Cystic craniopharyngioma

Cystic craniopharyngioma

Cystic craniopharyngiomas comprise more than 90% of the craniopharyngiomas.

Treatment

Intracystic treatment options for cystic craniopharyngioma provide data suggestive of durable cyst shrinkage and benefit beyond a pure volume reduction due to repeated fluid aspirations. The effect however is limited to the cystic craniopharyngioma portion without an effect on the solid component. There are multiple challenges relating to technical practicalities: Multicystic occurrence may limit treatment to one cyst only and therefore this approach does not provide the clinical benefit as wished. The thickness of the cyst wall may not allow successful penetration of the scope/catheter into the cyst and different catheter designs make the correct intracystic positioning of the catheter and its holes difficult. Intraoperative ultrasound and computed tomography (CT) have aided to confirm the correct catheter position; however, volume changes during subsequent treatment may influence the intracystic catheter tip location.

Hence the prospect of a minimally invasive intervention – such as an endoscopic insertion of a catheter with a subcutaneous Ommaya reservoir – and subsequent instillation of substances inducing shrinkage of the craniopharyngioma cyst(s), seems a promising strategy 1).

Intracystic bleomycin

A search in electronic databases CENTRAL (2014, Issue 1), MEDLINE/PubMed (from 1966 to March 2014) and EMBASE/Ovid (from 1980 to March 2014) with pre-specified terms, Reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2013) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in May 2014.

Randomized controlled trials (RCTs), quasi-randomized trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).

Two review authors independently performed the data extraction and ‘Risk of bias’ assessment. They used risk ratio (RR) for binary data and mean difference (MD) for continuous data. We planned that if one of the treatment groups experienced no events and there was only one study available for the outcome, we would use the Fischer’s exact test.

Zheng et al. could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. They did identify a RCT comparing intracystic bleomycin with intracystic phosphorus 32 (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59), neurological status (Fisher’s exact P value = 0.429), 3rd nerve paralysis (Fischer’s exact P value = 1.00), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer’s exact P value = 0.029 for both outcomes).

Since they identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed 2).

Phosphorus-32

Radioactive phosphorus 32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR.

Ansari et al reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients’ records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR.

Ansari et al performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors’ institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR.

Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and subsequent treatment was 1.67 ± 1.50 years (mean ± SD).

In this small but focused population, P32 treatment provided limited local control for cyst growth. Brachytherapy alone did not reliably avert the need for subsequent surgery or EBR 3).

Case series

11 non-consecutive adult cystic craniopharyngiomas (7 recurrent lesions) have been treated with Ommaya Reservoir System (ORS), in two neurosurgical centers. ORS was placed in nine cases using minimally invasive procedures: six burr hole endoscopic insertion and three navigated electromagnetic placement; in the remaining two patients, the Ommaya reservoir was used as a shunt to prevent cyst recollection during a transcranial approach.

The main presenting symptoms were visual impairment (75%), cognitive and behavioral disorders (66.7%), hypopituitarism (38%), headache (30.8%) and hypothalamic obesity (8%). The median follow-up period was 41.4 months. In all patients, the visual function and intracranial hypertension improved after decompression. Local tumor control was accomplished in eight patients (72.7%), without the need of adjuvant treatments. The endoscopic vision carried similar rates of tumor control than the stereotaxy (75% vs 66.7%).

In selected patients, tailored procedures are required to achieve long-term tumor control and as well limit surgery-related morbidity. ORS could represent a safe and effective treatment option for cystic craniopharyngiomas, providing also reduced surgical related morbidity especially in recurrent lesions and in patients nonsuitable for radical surgery 4).

