Clinical manifestations

Presentation and course

Patients can present with either asymptomatic or symptomatic colloid cysts. Asymptomatic colloid cysts are often found incidentally on imaging for other reasons, the most common of which is trauma (07). Patients with symptomatic colloid cysts most commonly present with one of three symptom complexes: (1) headache, papilledema, and occasionally false localizing motor and sensory signs; (2) progressive or fluctuating dementia with or without headache and raised intracranial pressure; or (3) paroxysmal severe headaches, nausea, vomiting, stupor, or coma without symptomatology between episodes (36). The first symptom complex is due to constantly elevated intracranial pressure from the cyst compressing the ventricular system, leading to obstructive hydrocephalus. The second symptom complex could be due to direct pressure on structures surrounding the third ventricle, like the medial thalamus, hypothalamus, fornix, corpus callosum, and infundibulum, leading to the mamillary bodies. These areas of the brain are involved in the limbic system, which plays a role in memory and other neuropsychiatric symptom manifestations (43; 60). Depression, anxiety attacks, paranoid ideation, memory difficulties, and decreased cognition are also observed occasionally and are often subtle. Surgical cyst removal, even in the absence of hydrocephalus, has been reported to sometimes ameliorate these symptoms (46). Finally, the transient nature of elevated intracranial pressure symptoms described in symptom complex 3 may be due to the colloid cyst moving in and out of the foramen of Monro on its pedicle with intermittent obstruction of CSF (40).

Individually, headaches are by far the most common symptom (89%), followed by nausea or vomiting (23%), visual decline (22%), dizziness or ataxia (20%), and cognitive decline (14%) (07). Of note, although headaches associated with colloid cysts can have a positional component characteristic of elevated intracranial pressure, they can also resolve or reduce in the supine position (05; 14; 70). Colloid cysts can present with some intraocular findings other than the papilledema traditionally associated with elevated intracranial pressure. For example, one report noted visual field deficits and findings suggestive of glaucoma (55), although another reported intraocular hemorrhage (09).

Untreated patients can develop fatal colloid cysts that may present with acute disturbances of consciousness, coma, and death because of ventricular outflow obstruction with resultant obstructive hydrocephalus (17; 66). Subarachnoid hemorrhage into the colloid cyst can occur, and such patients can manifest with a change in clinical symptoms and an increase in cyst size (51; 23).

Prognosis and complications

Colloid cysts are considered rare benign lesions as they are curable, developmental, and slow-growing malformations; however, they can eventually lead to serious complications, including sudden death from ventricular outflow obstruction (40; 30; 05). The risk of sudden neurologic deterioration or death has been reported at 3% to 35%, with fatal colloid cysts accounting for 0.0015% to 0.009% of all cases of sudden death (40; 68).

Although acute neurologic deterioration has been emphasized, most patients present with long-standing, intractable symptoms that allow for diagnosis and elective surgery. Asymptomatic, incidentally discovered colloid cysts rarely cause acute hydrocephalus or sudden neurologic deterioration in the absence of trauma. Although these lesions can remain the same size for many years, there is a 5% to 15% risk of progression within 5 years of initial diagnosis of an incidental colloid cyst managed nonoperatively (16).

Clinical vignette

The patient was a 36-year-old, right-handed, Caucasian woman who had an abrupt onset of severe headache while bending forward during intense household work. The headache prevented her from activities, and while walking to her bed to lie down, she collapsed to the floor. She was taken to the emergency room for evaluation. On examination, she was found to be stuporous with intact brainstem reflexes. An urgent CT scan of the brain was performed that demonstrated a hyperdense cystic lesion of the third ventricle with obstructive hydrocephalus. The clinical and neuroimaging findings were felt to be compatible with a colloid cyst of the third ventricle. She underwent an emergent ventriculostomy for acute hydrocephalus. Subsequently, she was taken to the operating room for more definitive therapy consisting of endoscopic evacuation of cyst contents and microsurgical resection of the cyst capsule. Thick protenacious material was aspirated from the cyst. Postoperative recovery was gradual but complete, with no discernible neurologic deficits. She was able to return to her usual activities, and a follow-up scan of her brain did not demonstrate any residual lesion or hydrocephalus.

