Pineal Cyst: A Review of Clinical and Radiological Features

Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region that are typically small and do not change in size over time. PCs appear as small, well circumscribed, unilocular masses that either reside within or completely replace the pineal gland. This article reviews and discusses the characteristic features of PCs—clinical, histological, and identifiable by various imaging modalities—which assist clinicians in narrowing the differential diagnosis for pineal lesions.

Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region found in 33% to 40% of autopsy series. Several retrospective studies have reported incidences of PCs that range from 1.5% to 10.8%. Incidence is higher in females than in males, is greatest between the ages of 21 and 30 years, and decreases with increasing age. Overall, females between 21 and 30 years of age have the greatest frequency at 5.82%.

The precise etiology of PCs remains unclear, and several investigators have suggested several theories explaining PC pathogenesis. During development, the walls of the third ventricle diverticulum proliferate to form the pineal gland. During this process, remnants of the diverticulum may form a cavity lined with cells that can differentiate into ependymal cells. PCs with an ependymal lining may consequently result from an enlargement of the embryonic pineal cavity. However, some PCs are not lined with ependymal cells, but are rather surrounded by a glial scar. This observation has led some investigators to believe that PCs can arise from ischemic degeneration of glial plaques. Others have suggested that PCs result from necrotic pineal parenchyma; however, the cause of the necrosis is unclear.

While these hypotheses may account for the pathogenesis of smaller cysts, the mechanisms underlying the formation of larger and symptomatic cysts have yet to be elucidated. Findings of microscopic cysts in autopsy series have led some investigators to believe that larger cysts may arise when smaller cysts coalesce to form larger lesions. However, given the stagnancy of growth in reports examining the natural history of PCs, this hypothesis is unlikely. Other investigators noting the presence of hemosiderin intraoperatively have suggested that cysts may form through hemorrhage. Klein and Rubinstein have suggested that the large female preponderance of PCs, particularly at younger ages during onset of puberty with decrease in incidence with older age, is suggestive of a hormonal influence on PC development. Indeed, a female prevalence has been noted in several studies, which could be explained by a hormonal component associated with the menstrual cycle or pregnancy.

Clinical features

The majority of pineal cysts are small, and roughly 80% of cysts are less than 10 mm in diameter. Cysts smaller than 10 mm in diameter are often asymptomatic, and larger cysts (diameter >15 mm) may lead to neurologic symptoms resulting from local mass effect on adjacent structures or hydrocephalus through compression of the aqueduct. Increased frequency and improved resolution of neuroimaging technologies and contrast administration have led to an increase in the detection of incidental PCs. Symptomatic lesions are often larger than those found incidentally, and occur most often in women in their second decade of life.

Histologically, PCs are composed of 3 distinct layers. The inner layer comprises fibrillar glial tissue, with or without hemosiderin, and is surrounded by a middle layer of pineal parenchymal tissue that can contain calcium deposits. The outermost layer is a thin layer of leptomeningeal fibrous tissue. During surgery, PCs appear smooth and unilocular with a tan outer layer. Cystic contents are variable and may contain watery, hemorrhagic, or coagulated fluid, and other reports have found that cyst contents can have elevated protein levels.

The natural course of PCs is typically benign, and several studies have found that PCs rarely change in size over time. Golzarian and colleagues found no detectable change in cyst size on magnetic resonance imaging (MRI) scans in 12 patients with follow-up longer than 1 year. Tamaki and colleagues reported on 31 patients with PCs with a follow-up ranging from 3 months to 4 years, and found stable disease except for a decrease in cyst size in 2 patients. In a study of 32 patients with a mean follow-up of 3.7 years (range 6 months to 9 years), Barboriak and colleagues found no change in cyst size in 75% of patients. Cysts completely resolved in 2 patients and decreased by 2 to 4 mm in 3 others. Cysts in 2 patients increased in size, and one patient had a newly formed cyst that was 12 mm in diameter. No correlation was found between changes in cyst size over the course of the study and follow-up duration, cyst size at initial diagnosis, or age. Recently, Al-Holou and colleagues reported a study of 106 young patients (<25 years old) with PCs and an average follow-up of 3 years. On follow-up MRI scans, 98 PCs (92%) did not change in size or imaging characteristics. Six PCs increased in size by an average of 4.4 mm in diameter, and 1 decreased in size. In addition, a change in cyst appearance on MRI, either the development of a posterior enhancing nodule or novel separations was noted in 4 cysts. Similar to previous findings, the vast majority of cysts do not change in size or appearance over time, and the initial cyst size, appearance on MRI, sex, and change in symptoms were not correlated with PC growth during later follow-up.

Given the high number of benign PCs found incidentally through MRI and the largely stagnant natural history of these asymptomatic PCs, it is unrealistic to follow up every patient. Rather, investigators have suggested periodic follow-up in patients with cysts that have abnormal imaging characteristics, in younger patients, and in patients with cysts larger than 10 mm. However, there has not been clear evidence suggesting that larger cysts or cysts with atypical imaging features are particularly prone to change in size or become symptomatic. Increases in cyst size in asymptomatic patients have not been associated with the development of symptoms. Lastly, studies have found that cysts greater than 5 mm in diameter are rare in elderly patients and also in patients younger than 10 years. It is possible that in asymptomatic cysts, small growth, particularly through adulthood, may merely reflect a benign and natural cyst growth and involution pattern not indicative of symptom development. Thus, several studies have suggested against interval imaging follow-ups for patients with PCs smaller than 14 mm.