References

1)

Bartels U, Laperriere N, Bouffet E, Drake J. Intracystic therapies for cystic craniopharyngioma in childhood. Front Endocrinol (Lausanne). 2012 Mar 27;3:39. doi: 10.3389/fendo.2012.00039. eCollection 2012. PubMed PMID: 22654864; PubMed Central PMCID: PMC3356106.
2)

Zheng J, Fang Y, Cai BW, Zhang H, Liu W, Wu B, Xu JG, You C. Intracystic bleomycin for cystic craniopharyngiomas in children. Cochrane Database Syst Rev. 2014 Sep 19;9:CD008890. doi: 10.1002/14651858.CD008890.pub3. Review. PubMed PMID: 25233847.
3)

Ansari SF, Moore RJ, Boaz JC, Fulkerson DH. Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma. J Neurosurg Pediatr. 2016 Apr;17(4):439-45. doi: 10.3171/2015.8.PEDS15317. Epub 2015 Dec 18. PubMed PMID: 26684761.
4)

Frio F, Solari D, Cavallo LM, Cappabianca P, Raverot G, Jouanneau E. OMMAYA RESERVOIR SYSTEM FOR THE TREATMENT OF CYSTIC CRANIOPHARYNGIOMAS: SURGICAL RESULTS IN A SERIES OF 11 ADULT PATIENTS AND REVIEW OF THE LITERATURE. World Neurosurg. 2019 Aug 7. pii: S1878-8750(19)32133-3. doi: 10.1016/j.wneu.2019.07.217. [Epub ahead of print] PubMed PMID: 31400528.

Update: Cystic metastases

Cystic metastases

Epidemiology

The development of cystic brain metastases remains a relatively rare occurrence.

Etiology

Metastatic brain tumors are normally composed of cystic components, however, the reasons for the cyst formation have not been clearly investigated 1). Stem 2) reported that the brain cyst fluid protein always presents in the inflammatory exudates. Cumings 3) also reported that the cyst fluid formation may be correlated with the tumor degeneration. Gardner et al 4) found that fluid accumulating in brain tumors runs in the normal drainage route, since there are no lymphatic vessels in the tumors.
Gamma knife radiosurgery (GKRS) is occasionally a useful tool for maintaining good brain status in patients with brain metastases (METs). Conversely, Ishikawa et al. experienced patients with delayed cyst formation (DCF) several years after GKRS, a complication not previously reported 5).

Differential diagnosis

The main challenge in discrimination between intracranial cystic lesions is to differentiate benign inflammatory cystic lesions (as cerebral abscess) from malignant cystic lesions (as cystic metastases and cystic glioma) which have totally different management.
Cerebral abscess.
Hydatid cyst.
Other intra-axial cysts, e.g. intracranial arachnoid cyst, neuroglial cyst, porencephalic cyst.
The most common tumors are, hemangioblastoma, pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma.
Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma 6).

Treatment

In a review, Kim et al. describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes 7).

Case series

2017

Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively.
The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p=0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction.
For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst 8).

2016

Lee et al. retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy.
The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage.
According to this results, they suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor 9).


A study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24-72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life 10).

2014

Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).
Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months.
Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time 11).

2013

Ebinu et al. reviewed a prospectively maintained database of brain metastases patients treated between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.
A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.
This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates 12).

2012

Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined.
Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement.
The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases 13).

2009

Hydrofiber dressing is a sodium carboxymethylcellulose hydrocolloid polymer with high fluid-absorptive capacity. This material was originally used as a dressing for exudative wounds. Hydrofiber dressing was used for 8 patients with cystic-type metastatic brain tumor. Tumor removal was performed after hydrofiber dressing was inserted into the cyst cavity to transform the tumor into a solid-type tumor.
Transformation of cystic-type metastatic brain tumors into smaller solid-type tumors using hydrofiber dressing facilitated en bloc resection of tumor. The dressing also absorbed residual cyst fluid and was thus also effective in preventing intraoperative dissemination of tumor cells. This approach enabled ideal en bloc resection in all patients. There were no adverse events.
These findings suggest hydrofiber dressing may be useful in surgery for cystic-type metastatic brain tumors 14).

2008

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor.
Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients.
The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis 15).

