(25-40) Sagittal section through the pituitary gland shows the anterior and posterior pituitary lobes, as well as the infundibular stalk connecting the hypothalamus to the neurohypophysis. (Courtesy A. Ersen, MD, B. Scheithauer, MD.)

nodular enhancement in craniopharyngioma 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. Both rarely calcify; both are common etiologies for pituitary "incidentalomas" on MR scans. Neither requires treatment, so the distinction is largely academic.

Other nonneoplastic cysts that can occur in the sellar region are dermoid (fat, calcification common) and epidermoid cysts (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).

RATHKE CLEFT CYST

Etiology and Pathology

•Remnant of embryonic Rathke cleft

•Intrasellar (40%), suprasellar (60%)

•Contents vary (CSF-like to thick mucoid)

•Endodermal lining + goblet cells

Imaging

•Hypointense (50%), hyperintense (50%) on T1WI

•Hyperintense on T2/FLAIR

•Look for

○Intracystic nodule (40-75%)

○"Claw" of enhancement representing stretched normal pituitary gland

(25-41) Graphic depicts location of anterior pituitary lobe cells. Lateral wings contain mainly GH and PRL cells. Corticotrophs (ACTH) and thyrotrophs (TSH) are in the median mucoid wedge. FSH/LH cells are distributed diffusely.

Neoplasms

Pituitary Adenomas

Terminology

Pituitary adenomas are adenohypophysial tumors composed of secretory cells that produce pituitary hormones (25-40) (25-41). Microadenomas are defined as tumors ≤ 10 mm in diameter, whereas larger adenomas are designated macroadenomas (25-42) (25-43) (25-44) (25-45).

Etiology

General Concepts. Cells with multipotent progenitor/stem- cell-like properties have been identified in the adult pituitary gland and may play a key role in tumorigenesis. Alterations in the normal microenvironment of pituitary stem cells may trigger uncoordinated proliferation and subsequent formation of pituitary adenomas.

Genetics. Adenomagenesis is a multistep, multicausal process that includes both initiation and progression phases. A number of activated oncogenes and loss of tumor suppressor gene functions are involved. In addition, several endocrine factors at either the hypothalamic or systemic level may induce adenohypophysial cell proliferation.

Mutations in the aryl hydrocarbon receptor-interacting protein gene (AIP) have been identified in patients with familial isolated pituitary adenoma syndrome (see below) but are rare in patients with sporadic pituitary adenomas.

Familial Pituitary Tumor Syndromes. Most pituitary adenomas are sporadic tumors and occur in adults. Approximately 5% of all pituitary adenomas are familial.

Four recognized inherited familial tumor syndromes with specific identified genetic defects are associated with pituitary adenomas: multiple endocrine neoplasia type 1 (MEN1), Carney complex, McCune-Albright syndrome (MAS), and familial isolated pituitary adenoma (FIPA) syndrome.

MEN1 is an autosomal-dominant disease with highly penetrant germline mutations that predisposes patients to develop tumors in hormone-secreting cells. MEN1 is characterized by combinations of more than 20 different endocrine and nonendocrine tumors. Pituitary tumors occur in 15-40% of MEN1 patients. MEN1-associated adenomas are often plurihormonal (most commonly secreting prolactin and growth hormone, GH), larger, and more invasive neoplasms.

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Carney complex is associated with spotty skin pigmentation, myxomas, endocrine tumors, and schwannomas. Adrenal involvement causing adrenocorticotrophic hormone (ACTH)- independent Cushing syndrome is seen in one-third to onehalf of patients with Carney complex. GH-producing pituitary tumors are seen in 10%.

MAS is defined by the triad of gonadotropin-independent sexual precocity, café au lait skin lesions, and fibrous dysplasia. Tumors or nodular hyperplasia of a number of endocrine glands lead to hypersecretory syndromes such as acromegaly, hyperprolactinemia, and Cushing syndrome. MAS is caused by a postzygotic mutation in the GNAS gene.

FIPA is a recently described condition in which affected family members develop only pituitary tumors. It includes familial pituitary tumors that are not associated with MEN1 and Carney complex.

