Sellar Region Tumors and Tumor-Like Conditions

Main Text

Preamble

The sellar region is one of the most anatomically complex areas in the brain. It encompasses the bony sella turcica and pituitary gland plus all the normal structures that surround it. Virtually any of these can give rise to pathology that ranges from incidental and innocuous to serious, potentially life-threatening, disease.

At least 30 different lesions occur in or around the pituitary gland, arising from either the pituitary gland itself (30-1) or the structures that surround it (30-2). These include the cavernous sinus and its contents, arteries (the circle of Willis), cranial nerves, meninges, CSF spaces (the suprasellar cistern and third ventricle), central skull base, and brain parenchyma (the hypothalamus).

Despite the overwhelming variety of lesions that can occur in this region, at least 75-80% of all sellar/juxtasellar masses are due to one of the “Big Five”: Macroadenoma, meningioma, aneurysm, craniopharyngioma (CP), and astrocytoma. All other lesions combined account for < 1/4 of sellar region masses.

We begin the chapter with normal variants, such as physiologic hypertrophy, that can mimic pituitary pathology. Congenital lesions (such as tuber cinereum hamartoma) that can be mistaken for more ominous pathology are also delineated. Pituitary gland and infundibular stalk neoplasms are then discussed. A brief consideration of miscellaneous lesions, such as lymphocytic hypophysitis (LH), pituitary apoplexy (PAP), and the postoperative sella, follows.

The goal of imaging is to determine the precise location and characteristics of a sellar mass, delineate its relationship to—and involvement with—surrounding structures, and construct a reasonable, limited differential diagnosis to help direct patient management. We then conclude the chapter with a summary of—and approach to—a differential diagnosis of sellar masses.

Diagnostic Considerations

Anatomic sublocation is the single most important key to establishing an appropriate differential diagnosis of a sellar region mass. The first step is assigning a lesion to one of three anatomic compartments, identifying it as an (1) intrasellar, (2) suprasellar, or (3) infundibular stalk lesion.

The key to determining anatomic sublocation accurately is the question, “can I find the pituitary gland separate from the mass?” If you cannot, and the gland is the mass, the most likely diagnosis is macroadenoma.

If the mass is clearly separate from the pituitary gland, it is extrapituitary and therefore not a macroadenoma. Other pathologies, such as meningioma in an adult or CP in a child, should be considered in such cases.

Clinical Considerations

The single most important clinical feature in establishing an appropriate differential diagnosis for a sellar region mass is patient age. Lesions that are common in adults (macroadenoma, meningioma, and aneurysm) are generally rare in children. A lesion in a prepubescent child—especially a boy—that looks like a macroadenoma is almost never a neoplasm. Nonneoplastic pituitary gland enlargement in children is much more common than tumors. Therefore, an enlarged pituitary gland in a child is almost always either normal physiologic hypertrophy or nonphysiologic nonneoplastic hyperplasia secondary to end-organ failure (most commonly hypothyroidism).

Some lesions that are common in children (e.g., opticochiasmatic/hypothalamic pilocytic astrocytoma and CP) are relatively uncommon in adults.

Sex is also important. Imaging studies of young menstruating female patients and postpartum women often demonstrate plump-appearing pituitary glands due to temporary physiologic hyperplasia.

Imaging Considerations

Imaging appearance is very helpful in evaluating a lesion of the sellar region. After establishing the anatomic sublocation of a lesion, look for imaging clues. Are other lesions present? Is the lesion calcified? Does it appear cystic? Does it contain blood products? Is it focal or infiltrating? Does it enhance? Does it enlarge or invade the sella turcica?

Normal Imaging Variants

Preamble

A number of variants occur in the pituitary gland and around the sella turcica; these should not be mistaken for disease on imaging studies. Pituitary hyperplasia can be abnormal, but it can also be physiologic and normal. An ES is a common normal variant but can be a manifestation of idiopathic intracranial hypertension (IIH) (pseudotumor cerebri).

Pituitary Hyperplasia

Physiologic increase in pituitary volume is common and normal in many circumstances (30-3). Physiologic hypertrophy of puberty and enlarged pituitary glands in young menstruating female patients is very common (30-4). Pituitary gland enlargement also occurs during pregnancy and lactation or in response to exogenous estrogen treatment.

