How to Work Up a Sellar-Suprasellar Mass

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Introduction  Intraoperative consultation Stains  Clinical questions  Imaging questions Differential diagnosis Hints

Introduction: Head

• Normal weight of the pituitary is about 0.6 gram.

• Major components: The pituitary is composed of the anterior pituitary (adenohypophysis) and posterior pituitary (pars nervosa).

• The adenohypophysis (represent about 80% of the pituitary) is composed of the pars distalis, pars intermedia, and pars tubularis.

• Surgical approach: A transphenoidal approach is often used for smaller lesions in the sellar. A craniotomy approach is used for lesions that are large and have suprasellar component.

Intraoperative Consultation (Frozen section): Head

• Touch preparation: Pituitary adenomas are very delicate and the regular squash preparation may sometime be too harsh for these cells.

• Squash preparation: They are very useful in the diagnosis of pituitary adenoma, lymphoma, inflammatory lesions, and glial tumors.

• Air dried fluid smear: If a diagnosis of craniopharyngioma is suspected, the machine oil like fluid that comes with the tumor can be smeared on the glass slide and air dried. Cholesterol crystals may be seen in these slides. Do not pass these slides through xylene because the cholesterol crystal will be removed.

• Frozen: Pituitary adenomas tend not to cut well with frozen section and the cytologic preparation will play a more important diagnostic role in some cases. Frozen section is still the cornerstone for diagnosis for other tumors such as craniopharyngiomas and meningiomas.

Helpful stains and procedures other than hematoxylin-eosin stain: Head

Immunohistochemistry

• Synaptophysin

• Pituitary hormones

• GFAP

• Ki-67

• Cytokeratin

Other stain

• Reticulin: This is a very important stain to separate pituitary adenoma from normal and hyperplastic anterior pituitary tissue, particularly in small biopsy material.

      Electron microscopy: 

• Electron microscopy might be helpful in phenotyping pituitary adenomas. A small piece of tumor tissue should be procured.

Important Clinical Questions: Head

• Is there any history of pituitary adenoma?

• Has the patient been treated with bromocriptine? Bromocriptine will change the morphology of prolactinomas.

• Is the patient pregnanted? Lymphocytic hypophysitis often but not always occur in pregnated women.

• Does the patient have any systemic autoimmune disease?

• Is there any acute onset of cranial nerve palsy and visual impairment? A combination of sudden onset headache, visual impairment, oculomotor and abducens nerve palsy is highly suggestion of pituitary apoplexy.

• Are the hormone levels normal? Prolactin may be modestly elevated due to “stalk-compression effect”.

• Does the patient have neurofibromatosis 1 (NF1)? NF1 is associated with astrocytomas and hamartomas arising in the optic nerve-hypothalamic area.

Important Imaging Questions: Head

• Is the lesion purely intrasellar, purely suprasellar, or with both intrasellar and suprasellar components? The presence of a suprasellar component is an important hint for differential diagnosis.

• Is the epicenter of the mass in the suprasellar? Craniopharyngiomas usually occur in the suprasellar region with downward (sellar) extension; they may occur entirely within the third ventricle or in the sella. Pituitary adenomas usually occur as intrasellar mass; the larger one may have suprasellar extension.

• Is the tumor cystic or solid? Many cystic lesions such as arachnoid cysts, Rathke’s cleft cysts are found in this area. In additons, craniopharyngiomas are also often cystic. In contrast, pituitary adenomas and meningiomas are usually solid.

• Is there any calcification? Craniopharyngiomas often but not always contain calcified material that can be detected by CT scan.

• Does the lesion enlarge the sella? An enlarged sella is more compatible with a slow growing lesion such as most pituitary adenomas, Rathke's cleft's cysts.

• Is the lesion extra-axial or intra-axial? This may help to differentiate intra-axial lesions that originate from the thalamus, optic nerve and floor of the ventricles to extra-axial lesions that arise from outside the brain.

General consideration in differential diagnosis: Head

Primary lesions in this area arise predominantly from three areas: the pituitary, the optic nerve and hypothalamus, the meninges and surrounding mesenchymal structures. The following is a list of the more commonly seen tumor.