Prolactinomas are found in 40% of all FIPA patients, somatotropinomas in 30%, and nonsecreting adenomas in 13%. In general, pituitary tumors in FIPA present earlier than sporadic pituitary adenomas, are significantly larger, and more often demonstrate cavernous sinus invasion.

Two FIPA subgroups have been identified based on genetic and phenotypic features. In 15-25% of cases, affected families have AIP gene mutations and autosomal-dominant inheritance. They typically develop growth hormone-secreting adenomas and prolactinomas, often in childhood. The second, much larger group has adult-onset disease and more varied types of adenoma. To date, no causative gene has been identified.

Pathology

Location. With rare exceptions, adenomas arise within the sella turcica. Reported ectopic sites include the sphenoid sinus (the most common site), nasopharynx, third ventricle, and suprasellar cistern. Such cases are designated ectopic pituitary adenoma.

Adenomas arise from the adenohypophysis. Specific sublocation follows the normal distribution of peptidecontaining 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. Adenomas vary in size from microscopic lesions (25-50A) (25-50B) to giant tumors more than 5 cm that invade the skull base and extend into multiple cranial fossae. Pituitary adenomas are usually solitary lesions. Multiple synchronous pituitary adenomas are unusual. "Double" or even "triple" adenomas are found in 1% of autopsies but rarely diagnosed on preoperative MR scans.

Gross Pathology. Macroadenomas are red-brown, lobulated masses that often bulge upward through the opening of diaphragma sella (25-43) or, less commonly, extend laterally toward the cavernous sinus. Approximately half of macroadenomas contain cysts and/or hemorrhagic foci.

Microscopic Features. Histologic examination shows a uniform population of round, polygonal, or elongated cells

(25-46) Series of MRs shows a small macroadenoma that measured 12 mm in height. The mass is isointense with GM on T1and T2WI and enhances strongly and uniformly .

with moderately abundant cytoplasm and inconspicuous nucleoli. Cellular atypia is uncommon, and mitoses are rare.

Staging, Grading, and Classification. Adenoma classification is now based on immunohistochemical profile and clinical presentation. The "tinctorial" characteristics of cells as seen on H&E preparations ("acidophilic," "basophilic," "chromophobic") are not precisely correlated with specific hormone production and are no longer used as diagnostic terms.

Pituitary adenomas are almost all WHO grade I tumors. MIB-1 and p53 immunoreactivity correlate with tumor invasion but do not indicate malignant transformation. Most adenomas are "typical" lesions with both MIB-1 and p53 under 3%. Adenomas with elevated MIB-1 greater than 3%, increased mitoses, and extensive p53 staining are considered atypical adenomas and correlate with early recurrence and more rapid regrowth (25-54).

Clinical Issues

Epidemiology. Pituitary adenomas are among the most common of all CNS neoplasms, accounting for 10-15% of primary intracranial neoplasms. Approximately 60% of patients undergoing surgery have macroadenomas, and 40% have microadenomas. However, microadenomas are much more common than macroadenomas at autopsy. Clinically silent incidental microadenomas are identified in 15-25% of autopsies.

Demographics. Peak age of presentation is between the fourth and seventh decades. Only 2% of pituitary adenomas are found in children. Most of these occur in adolescent girls. PAs in prepubescent boys are very rare.

(25-47) Sagittal T1WI , T2WI , FLAIR , and T1 C+ show a very large "snowman" or "figure eight" sellar and suprasellar mass. The pituitary gland cannot be identified as separate from the mass (macroadenoma).

Presentation. Almost two-thirds of pituitary adenomas secrete a hormone (~ 40-50%% prolactin, 10% GH, 6% corticotropin, 1% thyrotropin) and cause typical hypersecretory syndromes. The remaining one-third do not produce a hormone and are referred to as nonfunctioning (or nonsecreting or null cell) adenomas (Table 25-1).

Female patients with prolactinomas present with amenorrhea-galactorrhea syndrome, whereas male patients present with hypogonadism and impotence. GH-secreting tumors cause acromegaly in adults and gigantism in children. Patients with corticotroph tumors present with Cushing disease or Nelson syndrome (rapid enlargement of an adenoma following bilateral adrenalectomy). TSH-secreting adenomas cause hyperthyroidism.