Case reports

2015

A study describes the first case of histopathologically-confirmed brainstem metastasis originating from lung adenosquamous carcinoma, and discusses the outcomes of treatment by stereotactic aspiration combined with gamma knife radiosurgery (GKRS). A 59-year-old female presented with a cystic mass (15×12×13 mm; volume, 1.3 cm3) located in the pons, two years following surgical treatment for adenosquamous carcinoma of the lung. The patient received initial GKRS for the lesion in the pons with a total dose of 54.0 Gy, however, the volume of the mass subsequently increased to 3.9 cm3 over a period of three months. Computed tomography-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 2.0 cm3 of yellow-white fluid. Histology confirmed the diagnosis of adenosquamous carcinoma. Aspiration provided immediate symptomatic relief, and was followed one week later by repeat GKRS with a dose of 12.0 Gy. The patient survived for 12 months following the repeat GKRS; however, later succumbed to the disease after lapsing into a two-week coma. The findings of this case suggest that stereotactic aspiration of cysts may improve the effects of GKRS for the treatment of cystic brainstem metastasis; the decrease in tumor volume allowed a higher radiation dose to be administered with a lower risk of radiation-induced side effects. Therefore, stereotactic aspiration combined with GKRS may be an effective treatment for brainstem metastasis originating from adenosquamous carcinoma 16).

2009

A 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient’s previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated 17).


Cystic brain metastases from small-cell lung carcinomas are exceedingly rare and neurosurgical operations are not suitable for those cases considering invisible micrometastases. A 34-year-old female patient presented with small-cell lung carcinoma that metastasized to the brain as a solitary cyst with a thin wall 24 months after a good partial response to initial chemoradiotherapy. The brain mass volume and the main symptom of left hemiplegia, which made the Karnofsky performance status (KPS) fall to 30%, did not respond to whole brain irradiation. Therefore, an Ommaya reservoir was inserted, which dramatically improved the KPS to 70%. This minimally invasive surgical strategy is suitable even for patients with a poorer KPS bearing cystic brain metastases 18).

References

1)

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated? Stereotact Funct Neurosurg. 1999;72 Suppl 1:38-44. PubMed PMID: 10681689.
2)

Stem K. Chemical study of fluids obtained from cerebral cysts: Report on 56 cases. Brain. 1939;62:88. doi: 10.1093/brain/62.1.88.
3)

CUMINGS JN. The chemistry of cerebral cysts. Brain. 1950 Jun;73(2):244-50. PubMed PMID: 14791790.
4)

GARDNER WJ, COLLIS JS Jr, LEWIS LA. Cystic brain tumors and the blood-brain barrier. Comparison of protein fractions in cyst fluids and sera. Arch Neurol. 1963 Mar;8:291-8. PubMed PMID: 13946556.
5)

Ishikawa E, Yamamoto M, Saito A, Kujiraoka Y, Iijima T, Akutsu H, Matsumura A. Delayed cyst formation after gamma knife radiosurgery for brain metastases. Neurosurgery. 2009 Oct;65(4):689-94; discussion 694-5. doi: 10.1227/01.NEU.0000351771.46273.22. PubMed PMID: 19834373.
6)

Ramanathan N, Kamaruddin KA, Othman A, Mustafa F, Awang MS. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report. Malays J Med Sci. 2016 May;23(3):92-4. PubMed PMID: 27418876; PubMed Central PMCID: PMC4934725.
7)

Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. Review. PubMed PMID: 25977901; PubMed Central PMCID: PMC4426272.
8)

Oshima A, Kimura T, Akabane A, Kawai K. Optimal implantation of Ommaya reservoirs for cystic metastatic brain tumors preceding Gamma Knife radiosurgery. J Clin Neurosci. 2017 May;39:199-202. doi: 10.1016/j.jocn.2016.12.042. Epub 2017 Jan 20. PubMed PMID: 28117259.
9)

