784

(25-27A) Sagittal T1WI shows a thickened floor of the 3rd ventricle from fusion of the hypothalamus and an almost inapparent sella .

(25-27B) Coronal T1WI in the same patient shows two laterally displaced hyperintense pituitary glands .

Congenital Lesions

Pituitary Anomalies

Complete absence of the pituitary gland and stalk is rare and nearly always fatal at or soon after birth. Pituitary hypoplasia is much more common (2524). Many affected children have growth hormone deficiency and short stature, i.e., they are "pituitary dwarfs." These patients can be treated with hormone replacement therapy, so accurate diagnosis and early recognition of this disorder are essential.

Pituitary Hypoplasia

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.

Imaging abnormalities include a small sella and anterior pituitary lobe, hypoplasia or absence of the stalk, and an "ectopic" posterior pituitary "bright spot" seen as displacement of the T1 hyperintense posterior lobe into the infundibulum or median eminence of the hypothalamus (25-25) (25-26).

In general, the extent of MR abnormalities correlates with the severity of hormone deficiency. Patients with isolated GH deficiency are more likely to have a normal-sized adenohypophysis and infundibulum than those with multiple endocrine deficiencies.

Kallmann syndrome, also known as hypogonadotropic hypogonadism, is a neuronal migration disorder that results in hypoplastic or absent olfactory nerves and sulci. Various visual and septal anomalies as well as pituitary gland hypoplasia are common.

Pituitary Duplication

Pituitary duplication is a rare anomaly in which two pituitary stalks can be identified on the coronal view (25-27B) (25-27C). The tuber cinereum of the hypothalamus and mammillary bodies are fused into a single thick mass that is best visualized on midline sagittal views (25-27A). Associated craniofacial and craniocervical anomalies are common in these cases.

Unlike pituitary hypoplasia, pituitary duplication rarely causes hormone deficiencies. Instead, a spectrum of midline craniofacial and craniocervical segmentation and fusion anomalies are often seen. Female patients are more commonly affected.

Hypothalamic Hamartoma

Terminology

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

Etiology

(25-27C) Coronal T2WI in the same patient shows duplicated pituitary stalks . A duplicated pituitary is a rare congenital anomaly.

HHs are an anomaly of neuronal migration that probably occurs between gestational days 33 and 41. A syndromic abnormality that occurs with HH, Pallister-Hall syndrome (PHS), is caused by GLI3 frameshift mutations on chromosome 7p13.

Pathology

Location. The majority of HHs are located in the tuber cinereum, i.e., between the infundibular stalk in front and the mammillary bodies behind (25-28) (25-29). They can be pedunculated (25-30) or sessile (25-31). 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.

Size and Number. HHs are solitary lesions that vary in size from a few millimeters (25-32) to huge mixed solid-cystic lesions measuring several centimeters in diameter (25-33) (25-34).

Gross and Microscopic Features. HHs are well-defined round or ovoid soft tissue masses that resemble normal brain parenchyma. Histologically, HHs consist of well-differentiated small and large neurons interspersed with variable amounts of glial cells. Calcification, hemorrhage, and necrosis are rare

785

although very large lesions often contain well-delineated cysts.

Staging, Grading, and Classification. The most common classification of HHs is morphologic. HHs can be pedunculated or sessile. Pedunculated HHs are attached to the tuber cinereum and project into the suprasellar cistern. Sessile HHs are attached to the floor of the third ventricle and often incorporate the mammillary bodies. Projection into the suprasellar cistern is variable.

Clinical Issues

Demographics. HHs are rare lesions although up to one-third of patients with central precocious puberty have an HH. There is a moderate male predominance.

Presentation. Most HHs present between 1 and 3 years of age. Three-quarters of patients with histologically verified HHs have precocious puberty, and 50% have seizures.

(25-35) Coronal graphic shows a typical suprasellar Rathke cleft cyst interposed between the pituitary gland and the optic chiasm .

HH-associated seizures are highly variable, age dependent, and often refractory to treatment. Gelastic seizures (ictal laughing fits) are the most common type and vary from facial grinning to intense contractions of the diaphragm accompanied by body shaking. These gelastic seizures are more common with sessile tumors, whereas precocious puberty is more often present in patients with small pedunculated lesions. Patients may present with both seizures and precocious puberty.

Anomalies associated with HH include holoprosencephaly. Patients with Pallister-Hall syndrome have digital malformations and other midline (epiglottis/larynx) and cardiac, renal, or anal anomalies in addition to the HH.

Natural History. HHs generally remain stable in size. Hormonal suppressive therapy, i.e., luteinizing hormonereleasing hormone agonists, is helpful in some cases. Failure of medical therapy or rapid lesion growth may necessitate surgery.

Imaging

General Features. A nonenhancing hypothalamic mass between the infundibular stalk and mammillary bodies is the classic imaging appearance of HH (25-30).

CT Findings. NECT scan shows a homogeneous suprasellar mass that is isodense to slightly hypodense compared with brain. Intralesional cysts may be present in larger HHs. HHs do not enhance on CECT.

