SELLA AND PARASELLAR REGION

John R. Hesselink, MD, FACR

            The pituitary gland lies within a bony depression called the sella turcica within the sphenoid bone at the base of the brain. Its small size belies its many important functions. The pituitary gland has a central role in body growth, metabolism, and reproduction functions.

ANATOMY AND FUNCTION

            The pituitary gland consists of the anterior lobe (adenohypophysis), a pars intermedia, and the posterior lobe (neurohypophysis). The anterior lobe and pars intermedia are derived from Rathke's pouch. The anterior lobe is responsible for production and release of prolactin, adrenocorticotropin (ACTH), somatotropin (growth hormone), gonadotropin (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH). A portal-hypophysial system provides a direct vascular link between the median eminence of the hypothalamus and the anterior lobe. Releasing factors produced in the hypothalamus reach the pituitary through the portal system to direct release of the hormones.

            The posterior lobe and infundibulum (pituitary stalk) are direct extensions of the hypothalamus. Vasopressin (ADH) and oxytocin are produced within neurons of the supraoptic and paraventricular nuclei and transported via axonal flow to the posterior lobe. The hormones are stored in secretory granules until their release into nearby capillaries.

            The pituitary stalk transverses the suprasellar cisterns. The optic chiasm and nerves are located superior and anterior to the stalk and the supraclinoid carotid arteries are positioned laterally. The cavernous sinuses lie within the dura on either side of the pituitary gland and contain a meshwork of venous channels. The carotid arteries course through the middle of the sinuses. Cranial nerves 3 and 4 and the 1st (ophthalmic) and 2nd (maxillary) divisions of the 5th nerve are within the lateral walls of the cavernous sinuses. The 6th cranial nerve lies more medially within the sinus just below the cavernous carotid artery. The sphenoid sinus is immediately below the sella turcica.

THE NORMAL PITUITARY GLAND

            The shape of the pituitary gland is variable but the gland height should not exceed 8 mm. The gland normally increases in size and upward convexity in adolescent females and during pregnancy. The gland parenchyma is relatively homogeneous with standard spin-echo pulse sequences. However, very high resolution techniques will reveal a more heterogeneous texture. The anterior lobe is relatively isointense to gray matter on T1-weighted images except during the neonatal period when

it is hyperintense. The normal posterior lobe is hyperintense due to T1 shortening by the phospholipid components of the neurosecretory vesicles.

            Since the pituitary gland, stalk, and median eminence do not have a blood-brain barrier, they enhance routinely with gadolinium. The vascular plexus surrounding the stalk and the cavernous sinuses also enhance. The carotid arteries maintain a low-signal flow void.

PITUITARY PATHOLOGY

            Patients with diseases of the pituitary gland present with symptoms of endocrine dysfunction or with neurologic deficits from compression of adjacent structures. Mass lesions most often produce visual disturbances due to compression of the optic chiasm or optic nerves or a cranial neuropathy, but compression of the infundibulum can also be the cause of diabetes insipidus. The clinical presentation is helpful in differential diagnosis.

Abnormalities of Size and Position

            Benign pituitary hyperplasia

            As mentioned above, the pituitary gland normally enlarges around the time of birth, at puberty, and during pregnancy. Pathologic pituitary hyperplasia can be associated with a hyperfunctioning gland that mimics an adenoma. Symmetric enlargement and a homogeneous texture on plain and contrast scans help distinguish benign hyperplasia from a pituitary adenoma.

            The empty sella

            The empty sella results from herniation of arachnoid through an incompetent diaphragma sellae. Over time, CSF pulsations enlarge the sella and compress the gland against the floor of the sella. In most instances the empty sella is an incidental finding and asymptomatic. Occasionally, extreme compression of the gland may affect function, or traction upon the optic chiasm and nerves may cause visual symptoms.

            Sheehan's syndrome

            During pregnancy the pituitary gland enlarges and becomes more susceptible to circulatory disturbances. Sheehan's syndrome or postpartum necrosis results from pituitary hemorrhage and infarction associated with complicated deliveries. Initial imaging studies will reveal a hemorrhagic gland in a normal sized sella. Over time, the gland involutes, resulting in a partially and completely empty sella.

            Ectopic pituitary

            The presence of high signal intensity adjacent to the median eminence with absence of the normal pituitary bright spot within the sella on T1-weighted images is evidence for the ectopic pituitary. Many cases are associated with perinatal asphyxia and disruption of the normal hypothalamic-pituitary axis. Traumatic transection of the stalk can also result in abnormal accumulation of posterior lobe

hormones proximal to the disruption.