Lee SR, Oh JY, Kim SH. Gamma Knife radiosurgery for cystic brain metastases. Br J Neurosurg. 2016;30(1):43-8. doi: 10.3109/02688697.2015.1039489. Epub 2015 May 11. PubMed PMID: 25958957.
10)

Wang H, Qi S, Dou C, Ju H, He Z, Ma Q. Gamma Knife radiosurgery combined with stereotactic aspiration as an effective treatment method for large cystic brain metastases. Oncol Lett. 2016 Jul;12(1):343-347. Epub 2016 May 18. PubMed PMID: 27347148; PubMed Central PMCID: PMC4907086.
11)

Jung TY, Kim IY, Jung S, Jang WY, Moon KS, Park SJ, Lim SH. Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic brain metastases. Stereotact Funct Neurosurg. 2014;92(4):234-41. doi: 10.1159/000362935. Epub 2014 Aug 19. PubMed PMID: 25138737.
12)

Ebinu JO, Lwu S, Monsalves E, Arayee M, Chung C, Laperriere NJ, Kulkarni AV, Goetz P, Zadeh G. Gamma knife radiosurgery for the treatment of cystic cerebral metastases. Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):667-71. doi: 10.1016/j.ijrobp.2012.06.043. Epub 2012 Aug 9. PubMed PMID: 22885145.
13)

Higuchi F, Kawamoto S, Abe Y, Kim P, Ueki K. Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component. J Neurosurg. 2012 Dec;117 Suppl:17-22. doi: 10.3171/2012.7.GKS121001. PubMed PMID: 23205784.
14)

Okuda T, Teramoto Y, Yugami H, Kataoka K, Kato A. Surgical technique for a cystic-type metastatic brain tumor: transformation to a solid-type tumor using hydrofiber dressing. Surg Neurol. 2009 Dec;72(6):703-6; discussion 706. doi: 10.1016/j.surneu.2009.07.045. Epub 2009 Oct 15. PubMed PMID: 19836065.
15)

Franzin A, Vimercati A, Picozzi P, Serra C, Snider S, Gioia L, Ferrari da Passano C, Bolognesi A, Giovanelli M. Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis. J Neurosurg. 2008 Aug;109(2):259-67. doi: 10.3171/JNS/2008/109/8/0259. PubMed PMID: 18671638.
16)

DU C, Li Z, Wang Z, Wang L, Tian YU. Stereotactic aspiration combined with gamma knife radiosurgery for the treatment of cystic brainstem metastasis originating from lung adenosquamous carcinoma: A case report. Oncol Lett. 2015 Apr;9(4):1607-1613. Epub 2015 Feb 16. PubMed PMID: 25789009; PubMed Central PMCID: PMC4356421.
17)

Zigouris A, Pahatouridis D, Mihos E, Alexiou GA, Nesseris J, Zikou AK, Argyropoulou MI, Goussia A, Voulgaris S. Solitary cystic cerebral metastasis from transitional cell carcinoma of the bladder. Acta Neurol Belg. 2009 Dec;109(4):322-5. PubMed PMID: 20120215.
18)

Takeda T, Saitoh M, Takeda S. Solitary cystic brain metastasis of small-cell lung carcinoma controlled by a stereotactically inserted Ommaya reservoir. Am J Med Sci. 2009 Mar;337(3):215-7. doi: 10.1097/MAJ.0b013e3181833847. PubMed PMID: 19204557.

Cystic glioblastoma

Cystic glioblastoma is a descriptive term to one form of glioblastoma that contains large cystic component, rather than being a pathological subtype.

Epidemiology

It is a rare disease whose exact prevalence is unknown. Glioblastoma is usually seen as a unilateral solid tumor more commonly in the supratentorial compartment. The presence of cyst in the GBM is rare. Bilateral large cystic GBM is still rarer 1).
Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.


GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = -0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5΄-phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs. 2).


