Rathke Cleft Cyst

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Article initiated by:

Andrew Go Lee, MD, Brandon Le, Chaow Charoenkijkajorn, M.D., Mohammad Pakravan, Peter W. Mortensen, MD, Subahari Raviskanthan, MBBS

All contributors:

Nagham Al-Zubidi, MD, Peter W. Mortensen, MD, Sonali Singh MD

Assigned editor:

Sonali Singh MD

Review:

Assigned status Update Pending

 by Sonali Singh MD on August 22, 2023.

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Contributing Editors:	add

Rathke Cleft Cyst

Rathke Cleft Cysts are benign, sellar or suprasellar lesions located within Rathke’s cleft, itself an anatomic remnant from formation of the pituitary gland. While most commonly asymptomatic, they have been documented to manifest with pituitary dysfunction and ophthalmic findings, typically with visual field defects such as bitemporal hemianopsia. When symptomatic, it most often follows a chronic, indolent course that progresses over time, presenting with chronic headache, endocrine dysfunction, and visual field constriction. MRI imaging demonstrated ovoid masses that are hypodense, isodense, or hyperdense depending on solid and cystic components. Pathology reveals epithelial lined cysts filled with cholesterol-like contents. Management includes surgical intervention with favorable prognosis when gross total resection is achieved, though lesions may recur. Follow up will typically occur with imaging over the course of 5 years and patients will often require endocrine replacement, though ophthalmologic findings will resolve after resection and compression of the optic chiasm is resolved.

Disease Entity

Rathke’s cleft cysts (RCC) are epithelial-lined, benign cystic remnants located within Rathke’s Cleft, an anatomic remnant of the formation of the pituitary gland. Most often, they are discovered incidentally in the sellar or suprasellar region, but have been documented to manifest with ophthalmologic findings, typically in the form of visual field defects (e.g. bitemporal hemianopsia). When symptomatic, the course of the disease most often follows a progressive and gradual course involving chronic headache, endocrine dysfunction, and visual field constriction, though acute presentations secondary to necrosis and hemorrhage have also been shown to occur (i.e. Rathke’s Cleft Cyst Apoplexy).

Disease

Epidemiology

While reported to occur in all age groups, RCC are most common in adults with a peak incidence of 30-50 years of age . As imaging modalities become more advanced and commonplace, a more accurate estimation of the predominance of RCC will emerge, but imaging and postmortem studies have reported an incidence anywhere from 3-11% Most RCC remain asymptomatic, comprising only 2-9% of the underlying pituitary mass in those who undergo surgical management and treatment . RCC have been observed to occur more often in females among all age groups. Specifically, in pediatric populations undergoing treatment, female:male ratios of 1.5-3.7 and in clinical studies of adult populations, female:male ratios ranging from 1 to 5 have all been reported. Based on postmortem studies documenting female:male ratios of 7:30, however, it has been theorized that male cases are underreported and the greater clinical incidence of female patients is a results of earlier detection and treatment secondary to menstrual irregularities that stem from pituitary hormone dysfunction .

Etiology

RCC are intrasellar and suprasellar masses, with most lying medially rather than laterally. Rarely, they may extend into the sphenoid or cavernous sinus or frontal area. They are slow growing lesions and originate from epithelial cells within Rathke’s Cleft. Rathke’s Cleft is a remnant of the embryological formation of the pituitary gland, wherein surface ectoderm from the pharyngeal epithelium meets neuroectoderm from the diencephalon. These form Rathke’s pouch/adenohypophysis and the neurohypophysis, respectively. The space between the two structures is the vestigial pars intermedia or Rathke’s Cleft and is the site of Rathke’s Cleft Cysts and craniopharyngiomas. Biochemical studies of RCC have shown that the spectrum of pathological findings of simple columnar epithelium to squamous metaplasia and epithelium closely mirror the spectrum of lesions found in Rathke’s cleft, including adamantinomatous craniopharyngioma and papillary craniopharyngioma. One study found that nuclear and cytosolic ß-catenin is present in a number of Rathke’s cleft cysts, a feature characteristic and typically only seen with adamantinomatous craniopharyngiomas .