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

Natural History and Treatment. Although pituitary adenoma growth rates are quite variable, most enlarge slowly over a period of years. Malignant transformation is exceptionally rare.

Treatment options are numerous and include surgical resection, medical management, stereotactic radiosurgery, and conventional radiation therapy. Management strategy should be individualized for each patient.

Imaging

General Features. A sellar or combined intraand suprasellar mass that cannot be identified separately from the pituitary

(25-48) Lobulated, invasive sellar/suprasellar mass has multiple medium/small-sized T2 hyperintense cysts . Macroadenoma also invades the right cavernous sinus .

gland—the mass is the gland—is the most characteristic imaging finding.

CT Findings. Bone CT may show an enlarged, remodeled sella turcica. The lamina dura of the sellar floor is generally intact. Note, however, that "giant" pituitary adenomas may erode and extensively invade the skull base, mimicking metastasis or aggressive infection.

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

MR Findings

Macroadenomas. Macroadenomas are usually isointense with cortex (25-46) (25-47). The posterior pituitary "bright spot" is absent (20%) or displaced into the supradiaphragmatic cistern (80%) on T1-weighted sagittal scans. Small cysts and hemorrhagic foci are common. Fluid-fluid levels can be present but are more common in patients with pituitary apoplexy.

Adenomas are generally isointense with gray matter on T2WI but can also demonstrate heterogeneous signal intensity (2548). Hyperintensity along the optic pathways on T2/FLAIR occurs in 15-20% of cases in which macroadenomas compress the optic chiasm. Hemorrhagic adenomas "bloom" on T2*.

Most macroadenomas enhance strongly but heterogeneously on T1 C+ (25-49). Subtle dural thickening (a dural "tail") is present in 5-10% of cases.

(25-49) Bone CT (top left), CECT (top right) show a huge invasive pituitary macroadenoma . CECT, sagittal T1WI, coronal T1 C+ FS all show trapped pools of CSF adjacent to the tumor.

These are nonneoplastic peritumoral cysts.

Microadenomas. Unless they hemorrhage, small microadenomas may be inapparent on standard nonenhanced sequences. Many microadenomas appear slightly hypointense on T1 C+ (25-51) (25-52). Others enhance more strongly and may become isointense with the enhancing pituitary gland, rendering them virtually invisible.

Microadenomas enhance more slowly than the normal pituitary tissue. This discrepancy in enhancement timing can be exploited by using thin-section coronal dynamic contrastenhanced 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 (25-53).

Angiography. CTA in patients with suprasellar extension of macroadenoma may show the supraclinoid internal carotid and anterior choroidal arteries displaced laterally. DSA may demonstrate an enlarged meningohypophyseal trunk with prolonged vascular "stain" or "blush" in the tumor.

Cavernous/inferior petrosal venous sampling may be helpful in evaluating patients with ACTH-dependent Cushing syndrome.

Differential Diagnosis

The differential diagnosis of pituitary adenoma varies with size and patient demographics.

Pituitary Macroadenoma. The major differential diagnosis of pituitary macroadenoma is pituitary hyperplasia. Between 25 and 50% of endocrinologically normal women who are 18-35 years old have an upwardly convex pituitary gland on MR or CT examination. The height of the gland is usually at least 10

mm unless the patient is pregnant or lactating. Less commonly, end-organ failure (such as hypothyroidism) results in compensatory pituitary enlargement. As adenomas are very rare in children, if a prepubescent female patient or young male patient has an "adenoma-looking" pituitary gland, endocrine work-up is mandatory!

Tumors that can resemble pituitary adenoma include meningioma, metastasis, and craniopharyngioma. Meningioma and metastasis are very rare in children. Meningioma of the diaphragma sellae can usually be identified as clearly separate from the pituitary gland below. Additionally, a dural tail and diffuse avid enhancement may be seen. True isolated intrasellar meningiomas are very rare.