Cystic GBM may be confused rarely on radiology with tuberculoma as both may show a mass lesion with hypodense centre surrounded by a ring of enhancement. Peroperative cytological examination of smears prepared from fluid aspirated from cysts by rapid Diff-Quik method may prove beneficial for immediate diagnosis in suspicious cases and appropriate patient management may be carried out 3).

Outcome

The presence of cystic features in glioblastoma (GBM) has been described as a favorable prognostic factor, possibly because cystic GBMs showed comparatively little infiltration of the peritumoral brain parenchyma 4).

Case series

 2011

A retrospective review of 354 consecutive patients treated with resection of primary GBM was performed using medical records and imaging information obtained at the University of California, San Francisco from 2005 to 2009. Within this cohort, 37 patients with large cysts (≥ 50% of tumor) were identified. Clinical presentations and surgical outcomes were statistically compared between the cystic and noncystic patients.
There were no statistically significant differences in clinical presentation between groups, including differences in age, sex, presenting symptoms, tumor location, or preoperative functional status, with the exception of tumor size, which was marginally larger in the cystic group. Surgical outcomes, including extent of resection and postoperative functional status, were equivalent. The median actuarial survival for the patients with cystic GBM was 17.0 months (95% CI 12.6-21.3 months), and the median survival for patients with noncystic GBM was 15.9 months (95% CI 14.6-17.2 months). There was no significant between-groups difference in survival (p = 0.99, log-rank test). A Cox multivariate regression model was constructed, which identified only age and extent of resection as independent predictors of survival. The presence of a cyst was not a statistically significant prognostic factor.
This study, comprising the largest series of cases of primary cystic GBM reported in the literature to date, demonstrates that the presence of a large cyst in patients with GBM does not significantly affect overall survival as compared with survival in patients without a cyst. Preoperative discussions with patients with GBM should focus on validated prognostic factors. The presence of cystic features does not confer a survival advantage 5).

2004

A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (> or = 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9-24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1-16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01-18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8-6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively.
The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature 6).
1)

Kumar S, Handa A, Sinha R, Tiwari R. Bilateral cystic glioblastoma multiforme. J Neurosci Rural Pract. 2013 Oct;4(4):476-7. doi: 10.4103/0976-3147.120196. PubMed PMID: 24347967; PubMed Central PMCID: PMC3858779.
2)

Dahlberg D, Struys EA, Jansen EE, Mørkrid L, Midttun Ø, Hassel B. Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells. Neurosurgery. 2017 Jun 1;80(6):917-924. doi: 10.1093/neuros/nyw101. PubMed PMID: 28327992.
3)

Hasan M, Siddiqui B, Qadri S, Faridi S. Cystic glioblastoma multiforme masquerading as a cerebral tuberculoma. BMJ Case Rep. 2014 Oct 17;2014. pii: bcr2014206832. doi: 10.1136/bcr-2014-206832. PubMed PMID: 25326570; PubMed Central PMCID: PMC4202055.
4)

Utsuki S, Oka H, Suzuki S, Shimizu S, Tanizaki Y, Kondo K, Tanaka S, Kawano N, Fujii K. Pathological and clinical features of cystic and noncystic glioblastomas. Brain Tumor Pathol. 2006 Apr;23(1):29-34. PubMed PMID: 18095116.
5)

Kaur G, Bloch O, Jian BJ, Kaur R, Sughrue ME, Aghi MK, McDermott MW, Berger MS, Chang SM, Parsa AT. A critical evaluation of cystic features in primary glioblastoma as a prognostic factor for survival. J Neurosurg. 2011 Oct;115(4):754-9. doi: 10.3171/2011.5.JNS11128. Epub 2011 Jul 15. PubMed PMID: 21761969.
6)

Maldaun MV, Suki D, Lang FF, Prabhu S, Shi W, Fuller GN, Wildrick DM, Sawaya R. Cystic glioblastoma multiforme: survival outcomes in 22 cases. J Neurosurg. 2004 Jan;100(1):61-7. PubMed PMID: 14743913.
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