Spinal Clear Cell Meningioma Research Articles

P06.07 Germline mutation of SMARCE1 gene in a family with spinal meningiomas

Abstract BACKGROUND Meningioma is the most common benign primary intracranial tumor, arising from arachnoid cells of the meninges, but in 20% of cases displays aggressive behavior. Meningiomas are mainly sporadic and the familial forms are very rare. Meningioma account for a small subset (1–4%) of all pediatric brain tumors and may be associated with hereditary tumor predisposition syndrome caused by germline mutations of NF2, SMARCB1, SUFU, and SMARCE1 genes. MATERIAL AND METHODS We present a case of a 16-year-old girl with spinal clear cell meningiomas (CCMs) WHO II with a second spinal lesion identified during the follow-up. Considering the multiple lesions, we performed Whole Exome Sequencing (WES) on DNA from peripheral blood to search for an underlying CCMs tumor predisposition syndrome (#607174). RESULTS We identified a heterozygous frameshift variant c.439delA (p.Ser147fs) in SMARCE1, chromatin remodelling factor that acts as a tumor suppressor gene. Meningioma analysis by Sanger sequencing showed a loss of heterozygosity (LOH) of the wild-type allele. We identified the c.439delA in the constitutional DNA of the father and the sister but not in the mother. At the moment, the father is asymptomatic and the 14 years old sister showed two spinal lesions (meningiomas likely) at the first MRI. CONCLUSION We report a family study of hereditary tumor predisposition syndrome to CCMs with SMARCE1 mutation in which are present two asymptomatic carriers with different ages and gender. The asymptomatic carriers will undergo neurological examination and MRI of the brain and spine, according to a screening protocol. The incomplete penetrance phenomenon is known in SMARCE1-related families with CCMs and it is probably due to the interaction of SMARCE1 with yet unidentified genes.

Venous Anatomy Influence on the Approach Selection of a Petroclival Clear Cell Meningioma With Associated Multiple Spinal Meningiomas: 2-Dimensional Operative Video.

Preoperative careful evaluation of the sigmoid transverse sinus and its tributary veins is paramount for the safe surgical planning of petroclival lesions.1,2 When the vein of Labbé is running within the tentorium, classic petrosal approach involving transection of the tentorium is modified to avoid the risk of postoperative morbid temporal lobe venous infarcts.1-3 Thus, the surgical plan should be tailored to the specific patient anatomy as demonstrated in the presented case during which a transmastoid approach was followed, in the same surgical setting, by a middle fossa approach to resect a large petroclival clear cell meningioma with extension into Meckel cave. These meningiomas are WHO grade II tumors with a propensity to local recurrence and cerebrospinal fluid seeding.4 SMARCE1 mutations define this subtype of meningioma, with frequent familial inheritance, and predispose patients to both skull base and spinal clear cell meningiomas.5,6 Maximal surgical resection is the best initial treatment option allowing to withhold or delay the use of radiation in tumors frequently encountered in young patients.7 In this report, we demonstrate the microsurgical techniques deployed to achieve maximal resection of a petroclival clear cell meningioma and associated lumbar and sacral spinal meningiomas in a 20-yr-old patient with a familial SMARCE1 mutation. The patient agreed to the surgical intervention and to the use of her image.

A Giant Nondural-Based Lumbosacral Clear Cell Meningioma Mimicking Schwannoma: A Case Report and Review of the Literature.

Spinal clear cell meningiomas (CCMs) are rare and dural-based lesion usually affecting the younger population. We report the rare case of giant nondural-based spinal CCM mimicking schwannoma and review the literature. A literature search was performed at PubMed and Embase until January 1, 2020. A total of 19 cases of nondural-based spinal CCM was reported. The following relevant data were extracted: authors, publication year, patient and tumor characteristics, treatment, and outcome. The mean age of the presentation was 20.58 years. Twelve (63.16%) were female and seven patients (36.84%) were male. The most common location was lumbosacral region 15 (79%). Fifteen (79%) tumors had cranio-caudal dimension ≤2 vertebral level, and only four (21%) tumors had dimension ≥2 vertebral level. Gross total resection (GTR) was performed in 18 (95%) patients and subtotal resection (STR) in 1 patient. Recurrences were reported in five (26.14%) patients. Four of them showed recurrences within 6 months; earliest at 2.3 months in the patient had undergone STR. Our patient is 19-year-old male diagnosed with a lumbosacral intradural lesion. Craniocaudal dimension is ≥2 vertebral level shows the foraminal extension and vertebral scalloping. GTR is performed. Intraoperatively, the tumor has foraminal extension and shows attachment with right S1S2 nerve root. No dural attachment is found. Six-month follow-up magnetic resonance image shows no evidence of disease. Nondural-based spinal CCMs are extremely rare and should be kept as a differential diagnosis in young patients with giant intradural tumor, and whose radiological features suggesting of schwannoma. It affects young patients and usually involves more than one vertebral level. The chances of recurrences and metastasis are always high even after GTR; hence, close follow-up of the entire neuraxis is warranted.

