Clinical Features, Treatment, and Prognostic Factors of 56 Intracranial and Intraspinal Clear Cell Meningiomas

doi:10.1016/j.wneu.2017.12.173

World Neurosurgery

Volume 111, March 2018, Pages e880-e887

https://doi.org/10.1016/j.wneu.2017.12.173 Get rights and content

Highlights

•
The largest study of intracranial and intraspinal clear cell meningiomas from a single neurosurgical center.
•
CCM is a rare subtype of WHO grade II meningioma with a high rate of recurrence.
•
Because of CM's aggressive behavior, RT is recommended after the first surgery regardless of the extent of resection.
•
For recurrent patients, a second surgery combined with RT or chemotherapy might serve as an effective treatment.

Objective

Intracranial and intraspinal clear cell meningiomas (CCMs) are rarely reported because of their extremely low incidence, and the current understanding of CCM is poor. The purpose of this study was to analyze the incidence and the clinical, radiologic, pathologic, and prognostic features of intracranial and intraspinal CCMs.

Methods

Among 14,310 cases of intracranial and intraspinal meningiomas that were surgically treated between 2006 and 2016 at Beijing Tian Tan Hospital, 56 were chosen for analysis and retrospectively reviewed. To determine which parameters were associated with longer progression-free survival (PFS) and overall survival (OS), statistical analysis was performed.

Results

CCMs accounted for approximately 0.39% of all intracranial and intraspinal meningiomas. Patients with CCM had a mean age of 32.3 years and there was a female predilection (20 males and 36 females). Gross total resection was achieved in 35 cases, and subtotal resection was achieved in 21 cases. All patients were followed up for 10–206 months after surgery. Twenty-six patients experienced tumor recurrence, and the median PFS was 48.0 months. The 1-year, 3-year, and 5-year PFS was 87.5%, 59.8%, and 41.8%, respectively. Twelve patients died of tumor recurrence, and the median OS was not available. The 1-year, 3-year, and 5-year OS was 98.2%, 91.3%, and 65.8%, respectively. Univariate analysis showed that total tumor removal was significantly associated with a better prognosis. Multivariate analysis confirmed only Simpson grade III and IV resection as an independent risk factor for shorter PFS. Radiotherapy mildly improved PFS after both gross total resection and subtotal resection, showing no significant difference because of the small sample size and short follow-up duration.

Conclusions

CCM is a rare subtype of World Health Organization grade II meningioma. CCM typically involves young patients and shows a female predilection and high recurrence rate. When possible, total resection is the primary and most suitable treatment for CCM. For patients with primary tumors, radiotherapy is recommended after the initial operation regardless of the extent of resection. For patients with disease recurrence, secondary surgery combined with radiotherapy might serve as an effective treatment.

Introduction

Meningiomas are common intracranial and intraspinal tumors that originate from arachnoid cap cells and/or arachnoid trabeculae and are classified into 3 grades and 15 subtypes according to the 2016 World Health Organization (WHO) classification for brain tumors.1, 2 Clear cell meningioma (CCM) is a rare histopathologic variant that was originally described by Scheithauer in 1990 as representing <1% of all meningioma subtypes.3, 4 Histologically, CCM is characterized by sheets of polygonal cells with a clear cytoplasm, indicating a high glycogen concentration. Despite a benign histologic appearance, these tumors show aggressive behavior, with up to 60% recurring after resection.⁵ CCM tends to present in younger patients and represents a therapeutic challenge because of the propensity of CCM to recur and metastasize.⁶

Only approximately 100 intracranial and intraspinal CCMs have been reported in the English literature; most reports are isolated case studies, with the exception of a few clinical series studies.6, 7, 8, 9, 10, 11, 12 Because of the aggressive nature of CCM, the tumor must be distinguished from other varieties of meningioma. Given the rarity of this tumor type, data regarding the treatment strategy, prognostic factors, and survival are limited in the literature. In addition, the role of postoperative adjuvant radiotherapy (RT) for patients with CCM remains controversial. Thus, the best treatment approach for CCM remains elusive.