General Pathology

The diagnosis of RCC is based upon biopsy with histopathological confirmation. They vary in size, ranging anywhere from a few mm and up to 40 mm, with the majority between 10 and 20 mm in size . On a macroscopic scale, they are encapsulated by a delicate membrane composed of epithelium, with thick, gelatinous and mucoid material comprising their interior. Characteristic descriptions vary between “motor-oil” like, CSF-like, and milky. Microscopically, RCC are defined by cystic walls composed of simple or pseudostratified cuboidal or columnar epithelial cells, with variations including the presence of cilia, mucus-secreting goblet cells, and squamous metaplasia . The contents of the cyst itself include cholesterol and protein, with repots of xanthogranulomatous inflammation, especially with cyst rupture.

Diagnosis

Clinical Features

The ophthalmic manifestations of RCC include visual disturbance of both acuity and field, oculomotor palsy, and diplopia, with the most common amongst them being visual field loss . While visual disturbance is the most common presenting symptom in up to 47% of cases, other symptoms include endocrine dysfunction, most often in the form of hyperprolactinemia and diabetes insipidus, 16% and 21%, respectively, and chronic, intractable headache . The visual disturbance typifying RCC is bitemporal hemianopsia, a result of the lesion compressing the optic chiasm. The time course of presentation is most often insidious, with a mean duration of symptoms anywhere from a few days to a few years, a result of the slow-growing nature of RCC. Acute presentations, however, have been documented to occur, with sudden onset or increased severity of headache, visual disturbance, and alteration in mental status, a result of apoplexy of RCC with hemorrhage and necrosis of the cyst, resembling pituitary apoplexy.

Diagnostic procedures

Diagnostic Imaging

RCC appears on imaging as well-circumscribed, ovoid or dumb-bell shaped masses located within the intrasellar and suprasellar regions. Both computerized tomography (CT) and magnetic resonance imaging (MRI) modalities are utilized in the diagnosis of RCC. CT reveals homogenous lesions that are hypodense, isodense, or hyperdense and may or may not show enhancement. When present, enhancement is characteristically ring-like or capsular. Similarly, RCC presents on MRI as homogenous lesions that are well demarcated with occasional enhancement. Depending on cystic contents, they may appear hypointense or hyperintense. For example, CSF-like contents will appear hypointense on T1- and hyperintense on T2-weighted imaging, and the MRI findings are variable depending on the contents of the cyst. The most common imaging finding is hyperintensity on T2, found in about 70% of cases . Meanwhile, a highly suggestive finding for RCC is the presence of an intracystic, nonenhancing nodule with low T2 intensity and high T1 intensity in comparison to cystic fluid contents .

Management

While small, asymptomatic cysts do not require surgery and may be observed, clinically symptomatic lesions require surgical intervention. The goal of surgery is to drain cyst contents as well as to remove the capsule lining the cyst.

General treatment

The most common methodology for removal is via endonasal or sublabial transsphenoidal approach, with fenestration and drainage of the cyst . Reported cases of craniotomy have also been observed with larger and suprasellar cysts . Additionally, radiotherapy has shown to be helpful in the case of recurrence . Complications of surgical management include CSF leak in up to 25% of patients as well as transient and permanent Diabetes Insipidus, up to 67% and up to 20%, respectively .

Prognosis

Visual field disturbance experiences a high rate of resolution, with rates ranging from 33-100% . Recovery of pituitary dysfunction is more variable, with those who pre-operatively had panhypopituitarism experiencing resolution at lower rates than those with isolated, partial hypopituitarism. Recurrence and relapse of RCC ranges from 0 to 48%, most often recurring within 5-6 years after resection . Most often, if recurrence occurs it is single, but multiple recurrences have also been reported. A treatment algorithm for RCC has been proposed (see article by Trifanescu et al., 2012 ). Given the limited number of series of asymptomatic lesions, yearly clinical follow up with imaging at 1, 3, and 5 years following treatment stands as the standard, but the duration of follow up has not been determined.