Pathologic hyperplasia most commonly occurs in response to end-organ failure. Primary hypothyroidism, usually in the setting of longstanding primary hypothyroidism, is the most common cause of pathologic pituitary hyperplasia (30-5). Other etiologies of pathologic pituitary hyperplasia include ectopic excess of releasing hormones that may occur with pancreas tumors, neuroendocrine tumors, pheochromocytomas as well as ACTH-dependent Cushing disease, and other less common conditions.

NECT scans of pituitary hyperplasia show that the superior margin of the gland is convex upward, measuring 10-15 mm in height. There is no evidence of erosion of the bony sella turcica. Enhancement is strong and generally uniform on CECT.

MR demonstrates an enlarged gland that bulges upward and may even contact the optic chiasm. The enlarged pituitary is isointense with cortex on both T1- and T2WI. Dynamic contrast-enhanced MR scans with 2- to 3-mm slice thickness and small FOV show that the gland enhances homogeneously.

Pituitary hyperplasia must be distinguished from macroadenoma. Age, sex, and endocrine status are helpful. Primary neoplasms of the pituitary gland are rare in children, whereas physiologic enlargement is common. Remember: An enlarged pituitary gland in a prepubescent male patient is almost always hyperplasia, not adenoma!

Other important causes of a diffusely enlarged pituitary gland include LH. LH is most common in pregnant and postpartum female patients and may be difficult to distinguish from physiologic hyperplasia on imaging studies alone. Other etiologies include granulomatous, IgG4-related, and drug-related hypophysitis. If stalk enlargement is present, hypophysitis is more likely than hyperplasia.

Intracranial hypotension results in pituitary enlargement above the sella turcica in 50% of patients. These patients typically present with headaches related to decreased intracranial CSF pressure. The classic imaging appearance of intracranial hypotension includes diffuse dural thickening and enhancement, downward displacement of the brain through the incisura (“slumping midbrain”), and distention of the venous structures and dural sinuses. Patients may also present with small subdural hygromas or, rarely, with subdural hematomas. Additional helpful features for diagnosis include a decreased pontomesencephalic angle between the pons and midbrain and a decreased vertical distance between the pons and mammillary bodies, the mamillopontine distance.

Empty Sella

An empty sella (ES)is an arachnoid-lined, CSF-filled protrusion that extends from the suprasellar cistern through the diaphragma sellae into the sella turcica (30-6). An ES is rarely completely “empty”; a small remnant of flattened pituitary gland is almost always present at the bottom of the bony sella (30-7), even if it is inapparent on imaging studies. An ES is identified in ~ 5-10% of cranial MR scans.

The major differential diagnosis of an ES is a suprasellar arachnoid cyst that may herniate into the sella turcica (30-8). The bony sella is often not simply enlarged but eroded and flattened. Sagittal T2WI often shows an elevated, compressed third ventricle draped over the suprasellar arachnoid cyst. The optic chiasm is also typically elevated superiorly by the arachnoid cyst. Although often incidental, when they enlarge, arachnoid cysts may result in mass effect on the pituitary infundibulum and gland.

The other major consideration of patients with an ES is IIH a.k.a. “pseudotumor cerebri.” Both incidental ES and patients with IIH have an increased prevalence in obese female patients. Imaging findings also show some overlap, as both conditions often demonstrate an ES. In IIH, the optic nerve sheaths are often dilated, and the ventricles and CSF cisterns often appear smaller than normal. Patients with IIH will also typically have papilledema, which can be seen on MR as protrusion of the optic nerve papilla into the posterior globes (30-9).

Increased intracranial pressure (↑ ICP) caused by obstructive hydrocephalus usually results in displacement of the enlarged anterior third ventricle recesses—not the suprasellar cistern—toward or into the bony sella. Transependymal CSF migration is common in ↑ ICP but absent in ES.

Congenital Lesions

Pituitary Anomalies

A hypoplastic pituitary gland is the most frequent abnormality in children with isolated growth hormone deficiency, whereas stalk abnormalities are more common in children with multiple hormone deficiencies. Nearly 75% of children with hypopituitarism are male. Many affected have growth hormone deficiency and short stature.