Pituitary Adenoma

            Pituitary adenomas arise within the anterior lobe (adenohypophysis) of the gland . Tumors less than 1 cm are called micro adenomas. Clinical symptoms depend on whether the tumor is secreting or nonsecreting. Nonsecreting adenomas grow and compress adjacent structures, most commonly causing a bitemporal hemianopsia due to chiasmatic compression. Lateral extension into the cavernous sinuses can result in cranial nerve palsies.

            Secreting adenomas manifest with specific endocrine syndromes. Secreting tumors present earlier and are often smaller and confined to the gland. Prolactinomas are the most common functioning adenoma, presenting with amenorrhea, galactorrhea, and infertility. Serum prolactin levels are often greater than 100 ng/ml (normal < 20 ng/ml). Growth hormone-secreting tumors present with acromegaly in adults. Cushing's disease is heralded by symptoms and signs of hypercortisolism. These tumors are invariably microadenomas and are the most challenging for imaging. Ectopic sources of ACTH must also be considered.

            On plain T1-weighted images, microadenomas are usually hypointense compared with the normal gland. They may be slightly hyperintense on T2-weighted images, but more often the contrast is better on T1-weighted scans. Secondary signs of microadenoma include asymmetric upward convexity of the gland surface, deviation of the infundibulum, and focal erosion of the sellar floor. Coronal and sagittal are the preferred imaging planes for pituitary adenomas.

            The macroadenomas are more or less isointense to the normal gland and brain parenchyma, unless cystic or hemorrhagic components are present. Hemorrhage is depicted better by MR than CT, and the signal characteristics suggest the age of the hemorrhage. Central necrosis is not common until the tumors become quite large. Pituitary apoplexy refers to acute hemorrhagic necrosis of a macroadenoma, and patients may present with symptoms related to mass effect of the hematoma or associated subarachnoid hemorrhage.

            The enhancement characteristics of pituitary adenomas followed those observed with CT. With microadenomas, the normal gland enhances more than the tumor to increase the conspicuity of the small lesions. Gadolinium significantly increases the sensitivity of MR for detecting microadenomas. If scanning is delayed more than 30 minutes after injection of the gadolinium, the microadenoma may become isointense to the normal gland. The macroadenomas exhibit homogeneous enhancement and are clearly demarcated from normal suprasellar structures. Cavernous sinus extension is seen better on plain scans because the tumor tissue is contrasted against the flow void within the sinuses. On Gd-enhanced scans, the flow void is maintained within the carotid arteries, but both the cavernous sinuses and the macroadenoma enhance, so they cannot be separated easily.

Other Rare Tumors

            Choristoma

            Also called pituicytoma, granular cell tumor, and myoblastoma, the choristoma is a rare benign tumor arising in the neurohypophysis or infundibulum. The cell of origin is uncertain, but histology reveals large polygonal cells with small nuclei and granular cytoplasm. The MR signal characteristics are variable depending on the presence of cystic components. The solid parts of the tumor will enhance.

            Metastasis

            Although commonly reported in autopsy series, most metastases to the pituitary gland are small and clinically silent. Larger lesions may present with diabetes insipidus. The common primary sources include lung, breast, lymphoma, and leukemia. The most helpful distinguishing feature is rapid tumor growth.

Diabetes Insipidus

            Diabetes insipidus (DI) is characterized by a disturbance of water balance and can be central or renal in origin. Central DI is caused by insufficient secretion of ADH due to hypothalamic or pituitary dysfunction. Transient DI is common after surgery in the suprasellar region.

            Aside from the primary disease process, the classic MR finding is absence of the posterior pituitary bright spot. Since production of ADH is deficient, a decreased amount of secretory granules and phospholipids are present in the posterior lobe.

Lymphocytic Hypophysitis

            This inflammatory disease occurs during preg nancy or in the postpartum period. Hyperprolactinemia is often present and is associated with headache, visual loss, amenorrhea, and failure of lactation. An autoimmune reaction is thought to occur during involution of the pituitary gland in the postpartum period. MR images show diffuse enlargement of the anterior lobe and pituitary stalk. Bright enhancement occurs with gadolinium. The enhancement often extends along the diaphragma sellae, suggesting a periglandular component of the inflammatory process.

SUPRASELLAR PATHOLOGY

Craniopharyngioma

            Craniopharyngiomas originate from epithelial remnants of Rathke's pouch, usually at the junction of the infundibulum and the pituitary gland. They are benign slow-growing tumors composed of both solid epithelial tissue and cystic components. The cysts contain variable amounts of cholesterol, keratin, necrotic debris, proteinaceous fluid and hemorrhage. Calcification is present in 75 to 85% of cases.

