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Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 54-62

Symptomatic improvement following resection of cystic pineal lesions

1 Department of Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA
2 Department of Radiology, Medical University of South Carolina, Charleston, South Carolina, USA
3 Department of Pathology, Medical University of South Carolina, Charleston, South Carolina, USA

Date of Web Publication02-Nov-2021

Correspondence Address:
Dr. Sunil J Patel
Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29425
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_409_21

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Introduction: Pineal cysts have proven to be a challenging pathology for neurosurgeons. Due to occasional nonspecific symptoms, as well as a wide range of possible morphology and diagnoses, literature is scarce, and little evidence-based management guidelines exist.
Methods: We present a retrospective review of 38 patients who underwent a surgical resection of a pineal lesion in a single center by a single surgeon between 2012 and 2018. Symptoms, imaging characteristics of the lesion, pathology report, and postoperative radiographic and clinical outcomes were collected.
Results: Thirty-eight patients were selected. The most common preoperative symptoms included headaches (97%), visual disturbances (89%), cognitive disturbances (58%), and nausea/vomiting (53%). Preoperative radiographic measures showed no relationship to the pathological diagnosis of pineal cyst or pineocytoma (P > 0.05) except for mass effect on the tectal plate that was associated with pineocytoma (P < 0.05). Lesion pathology breakdown: 23 (60%) – World Health Organization Grade I pineocytoma, 14 (37%) – simple pineal cysts, and 1 (3%) – pineal parenchymal tumor of intermediate differentiation. The mean follow-up was 24 months. Headaches and visual disturbances were relieved in 78% and 58% of patients, respectively. Cognitive disturbances were found to be correlated with pineal cyst (P < 0.01). Patients with hyperintense fluid-attenuated inversion recovery signal and enhancement on preoperative magnetic resonance imaging were found to be at higher risk of not experiencing full symptom resolution (P < 0.05). Finally, if no symptom resolution occurred, then higher chance of patients not returning to work was seen (P < 0.05).
Conclusion: Albeit challenging to treat, careful examination of presurgical imaging findings and surgical resection of appropriately selected pineal lesions can lead to significant relief of preoperative symptoms and overall meaningful improvement.

Keywords: Clinical outcome, headache, pineal cyst, pineal parenchymal tumor, pineocytoma, surgical resection

How to cite this article:
F. Porto GB, Alshareef MA, Lowe SR, Chatterjee AR, Welsh CT, Carroll S, Patel SJ. Symptomatic improvement following resection of cystic pineal lesions. Int J Neurooncol 2021;4, Suppl S1:54-62

How to cite this URL:
F. Porto GB, Alshareef MA, Lowe SR, Chatterjee AR, Welsh CT, Carroll S, Patel SJ. Symptomatic improvement following resection of cystic pineal lesions. Int J Neurooncol [serial online] 2021 [cited 2022 May 22];4, Suppl S1:54-62. Available from: https://www.Internationaljneurooncology.com/text.asp?2021/4/3/54/329804

  Introduction Top

Resection of pineal gland cysts (or cystic pineal glands) represents an emerging controversy in neurosurgery. While radiographically, simple cystic lesions in the pineal recess are generally considered to be pineal cysts, it may be difficult to distinguish a simple cyst from a pineal neoplasm based on imaging alone.[1] Furthermore, these lesions are often discovered incidentally, or on workup for symptoms such as headache or nausea.[2] The current understanding of the incidence of pineal cysts suggests a prevalence of around 1% in retrospective magnetic resonance imaging (MRI) studies.[3],[4] The incidence of other cystic pineal neoplasms such as pineocytoma is less well defined but considerably more rare, with some authors estimating pineocytoma to represent 0.5% of all intracranial tumors.[5]

Despite the relatively high incidence of pineal cysts in the adult population, definitive guidelines are lacking on management. While management of patients with small lesions with no symptoms, and likewise management of those with large cysts and obstructive hydrocephalus or Parinaud syndrome is straightforward, management of those with what are often referred to as “nonspecific” symptoms, such as headache, nausea, or vision disturbance, is controversial and ill defined. Indeed, given the increasing discovery of pineal cysts on neuroimaging, determination of causality between a cystic pineal lesion and a nonspecific symptom such as headache is difficult. This has resulted in a wide range of published opinions on preferred management for these lesions, with some authors recommending simple observation or even discharge from neurosurgery clinic,[3],[6] to surgical resection for headaches and certain other nonspecific symptoms.[7],[8]