Imaging abnormalities include a small sella and anterior pituitary lobe, hypoplasia or absence of the stalk, and an “ectopic” posterior pituitary “bright spot” (PPBS) seen as displacement of the T1-hyperintense posterior lobe into the infundibulum or median eminence of the hypothalamus (30-10).

Pituitary duplication is a rare anomaly in which two pituitary stalks are present. The tuber cinereum of the hypothalamus and mammillary bodies are fused into a single thick mass. Associated craniofacial and craniocervical anomalies are common in these cases. Female patients are more commonly affected.

Hypothalamic Hamartoma

Hypothalamic hamartoma (HH), a.k.a. diencephalic or  tuber cinereum hamartoma, is a nonneoplastic congenital malformation associated with precocious puberty, behavioral disturbances, and gelastic seizures.

The majority of HHs are located in the tuber cinereum, i.e., between the infundibular stalk anteriorly and the mammillary bodies posteriorly. They can be pedunculated or sessile. Pedunculated lesions extend inferiorly from the hypothalamus into the suprasellar cistern, whereas sessile HHs project from the floor of the third ventricle into its lumen. HHs are solitary lesions that vary in size from a few millimeters to huge mixed solid/cystic lesions measuring several centimeters in diameter.

Most HHs present between 1-3 years of age. 3/4 of patients with histologically verified HHs have precocious puberty, and 50% have seizures, often “gelastic” (ictal laughing fits). Gelastic seizures are more common with sessile tumors, whereas precocious puberty is more often present in patients with small, pedunculated lesions.

NECT scan shows a homogeneous suprasellar mass that is isodense to slightly hypodense compared with brain. HHs do not enhance on CECT.

Pedunculated HHs are shaped like a collar button on sagittal T1WI, extending inferiorly into the suprasellar cistern. Signal intensity is usually isointense to normal gray matter on T1WI and iso- to slightly hyperintense on T2/FLAIR (30-13A). Intralesional cysts may be present in larger HHs. HHs do not enhance with contrast (30-13B). If contrast enhancement is present, a more aggressive neoplastic lesion should be considered.

The differential diagnoses of HH are CP and chiasmatic/hypothalamic astrocytoma. CP is the most common suprasellar mass in children. Over 90% of CPs are cystic, 90% calcify, and 90% show nodular and rim enhancement. Optic pathway/hypothalamic pilocytic astrocytoma is the second most common pediatric suprasellar mass. Astrocytomas are hyperintense on T2/FLAIR and often enhance on T1 C+.

Rathke Cleft Cyst

Rathke cleft cyst (RCC) is a benign endodermal cyst of the sellar region, thought to arise from remnants of the fetal Rathke pouch. Approximately 40% are completely intrasellar and 60% are either suprasellar or combined intra- and suprasellar (30-14).

Most RCCs are asymptomatic and discovered incidentally at imaging. Symptomatic RCCs cause pituitary dysfunction, visual disturbances, and headache. Mean age at presentation is 45 years. Most RCCs remain stable and do not change in size or signal intensity. They do not undergo malignant degeneration.

NECT scans show a well-delineated round or ovoid mass within or just above the sella. 3/4 of RCCs are hypodense, 20% are of mixed density, and 5-10% are hyperdense. Calcification is rare. Lack of calcification helps differentiate an RCC from a CP.

Signal intensity varies with cyst contents; 1/2 of RCCs are hypointense on T1WI and 1/2 are hyperintense (30-15). The majority are hyperintense on T2WI (30-16), whereas 25-30% are iso- to hypointense. A hypointense intracystic nodule occurs in 40-75% of cases (30-16). RCCs are almost always hyperintense on FLAIR. An enhancing rim (claw sign) of compressed pituitary gland can often be seen surrounding the nonenhancing cyst on T1 C+(30-17).

The major differential diagnosis of RCC is an adamantinomatous CP. Calcifications are common in CP. The rim or nodular enhancement in CP is generally thicker and more irregular than the “claw” of enhancing pituitary gland that surrounds the nonenhancing RCC. A cystic pituitary adenoma—especially a nonfunctioning cystic microadenoma—can be difficult to distinguish from a small intrasellar RCC.