In this study, we present an analysis of a consecutive cohort of 56 patients with histologically confirmed intracranial or intraspinal CCM from one of the largest neurosurgical centers in China and describe the clinical, radiologic, and pathologic features of these patients. In addition, we analyze the features that are associated with longer progression-free survival (PFS) and overall survival (OS) and further investigate the proper treatment of intracranial and intraspinal CCM.

Section snippets

Clinical and Radiologic Records

A total of 14,310 patients with intracranial and intraspinal meningiomas were surgically treated and pathologically confirmed at Beijing Tian Tan Hospital between 2006 and 2016, and the clinical data and operation records of the CCM cases were retrospectively reviewed. The following information was recorded: patient age, sex, symptoms at disease onset, disease duration, preoperative diagnosis, tumor size, location, magnetic resonance imaging (MRI) features, extent of tumor removal, and surgical

Incidence and Clinical Features of Intracranial and Intraspinal CCM

The incidence of CCM among the intracranial and intraspinal meningiomas was 0.39% (56 of 14,310 cases). The clinical data are summarized in Table 1. The ages of the 56 patients (20 males and 36 females) at the onset of symptoms ranged from 4 to 77 years, and the mean age was 32.3 ± 17.3 years (mean ± standard deviation). The duration from symptom onset to hospital admission ranged from 2 weeks to 6 years; the median duration was 6 months. The 48 patients with cranial involvement presented with

Discussion

Intracranial or intraspinal CCM, also termed glycogen-rich meningioma, is a rare central nervous system neoplasm. Few series of CCM have been reported because of the extremely low incidence of CCM.6, 7, 8, 9, 10, 11, 12 Approximately 14,310 patients with meningiomas were surgically treated in our hospital between 2006 and 2016. Among them, 56 patients had pathologically confirmed CCM. To our knowledge, this is the largest series of intracranial and intraspinal CCMs from a single neurosurgical

Conclusions

CCM is a rare subtype of WHO grade II meningioma with a high rate of recurrence and death. CCM more frequently affects young people than older people and has a female predilection. Simpson grade I and II resection under relatively safe conditions remains the primary and most suitable treatment for CCM. Because of the aggressive nature of CCM, the recommended treatment for patients with CCM is RT after the first surgery regardless of the extent of resection. For recurrent patients, second

Acknowledgments

We would like to thank all the patients who trusted us and all the physicians and staff who helped this study.