Surgical indication for pineocytoma is more straightforward, as the current consensus is gross total resection, and is the preferred means of achieving oncologic benefit.[5],[9],[10] However, studies specifically comparing imaging with histopathology of cystic pineal lesions have warned of the inability to distinguish benign pineal glial cysts from cystic pineal region tumors.[2],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] Furthermore, as with pineal cysts, there is no real evidence to support or refute a causal link between the presence of a small cystic pineocytoma and the presence of nonspecific symptoms.

Herein, we present our experience with a cohort of 38 patients who underwent surgical resection of cystic pineal lesions which on pathologic diagnosis were found to represent both pineal cyst and pineocytoma. We report the symptomatology of the cohort to better define which constellation of nonspecific symptoms is most likely to improve following surgery as well as the radiographic findings and surgical complications in this patient population.

  Methods Top

Study population

After obtaining approval from the institutional review board, a retrospective chart review was undertaken of all patients who had undergone resection of a cystic lesion in the pineal recess at our institution beginning in 2012 and ending in 2018. Patients with cystic pineal lesions resected for reasons other than obvious compressive symptoms (i.e., Parinaud syndrome or hydrocephalus), for diagnosis (e.g., biopsy), or obvious malignancy were included for review. Demographics, clinical characteristics, surgical characteristics, and radiographic characteristics were reviewed and analyzed.

Surgical selection criteria

Patients were deemed surgical candidates if they had a cystic pineal lesion exhibiting disabling headaches refractory to medical management in conjunction with other nonspecific symptoms, similar to the indications expressed by Kalani et al.[7] Surgery was not offered to patients solely presenting with clear migraine headaches. The final decision for surgical or conservative management was taken by the senior author (SJP). All patients must have sought consultation with either their primary care physician or a neurologist preoperatively for headache management without benefit. Patients were extensively counseled by the senior author preoperatively regarding the risks and benefits of the operation, including the risk of failure to improve symptomatically, along with the usual risks of a craniotomy to resect a pineal region lesion. Patients were clearly informed preoperatively that they may gain no relief of symptoms from surgery. All patients consenting to surgical resection had been offered continued observation with serial MRI scans as an alternative.

Data collection and outcomes – clinical

All patients were assessed postoperatively by the lead and senior authors independently. The senior authors assessed patients at the time of postoperative follow-up (1 week–1 month postoperatively) and at last documented clinical follow-up. The lead author assessed patients independent of the senior author at the time of most recent follow-up via telephone interview. All recorded clinical parameters assessed at the preoperative visit were again confirmed. No discrepancies between the assessments of the lead and senior authors were identified.

Data collection and outcomes – radiographic

Preoperative MRI studies were available for all patients. These included diffusion-weighted images, axial T2-weighted images (conventional spin echo with repetition times [TRs] ranging from 2800 to 3500 ms and echo times [TEs] ranging from 98 to 128 ms with a section thickness of 5-mm and 1-mm intersection gap), and both axial and sagittal T1-weighted images (conventional spin echo with TRs ranging from 400 to 700 ms and TEs ranging from 9 to 14 ms and a section thickness of 3–6 mm with an intersection gap of 0.5–1.0 mm). Both pre- and post-multihance gadolinium contrast sequences (Bracco, Milan, Italy) were available at 1.5 or 3.0 Tesla field strength. All the postcontrast sequences were performed within 10 min of contrast administration. The maximal pixel size in the plane of imaging was 1.28 mm × 0.96 mm to 1.6 mm × 1.2 mm. These studies were performed on a variety of MR manufacturer platforms. Preoperative MRI was independently assessed by a board-certified attending neuroradiologist (ARC). Morphometric measurements of the pineal cystic mass included the maximal transverse diameter on axial imaging and maximal AP diameter on the mid-sagittal imaging of the cystic and solid components. The cystic component imaging characteristics recorded included the T1, T2, and fluid-attenuated inversion recovery (FLAIR) signal intensity relative to cerebrospinal fluid (CSF). Any enhancement of the mass was characterized as irregular or homogeneous. Cystic component wall thickness in millimeters, wall nodularity, the presence of single or multiple septations, mass effect on the tectal plate as moderate or severe, and degree of aqueductal stenosis were recorded. An MRI diagnosis of pineal cyst was made by meeting the following four criteria originally proposed by Barboriak et al.: round or ovoid area of signal abnormality centered in the pineal recess, hypointensity of the abnormality on T1-weighted images and isointensity to CSF on T2-weighted images, internal homogeneity on T2-weighted images, a maximum of one internal septation, and no marginal lobulation or contrast-enhancing nodularity >2 mm in thickness.[23] An MRI diagnosis of a pineal cyst with atypical features was considered if there was wall nodularity, wall thickness of >2 mm, or multiple septations.[11],[12]