Metastasis to the stalk and/or pituitary gland from an extracranial primary neoplasm is uncommon. Lung and breast are the most common sources. Most pituitary metastases are secondary to spread from adjacent bone or the cavernous sinus, generally occurring as a late manifestation of known systemic tumor. Hematogeneous metastases to the pituitary gland do occur but are rare. CNS metastases elsewhere in the brain are common but not invariably present.

Craniopharyngioma is the most common suprasellar tumor of childhood, whereas pituitary adenomas in children are rare. Craniopharyngiomas in middle-aged adults are typically solid papillary tumors that do not calcify as the adamantinomatous ones do. Often in adults with craniopharyngioma, the pituitary gland can be identified as anatomically separate from the mass.

Pituitary carcinoma is exceedingly rare (see below). Because of this rarity, even the most aggressive-looking pituitary tumors are statistically far more likely to be adenomas than carcinomas.

Nonneoplastic entities that can mimic macroadenoma include aneurysm and hypophysitis. An aneurysm arises eccentrically from the circle of Willis and is usually not in the midline directly above the sella. Paramedian saccular aneurysms are hyperdense on NECT and may demonstrate rim calcification, whereas pituitary adenomas rarely calcify. A "flow void" with or without laminated clot along the aneurysm wall is common on MR.

Hypophysitis is much less common than macroadenoma but can appear virtually identical to an adenoma on imaging studies. Lymphocytic hypophysitis—the most common type—typically occurs in peripartum or postpartum female patients or as an autoimmune hypophysitis in patients treated with immunomodulating therapies (e.g., ipilimumab for metastatic malignant melanoma).

Pituitary Microadenoma. Pituitary microadenoma may be difficult to distinguish from incidental nonneoplastic intrapituitary cysts such as Rathke cleft cyst or pars intermedia cyst. Microadenomas enhance; cysts are seen as nonenhancing foci within the intensely enhancing pituitary gland. A small hemorrhagic microadenoma may appear identical to a Rathke cleft cyst that contains proteinaceous fluid, as both are hyperintense on T1WI.

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PITUITARY ADENOMA: IMAGING AND DDx

CT

•Sella usually enlarged, remodeled, cortex intact

•Invasive adenomas erode, destroy bone

•Majority are isodense with brain

○Cysts (15-20%)

○Hemorrhage (10%)

○Ca++ rare (1-2%)

MR

•Usually isointense with cortex

•Heterogeneous signal intensity common (cysts, hemorrhage)

•Strong, heterogeneous enhancement

•10-30% of microadenomas seen only with dynamic T1 C+

Differential Diagnosis

•Pituitary hyperplasia (know patient age, sex!)

○Physiologic (young/pregnant/lactating female patients)

○Nonphysiologic (end-organ failure)

•Other tumors

○Meningioma, craniopharyngioma, metastasis

○Pituitary carcinoma exceptionally rare

○Aggressive-looking adenoma is almost never malignant!

•Nonneoplastic lesions

○Aneurysm

○Hypophysitis

Pituitary Carcinoma

Pituitary carcinoma (PCa) is very rare, representing less than 0.2% of all operated adenohypophysial neoplasms. Its estimated prevalence is 4 per 1 million person-years. Most PCas arise as metastases from multiple recurring invasive adenomas; de novo malignancy is unusual. Survival is inversely proportionate with increasing age.

Conventional histologic criteria for malignancy (necrosis, nuclear atypia, pleomorphism, mitotic activity) are insufficient for diagnosis. A true PCa must exhibit either frank brain invasion or CSF/systemic metastases (25-55).

PCa has no unique imaging features and may be indistinguishable from an invasive but histologically typical adenoma. Only documentation of craniospinal metastases or systemic tumor spread can confirm the diagnosis.

Pituitary Blastoma

Pituitary blastoma is a recently described pituitary tumor in neonates and infants characterized by large glandular structures that resemble Rathke epithelium and adenohypophysial cells. Arrested pituitary development and unchecked proliferation are the likely etiology of this unusual tumor.