            Craniopharyngiomas have a variable appearance on MR, depending on their solid or cystic nature and the specific cyst contents. The solid lesions are hypointense on T1-weighted images and hyperintense on T2-weighted images. The cysts also have a long T2, but if they have a high cholesterol content or methemoglobin, shortening of T1 results in high signal intensity on T1-weighted images. Other features of craniopharyngioma include truncation of the dorsum sellae and upward growth into the third ventricle. Calcification is not reliably detected with MR, a disadvantage for differential diagnosis.

Rathke's Cleft Cyst

            These benign cysts arise from remnants of Rathke's cleft in the region of the pars intermedia. They are lined by a single layer of ciliated columnar or cuboidal epithelium, often containing goblet cells. Initially intrasellar, they enlarge and extend into the suprasellar region as they accumulate fluid, mucous, and cellular debris.

            Rathke's cleft cysts are smoothly marginated and well-defined lesions. The MR signal characteristics are variable, depending on the cyst contents. The cyst capsule may enhance, but the lack of nodular enhancement helps distinguish these lesions from craniopharyngiomas.

Chiasmatic & Hypothalamic Gliomas

            Chiasmatic gliomas occur primarily in children and young adults. Patients with neurofibromatosis are particularly at risk for developing optic and chiasmatic gliomas. These tumors are usually low grade but have a propensity to infiltrate along the visual pathways. Hypothalamic gliomas tend to behave more aggressively and produce symptoms earlier. They present with hypothalamic syndromes, such as diabetes insipidus, inappropriate ADH secretion, Fröhlich's syndrome, or disturbances of temperature, appetite, or metabolism.

            Chiasmatic gliomas are usually isointense or slightly hypointense on T1-weighted images and hyperintense on T2-weighted images. Expansion of the chiasm and optic tracts is seen best on coronal images. The sagittal plane often provides a longitudinal view of the proximal optic nerves. Posterior extension to the lateral geniculate body and beyond into the optic radiations is displayed best on axial T2-weighted or gadolinium enhanced images. Cystic components may be present, and occasionally exophytic growth extends into the suprasellar and interpeduncular cisterns.

            MR is especially good for detecting and delineating hypothalamic gliomas. Subtle deformity of the inferior recesses of the third ventricle can be visualized on coronal and sagittal views. These tumors have a tendency to infiltrate the adjacent thalamus and upper brain stem. Signal characteristics are similar to the chiasmatic gliomas, and they may also exhibit exophytic features. As a rule, both tumors enhance to a moderate degree and in a homogeneous fashion, except for the cystic portions.

Hamartoma of the Tuber Cinereum

            These benign tumors consist of hyperplastic hypothalamic glial and neural tissue. Patients present with precocious puberty due to disruption of the normal hypothalamic inhibition of gonadotropin production during the prepuberty years. These lesions grow very slowly and often appear unchanged on serial imaging studies.

            Hamartomas are sessile or pedunculated masses positioned between the infundibulum and mamillary bodies. They are usually isointense to brain on T1-weighted images and mildly hyperintense on T2-weighted images. The lack of contrast enhancement distinguishes these tumors from hypothalamic glioma and germinoma.

Lymphoma

            Primary malignant lymphoma is a non-Hodgkin's lymphoma that occurs in the brain in the absence of systemic involvement. These tumors are highly cellular and grow rapidly. The hypothalamus and cavernous sinuses are favorite sites in the perisellar region. Most occur in patients who are immunocompromised secondary to chemotherapy, HIV infection, or in organ transplant recipients who are on immunosuppressant drugs. Lymphomas typically appear as homogeneous, slightly hyperintense masses on T2-weighted images. Intratumoral cysts, hemorrhage, or necrosis are unusual. Most lymphomas show bright homogeneous contrast enhancement.

Germinoma

This germ cell tumor occurs in children and young adults, most commonly in the pineal and suprasellar regions. Germinomas have a propensity to invade the hypothalamus and grow into the third ventricle, resulting in endocrine dysfunction. Dissemination through the CSF pathways is a known complication of germinoma.

            Germinomas are most often isointense with the brain on T1- and T2-weighted images. A few lesions exhibit long T1 and T2, which may correlate with embryonal cell elements. These tumors are well defined and enhance to a moderate degree, usually without central necrosis, cystic change, or hemorrhage. Enhanced scans are essential to assess CSF spread of tumor. In young patients with germinoma, the difficulty of visualizing calcium is a disadvantage of MR, as this may be the only evidence of tumor.