Biological basis

Etiology and pathogenesis

The etiology of colloid cyst is unknown as most cases tend to occur sporadically (13). It is thought that the membrane of the cyst originates from ectopic endodermal elements that migrate into the velum interpositum during the development of the central nervous system. It is then filled postnatally with gelatinous matter (77).

Genetics. Reports of familial colloid cysts in 40 families that involve 83 patients support the growing evidence for the possibility of genetic predisposition in the development of colloid cysts (41; 27; 54). Although there is no consensus on the precise pattern of the genetic predisposition, some authors postulate an autosomal dominant pattern of occurrence (08), although others argue that an autosomal recessive pattern is more plausible (69). Some authors posit that the inheritance is probably multifactorial (71). A large prospective clinical case series analyzed 13 families and their first-degree relatives affected with colloid cysts (26 patients) and reported an estimated familiar colloid cyst rate of 3.4%. The early diagnosis of first-degree relatives with colloid cysts is advised because of the higher risk of symptomatic lesions (61.5% to 89.5%) and mortality (7.7% to 12.3%) compared with those without a family history (27). The first-degree relatives of patients with colloid cysts who develop symptoms suggestive of raised intracranial pressure should be evaluated with MRI screening, and genetic screening is recommended for monozygotic twins (13; 41).

Pathology. Colloid cysts are smooth, spherical masses that arise in the anterior and dorsal regions of the roof of the third ventricle. The wall is a thin membrane enclosing a soft gray proteinaceous material or a dense hyaline substance. The state of the cyst contents varies with the degree of hydration, from thick fluid to a solid gel, and this variation in turn affects the appearance on neuroimaging studies. The wall is composed of fibrous connective tissue lined by benign columnar ciliated epithelial cells (25).

Pathophysiology. Although generally regarded as a malformation, the lineage of colloid cysts remains controversial. A neuroectodermal derivation for colloid cysts has been assumed based on structural and embryological considerations as well as their intraventricular location. Potential precursors include choroid plexus, ependyma, primitive neuroectoderm, and the paraphysis. Uncertainty over the specific nature of epithelium lining colloid cysts is reflected in the all-encompassing synonym "neuroepithelial cyst" that is often applied (38). Two immunohistochemical studies using histologic antigens and monoclonal antibodies indicated that colloid cyst epithelium is immunohistochemically different from that of normal or neoplastic choroid plexus. In one, the immunophenotype of colloid cysts was similar to foregut-derived epithelia of enteric and Rathke pouch cysts, supporting endodermal origin for these cysts (39). This observation was further supported by studies on the nature of the cyst contents themselves. These studies indicate that the carbohydrate epitopes exhibited by cysts and their contents are also consistent with an endodermal origin (76).

There are four ventricles (paired lateral, third, and fourth) connected by foramina comprising the ventricular system of the brain that produces CSF, which serves to provide nourishment, waste removal, and protection to the brain (73). The foramen of Monro connects the lateral ventricles to the midline third ventricle, and the aqueduct of Sylvius connects the third ventricle to the fourth ventricle. CSF then flows through the midline foramen of Luschka and the paired foramina of Magendie to reach the subarachnoid space. Most colloid cysts develop just posterior to the foramen of Monro (43). Obstruction anywhere along the intraventricular system can lead to hydrocephalus, which can be fatal.

The most popular hypothesis to explain fatal colloid cysts is the “ball-valve effect” where a colloid cyst moves on its pedicle, which is attached to the ventricular wall and blocks the foramen of Monro, resulting in acute obstructive hydrocephalus. Other theories include cystic apoplexy leading to cyst enlargement and acute obstructive hydrocephalus, mass effect on the hypothalamus leading to the release of catecholamines and subsequent cardiac arrest, head trauma capable of shearing forces that severs the attachment of the cyst to the ventricular wall, and generalized cerebral edema from when a growing colloid cyst raises the pressure in the superior sagittal sinus leading to venous stasis (40).