Other nonneoplastic cysts that can occur in the sellar region are dermoid (fat, calcification common) and epidermoid cysts (ECs) (rarely midline, usually CSF-like, DWI hyperintense), arachnoid cysts (larger, CSF-like, lacking an intracystic nodule), and inflammatory cysts (e.g., neurocysticercosis; multiple far more prevalent than solitary cysts).

Neoplasms

Pituitary Adenomas

Terminology

Pituitary adenomas, now a.k.a. pituitary neuroendocrine tumors (PitNET) according to the new 2021 WHO classification, are adenohypophysial tumors composed of secretory cells that produce pituitary hormones. Microadenomas are defined as tumors ≤ 10 mm in diameter, whereas larger adenomas are designated macroadenomas (30-18)(30-19)(30-20).

Pathology

Location

Adenomas/PitNETs arise from the adenohypophysis. Specific sublocation follows the normal distribution of peptide-containing cells. Prolactinomas and growth-hormone-secreting tumors—the two most common pituitary adenomas—tend to arise laterally within the adenohypophysis, whereas thyroid-stimulating hormone (TSH)- and ACTH-secreting tumors are more often midline.

Size and Number

These adenomas/PitNETs vary in size from microscopic lesions to giant tumors that invade the skull base and extend into multiple cranial fossae.

Gross Pathology

Macroadenomas/PitNETs are red-brown, lobulated masses that often bulge upward through the opening of diaphragma sella (30-19) or, less commonly, extend laterally toward the cavernous sinus. Approximately 1/2 of macroadenomas/PitNETs contain cysts &/or hemorrhagic foci. These are typically nonaggressive tumors with low recurrence rates. However, when there is craniospinal dissemination &/or systemic metastases, these are called pituitary carcinomas. These carcinomas are rare, representing < 0.5% of all pituitary adenomas/PitNETs.

Clinical Issues

Epidemiology

Pituitary adenomas/PitNETs are among the most common of all CNS neoplasms, accounting for 10-15% of primary intracranial neoplasms. Microadenomas are much more common than macroadenomas; clinically silent incidental microadenomas are identified in 15-25% of autopsies.

Peak age of presentation is between 4th-7th decades. Only 2% of pituitary adenomas/PitNETs are found in children. Most of these occur in adolescent girls. Pituitary adenomas/PitNETs in prepubescent boys are very rare.

Presentation

Almost 2/3 of pituitary adenomas/PitNETs secrete a hormone (~ 40-50% prolactin, 10% growth hormone, 6% corticotropin, 1% thyrotropin) and cause typical hypersecretory syndromes. 1/3 do not produce hormones and are referred to as “nonfunctioning” or “null cell” adenomas/PitNETs.

Macroadenomas generally present with mass effect. Headache and visual disturbances are common. Diabetes insipidus is rarely associated with pituitary adenoma/PitNETs, so its presence should prompt consideration of an alternative diagnosis.

Although pituitary adenoma/PitNET growth rates are quite variable, most enlarge slowly over a period of years. Malignant degeneration into pituitary carcinoma is exceptionally rare and is diagnosed when craniospinal spread or distant metastases are identified. Treatment options are numerous and range from medical treatment to surgical resection and radiation therapy. Chemotherapy is reserved for pituitary carcinomas.

Imaging

General Features

A sellar or combined intra- and suprasellar mass that cannot be identified separately from the pituitary gland (the mass is the gland) is the most characteristic imaging finding.

CT Findings

Pituitary adenomas/PitNETs demonstrate variable attenuation on NECT scans. Macroadenomas are usually isodense with gray matter, but cysts (15-20%) and hemorrhage (10%) may be seen. Calcification is rare (< 2%). Moderate but heterogeneous enhancement of macroadenomas/PitNETs is typical on CECT.

Bone CT may show an enlarged, remodeled sella turcica. “Giant” pituitary adenomas/PitNETs may erode and extensively invade the skull base (30-24).