Pathology for each patient was reviewed by an attending neuropathologist at our institution. If the initial pathologic diagnosis suggested pineocytoma, that specimen was reviewed independently from the diagnosing pathologist by a separate attending neuropathologist (SC) and the diagnosis of pineocytoma was confirmed in all cases. The World Health Organization diagnostic criteria were used for the diagnosis and grading of these neoplasms, as described by Louis et al.[24]

Data analysis

Mean and corresponding standard deviation were used for expressing quantitative data. Independent two-sample t-test was used for comparison of variables, and statistical significance was defined as P < 0.05.

  Results Top


A total of 38 subjects were identified on retrospective review as having undergone resection of a pineocytoma within the study timeframe. The mean patient age was 37.7 years (range: 18–55 years). Thirty-four patients were female and 4 were male. No patient had clinically apparent neurologic deficit at preoperative evaluation.

Presenting symptoms

Thirty-seven (97%) patients presented with headaches, often described as a constant pressure headache. Pressure headaches were described as their head feeling under pressure or in a vice with episodic exacerbations. The other most common symptoms were visual disturbances (n = 34, 89%), cognitive disturbances (22, 58%), and nausea/emesis (20, 53%). Less frequent symptoms included fatigue, insomnia, memory disturbance, photophobia, gait disturbances, and hemibody sensory disturbance [Table 1].
Table 1: Patient characteristics, symptoms, and preoperative diagnosis

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Radiographic characteristics

[Table 1] shows the MRI biomarker measures for each patient. Six out of 38 (16%) of these patients had pineal lesions with abnormal MRI characteristics suspicious for a tumor, 3 (8%) had the appearance of a pineal cyst with mass effect on the tectal plate, 8 (21%) had the appearance of a pineal cyst with atypical features, 4 (11%) had the appearance of a pineal cyst on noncontrast imaging needing further imaging, and 17 (45%) had the appearance of a typical pineal cyst.

FLAIR hyperintensity, AP diameter >10 mm, enhancement, wall thickness >2 mm, wall nodularity, presence of septations, and aqueductal stenosis showed no discernible relationship to the pathological final diagnosis of pineal cyst or pineocytoma (P > 0.05). Mass effect on the tectal plate, however, was associated with a significantly higher probability of pathological diagnosis of pineocytoma (P = 0.0045 < 0.05, 95% confidence interval [CI]: 0.16–0.82) [Table 2].
Table 2: Radiographic and pathology features

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Pathology of the lesion

All of the lesions had one or more cystic structures on macroscopic examination. The cysts in the nonneoplastic pineal glands tended to be in the central glial area of the pineal gland [Figure 1]a with compression of the surrounding pineal tissue. The pineocytoma cysts were more variable in location, the cells more numerous, with loss of the normal nested architecture, and the nuclei slightly larger with more irregular nuclear membranes [Figure 1]b. No mitotic activity was identified. The pineal parenchymal tumor of intermediate differentiation also demonstrated a diffuse pattern with an even higher level of cellularity but less than that seen in pineoblastoma. The nuclei were even larger and more irregular, with occasional larger, more bizarre nuclei [Figure 1]c. Mitotic activity was low.
Figure 1: (a) Low-power view of a pineal cyst demonstrating a pseudocyst in the central glial region of the pineal with surrounding compressed pineal parenchyma (H and E, ×2). (b) Pineocytoma at intermediate power showing increased cellularity and sheets of cells rather than a normal nested pattern (H and E, ×20). (c) Pineal parenchymal tumor of intermediate differentiation at intermediate power demonstrating even greater cellularity in sheets (H and E, ×20)