Epidemiology

Colloid cysts of the third ventricle represent approximately 0.5% to 1% of primary intracranial mass lesions (37). There is no sexual predominance. The incidence of colloid cysts of the third ventricle is estimated to be 0.9 per 1 million persons annually, and the prevalence is around one in several thousand (59). However, data from a systematic review of brain MRI findings reported a prevalence of two incidental colloid cysts out of 15,559 patients (48), and another population-based study of the brain MRI of 5800 patients in the Netherlands estimated the prevalence of colloid cysts as 1 out of 5800 (10). Although colloid cysts are congenital lesions, they usually remain asymptomatic until 20 to 50 years of age; the symptomatic lesions are less common in children, but reports from case series of affected children suggest that they tend to have more aggressive clinical features and rapid neurologic deterioration compared to adults (28; 75).

Prevention

There are no preventive measures that decrease the occurrence of colloid cysts.

Differential diagnosis

Confusing conditions

The differential diagnosis includes any third ventricular mass, including choroid plexus papillomas, glial tumors, metastases, craniopharyngioma, granuloma, hematomas, basilar artery aneurysms, and, rarely, suprasellar pituitary adenomas. Metastatic lesions to the choroid plexus may resemble colloid cysts, especially solitary lesions without other intracranial metastases.

Associated or underlying disorders

Colloid cysts are usually associated with hydrocephalus, and patients with bilateral lateral ventriculomegaly should be properly evaluated to confirm or exclude colloid cyst of the third ventricle.

Diagnostic workup

The diagnosis of colloid cysts can be made definitively with CT or MRI in most cases. On CT scanning, a colloid cyst appears as a distinctive isodense or hyperdense lesion at the foramen of Monro; variable contrast enhancement is noted. Calcifications are not seen within the cyst or in the cyst wall. A distinctive MRI appearance with high signal intensities noted on both T1- and T2-weighted images reflects the high protein content of the viscous cyst material (37; 59). In cases where some of the cyst contents are solid, there is a variable radiographic appearance.

Management

Risk stratification. There is no clear guidance on the management of incidentally diagnosed colloid cysts. Close observation with serial neuroimaging studies may be a safe management strategy. To better risk stratify patients into those who may require surgical intervention given the risk for hydrocephalus versus those who can proceed with close observation, Beaumont and colleagues detailed three anatomic risk zones in the third ventricle on the sagittal plane using vertical lines drawn from the mamillary bodies and tangential to the massa intermedia and a parallel line drawn from the anterior aspect of the aqueduct of Sylvius upwards (07). Zone 1 encompasses the third ventricle anterior to the first line; zone 2 is the area between the first and second line; and zone 3 is posterior to the second line. Zones 1 and 3 were considered risk zones as none of the patients studied with zone 2 lesions presented with obstructive hydrocephalus. This was incorporated into the Colloid Cyst Risk Score (CCRS) used to predict symptomatic clinical status and stratify risk for hydrocephalus in patients presenting with a colloid cyst in the third ventricle. One point is given for age under 65 years, headache, axial diameter of cyst 7mm or larger, fluid-attenuated inversion recovery (FLAIR) hyperintensity, and location in an anatomic risk zone. A CCRS of 4 or higher was significantly associated with obstructive hydrocephalus (p< 0.0001, RR 19.4) (07; 01; 80).

Table 1. Colloid Cyst Risk Score (CCRS)

A modified CCRS was developed by Burnhan Janjua and colleagues in 2020 to include factors like gender, additive size gradation based on cyst size, and objective risk quantification of hydrocephalus. The total potential score is 8; patients with a score lower than 4 can be managed conservatively, whereas patients with a score greater than 7 are at risk of symptomatic progression and should be evaluated for surgery (12).

In 2024, Murali and colleagues proposed reclassifying the “anatomic risk zones of colloid cysts” described by Beaumont and associates, with newer landmarks to improve the specificity and positive predictive value for the occurrence of hydrocephalus. Sometimes larger colloid cysts displaced the massa intermedia posteriorly, leading clinicians to classify these cysts as zone 1 cysts and, thus, higher risk when they may not be. Using 122 cases of colloid cysts in the third ventricle diagnosed incidentally or symptomatically, Murali and colleagues suggested drawing the first line from the mamillary body to the coronal suture (MB-Coronal line) to account for this and a second line from the anterior aspect of the aqueduct of Sylvius parallel to the MB-Coronal line. Zone 1 is anterior to the first line, zone 2 in the middle, and zone 3 posterior to the second line. By changing the zoning method, there was a higher specificity (36.2% vs. 5.2%) and positive predictive value (63.3% vs. 54.2%) for the occurrence of hydrocephalus in patients with a colloid cyst when compared to the CCRS (50). Although this adds new insight into risk stratification, this scoring system still needs to be validated.