MR Findings

Macroadenomas

Macroadenomas are usually isointense with cortex on T1WIs (30-22). Small cysts and hemorrhagic foci are common. Fluid-fluid levels can be present but are more common in patients with pituitary apoplexy (PAP).

Adenomas are generally isointense with gray matter on T2WI but can also demonstrate heterogeneous signal intensity (30-23). Hemorrhagic adenomas “bloom” on T2* sequences.

Most macroadenomas enhance strongly but heterogeneously on T1 C+(30-22). Subtle dural thickening (a dural “tail”) is present in 5-10% of cases.

Approximately 10% of pituitary adenomas invade the cavernous sinus, which often prevents complete surgical resection. There are several classification systems used to evaluate cavernous sinus invasion. The Knosp system assesses the impact of the tumor on the lateral cavernous sinus and encasement of the internal carotid artery (ICA), based on MR findings. The Knosp classification includes five grades: Grade 0 (normal) to grade 4 (complete encasement of cavernous ICA). A higher grade implies higher likelihood of cavernous sinus invasion, which translates into greater surgical risk and lower likelihood of gross total resection. MR imaging findings of tumor between the lateral cavernous carotid artery and the lateral dural sinus wall is a reliable feature of cavernous sinus invasion (30-21)(30-23)(30-24).

Microadenomas

Unless they hemorrhage, small microadenomas may be inapparent or mildly hypointense on standard nonenhanced sequences (30-25). Many microadenomas appear slightly hypointense on T1 C+(30-26)(30-27), as they enhance less than the normal pituitary gland, which lacks a blood-brain barrier. Others enhance more strongly and may become isointense with the enhancing pituitary gland, rendering them virtually invisible on delayed postcontrast imaging.

Microadenomas enhance more slowly than the normal pituitary tissue. This discrepancy in enhancement timing can be exploited by using thin-section coronal dynamic contrast-enhanced scans. Fast image acquisition during contrast administration can often discriminate between the slowly enhancing microadenoma and rapidly enhancing normal gland. Between 10-30% of microadenomas are seen only on dynamic T1 C+ imaging.

Differential Diagnosis

The major differential diagnosis of pituitary macro adenoma is pituitary hyperplasia. Tumors that can resemble pituitary adenoma/PitNETs include meningioma, metastasis, and CP. Meningioma of the diaphragma sellae can usually be identified as clearly separate from the pituitary gland below with different signal intensity and enhancement than the pituitary gland. Meningiomas also typically have an enhancing dural tail and avid homogeneous enhancement.

Metastasis to the stalk &/or pituitary gland from an extracranial primary neoplasm is uncommon. Lung, breast, and systemic lymphoma are the most common sources. Lymphoma involving the sellar region is often infiltrative and may show low T2 signal.

Adamantinomatous CP is the most common suprasellar tumor of childhood, whereas pituitary adenomas/PitNETs in children are rare. Papillary CPs in middle-aged adults are typically solid papillary tumors that infrequently calcify. In adults with CP, the pituitary gland can usually be identified as anatomically separate from the mass.

Nonneoplastic entities that can mimic macroadenoma include hypophysitis and, rarely, aneurysm. An aneurysm arises eccentrically from the circle of Willis and is usually not in the midline. Flow voids are typically present on MR.

Pituitary micro adenoma may be difficult to distinguish from incidental nonneoplastic intrapituitary cysts, such as RCC or pars intermedia cyst. Microadenomas enhance; cysts are seen as nonenhancing foci within the intensely enhancing pituitary gland. A cystic microadenoma cannot be reliably distinguished from other benign pituitary cysts.

Pituitary Carcinoma

Pituitary carcinomas are rare and represent between 0.12-0.4% of all pituitary tumors. They are characterized by craniospinal dissemination &/or systemic metastases. Pituitary carcinomas do not have unique imaging features and may be indistinguishable from an invasive, but histologically typical, adenoma. Diagnosis is made at time of craniospinal metastases or systemic tumor spread.