    Primary Tumor

• Pituitary adeomatous tumos

• Pituitary adenoma

• Pituitary adenoma-neuronal choristoma (PANCH)

• Invasive pituitary adenoma

• Pituitary carcinoma

• Granular-cell tumor (pituicytoma)

• Craniopharyngioma

• Glial neoplasm

• Meningioma

• Germ cell tumor, epidermoid cyst, and dermoid cyst

• Chordoma

• Hypothalamic hamartoma and hamartoblastoma

• Langerhans’ histiocytosis

• Gangliocytoma

• Others

    Secondary tumor

• Metastatic carcinoma

• Metastatic melanoma

• Leukemic and lymphomatous involvement

• Langerhans' histiocytosis

• Others

    Pseudotumor

• Pituitary hyperplasia

• Lymphocytic hypophysitis

• Lymphocytic infundibuloneurohypophysitis

• Granulomatous hypophysitis

• Plasma cell-granuloma, primary intracranial or secondary

• Giant cell granuloma

• Sarcoidosis

• Pituitary apoplexy

• Rathke's cleft cyst

• Mucocele from the paranasal sinuses

• Abscess

• Arachnoid cyst

• Others

Useful Hints: Head

Bromocriptine treated prolactinoma: Prolactinomas treated with bromocriptine are often fibrotic and have atrophic cells. The combination of these two features at frozen section would be highly suggestive of a primary or metastatic small blue cell tumor. The morphologic features of the adenomatous cells are often far better recognized on squash preparations than on frozen sections. Knowing the history is also very helpful.

Blood supply:

• Three pairs of arteries- superior, middle, and inferior hypophysial arteries; all arise from the internal carotid artery. The superior hypophyseal artery brnches into an external plexus and internal plexus.

• Anterior pituitary blood supply: About 70-90% of the blood supply came from the long portal vein and is supplied by the superior hypophyseal arteries. About 10-30% of blood originates in the short portal vessel that link the infundibular stem or process to the anterior pituitary. The middle hypophyseal arteryies give rise to the subcapsular artery and the artery of the fibrous core, they may provided a minor blood supply to the anterior pituitary. The inferior hypophyseal arteries supply the pituitary stalk, the neural lobe and the lower pituitary stalk.

Infarction:

• Hypothalamic infarction: Damage to the superior hypophysial artery may lead to infarction of the hypothalamus and cause diabetes insipidus.

• Anterior pituitary infarction: Damage to the long portal vessels, such as low stalk disruption, will lead to anterior pituitary infarction.

• Apoplexy: Acute hemorrhagic infarction of the pituitary adenoma will lead to rapid expansion of the tumor. The results of this fulminant expansion of a sellar-suprasellar mass will lead to visual impairment, severe headache, altered mental status, lethargy, coma, and intracranial pressure. This series of serious clinical events is known as pituitary apoplexy. 

Radiation induced pituitary tumors are almost always sarcomas or glial tumors. Ionizating radiation does not usually induce pituitary adenoma in human.

"Stalk-compression effect": The release of prolactin is negatively regulated by the hypothalamus through the portal system (involve dopamine). Any compression of the pituitary stalk will lead to the loss of suppression and results in increased release of prolactin. But the prolactin level should not exceed 150 ng/mL. Prolactin secreting adenomas usually have higher serum prolactin level.

Hyperprolactinemia is demonstrated in approximately 40% of acromegalic patients. Some of these are resulted from the "stalk-compresion effect”, others are due to tumoral production.

Sparsely granulated growth hormone adenoma: Look for pleomorphism and multinucleation, and fibrous bodies. A combination of these may suggest a sparsely granulated growth hormone adenoma and they usually behave aggressively.

Langerhans’ histiocytosis: While Langerhans’ histiocytosis is a rare entity in the brain, they do arise most often in the hypothalamus area. They should also be differentiated from lymphoma and leukemia. 

Introduction  Intraoperative consultation Stains  Clinical questions  Imaging questions Differential diagnosis Hints

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