Spinal Clear Cell Meningioma without Dural Attachment: Case Report and Review of Literature

Spinal Clear Cell Meningioma without Dural Attachment: Case Report and Review of Literature

Spinal Clear Cell Meningiomas: Clinical Features and Factors Predicting Recurrence

As a World Health Organization grade II tumor of the nervous system, clear cell meningioma (CCM) is an uncommon histologic variant of meningioma. Spinal CCMs are even rarer, with <100 spinal CCMs reported in the English literature. We present this study to characterize clinical manifestations of spinal CCMs and determine the factors predicting recurrence. A literature search was performed for relevant case reports and series in PubMed and Embase until September 1, 2019. These articles were reviewed to identify clinical features, treatment modalities, and prognosis of patients with spinal CCMs. Eighty-four spinal CCMs were analyzed. Of these patients, 36 (42.9%) were young (age ≤18 years), and the mean age at resection was 24 years. Fifty-three patients (63.1%) were female and 31 (36.9%) were male. Most of the tumors (56/84, 66.7%) were located in the lumbar region. In 31 patients (36.9%) >2 segments in the craniocaudal direction were involved (number of involved segments ≥3 levels). Gross tumor resection was performed in 77 patients (91.7%). Twenty patients (23.8%) showed radiographic evidence of recurrence during follow-up. Recurrence-free survival at 1, 5, and 10 years after resection of spinal CCM was 87%, 71%, and 47%, respectively. Multivariate analysis showed that age ≤18 years (hazard ratio [HR], 3.64; P= 0.024), subtotal resection (HR, 3.43; P= 0.031), and segments involving ≥3 levels (HR, 5.66; P= 0.002) were associated with increased recurrence. Spinal CCMs have their own unique clinical features compared with conventional spinal meningiomas and intracranial CCMs. Spinal CCMs have a predilection to affect younger patients, are prone to appear in the lumbar region, and have a high recurrence rate. Age ≤18 years, subtotal resection, and involvement of long segments (≥3 levels) are positive predictors of recurrence.

Clinical features and surgical outcomes of spinal clear cell meningioma: An institutional experience

Clear cell meningiomas are uncommon tumors in the spinal canal. The clinical and radiological features, clinicopathological characteristics, treatment results, and long-term outcomes of this rare entity are still uncertain. The authors review their experience in a surgical series of 10 patients with histologically proven spinal clear cell meningioma treated at a single institution and discuss clinical features, radiological findings, and surgical outcomes. There were 3 male and 7 female patients with a mean age of 25.5 ± 17.7 years. The mean follow-up period was 68.4 ± 32.7 months. One tumor was in the cervical spine, 2 were in the thoracic spine, 2 were in the thoracolumbar spine, and 5 were in the lumbar or lumbosacral spine. Gross total resection of the tumor with a well-demarcated dissection plane was achieved in 9 patients, while subtotal resection was achieved in 1 patient, and no patients underwent postoperative radiotherapy. Symptoms present before surgery had improved in 9 patients at the last follow-up. Postoperative follow-up magnetic resonance imaging showed no recurrence/regrowth in the 9 patients with total removal and 1 patient with subtotal removal during the mean follow-up periods of 68.4 months and 56.0 months, respectively. Clear cell meningiomas should be considered in the differential diagnosis of young female patients with spinal tumors involving the lower thoracic, lumbar or sacral region. Although the nature of this disease is aggressive, spinal clear cell meningiomas are amenable to surgery. The risk of long-term lesion recurrence is low if complete removal can be achieved, and follow-up imaging is still needed.

Hereditary clear cell meningiomas in a single family: three-cases report

Clear cell meningiomas (CCMs) are rare subtypes of meningiomas and usually treated by maximum safely achievable tumor resection. We here present three hereditary cases with CCMs which were confirmed by Sanger sequencing of lymphocyte DNA. Gross total resection was achieved in a 5-year-old son with a spinal CCM and a 34-year-old father with a CCM in the cerebellopontine angle (CPA). For a 14-year-old daughter with CCM in the CPA, total resection was not achieved due to its large size. Early detection by screening high-risk family with CCM is strongly recommended.