Histology shows small undifferentiated blastema-like cells interspersed with large pituitary secretory cells. Mitotic activity is variable. Imaging findings are nonspecific and

(25-58) Sagittal graphic shows a predominantly cystic, partially solid suprasellar mass with focal rim calcifications. Note the small intrasellar component and fluid-fluid level. The fluid, rich in cholesterol, is dark and viscous.

resemble those of macroadenoma. The few described cases show a heterogeneously enhancing sellar/suprasellar mass, often invading the cavernous sinus.

Lymphoma

Primary CNS lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma restricted to the brain, spinal cord, eye, and meninges. The most common location for primary CNS lymphoma is along a CSF surface, typically in the periventricular white matter. The hypothalamus, infundibulum, and pituitary gland are less common sites for PCNSL. The vast majority of PCNSL is diffuse large B-cell lymphoma (90-95%). PCNSL is discussed in more detail in Chapter 24. This section will focus on the pituitary axis.

Imaging of PCNSL varies with immune status. In the immunocompetent patient, PCNSL is hyperdense on CT related to the high nuclear:cytoplasmic ratio. PCNSL is usually isointense or slightly hypointense on T1WI and isointense to gray matter on T2WI. PCNSL shows homogeneous enhancement on postcontrast MR and may appear more infiltrative than the more common pituitary adenoma (25-56). DWI typically shows diffusion restriction related to the high cellularity. PCNSL involving the pituitary axis may affect the infundibulum, pituitary gland, or the hypothalamus. Patients often present with diabetes insipidus or panhypopituitarism.

Germinoma

A germinoma is the most common intracranial germ cell tumor, representing two-thirds of intracranial germ cell tumors and 1-2% of all primary brain tumors. Germinomas are located in the pineal region most commonly (50-65%) and the suprasellar region in approximately 25-35% of cases. Less

(25-59) Sagittal autopsy specimen of adamantinomatous craniopharyngioma shows a small solid intrasellar componentand a large suprasellar cystic component that adheres to adjacent brain . (Courtesy R. Hewlett, MD.)

common locations include the basal ganglia and thalami. Germinomas may present as synchronous pineal and suprasellar masses. Germinomas are tumors of young patients with the vast majority presenting in patients in the first two decades. The peak age at presentation is between 10-12 years old.

Germinomas are WHO grade II tumors that are typically treated with radiation therapy following a biopsy. Germinomas of the suprasellar region most commonly present with diabetes insipidus. Less common presenting signs include visual loss and hypothalamic-pituitary dysfunction with decreased growth and precocious puberty.

Germinomas of the suprasellar region are classically hyperdense on CT, similar to lymphoma. When involving the pituitary axis, a germinoma involves the infundibulum and/or neurohypophysis and often presents in a child with an absent posterior pituitary "bright spot" (25-57). Diffuse enhancement of an enlarged infundibulum 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. The molecular pathogenesis of CP is unknown. Reactivation of the Wnt signaling pathway may be one factor in the pathogenesis of adamantinomatous CPs.

Pathology

Location. Completely intrasellar CPs are rare. CPs are primarily suprasellar tumors (75%). A small intrasellar component is present in 20-25% of cases (25-58). Occasionally, CPs (especially the papillary type) arise mostly or entirely within the third ventricle (25-64).

Size and Number. CPs are solitary lesions that range in size from a few millimeters to several centimeters. Lesions larger than 5 cm are common. Giant CPs may extend into both anterior and middle cranial fossae (25-63). Posteroinferior extension between the clivus and pons down to the foramen magnum can be seen in exceptionally large lesions.

Gross Pathology. Two types of craniopharyngiomas are recognized: adamantinomatous and papillary. About 90% of all CPs are adamantinomatous; 10% are papillary.

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The typical gross appearance of an adamantinomatous CP is that of a multilobulated, partially solid but mostly cystic suprasellar mass (25-59) (25-61). Multiple loculated cysts are common. The cysts often contain dark, viscous, "machinery oil" fluid rich in cholesterol crystals (25-58). The surfaces of adamantinomatous CPs are often irregular and infiltrative, adhering 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. When they contain cysts, the fluid is clear (unlike the "machinery oil" cholesterol-rich contents of adamantinomatous CPs).