Pituitary Blastoma

Pituitary blastoma is a very rare tumor that usually occurs in children under two years of age. It is an embryonal neoplasm of the sellar region composed of three types of cells: Primitive blastema cells, neuroendocrine cells, and Rathke pouch epithelium. These tumors are located in the sellar and suprasellar regions, and cavernous sinus invasion is common. Cushing syndrome is one of the most common presenting symptoms.

Germinoma

Germinomas are discussed in detail in Chapter 25. Germinomas of the suprasellar region are classically hyperdense on CT, similar to lymphoma. When involving the pituitary axis, a germinoma involves the infundibulum &/or neurohypophysis and often presents in a child with an absent PPBS. T2 hypointensity and diffuse enhancement of an enlarged infundibulum/anterior third ventricle is the typical MR appearance. Diffusion restriction on DWI is typical.

Craniopharyngioma

Terminology and Etiology

Craniopharyngioma (CP) is a benign, often partly cystic sellar/suprasellar mass that probably arises from epithelial remnants of Rathke pouch.

Pathology

Completely intrasellar CPs are rare. CPs are primarily suprasellar tumors (75%). A small intrasellar component is present in 20-25% of cases. Occasionally, CPs (especially the papillary type) arise mostly or entirely within the third ventricle.

Lesions > 5 cm are common. Giant CPs may extend into both anterior and middle cranial fossae. Posteroinferior extension between the clivus and pons down to the foramen magnum can be seen in exceptionally large lesions.

Two types of CPs are recognized: Adamantinomatous (90%) and papillary (10%). The typical gross appearance of an adamantinomatous CP is that of a multilobulated, partially solid, but mostly cystic, suprasellar mass (30-28). Multiple loculated cysts are common. The cysts often contain dark, viscous, “machinery oil” fluid rich in cholesterol crystals (30-29). Adamantinomatous CPs often adhere to adjacent structures, such as the hypothalamus.

Papillary CP is usually a discrete encapsulated mass with a smooth surface that does not adhere to adjacent brain. Papillary CPs are often solid with a cauliflower-like configuration (30-34). When they contain cysts, the fluid is clear (unlike the “machinery oil” cholesterol-rich contents of adamantinomatous CPs).

Both adamantinomatous and papillary CPs are WHO grade 1 neoplasms. MIB-1 is low.

Clinical Issues

CP is the most common nonglial neoplasm in children, accounting for 6-10% of all pediatric brain tumors and slightly > 1/2 of suprasellar neoplasms.

CPs occur nearly equally in children and adults. Adamantinomatous CPs have a bimodal age distribution with a large peak at 5-15 years and a second, smaller peak at 45-60 years. CPs are rare in newborns and infants; only 5% arise in patients between birth and five years of age. Papillary CPs almost always occur in adults with a peak incidence at 30-59 years.

Patients most commonly present with visual disturbances, either with or without accompanying headache. Endocrine deficiencies, including growth failure, delayed puberty, and diabetes insipidus, are common.

CPs are slow-growing neoplasms with a propensity to recur following surgery. More than 85% of patients survive at least three years following diagnosis. However, the recurrence rate at 10 years approaches 20-30%, even in patients with gross total resection.

Imaging

General Features

A partially calcified, mixed solid/cystic extraaxial suprasellar mass in a child is the classic appearance of adamantinomatous CP. A compressed, displaced pituitary gland can sometimes be identified as separate from the mass. If the mass is large, associated hydrocephalus may be present.

CT Findings

Adamantinomatous CPs follow a “rule of 90,” i.e., 90% are mixed cystic/solid, 90% are calcified, and 90% enhance (30-30). Papillary CPs rarely calcify. They are often solid or mostly solid (30-35).

MR Findings

Signal intensity varies with cyst contents (30-31). Multiple cysts are common, and intracystic fluid within each cyst varies from hypo- to hyperintense compared with brain on T1WI (30-33).

CP cysts are variably hyperintense on T2WI and FLAIR. The solid nodule is often calcified and moderately hypointense. Hyperintensity extending along the optic tracts is common and usually represents edema, not tumor invasion. Cyst walls and solid nodules typically enhance following contrast administration (30-31C).

MRS shows a large lipid-lactate peak, characteristic of the cholesterol and lipid constituents of a CP. pMR shows low rCBV.