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Clear cell meningiomas (CCM) are an uncommon meningioma subtype marked by aggressive growth and high rates of recurrence despite initial resection. The present study evaluates the adjuvant benefit of stereotactic radiosurgery (SRS) for residual or recurrent tumors.
After review of our prospectively maintained database, we identified 6 patients (3 female) with histologically confirmed Grade 2 CCMs. The median age of the patients at the time of SRS was 45 years. Five patients had undergone prior gross total surgical resection and 1 patient had subtotal resection before SRS. The median SRS treatment volume was 4.7 cc and the median radiosurgical margin dose was 13 Gy (range: 10–15 Gy).
The median follow-up time was 35.5 months (range 6–168 months). Three patients achieved tumor control after the first SRS procedure. Three patients experienced tumor progression at 4, 22, and 32 months after initial SRS. Tumor control was obtained in 2 of these patients after additional SRS. One patient with multiple SRS procedures had suspected adverse radiation effect that was successfully treated with corticosteroids followed by bevacizumab.
Tumor control was maintained in 5 of 6 patients after one or more SRS procedures. SRS should be considered for early intervention after surgical resection of CCM. To maximize the tumor control rate, patients with diagnosed CCM should be treated more generously and higher margin dose should be prescribed. Patients with CCM should be counselled that more than one SRS may be necessary to provide sustained tumor control.
SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome
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We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few familial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1.
Spinal clear cell meningioma without dural attachment: a case report and literature review
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Clear cell meningiomas (CCM) are a very rare histologic subtype of meningioma usually affecting younger patients. The reported data on spinal CCM are extremely rare. Until today, only 89 cases have been reported. Furthermore, CCM without dural attachment is even rarer since only 19 cases have been reported in English literature. In this article, we present the twentieth case of a spinal CCM without dural attachment. Our patient was a 58-year-old female who was presented with pain in her lower back and bilateral sciatica for 6 months. Magnetic resonance imaging showed an intra-dural well-demarcated lesion at L3. Via a posterior approach, total resection was possible due to the lack of dural adhesion of the tumor. Histologic diagnosis was clear cell meningioma.
Clear Cell Meningioma: A Clinicopathologic Study of a Rare Meningioma Subtype in 35 Patients
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Clear cell meningioma (CCM) is a rare histologic variant, accounting for only 0.2%–0.8% of all meningiomas. Given their relative infrequency, few cases have been reported. We have presented one of the largest series of patients with intracranial CCM and reported the treatments and outcomes of these patients.
Patients with histologically proven CCM from 2003 to 2018 were identified for inclusion in the present study. Relevant clinical and radiographic data were obtained via retrospective review and analyzed. Kaplan-Meier and Cox proportional hazards analyses were used to compare overall and progression-free survival.
A total of 35 patients had undergone surgical resection for CCM, including 18 women and 17 men, with a mean age of 59.3 years. Gross total resection was achieved in 22 patients (62.9%), and 11 patients (31.4%) had received adjuvant postoperative radiotherapy. Tumors recurred in 17 patients (48.6%), with a mean time to recurrence of 31.3 months. The mean postoperative follow-up was 66.3 months. On multivariable analysis, adjuvant radiotherapy and gross total tumor resection were both independently associated with prolonged progression-free survival (P < 0.033), although not with overall survival (P >0.274).
The data from the present series of 35 patients with CCM have shown distinct contrasts to previous series, with an older mean age and a nearly 1:1 male/female ratio. Although gross total resection and adjuvant postoperative radiotherapy were both independently associated with longer progression-free survival for patients with CCM, tumor recurrence has remained a challenge in the treatment of these patients.
An Aggressive Extension of Dumbbell-Type Pediatric Skull Base Meningioma: A Case Report with Review of the Literature
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Citation Excerpt :
About 1 year after postoperative proton therapy, the tumor has shown no sign of recurrence. However, some cases have reported multiple recurrences even though the CCM was totally excised.44,46 The recurrence rate of CCM seems to be uncorrelated with the MIB-1 labeling index of the first surgical specimens.
Pediatric meningiomas account for less than 2% of pediatric brain tumors. Pediatric clear cell meningiomas (CCMs) occurring in the posterior fossa are particularly rare. Therapeutic strategies differ among the previous pediatric CCM case reports. Therefore, to clarify the clinical features of pediatric CCMs, we report a rare case of dumbbell-type pediatric CCM and a corresponding literature review.
A 7-year-old boy with complaints of headache, left facial palsy, dysarthria, and left-sided ataxic gait was emergently admitted to our hospital. His consciousness level was slight stupor, with Glasgow Coma Scale score 3-5-6, and he showed left ptosis, dysarthria, and ataxias of the left trunk and extremities. Magnetic resonance imaging (MRI) scan showed acute obstructive hydrocephalus because of the tumor's compression of the brainstem. The dumbbell-shaped tumor extended from the lateral wall of the cavernous sinus, through the left Meckel's cave, to the cerebellopontine angle. Physical examination and perioperative MRI scan showed no evidence regarding neurofibromatosis type I or II. The tumor was removed in a 2-staged operation. Postoperative proton therapy was done to treat some residual tumors. One year after postoperative proton therapy, there is no recurrence, and apart from left corneal and facial hypesthesia, he is healthy.
We reported a rare case of pediatric skull base–type CCM with huge extension originating from the anteromedial wall of Meckel's cave firmly adhered to the cavernous sinus wall to the posterior fossa that was successfully treated with surgery and postoperative proton therapy. CCM has a high recurrence rate; therefore, careful prolonged follow-up is needed.
Pediatric clear cell meningioma involving the middle cranial fossa in the context of NF2 and SMARCE1 mutations
2020, Annals of Diagnostic Pathology
Citation Excerpt :
CCM typically arise in younger adults, with a mean age of approximately 30 years [6,7]. Though CCMs can occur in either intracranial or spinal locations in all ages, the relative frequency may differ between children and adults, with the spinal location possibly being more common in pediatrics [7,9,14,15]. This is difficult to evaluate because few cases of pediatric CCM have been described.
Meningiomas are an uncommon entity in children and adolescents. <30 cases of pediatric clear cell meningioma (CCM), a World Health Organization (WHO) Grade II tumor, have been reported in the literature. These tumors are more likely to recur than the more common WHO Grade I meningiomas, especially with incomplete surgical resection. CCMs are most commonly found in the spine and posterior cranial fossa. Recently, SMARCE1 mutations have been linked to the development of CCM. To evaluate the progression of pediatric CCM in the context of emerging genetic knowledge, we reviewed all 45 cases of CCM at our institution for a 23 year period (1997–2019) to identify pediatric cases. Forty-four of the tumors arose in adults from age 34–81 years. The one pediatric case originally presented at age 4 years; the patient was found to have a CCM in the left cavernous sinus projecting into the posterior fossa, associated with a novel germline SMARCE1 mutation and somatic NF1 and DMD mutations. After two years, the patient had a recurrence of the tumor and underwent a second resection. This is the 5th reported case of CCM in the middle cranial fossa, and the only recurrent case, as well as the only reported case of recurrent pediatric CCM associated with a germline SMARCE1 mutation. Further study of the natural history of tumors associated with germline SMARCE1 loss could potentially inform prognosis.