Symptoms

Symptomatic pineal cysts are rare and, consequently, reports have been rare as well. Most pineal cysts are found incidentally, and are asymptomatic and independent of initial presenting symptoms. Even when there is growth in an initially asymptomatic PC, the lesion is likely to remain asymptomatic. However, when symptoms do develop, clinical manifestations of PCs and other pineal pathologies are intimately tied to the unique location and physiology of the pineal gland.

Pinocytes, the main parenchymal cell within the pineal gland, link sympathetic input from the retina to the production of melatonin, which is involved in the regulation of wake-sleep cycles and the release of other hormones. However, it is unclear as to what extent the presence of PCs alter the regular production and secretion of these hormones. Significant compromise of pineal gland function may lead to irregular melatonin production and be subsequent to hormonal imbalance. Precocious puberty is one of the more common endocrine imbalances associated with PCs, and rarer symptoms reported include hypogonadism and diabetes insipidus.

Given the sensitive location of the pineal gland, even small masses may have potentially serious consequences. Cerebellar, corticospinal, and sensory disturbances may result from direct compression of the midbrain. If large enough, PCs can lead to hydrocephalus associated with aqueductal compression, blockage of the vein of Galen, and symptoms of raised intracranial pressure. Compression of the superior colliculus leads to Parinaud syndrome, characterized by number of abnormalities in eye movement and pupillary function including upgaze palsy, light-near dissociation of pupils, and convergence-retraction nystagmus.

Headaches are the most common neurologic symptom of patients with pineal cysts. In a case-control study examining the association between headaches and pineal cysts, Seifert and colleagues found that patients with PC were twice as likely to develop headaches when compared with age-matched and sex-matched controls (51% vs 25%) and that the most frequent presenting symptom was migraines (26%). Of the 51 patients with PCs, 14% presented with migraine with aura, whereas only 2% of the patients in the control group had migraines with aura. While there have been some reports that large benign cysts can lead to hydrocephalus resulting in headache, many investigators suggest that the mechanisms producing headaches in patients with PCs are not associated with compression or mass effect. In support of this, many patients with PCs exhibiting compression of the quadrigeminal lamina as determined by MRI are asymptomatic. The observation that none of these patients had hydrocephalus and that size of the PC did not vary between patients with and without headaches in the study by Seifert and colleagues led the investigators to propose a possible role of abnormal melatonin production, rather than mass effect, to be responsible for the reported headaches. Evidence from other studies has demonstrated a link between headache disorders and melatonin, but the precise mechanisms underlying the association with PCs are still unclear.

Other less common nonspecific signs include seizures, headaches, vertigo, blurred vision, hemiparesis, and vomiting. Rarer complications that have been reported include pineal apoplexy resulting from intracystic hemorrhage, development of secondary parkinsonian symptoms (eg, resting tremor), development of choroid plexus papilloma, and aseptic meningitis from cyst rupture.

Symptoms

Symptomatic pineal cysts are rare and, consequently, reports have been rare as well. Most pineal cysts are found incidentally, and are asymptomatic and independent of initial presenting symptoms. Even when there is growth in an initially asymptomatic PC, the lesion is likely to remain asymptomatic. However, when symptoms do develop, clinical manifestations of PCs and other pineal pathologies are intimately tied to the unique location and physiology of the pineal gland.

Pinocytes, the main parenchymal cell within the pineal gland, link sympathetic input from the retina to the production of melatonin, which is involved in the regulation of wake-sleep cycles and the release of other hormones. However, it is unclear as to what extent the presence of PCs alter the regular production and secretion of these hormones. Significant compromise of pineal gland function may lead to irregular melatonin production and be subsequent to hormonal imbalance. Precocious puberty is one of the more common endocrine imbalances associated with PCs, and rarer symptoms reported include hypogonadism and diabetes insipidus.

Given the sensitive location of the pineal gland, even small masses may have potentially serious consequences. Cerebellar, corticospinal, and sensory disturbances may result from direct compression of the midbrain. If large enough, PCs can lead to hydrocephalus associated with aqueductal compression, blockage of the vein of Galen, and symptoms of raised intracranial pressure. Compression of the superior colliculus leads to Parinaud syndrome, characterized by number of abnormalities in eye movement and pupillary function including upgaze palsy, light-near dissociation of pupils, and convergence-retraction nystagmus.

