pathway (Kumar).

Pituitary adenomas are positive for neuroendocrine markers (e.g. synaptophysin, neuron-specific enolase (NSE)), low molecular weight keratins as well as markers specific to the hormone being produced (e.g. ACTH, PRL, GH).

Pituitary tumors represent 10-15% of all intracranial tumors and are usually found in adults (peak incidence between the 3rd and 5th decades). Incidental pituitary tumors are found in approximately 1%-25% of autopsies (Khan, Kumar).

Pituitary adenomas may lead to endocrine or compressive symptoms, but mortality rate is low. Surgery by a transsphenoidal approach can cure most microadenomas, but tumors larger than 1cm may recur. Prognostication remains problematic, as proliferative markers such as Ki-67 are not consistently predictive of invasiveness or recurrence.