Arachnoid Cyst, Epidermoid, Dermoid

            Arachnoid cyst

            Arachnoid cysts are CSF-containing cysts that are found in the middle fossa, posterior fossa, suprasellar cistern, or near the vertex. They are benign but slowly grow as they accumulate fluid, compressing normal brain structures. Arachnoid cysts are smoothly marginated and homogeneous. They are not calcified and do not enhance. The diagnosis is supported by the cyst fluid being isointense with CSF on all pulse sequences.

            Epidermoid cyst

            Epidermoid cysts are referred to as "pearly tumors" because of their glistening white appearance at surgery. They arise from epithelial cell rests in the basal cisterns. They are benign and grow slowly along the subarachnoid spaces and into the various crevices found at the base of the brain.             Intradural epidermoids are usually quite large with lobulated outer margins and an insinuating pattern of growth. They have a heterogeneous texture and variable signal intensity on MR. Most are slightly higher signal than CSF on both T1 and T2-weighted images. An occasional epidermoid has a very short T1 and appears bright on T1-weighted images. The heterogeneous signal pattern is likely related to varying concentrations of keratin, cholesterol, and water within the cyst, as well as the proportion of cholesterol and keratin in crystalline form. Calcification is sometimes present. Epidermoid tumors do not enhance with contrast.

            Dermoid cyst

            Dermoid cysts have both dermal and epidermal derivatives, accounting for their more varied histologic and MR appearance. They are primarily midline lesions, occurring in the pineal and suprasellar regions. Dermoids have some distinctive features on MR. They tend to be heterogeneous owing to the multiple cell types within them. Fatty components are common, producing high signal on T1-weighted images. Axial and sagittal scans may reveal a fat-fluid level, or a level between fat and matted hair within the cyst. Rupture of a dermoid and leakage of cyst contents into a ventricle or subarachnoid space may produce an ependymitis or meningitis, respectively.

Granulomatous Disease

            Langerhan's cell histiocytosis

            Formerly called histiocytosis X and eosinophilic granuloma, this disease is a multisystem disorder involving the skin, bones, orbit, lungs, and the CNS. Proliferation of histiocytes form granulomas in and around the hypothalamus and infundibulum. Diabetes insipidus is the most common presentation, but patients can also develop other endocrine dysfunctions or visual impairment. MRI typically shows a thickened infundibulum or a hypothalamic mass that is isointense on T1, hyperintense on T2-weighted images, and enhances with contrast material. The normal posterior pituitary bright spot is frequently absent.

            Sarcoid

            Sarcoidosis is a granulomatous disease of unknown etiology. In approximately 5% of cases, the CNS is involved as a granulomatous infiltration of the meninges and underlying parenchyma, most notably at the base of the brain. Cranial nerve palsies, chronic meningitis and hypothalamic-pituitary dysfunction are frequent manifestations. Sarcoidosis is generally a multifocal process. MR is well suited to imaging the focal pituitary and hypothalamic lesions. The basal cisterns may enhance diffusely in patients with meningeal sarcoidosis, but a nodular pattern usually distinguishes it from the infectious varieties.

            Tuberculosis

            Tuberculous meningitis remains an important disease, becoming more common as an infectious agent in AIDS patients. As a rule, the evolution is less rapid than in pyogenic infections. Vasculitis and cerebral infarction, caused by inflammatory changes in the basal cisterns, are more prevalent. The MR features of tuberculous meningitis are similar to the bacterial agents, but the chronic inflammation induces thick granulation tissue that produces a more striking enhancement pattern. A basal meningeal process associated with lacunar infarcts should suggest the diagnosis of tuberculosis.

CAVERNOUS SINUS AND PARASELLAR PATHOLOGY

Meningioma

            Meningiomas account for 15% of all intracranial tumors and are the most common extra-axial tumor. They originate from the dura or arachnoid and occur in middle-aged adults. Women are affected twice as often as men. Meningiomas are well-differentiated, benign, and encapsulated lesions that indent the brain as they enlarge. Parasellar meningiomas commonly involve the cavernous sinus and produce an ophthalmoplegia. Meningiomas can induce an osteoblastic reaction in the adjacent bone, resulting in a characteristic focal hyperostosis. They are also hypervascular, receiving their blood supply predominantly from dural vessels.

            Most meningiomas are isointense to brain on T1- and T2-weighted images. A heterogeneous internal texture is found in all but the smallest meningiomas. The mottled pattern is likely due to a combination of flow void from vascularity, focal calcification, small cystic foci, and entrapped CSF spaces. Hemorrhage is not a common feature. An interface between the brain and lesion is often present, representing a CSF cleft, a vascular rim, or a dural margin. MR has special advantages over CT in assessing cavernous sinus involvement and arterial encasement. Meningiomas show intense enhancement with gadolinium and are sharply circumscribed. They have a characteristic broad base of attachment against a dural surface. Contrast scans are especially helpful for imaging the en plaque meningiomas that occur at the skull base.