In summary, modifications are still being made to generate an optimal risk stratification score for colloid cysts. In the interim, however, the Beaumont CCRS remains a relative standard until additional validations are completed for newer scoring systems.

Conservative management. Conservative management of asymptomatic colloid cysts is a viable option. There are six case reports of patients managed with serial neuroimaging who subsequently had spontaneous regression of their lesions in the literature (26; 56; 74; 16; 49; 44). Turel and colleagues suggested that patients with an asymptomatic colloid cyst that is less than 10 mm should have an initial follow-up image 6 to 12 months after diagnosis, and subsequent serial follow-up neuroimaging should be done annually (74).

Surgical management. Present management options for symptomatic colloid cysts include management of hydrocephalus and resection of the intraventricular mass. For patients presenting with symptomatic ventriculomegaly, placement of an emergent external ventricular drain may be required in the acute setting before cyst resection. Hydrocephalus persisting after surgical resection of cysts is typically treated with a ventriculoperitoneal shunt.

Resection of intraventricular colloid cysts is most commonly performed via microsurgical (transcortical-transventricular or interhemispheric-transventricular) or endoscopic approaches with very low mortality rates (0.6% to 1.4%) (19; 53; 15).

Outcomes

There is no consensus on which surgical technique is superior for the treatment of colloid cysts (15; 63; 62). Data suggest that microsurgical approaches afford a higher rate of complete removal and a lower recurrence rate compared to endoscopic treatment (32; 21; 62). In a meta-analysis comparing the outcomes of 1278 patients treated with either approach, those treated with microsurgery had a higher incidence of complete surgical resection (97% vs. 58%) and lower recurrent rate (0.38% vs. 3%) relative to endoscopic treatment (65). Similarly, another meta-analysis reported a higher gross total resection rate (98.15% vs. 91.29%) and lower recurrent rate (0.00% vs. 1.78%) for the microsurgical approach compared to endoscopic surgical treatment (62).

Although the patients treated with the endoscopic approach may not achieve complete resection of the tumor capsule, most of the patients have a low risk of complications, morbidity, mortality, and recurrence in the long term (78; 33). In addition, the endoscopic approach is now assuming a standard front-line surgical option for the treatment of colloid cysts because of the significantly reduced rate of perioperative morbidity and lower cost (63; 06), and it has also decreased the rate of seizures (15% in microsurgery vs. 5% in endoscopic) and readmission rates (65; 15). Furthermore, both the operative time and length of hospital stay are reduced significantly with endoscopic resection (31; 22; 62). Refinements in technical expertise and instrumentation have made the endoscopic technique an efficient surgical option even for large (greater than 20 mm) and giant (greater than 30 mm) colloid cysts (04).

Conversion from endoscopic to microsurgical resection has also been reported (53; 78). One study demonstrated that microsurgical resection of colloid cysts led to a sustained improvement in neurocognitive function, presumably due to the reduction of hydrocephalus or reduction of mass effect on the fornix (60). Morbidity and mortality include intraoperative bleeding, postoperative hydrocephalus, cerebrospinal fluid leak, subdural hematoma, cognitive deficits, seizures, and transient and permanent memory disturbances (67; 34; 72; 52; 20; 02; 14; 35). The amnestic syndrome is caused by bilateral fornix damage; sparing of the left fornix alone is sufficient to ensure a more favorable outcome (47). Clinical and radiological follow-up are necessary to assess and ensures lesion-free survival.

Special considerations

Pregnancy

There can be a sudden increase in the size of a colloid cyst, leading to acute hydrocephalus in pregnancy. Therefore, patients with asymptomatic colloid cysts of the third ventricle who desire pregnancy should be monitored closely (24).

Anesthesia

The management of a patient with an asymptomatic colloid cyst who is being evaluated for operation due to another surgical pathology requires special anesthetic considerations. Anesthesia can change CSF pressure, which may precipitate acute hydrocephalus. However, epidural anesthesia minimizes pain and has the least risk of fluctuation in CSF pressure (58).