Microscopic Features. Adamantinomatous CPs have a peripheral layer of palisading stratified squamous epithelium surrounding nodules of "wet" keratin. Cholesterol "clefts" and squamous debris are typical. Calcification is common.

(25-66A) NECT in a 44y man with headaches and psychiatric symptoms shows a well-defined, hypodense, noncalcified massin the suprasellar cistern.

Papillary CPs have solid sheets of well-differentiated squamous epithelium. Crude epithelial pseudopapillae form around fibrovascular stromal cores. Occasional goblet cells are present.

Staging, Grading, and Classification. Both adamantinomatous and papillary craniopharyngiomas are WHO grade I neoplasms. MIB-1 is low.

CRANIOPHARYNGIOMA: ETIOLOGY AND PATHOLOGY

Etiology

• Epithelial remnants of Rathke pouch

Pathology

•2 types

○Adamantinomatous (90%)

○Papillary (10%)

○Both are WHO grade I

•Adamantinomatous

○Multiple cysts

○Squamous epithelium, "wet" keratin

○Cholesterol-rich "machinery oil" fluid

•Papillary

○Solid > > cystic (clear fluid)

○Almost always adults (40-55 years old)

Clinical Issues

Epidemiology. CP is the most common nonglial neoplasm in children, accounting for 6-10% of all pediatric brain tumors and slightly more than half of suprasellar neoplasms.

Demographics. CPs occur nearly equally in children and adults. Adamantinomatous CPs have a bimodal age

(25-66B) FLAIR scan shows that the mass does not suppress. Note the hyperintensity in the hypothalamus and optic tracts . Papillary craniopharyngioma was found at surgery. No parenchymal tumor invasion was present.

distribution with a large peak between 5 and 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 5 years of age.

Papillary CPs almost always occur in adults with a peak incidence between 40 and 55 years.

Presentation. Symptoms vary with tumor size and patient age. Patients most commonly present with visual disturbances, either with or without accompanying headache. Large tumors compress the infundibular stalk ("stalk effect") resulting in abnormal pituitary function (often with mild elevation of prolactin). Endocrine deficiencies including growth failure, delayed puberty, and diabetes insipidus are common.

Natural History. CPs are slow-growing neoplasms with a propensity to recur following surgery. More than 85% of patients survive at least 3 years following diagnosis. However, the recurrence rate at 10 years approaches 20-30% even in patients with gross total resection. Recurrence is significantly more common with larger and incompletely excised lesions.

Approximately half of long-term survivors experience reduced quality of life, mostly due to morbid hypothalamic obesity. Spontaneous malignant transformation to squamous cell carcinoma is rare. Most cases of CP malignant degeneration occur in patients with multiple recurrences and prior radiotherapy.

Treatment Options. Gross total resection is the best treatment option. Hypothalamic injury is the major risk, especially with large adamantinomatous CPs.

Imaging

General Features. A partially calcified, mixed solid and cystic extraaxial suprasellar mass in a child is the classic appearance. A compressed, displaced pituitary gland can sometimes be identified as separate from the mass.

CT Findings. Adamantinomatous CPs follow a "rule of ninety," i.e., 90% are mixed cystic/solid, 90% are calcified, and 90% enhance (25-62).

Papillary CPs rarely calcify. They are often solid or mostly solid. When they contain intratumoral cysts, the cysts are usually smaller and less complexappearing than those seen with adamantinomatous CPs.

MR Findings. Signal intensity varies with cyst contents (25-60). Multiple cysts are common, and intracystic fluid within each cyst varies from hypoto hyperintense compared with brain on T1WI (25-62).

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 (25-66) (25-67A).

The cyst walls and solid nodules typically enhance following contrast administration (25-62) (25-67).

MRS shows a large lipid-lactate peak, characteristic of the cholesterol and lipid constituents of a CP. pMR shows low rCBV (25-60).