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Surgical complications

Thirty-six patients (95%) underwent resection of their lesion via an occipital transtentorial approach and 2 patients (5%) underwent posterior fossa craniotomy for a supracerebellar infratentorial approach. Postoperatively, three patients (8%) developed an upgaze palsy that resolved in two patients by discharge, and in one gradually after 2 years. Two patients (5%) developed a pseudomeningocele that required ventriculoperitoneal shunting, one patient developed a superficial wound infection that resolved with antibiotics, and six patients (16%) had surgical site tenderness of the plate requiring hardware explantation [Figure 2].
Figure 2: Summary of surgical complications (%)

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Clinical follow-up

The mean follow-up was 24 months, with a range of 11–37 months. At last postoperative follow-up, pressure headaches were relieved in 29 of 37 patients (78%). Of those, a small subset of patients was previously diagnosed with migraine-type headache, and in this group, only three of seven patients reported relief. One patient experienced return of headaches after a head trauma and had experienced relief of symptoms prior to this. Nausea was relieved in 15 of 20 patients (39%) and blurry vision in 20 of 34 patients (58%). [Figure 3] demonstrates the % presenting symptom improvement for symptoms evaluated. Preoperatively, 28 patients (74%) were unable to attend work or school due to their symptoms. At the time of last follow-up, only 12 of the 38 patients remained employed or in school. Of the 24 patients who did not have a postoperative complication, 10 remained employed or in school at last follow-up.
Figure 3: % symptomatic improvement in patients presenting with each of the specified signs and symptoms

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Symptom predictors for final pathology and correlation to radiographic findings and functional outcomes

[Table 3] correlates preoperative symptomatology with final histopathology. There was no statistical significance between symptom and pathology for all symptoms documented except for reported cognitive disturbances, in which case patient was more likely to have a pineal cyst as final diagnosis (P = 0.004 < 0.01, CI: −0.76 to − 0.15). The number of patients not working prior to surgical intervention was not significant between the two pathologies (P = 0.441, 95% CI: −0.19–0.42).
Table 3: Preoperative finding correlation to final histology

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When it comes to radiographic characteristics, patients in whom lesions had hyperintense signal on FLAIR imaging (P = 0.0382 < 0.05, CI: −0.58 to −0.02) and enhancement (P = 0.0166 < 0.05, CI: −0.71 to −0.08) were statistically less likely to appreciate complete symptom resolution (compared to presenting evaluated symptoms). These findings could be related to chronic compression and long-standing lesion, thus worse neurologic outcomes. Other radiographic signs evaluated were not significant in predicting complete symptom resolution. Finally, if there is complete symptom resolution, patients were more likely to return to work (P = 0.0274 < 0.05, CI: 0.05–0.78) [Table 4].
Table 4: Predictors for complete resolution of all patient symptoms at 2 years

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Case example

A 22-year-old female presented to us with an 18-month history of severe headaches, which she described as a pressure headache around her head radiating to an area behind the eyes. The severity of these headaches had increased slowly over the preceding 18 months. In addition, the patient had complaints of vertiginous symptoms, gait instability, blurred vision, and cognitive difficulty described as a “fog.” Her symptoms had been debilitating enough to force her to withdraw from university, despite medical therapy. MRI scan revealed a simple cystic lesion of the pineal gland measuring 14 mm in diameter. Mild compression of the midbrain tectum was noted without accompanying aqueductal stenosis or hydrocephalus [Figure 4].
Figure 4: (a) Magnetic resonance imaging T1 with gadolinium contrast sagittal view demonstrating a 14 by 9 mm pineal cyst. (b) One-year postoperative magnetic resonance imaging with contrast demonstrating complete resection and no evidence of recurrence

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After careful discussion of the risks and benefits, the patient elected to undergo a left-sided occipital transtentorial approach for resection. Pathology was reported as a simple pineal cyst. At the time of last follow-up (12 months postoperatively), the patient reports significant relief of headaches and resolution of her other accompanying symptoms. Postoperative MRI scan demonstrated gross total resection, and the patient has returned to school full time with an improved academic performance.