Differential Diagnosis

The major differential diagnosis of CP is Rathke cleft cyst (RCC). RCCs do not calcify, appear to be much less heterogeneous, and do not show nodular enhancement. RCCs often have an intracystic nodule. The ADC of RCC is significantly increased compared with that of cystic CPs. Immunohistochemistry is helpful, as RCCs express specific cytokeratins that CPs do not.

Hypothalamic/chiasmatic astrocytoma is usually a solid suprasellar mass that is clearly intraparenchymal. Calcifications and cysts are uncommon. These tumors are T2 hyperintense and have variable enhancement.

Pituitary adenoma is rare in prepubescent children (peak age period for CP). A dermoid cyst can be hyperintense on T1WI related to lipid contents and may demonstrate calcification. Dermoid cysts may present with rupture into the subarachnoid spaces. An epidermoid cyst (EC) is usually off-midline with DWI restriction. Suprasellar ECs are uncommon. Neither dermoid cysts nor ECs enhance.

Nonadenomatous Pituitary Tumors

The 2021 WHO recognizes three rare, histologically distinct pituitary region neoplasms: Pituicytoma, spindle cell oncocytoma (SCO), and granular cell tumor of the sellar region. These three tumors constitute a distinct family of low-grade neoplasms that arise from pituicytes, modified glial cells that reside in the posterior pituitary or infundibulum (30-36). They all show expression of thyroid transcription factor 1 (TTF-1). These tumors likely represent a spectrum of a single nosologic entity. All are WHO grade 1 tumors. These tumors arise in adults in the fifth and sixth decades of life. Most patients present with headaches, visual disturbances, or panhypopituitarism and rarely present with diabetes insipidus. These tumors are slow growing and typically curable by surgical resection.

Pituicytoma arises from modified glial cells (“pituicytes”) that reside in the infundibular stalk and neurohypophysis. The majority of pituicytomas are isointense with brain on T1WI and hyperintense on T2WI. They usually arise along the infundibulum or neurohypophysis and enhance homogeneously following contrast enhancement (30-36A). Imaging may mimic an adenoma.

Like pituicytoma, granular cell tumor is a tumor of the neurohypophysis and may be asymptomatic. Granular cell tumors are typically suprasellar masses. They are hyperdense on NECT and isointense with brain on both T1- and T2WI. Granular cell tumors enhance strongly and homogeneously following contrast administration (30-36B).

SCO has imaging findings that are similar to—and cannot be distinguished from—those of pituitary adenoma/PitNET, pituicytoma, or LH. These tumors are typically sellar and suprasellar (30-36C). They are reportedly highly vascular.

Miscellaneous Lesions

Hypophysitis

Hypophysitis is an inflammation of the pituitary gland. There are two main histologic forms of hypophysitis: Lymphocytic hypophysitis (LH) (30-37)and non-LH. We focus on LH, the most common form. We then briefly discuss non-LH, including granulomatous hypophysitis, and some of the newly described entities that are often characterized by plasma cell infiltrates.

Lymphocytic Hypophysitis

LH is also called lymphocytic adenohypophysitis, primary hypophysitis, and stalkitis. LH is an uncommon autoimmune inflammatory disorder of the pituitary gland (30-37). Between 80-90% of patients with LH are female; 30-60% of cases occur in the peripartum period.

The most common presenting symptoms are headache and multiple endocrine deficiencies with partial or total hypopituitarism. Diabetes insipidus is common. ACTH deficits often appear first. Hyperprolactinemia occurs in 1/3 of all patients, probably secondary to stalk compression known as “stalk effect.”

Imaging shows a combined intra- and suprasellar mass with a thickened, nontapering infundibular stalk (30-37)(30-39). A rounded, symmetrically enlarged pituitary gland is common. The sellar floor is intact, not expanded or eroded. The posterior pituitary “bright spot” (PPBS) is absent in 75% of cases. LH enhances intensely and uniformly.

The major differential diagnosis for LH is nonsecreting pituitary macroadenoma. The distinction is important, as treatment differs significantly. LH is often treated medically, unless there is significant potential for vision loss, whereas surgical resection is the primary treatment for pituitary macroadenoma. Macroadenomas can be giant, but LH only occasionally exceeds 3 cm in diameter. Clinical findings are also helpful, as LH commonly presents with diabetes insipidus.