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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleClinical Features, Treatment, and Prognostic Factors of 56 Intracranial and Intraspinal Clear Cell Meningiomas

Highlights

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Clinical and Radiologic Records

Incidence and Clinical Features of Intracranial and Intraspinal CCM

Discussion

Conclusions

Acknowledgments

Lancet Neurol

Surg Neurol

Pathol Res Pract

Clin Neurol Neurosurg

The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary

Acta Neuropathol

Tumors of the meninges: proposed modifications of the World Health Organization classification

Acta Neuropathol

Clear cell meningioma: case report and review of the literature

Pediatr Dev Pathol

Clear cell meningiomas: three case reports with genetic characterization and review of the literature

Neurosurgery

Intracranial clear cell meningioma: a clinicopathologic study of 15 cases

Acta Neurochir (Wien)

Clear cell meningioma. A clinicopathologic study of a potentially aggressive variant of meningioma

Am J Surg Pathol

Clear cell meningioma, an uncommon variant of meningioma: a clinicopathologic study of nine cases

J Neurooncol

Clear cell meningioma with frequent chordoid features and aggressive behavior: a clinicopathologic study of ten cases at a single institution

J Neurooncol

Clear cell meningioma: clinical features, CT, and MR imaging findings in 23 patients

J Comput Assist Tomogr

Clinical features of clear cell meningioma: a retrospective study of 36 cases among 10,529 patients in a single institution

Acta Neurochir (Wien)

Pediatric intracranial clear cell meningioma: a clinicopathological study of seven cases and literature review

Childs Nerv Syst

The recurrence of intracranial meningiomas after surgical treatment

J Neurol Neurosurg Psychiatry

Secretory meningiomas: a benign subgroup causing life-threatening complications

Neuro Oncol

Original Article
Clinical Features, Treatment, and Prognostic Factors of 56 Intracranial and Intraspinal Clear Cell Meningiomas