Spinal Clear Cell Meningioma: Clinical Study with Long-Term Follow-Up in 12 Patients

Clear cell meningioma (CCM) is a rare histologic subtype of meningioma. The features of CCMs have commonly been based on intracranial cases. However, CCMs in the spinal cord are even rarer, and their natural history, management, and prognosis remain ill-defined. From January 2006 to January 2018, 12 patients with spinal CCM were treated in our hospital. The clinical features, radiologic findings, diagnosis, treatment, and outcome of these patients were analyzed retrospectively. Additionally, we performed a review of the reported data on spinal CCMs. CCMs accounted for 2.8% of all the spinal meningiomas treated in our hospital. The most common localization of this disease was the lumbar region (7 of 12). The mean age at diagnosis was significantly younger than that of patients with spinal meningiomas (28.8 ± 13.4 years vs. 54.0 ± 14.4 years). During the follow-up period, 5 patients (41.7%) experienced tumor recurrence. Kaplan-Meier analysis showed that younger patients had a significantly shorter progression-free survival time than older patients. The review of the reported data showed that 55 cases of spinal CCMs had been reported. Nineteen patients (38.0%) had developed local recurrence, with a 5-year progression-free survival rate of 33.3%. Spinal CCMs are extremely rare tumors with a predilection to affect younger patients and have a high recurrence rate. Although gross total resection is considered to be the optimal treatment, radiotherapy could be considered for patients who had undergone subtotal resection or for younger patients, regardless of the extent of removal. Close follow-up of the entire neuraxis for years is crucial.

Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas.

We recently reported SMARCE1 mutations as a cause of spinal clear cell meningiomas. Here, we have identified five further cases with non-NF2 spinal meningiomas and six with non-NF2 cranial meningiomas. Three of the spinal cases and three of the cranial cases were clear cell tumours. We screened them for SMARCE1 mutations and investigated copy number changes in all point mutation-negative samples. We identified two novel mutations in individuals with spinal clear cell meningiomas and three mutations in individuals with cranial clear cell meningiomas. Copy number analysis identified a large deletion of the 5' end of SMARCE1 in two unrelated probands with spinal clear cell meningiomas. Testing of affected and unaffected relatives of one of these individuals identified the same deletion in two affected female siblings and their unaffected father, providing further evidence of incomplete penetrance of meningioma disease in males. In addition, we found loss of SMARCE1 protein in three of 10 paraffin-embedded cranial clear cell meningiomas. Together, these results demonstrate that loss of SMARCE1 is relevant to cranial as well as spinal meningiomas. Our study broadens the spectrum of mutations in the SMARCE1 gene and expands the phenotype to include cranial clear cell meningiomas.

Delayed Manifestation of Sacral Clear Cell Meningioma Distent Metastasis or Multifocal Disease?

Study design: The authors report on a clear cell meningioma (CCM) of the sacrum revealed 17 years after a removal of a spinal lesion. A review of 29 spinal CCM previously reported was done. Objective: To focus on clinical and biological behaviour of CCM. Summary of background data: CCM is a rare subtype characterrized by its inordinately aggressive clinical course despite its benign appearance. The tumour shows proclivity for the cerebellopontine angle and cauda equine region. Recurrence and metastasis have been commonly reported. Method: A 26 year-old man presented with low back pain related to a lytic lesion of the sacrum. He had a history of an intradural extramedullary meningioma of the cervical spine removed when he was 9 year-old. CT scan revealed a sacral osteolytic lesion with anterior and lateral extension. Open biopsy revealed a clear cell meningioma. That was the same pattern of the tumour removed 17 years before. Results: Our patient was managed conservatively by palliative radiation therapy. At 2 years follow-up, he experienced improvement of pain and walking. Conclusion: CCM is an aggressive tumour with a high risk of metastases through cerebrospinal fluid. A follow up with spinal MRI should be performed.

Pediatric spinal clear cell meningioma

In this report the authors describe a unique case of spinal clear cell meningioma in a 13-year-old girl. Clear cell meningiomas (CCMs) are not uncommon. To the authors' knowledge, 14 cases of pediatric CCM occurring in the spinal canal have been reported. Factors lending resistance to meningioma initiation and invasion are analyzed. This 13-year-old girl presented with pain radiating down her left leg. Admission MR imaging showed an inhomogeneous enhancing intradural-extramedullary mass at the L4-5 level. Resection revealed a CCM, and radiotherapy was subsequently administered. Postoperatively there has been no recurrence in > 2 years. In this paper the authors report a case of CCM and provide a comprehensive literature review on this disease. Current recommendations for its management are still debatable, especially in the pediatric population, and the authors propose an algorithm for its treatment and surveillance.

A lumbar clear cell meningioma with foraminal extension in a renal transplant recipient

Spinal meningiomas are characteristically dural based. We report a lumbar clear cell meningioma extending into the intervertebral foramen without dural attachment which mimics a neurilemmoma. This is a rare finding, with no other reported cases in the literature. The importance of recognizing clear cell meningioma relates specifically to its inordinately aggressive clinical course. Compared to with of spinal clear cell meningiomas reported to date, our case showing the extension into the intervertebral foramen and mimicking a neurilemmoma is rather unique. Clear cell meningioma may be confused with other clear cell tumors, especially with the similar-looking metastatic renal cell carcinoma, which should be carefully ruled out in our case – an immunosuppressed renal transplant recipient.