The stalk is usually normal in pituitary hyperplasia, although patient age and sex are similar. Metastasis usually occurs in older patients with known systemic primary tumor.

Granulomatous hypophysitis may occur secondary to infection, sarcoidosis, or Langerhans cell histiocytosis. Granulomatous hypophysitis is less common than LH, has a different epidemiologic profile, and tends to enhance more heterogeneously. IgG4-and drug-related hypophysitis are very rare. Imaging features are similar to classic hypophysitis (30-38).

Granulomatous Hypophysitis

Granulomatous hypophysitis has different epidemiologic characteristics than LH does. Granulomatous hypophysitis is equally common in both sexes, and there is no association with pregnancy.

Granulomatous hypophysitis can be primary (idiopathic) or secondary. Secondary granulomatous hypophysitis is far more common than primary granulomatous hypophysitis and typically results from necrotizing granulomatous inflammation. Infectious/inflammatory secondary granulomatous hypophysitis can be caused by TB, sarcoid, fungal infection, syphilis, Langerhans cell histiocytosis, Wegener granulomatosis, Erdheim-Chester disease, granulomatous autoimmune hypophysitis, ruptured RCC, or CP. Secondary granulomatous hypophysitis may also occur as a reaction to systemic inflammatory disorders, such as Crohn disease. Imaging findings are nonspecific, resembling those of LH or pituitary adenoma.

Primary granulomatous hypophysitis is a rare inflammatory disease without identifiable infectious organisms. The precise etiology of primary granulomatous hypophysitis is unknown. Nonnecrotizing granulomas with multinucleated giant cells, histiocytes, and various numbers of plasma cells and lymphocytes are typical. Primary granulomatous hypophysitis usually presents with diabetes insipidus. A symmetric sellar mass that enhances strongly but heterogeneously is seen on imaging studies.

Other Hypophysitis Variants

A number of new hypophysitis variants have been recently described. IgG4-related hypophysitis has a marked mononuclear infiltrate mainly characterized by increased numbers of IgG4-positive plasma cells. Imaging findings resemble those of lymphocytic infundibuloneurohypophysitis. The pituitary stalk and posterior pituitary lobe are enlarged and enhance intensely following contrast administration.

Drug-related hypophysitis has been reported in cases of cancer immunotherapy with antibodies that stimulate T-cell responses (e.g., ipilimumab) (30-38). Clinicians and radiologists should be aware of autoimmune-induced hypophysitis as a complication of new treatments. Imaging of drug-related hypophysitis usually shows enlargement of the pituitary gland with or without infundibulum.

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis is discussed in detail in Chapter 29. Langerhans cell histiocytosis typically presents with diabetes insipidus. The typical patient is under two years of age.

The classic imaging of Langerhans cell histiocytosis of the pituitary axis is an absent PPBS with a thickened, enhancing pituitary infundibulum (30-40). Langerhans cell histiocytosis may also present as a sellar and suprasellar mass. The major differential diagnosis of Langerhans cell histiocytosis in a child is germinoma. In an adult, the major differential diagnosis of Langerhans cell histiocytosis affecting the pituitary axis is neurosarcoid or hypophysitis.

Neurosarcoid

Neurosarcoid is a multisystem inflammatory disease characterized by noncaseating epithelioid cell granulomas. Neurosarcoid is discussed in more detail in Chapter 15. Neurosarcoid may present as diffuse or focal dural (pachymeningeal) &/or leptomeningeal thickening and enhancement, pituitary infundibulum &/or hypothalamic thickening and enhancement, cranial nerve enhancement, brain parenchymal lesions, or, less commonly, choroid plexus lesions.

The main differential diagnoses for pituitary axis neurosarcoid are LH, lymphoma, and metastatic disease.

INFUNDIBULAR STALK MASSES

Adults

• Neurosarcoid (isolated stalk lesion rare)

• Hypophysitis (“stalkitis”)

• Metastasis

• Lymphoma

• Pituicytoma

• IgG4-related disease

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