  Discussion Top

Apart from clear-cut cases of Parinaud syndrome or obstructive hydrocephalus, until recently relatively little work has been done to investigate if pineal region masses can be responsible for other clinical symptoms. The general consensus has been that in the large majority of cases, pineal cysts <10 mm in size are typically not a source of headaches,[2],[25],[26] and indeed, a recent survey found that 85% of neurosurgeons would not offer surgical treatment for a pineal cyst with nonspecific symptoms only.[9]

Early reports on surgery for pineal cysts focused on resection of large cysts with obvious tectal compression, often in conjunction with hydrocephalus, Parinaud syndrome, or both. A 1992 review found 27 total reported cases in the literature at that time, noting that patients often complain of paroxysmal headache, throbbing, and holocranial in character.[27] Interestingly, at this time, other authors had noted that cerebellar or sensory deficits may also rarely be present in patients with large cysts.[28],[29] While these early series were predominantly composed of patients harboring large cysts with overt gaze palsies, hydrocephalus, or papilledema, the authors did note good resolution of headache. Other authors around this time even noted improvement in certain psychiatric symptoms after cyst removal,[30],[31] and a recent case report showed a similar result after excision of a pineal epidermoid cyst.[32] It is interesting to note that several studies report pineal cysts as diagnosed on the basis of imaging are up to twice as likely to have headaches, but the severity of headache in these reports is not associated with size.[20],[33],[34] In our series, most nonspecific symptoms associated with pineal lesions preoperatively were found to improve postoperatively, including drastic reductions specifically in pressure-like headaches, cognitive disturbances, nausea/vomiting, photophobia, and gait disturbances.

Despite these early reports, Hajnsek et al., were among the first groups since the mid-1990s to discuss symptomatic improvement in patients with expansile lesions of the pineal region. While it is worth noting that their patients again differed from ours most significantly in that their surgical lesions were all >15 mm in size, it is salient to note that all seventy surgical patients had relief of headaches and diplopia, nausea, vomiting, and blurred vision.[35] Kalani et al., were the first group in many years to specifically study how resection of small pineal cysts without evidence of hydrocephalus or Parinaud syndrome might impact headache symptomatology. This study demonstrated relief of headaches in 18 consecutive patients.[7],[36] Further recent studies have shown good results in terms of nonspecific symptom relief with surgical pineal cyst resection in conjunction with an acceptable complication profile.[8],[37],[38] It is most interesting to note that Eide and Ringstad noted a high degree of symptom resolution with complete surgical excision but not cyst fenestration or shunting.[38]

The question that naturally follows is: What mechanism is responsible for these nonspecific symptoms and their subsequent resolution following surgical resection? Both Wisoff and Epstein and Kalani et al. propose that intermittent obstruction of the Sylvian aqueduct (analogous to colloid cysts of the third ventricle) is responsible for headaches in this cohort, with Wisoff and Epstein noting that the headaches tend to progress in intensity and take on a more continuous character.[27] This characteristic is consistent with our cohort, who were generally healthy, and then noted onset of headaches in adulthood, which generally progressed to a continuous, disabling character, with no relief provided by conservative measures. Eide and Ringstad postulated that mass effect could lead to compression of the deep venous drainage and result in a central venous hypertension syndrome, leading to nonspecific symptoms.[22]

However, if aqueductal compression was the sole mechanism for symptomatology in these patients, it is difficult to explain why symptoms other than paroxysmal headache are present in nonhydrocephalic patients and often improve with surgery, particularly gait disturbance, sensory disturbance, cognitive dysfunction, and visual disturbance. It would also be difficult to understand why cyst fenestration fared worse overall in terms of symptom relief as compared to total cyst excision in one study.[38]