Headaches are the most common neurologic symptom of patients with pineal cysts. In a case-control study examining the association between headaches and pineal cysts, Seifert and colleagues found that patients with PC were twice as likely to develop headaches when compared with age-matched and sex-matched controls (51% vs 25%) and that the most frequent presenting symptom was migraines (26%). Of the 51 patients with PCs, 14% presented with migraine with aura, whereas only 2% of the patients in the control group had migraines with aura. While there have been some reports that large benign cysts can lead to hydrocephalus resulting in headache, many investigators suggest that the mechanisms producing headaches in patients with PCs are not associated with compression or mass effect. In support of this, many patients with PCs exhibiting compression of the quadrigeminal lamina as determined by MRI are asymptomatic. The observation that none of these patients had hydrocephalus and that size of the PC did not vary between patients with and without headaches in the study by Seifert and colleagues led the investigators to propose a possible role of abnormal melatonin production, rather than mass effect, to be responsible for the reported headaches. Evidence from other studies has demonstrated a link between headache disorders and melatonin, but the precise mechanisms underlying the association with PCs are still unclear.

Other less common nonspecific signs include seizures, headaches, vertigo, blurred vision, hemiparesis, and vomiting. Rarer complications that have been reported include pineal apoplexy resulting from intracystic hemorrhage, development of secondary parkinsonian symptoms (eg, resting tremor), development of choroid plexus papilloma, and aseptic meningitis from cyst rupture.

Radiological features

PCs appear as small, adequately circumscribed, unilocular masses within the pineal gland typically measuring less than 10 mm in diameter. Cysts can range from 5 to 15 mm in many asymptomatic patients and can also be as large as 45 mm in diameter in symptomatic cases. PCs can either reside within or completely replace the pineal gland. Signal intensity is variable and is dependent on the cystic components. In addition, PCs typically do not exhibit compression of adjacent structures including the cerebral aqueduct, vein of Galen, and the quadrigeminal plate.

Computed Tomography

On computed tomography (CT), PCs can appear hypodense relative to cerebrospinal fluid (CSF) ( Fig. 1 ). Regions or nodules of hyperdensity may be detected because of hemorrhage or calcification. Roughly 25% to 33% of PCs may contain thin rim calcifications along cyst walls. However, the contents of the PC can be either homogeneous or heterogeneous, and may have either a unilocular or polycystic appearance. On contrast imaging, PCs exhibit contrast enhancement peripherally. Some investigators have noted that smaller pineal cysts are not clearly detectable on CT and should require further MRI for confirmation. In a retrospective study by Tamaki and colleagues, 32 patients with PCs received initial CT scans. A low-density mass diagnostic of a PC was found in 12 patients (37.5%). In addition, CT imaging revealed slight dotted or nodular sharply enhancing calcifications along the cyst walls. However, in the remaining 20 patients (63%), CT imaging did not identify the PCs, and additional imaging was required. Similarly, Fain and colleagues found calcification in only 3 of 9 patients (33%) through CT. This failure to show PCs on CT scans is likely due to the similar densities of CSF and PCs.

Magnetic Resonance Imaging

On MRI, PCs are sharply defined ovoid lesions with smooth margins ( Fig. 2 ). The contents of PCs are homogeneous and lack intracystic trabeculations. Because cystic contents are typically aqueous or contain protein, PCs usually have signal characteristics similar to CSF. Several studies using traditional MRI techniques to examine PCs have reported their configurations and imaging characteristics.

In one of the earlier retrospective MR studies of PCs, Lee and colleagues reviewed 1000 MR scans and identified 15 patients with PCs. The majority of cases were incidental findings on routine MRI. Patients were scanned with either a 1.5-T or 0.35-T imaging unit. Mean age was 30 years, and cyst diameters ranged from 5 to 15 mm. On imaging, PCs often had smooth borders with homogeneous cystic contents. On T1-weighted imaging (T1-WI), 11 out of 15 (73.3%) showed slightly increased signaling intensity, and the remaining 4 (26%) were isointense relative to CSF in adjacent ventricles. On T2-weighted imaging (T2-WI), 10 (66.7%) showed markedly increased signaling intensity, 3 (20%) were slightly increased, 1 (6.7%) was isointense, and 1 (6.7%) was hyperintense relative to CSF. The cyst walls were thin and ranged from 1.0 to 2.0 mm, and there was no evidence of compression of the third ventricle or collicular plates, or hydrocephalus.

Jinkins and colleagues reported the imaging characteristics of 60 patients with PCs. Most cysts appeared unilocular while 2 (3.3%) showed septations. On T1-WI (repetition time/echo time 500/20 ms, thickness 5 mm), 37 (62%) were hyperintense, 17 (28%) were isointense, and 6 (10%) were hypointense. On proton-density–weighted imaging (PD-WI) (2400/30 ms, 5 mm), 43 (72%) were hyperintense, 14 (23%) were isointense, and 2 (5%) were hypointense. Finally, on T2-WI (2400/80 ms, 5 mm), 23 (38%) were hyperintense, 34 (57%) were isointense, and 3 (5%) were hypointense. All patients receiving T1-WI immediately following intravenous (IV) administration of gadolinium showed a thin rim of enhancement. In addition, in 2 patients receiving IV gadolinium following delay of up to 60 minutes, T1-WI showed central enhancement of the lesion ( Fig. 3 ). Thinning of the superior colliculi of the quadrigeminal plate was observed in 19 patients (32%), and no hydrocephalus was detected in any patient.