Nerve Sheath Tumors

            Schwannomas in the parasellar region arise from the trigeminal nerve and rarely from the 3rd, 4th, and 6th cranial nerves. The cisternal, cavernous, or extracranial components of the nerves can be involved. They are well-encapsulated, benign tumors, and their more or less globular shape distinguishes them from the broad-based meningiomas. Schwannomas are isointense on T1 and mildly hyperintense on T2-weighted images. Cystic components may be present, and occasional hemorrhage and calcification can further contribute to a heterogeneous appearance. The solid portions of theses tumors enhance brightly with intravenous contrast.

Skull Base Tumors

            Primary, secondary, and metastatic tumors of the skull base can involve the parasellar region. The primary tumors include chordoma, chondroma, chondrosarcoma, and plasmacytoma. Secondary tumors are most often carcinomas from the nasopharynx and paranasal sinuses. The common metastases are from lung, breast, and prostatic carcinoma, but other tumors can also metastasize to the skull.

            Chordoma is a rare neoplasm, but it is the most common primary of the clivus. They arise from notochordal remnants in the clivus, meninges along the prepontine cistern, sphenoid or nasopharynx. The most common site is near the spheno-occipital synchondrosis. Chordomas are slow-growing and erode bone by direct extension. The soft tissue mass readily extends into the sella, perisellar, prepontine cistern, sphenoid sinus and middle fossa. Cartilaginous foci, bone fragments and calcifications are interspersed within the tumor matrix. Chondroma is a benign tumor that arises from cartilage cell rests at the skull base. Chondrosarcoma is the malignant counterpart that often originates from a preexisting benign lesion. Calcification is common in both tumors. Plasmacytoma is another rare tumor of the skull base that is derived from plasma cells. With time, many evolve to multiple myeloma.

            Chordomas and chondrosarcomas can be difficult to identify on T1-weighted axial images alone due to low contrast with the adjacent cortical bone and CSF, but alteration of the normal high signal clival fat is a sensitive indicator of disease. Plasmacytoma also has no distinctive MR features to allow for a definitive diagnosis. Enhancement with gadolinium is helpful to assess the intracranial components of these tumors.

Vascular Lesions

            Aneurysm

            Aneurysms in the perisellar area arise from the circle of Willis or the intracavernous carotid arteries. A distinctly heterogeneous internal texture on MR images is due to flow effects and thrombus formation. Low signal intensity is caused by high flow and chronic hemorrhage; high signal may represent slow flow or subacute hemorrhage. Flow within the patent lumen may also cause a band of artifact in the phase-encoding direction on spin-echo images. Pneumatization of the anterior clinoid or calcification can simulate the flow void of an aneurysm. MR angiography is helpful to confirm the diagnosis of aneurysm.

            Carotid-Cavernous Fistula

            The fistulous connection may be directly between the cavernous carotid artery and the cavernous sinus or may be the result of a dural arteriovenous malformation in the parasellar region. Arterial pressures cause expansion of the cavernous sinus and dilatation of parasellar and orbital veins. Patients present with proptosis, chemosis, and visual loss. The presence of flow effects and flow artifacts confirms the diagnosis on MR images.

Inflammation

            Tolosa-Hunt syndrome

            Patients present with painful ophthalmoplegia and visual deficits. Similar to orbital pseudotumor pathologically, Tolosa-Hunt syndrome is also characterized by occasional spontaneous remission, recurrent attacks, and prompt response to steroids. The granulomatous inflammation can lead to cavernous sinus thrombosis and secondary arteritis of the cavernous carotid artery. MRI reveals enlargement of the cavernous sinus and enhancement of the inflammatory tissue.

            Sphenoid sinus infections

            Inflammatory and infectious diseases of the sphenoid sinus can secondarily involve the sella and parasellar regions. Pyogenic and fungal infections can extend through the thin bone at the skull base to produce an epidural abscess. Extension into the cavernous sinus can lead to cranial nerve palsies, cavernous sinus thrombosis and carotid artery occlusion. Some of the fungal infections, such as aspergillosis and mucormycosis, are particularly aggressive and have a propensity to extend along vascular structures, leading to cerebral infarction and abscess formation. The combination of sphenoid sinus and intracranial involvement on plain and contrast-enhanced scans is the key to making the diagnosis.

REFERENCES