CRANIOPHARYNGIOMA: CLINICAL ISSUES, IMAGING, AND DDx

Clinical Issues

•> 50% of pediatric suprasellar neoplasms

•Occurs equally in children, adults

○Peak in children = 5-15 years; peak in adults = 40-55 years

○Papillary type much more common in adults

•Slow growth

○Recurrence common

○Malignant transformation rare

Imaging

•CT

○Can be giant (> 5 cm), involve multiple fossae

○Adamantinomatous: 90% cystic, 90% calcify, 90% enhance

○Papillary: solid > cystic

•MR

○Variable signal on T1WI

○Usually hyperintense on T2/FLAIR

○Enhancement (nodular or rim) 90%

○MRS: large lipid-lactate peak

Differential Diagnosis

• Rathke cleft cyst

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. 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.

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(25-67A) Axial FLAIR image in a 47y patient with headaches shows a suprasellar mass with edema in the adjacent optic tracts .

(25-67B) Coronal T2WI in the same patient shows the cystic mass with a focal inferior nodule . No calcification was seen on CT (not shown).

(25-67C) Sagittal T1 C+ shows enhancement of the suprasellar mass and nodule at the anterior 3rd ventricle. This is craniopharyngioma.

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

Nonadenomatous Pituitary Tumors

Primary nonadenomatous pituitary gland tumors are rare, poorly understood entities. The 2007 WHO Classification of Tumours of the Central Nervous System clarified matters, formally recognizing three histologically distinct pituitary region neoplasms: pituicytoma, spindle cell oncocytoma (SCO), and granular cell tumor. All are WHO grade I tumors. The 2016 WHO Classification of Tumours of the Central Nervous System further classified these three tumors, recognizing that all show nuclear expression of TTF1, suggesting that they all may constitute a spectrum of a single nosologic entity.

(25-68) Sagittal graphic shows a pituicytoma involving the infundibular stalk and neurohypophysis. (25-69) Sagittal T1 C+ scan in a 22y woman with delayed growth and hypopituitarism shows an enhancing infundibular mass that is clearly separate from the pituitary gland . Imaging findings have remained stable over many years. This is presumed pituicytoma.

(25-70A) Sagittal T1WI in a 69y woman with headaches, visual symptoms shows a sellarsuprasellar mass that is well delineated and isointense with brain. The pituitary gland cannot be distinguished as separate from the mass. (25-70B) Coronal T1 C+ image shows that the lesion enhances strongly and uniformly. Preoperative diagnosis was pituitary macroadenoma. Spindle cell oncocytoma was diagnosed at histologic examination.

Pituicytoma

Previously also known as "choristoma" and "infundibuloma," pituicytoma arises from modified glial cells ("pituicytes") that reside in the infundibular stalk and neurohypophysis (25-68).

Visual disturbance with or without headache is the most common presenting symptom. Patients with pituicytoma almost never present with diabetes insipidus, galactorrhea, or prolactinemia.

Pituicytoma can appear as either an intrasellar or a suprasellar mass. 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 (25-69).

Pituicytoma is the only one of the nonadenomatous tumors that can present as a purely intrasellar mass. An intrasellar

mass that is clearly separate from the anterior pituitary gland and enhances homogeneously is most likely a pituicytoma.

Spindle Cell Oncocytoma

SCO, also previously known as folliculostellate cell tumor, consists of "spindled" oncocytes containing granular, mitochondria-rich cytoplasm.

Visual disturbance, panhypopituitarism, and headache are the most common presenting symptoms. SCOs do not appear to cause diabetes insipidus.

To date, all pathologically proven cases have presented as mixed intrasellar and suprasellar infiltrating pituitary lesions. Imaging findings are similar to—and cannot be distinguished from—those of pituitary adenoma or lymphocytic hypophysis

(25-70).

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Granular Cell Tumor

Like pituicytoma, granular cell tumor is a tumor of the neurohypophysis. Many granular cell tumors are asymptomatic and discovered incidentally at autopsy. Some enlarge with time, becoming symptomatic in middle-aged or older adults. Visual disturbance, headache, and amenorrhea are common. Similar to pituicytoma and SCO, granular cell tumors rarely present with diabetes insipidus, prolactinemia, or galactorrhea.

Granular cell tumors are typically suprasellar masses. They are hyperdense on NECT (25-71A) and isointense with brain on both T1and T2WI. Granular cell tumors enhance strongly and homogeneously following contrast administration (25-71).