MR Findings. 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 isoto slightly hyperintense

(25-36) Sagittal T1WI in an asymptomatic patient shows a tiny hyperintense suprasellar mass that appears separate from the pituitary gland "bright spot" of the neurohypophysis . This is presumed Rathke cleft cyst.

on T2/FLAIR. The degree of T2 hyperintensity is directly related to the proportion of glial versus neuronal tissue in the lesion.

HHs do not enhance following contrast administration. If there is enhancement in the lesion, consider a glial tumor.

MRS shows mildly decreased NAA and slightly increased choline, consistent with reduced neuronal density and relative gliosis. Myoinositol is elevated, which is consistent with an increased glial component compared with normal brain.

Differential Diagnosis

The differential diagnoses of HH are craniopharyngioma and chiasmatic/hypothalamic astrocytoma. Clinical features are very helpful in distinguishing HH from these lesions.

Craniopharyngioma is the most common suprasellar mass in children. Over 90% of craniopharyngiomas 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

Terminology

Rathke cleft cyst (RCC) is a benign endodermal cyst of the sellar region.

788

Etiology

RCCs are thought to arise from remnants of the fetal Rathke pouch. When the embryonic stomodeum (the primitive oral cavity) invaginates and extends dorsally, it forms the endoderm-lined craniopharyngeal duct. It meets an outgrowth from the third ventricle, giving rise to the hypophysis. The anterior wall of the pouch forms the anterior lobe and pars tuberalis, whereas the posterior wall forms the pars intermedia. The interposed lumen forms a narrow "cleft"—Rathke cleft—that normally regresses by the twelfth gestational week. If it persists and expands, it forms an RCC.

Pathology

Location. RCCs are limited to the sellar region. Approximately 40% are completely intrasellar, generally positioned between the anterior lobe and pars intermedia, whereas 60% are suprasellar (25-35) (25-36).

(25-37A) NECT scan shows a hyperdense mass projecting superiorly into the suprasellar cistern . Only 5-10% of Rathke cleft cysts are hyperdense on CT. The lack of calcification helps differentiate a Rathke cleft cyst from a craniopharyngioma. (2537B) Coronal T1WI scan in the same patient shows that the mass is homogeneously hyperintense.

(25-37C) T2WI in the same patient shows that the cyst is hypointense and contains an even more hypointense intracystic nodule . An intracystic nodule may be seen in up to 75% of patients with Rathke cleft cyst. (2537D) A rim ("claw") of enhancing pituitary glandis seen around the cyst. Rathke cleft cyst with intracystic nodule was found at surgery. Lack of enhancement within the cyst and an intracystic nodule allow accurate preoperative diagnosis.

Size and Number. Most symptomatic RCCs are 5-15 mm in diameter. Occasionally, an RCC becomes very large and can compress the optic chiasm and adjacent brain and erode into the skull base. An enlarged sella turcica may be seen with RCCs.

Gross Pathology. RCCs are smoothly lobulated, sharply marginated cysts. Cyst contents vary from clear and CSF-like to thick yellow inspissated mucoid material.

Microscopic Features. RCCs are endodermal (not ectodermal) cysts. They are lined by a single layer of ciliated cuboidal or columnar epithelium together with various amounts of goblet cells. On immunohistochemical studies, RCCs express cytokeratins 8 and 20.

Clinical Issues

Demographics. Although RCCs occur at all ages, mean age at presentation is 45 years.

Presentation. Most RCCs are asymptomatic and discovered incidentally at imaging or autopsy. Symptomatic RCCs cause pituitary dysfunction (~70%), visual disturbances (~45-55%), and headache (~50%).

Occasionally RCCs present with "cyst apoplexy," usually—but not invariably—caused by sudden intracystic hemorrhage. Symptoms are generally indistinguishable from those of pituitary apoplexy.

Natural History. Most RCCs are stable and do not change in size or intensity characteristics. RCCs do not undergo malignant degeneration.

Imaging

CT Findings. NECT scans show a well-delineated round or ovoid mass within or just above the sella turcica. Threequarters of RCCs are hypodense on NECT, whereas 20% are mixed hypoand isodense. Between 5 and 10% are

789

hyperdense (25-37A). Calcification is uncommon compared with craniopharyngioma.

MR Findings. Signal intensity varies with cyst contents. Half of all RCCs are hypointense on T1WI, and half are hyperintense (25-37B). The majority of RCCs are hyperintense on T2WI (2538A), whereas 25-30% are isoto hypointense (25-37C). Careful inspection reveals an intracystic nodule in 40-75% of cases (25-37C) (25-38A).

RCCs are almost always hyperintense on FLAIR (25-39A). An enhancing rim ("claw" sign) of compressed pituitary gland can often be seen surrounding the nonenhancing cyst (25-37D)

(25-38B) (25-39B).

Differential Diagnosis

The major differential diagnosis of RCC is craniopharyngioma. Floccular, rim, or nodular calcifications are common in craniopharyngioma, whereas RCCs rarely calcify. The rim or