Several studies have addressed the contribution of melatonin in the pathogenesis of headache, with one report suggestive of exogenous melatonin administration providing relief of symptoms in primary headache disorders and certain chronic pain syndromes.[39],[40] However, the literature on the impact of a pineal cyst and subsequent resection is inconsistent, with one study finding normal melatonin secretion in the presence of a pineal cyst and subsequent loss of endogenous melatonin secretion after resection;[41] Meyer et al., reported a case of a teenager with a large pineal cyst and headaches who demonstrated low melatonin levels that subsequently normalized after cyst resection.[42] Interestingly, the patient's headaches were partially relieved by exogenous melatonin administration prior to surgical excision.

In our series, we were able to identify mass on tectal plate on MRI as a statistically significant feature putting patients at a higher chance of having a pineocytoma as final diagnosis. If cognitive disturbances were present, the patient was more likely to have a pineal cyst. Furthermore, our series did not demonstrate a difference in outcomes based on pathology (i.e. pineal cyst vs. pineocytoma) or cyst size although we did show that if there is complete resolution presenting symptoms, patients were more likely to return to work. While the idea that an intermittent obstruction of the third ventricular outflow has merit, it likely does not explain the entire constellation of symptoms. However, the other proposed hypotheses in the literature are also, while intriguing, lacking in terms of overall evidence. It may simply be that the mechanism for these symptoms remains to be elucidated or is perhaps a combination of factors noted above, or of some factors not fully appreciated at the current time.[43],[44]


This study is limited by selection bias as patients were referred specifically for intractable headaches who already had a diagnosis of pineal cystic lesions based on imaging and their clinical outcomes were retrospectively evaluated. As such, this is a vulnerable patient population often willing to try anything to obtain relief of symptoms, which may cloud the patients' final subjective assessment of their results.

This study is additionally limited by the inherent subjectivity in assessment of the clinical symptoms and potential placebo effect. However, the response rate for specific symptoms including headache was greater than what would even under generous circumstances be attributable to placebo effect. However, the degree of expectation preoperatively in this cohort could certainly induce some degree of placebo effect into the final result. In addition, lack of an obvious pathophysiologic mechanism to explain the appearance (and resolution) of these symptoms in the setting of these lesions makes the ex facie dismissal of this association commonplace and makes argument for a causal relationship more difficult.

Finally, a word of caution is germane to the discussion. It is our responsibility, and our responsibility alone, to be good stewards of our craft and act in the best interest of our patients in a fiduciary role. Resection of pineal lesions is not a benign operation, even in the most experienced of hands.[36] Furthermore, we must be cognizant that we are proposing an operation for headache and other nonspecific symptoms, and as such, the clinician must be particularly mindful and vigilant before considering any sort of operation with the adverse event profile of a pineal surgery. We must not consider such an intervention at all unless we are certain that alternative diagnoses have been thoroughly excluded, conservative management has definitively failed, and that we are particularly diligent in our patient selection and informed consent process. While it is likely that this sort of intervention has benefit in a select cohort of patients, that exact cohort remains to be fully defined, and it is our duty to show restraint and first do no harm.

  Conclusion Top

In our retrospective review, we identified a subset of patients with pineal lesions who symptomatically responded well to surgery for resection of the lesion. In our cohort, patients with headaches characterized by intense pressure, nausea, and blurred vision were most likely to report symptomatic improvement. In the subset of patients with gait difficulty and cognitive slowing, good relief of symptoms is also seen. While many other symptoms were noted in this group, they were in general rather infrequent with a variable degree of recovery. While our series is not without substantial limitations, we feel this adds to the rather sparse literature on surgery for these types of lesions and provides further evidence for a more detailed study into this interesting syndrome.

Financial support and sponsorship

REDCap project, SCTR-Biomedical Informatics Center (BMIC) grant support (NIH/NCATS UL1 TR001450).

Conflicts of interest

REDCap project, SCTR-Biomedical Informatics Center (BMIC) grant support (NIH/NCATS UL1 TR001450).

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]


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