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Atypical Intracranial Meningioma with Metastasis to C7 Vertebral Body: A Case Report
Accepted Manuscript Atypical Intracranial Meningioma with Metastasis to C-7 Vertebral Body: A Case Report Ayobami Ward, Aida Risman, Sharmila Segar, Suash Sharma, M.D., John Vender, M.D. PII:
S1878-8750(18)32614-7
DOI:
https://doi.org/10.1016/j.wneu.2018.11.067
Reference:
WNEU 10751
To appear in:
World Neurosurgery
Received Date: 13 September 2018 Revised Date:
6 November 2018
Accepted Date: 8 November 2018
Please cite this article as: Ward A, Risman A, Segar S, Sharma S, Vender J, Atypical Intracranial Meningioma with Metastasis to C-7 Vertebral Body: A Case Report, World Neurosurgery (2018), doi: https://doi.org/10.1016/j.wneu.2018.11.067. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Atypical Intracranial Meningioma with Metastasis to C-7 Vertebral Body: A Case Report
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Authors Ayobami Ward1, Aida Risman1, Sharmila Segar1, Suash Sharma M.D.,2 John Vender M.D.1
Affiliations Department of Neurosurgery, Medical College of Georgia at Augusta University 2. Department of Pathology, Medical College of Georgia at Augusta University
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Corresponding Author John Vender, M.D. Interim Chair Department of Neurosurgery Medical College of Georgia at Augusta University Medical College of Georgia BI-3088; 1120 15th Street August, GA 30912 | Email: [email protected]
Key Words meningioma, metastatic, spine, atypical, radiosurgery, resection
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Funding Sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No portion of this work has been presented or published in any form prior to this submission
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Abstract Extracranial metastasis, mainly a feature of WHO grade III meningiomas, is only rarely reported in grade II meningiomas. We report a case of a 48-year-old man who was initially
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diagnosed in 2010 with an occipital convexity meningioma based on CT/MRI and treated with surgical therapy + gamma knife. The first operation achieved a macroscopically complete
resection. The tumor was histologically classified as an atypical meningioma. Patient had a recurrence in 2014 on the left tentorial leaflet as noted on post-contrast MRI. Patient was
asymptomatic, without focal neurological deficits. In 2016, patient reported new onset pain in the
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neck and left upper extremity. MRI indicated complete replacement of the C7 vertebral marrow, with a soft tissue component extending posteriorly into the epidural space that appeared to be
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flattening the thecal sac but without evidence of abnormal cord signal. Histopathology of resection confirmed atypical meningioma. This case represents a rare instance of intra-osseous spine as the first site of metastasis of WHO grade II atypical meningioma, and is the first reported case of extracranial metastasis of a meningioma to the C-7 vertebral body.
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Key Words: meningioma, metastatic, spine, atypical, radiosurgery, resection
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Introduction Meningiomas are mostly benign slow-growing neoplasms derived from arachnoid meningothelial cells that represent the most common central nervous system neoplasms in adults, constituting about 36% of all intracranial tumors.1,2 Meningiomas are typically solitary (>90%),
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appear more commonly in women than in men, and are subclassified by location, type, and histological characteristics3. Majority of meningiomas are benign, and classified as World Health Organization (WHO) Grade I. About 20-25% meningiomas are WHO grade II, and 1-6% are WHO Grade III2,4; these are more commonly seen in men. WHO Grade II meningiomas are
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subclassified into atypical (most common), clear cell and chordoid meningiomas. Grade III meningiomas are subclassified into anaplastic, papillary and rhabdoid subtypes.2 Atypical
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meningiomas are characterized by either frequent mitoses (≥4 per 10 HPF), brain invasion on histology, or three or more of the following: Sheeting architecture, hypercellularity, prominent nucleoli, small cells with high N:C ratio, and foci of spontaneous necrosis2,5. Grade II (29-52%) and Grade III (50-94%) meningiomas typically have a more aggressive behavior and higher rate of recurrence than Grade I (7-25%), even after gross total resection.1,2,6-8 With gross total resection and radiotherapy, WHO grade II meningiomas show 74-100% 5-year progression-free
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survival, whereas WHO grade III meningiomas show 47-61% 5-year overall survival rates.1
Extracranial metastasis in meningiomas is exceedingly rare, estimated to appear in 0.1% of intracranial cases1,9-12. While incidence of distant metastases in malignant/WHO grade III
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meningioma is approximately 43%, rare cases of metastasis of grade II meningiomas have also been reported.1,13 The most frequent site of extracranial metastasis is the lung (60%), with other
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sites such as the liver, lymph nodes, and bone being less common14-16. Given the rarity and consequent lack of standardized management of extracranial metastasis of meningioma, documentation of such cases is of the utmost importance. We report a rare instance of intraosseous spine as the first site of metastasis of WHO grade II atypical meningioma, and the first known case of a metastatic meningioma to the C-7 vertebral body in the literature.
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Case Report History A 48-year-old man was self-referred to our outpatient service in June 2010 with a past clinical history of atypical meningioma of the right occipital convexity. Patient was previously
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treated in August 2009 with craniotomy and resection, intensity-modulated radiation therapy (IMRT), and stereotactic radiosurgery with gamma knife (15 Gray) to the margin at an outside hospital. Patient remained free of any focal neurological deficits, seizures, headaches, or visual difficulties. Contrast enhanced MRI indicated post-radiation changes. Follow up scans from
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2010-2014 showed no interval change.
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Examination
In November 2014, routine follow up MRI indicated a more conspicuous enhancement of the left tentorial leaflet with mild nodularity, consistent with a small tentorial leaflet meningioma without mass effect. The meningioma showed no growth over the course of 2 years serial MRI monitoring. In August of 2016, routine MRI indicated that the left tentorial leaflet meningioma had marginally increased in size (5.4 x 14.3 x 8.1 mm in 2015, 7.3 x 15.6 x 8.3 mm in 2016)
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[Fig. 1A-C]. Over the following 6 months, the patient began to complain of neck pain localized to the mid/lower cervical area associated with left upper extremity pain and digital paresthesia in the ulnar nerve distribution. This pain and paresthesia was refractory to conservative management. MRI of the brain indicated stable characteristics of the tentorial meningioma, but
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cervical spine MRI indicated a complete replacement of the C7 vertebral body marrow with a soft tissue component extending posteriorly through the posterior cortical buttress of the
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vertebral body into the epidural space [Fig. 2]. This lesion appeared to be flattening the thecal sac without evidence of abnormal cord signal.
Operation and Pathologic Findings Patient underwent CT guided biopsy of the vertebral lesion. The pathology report found scant crushed cells with weak EMA staining but lacking CD138 and CD79a markers, consistent with features (although not definitive) of meningioma rather than plasma cell neoplasm. Patient underwent complete removal of the lesion and stabilization of the spine after removal. Histopathology of tumor resection showed a meningothelial neoplasm infiltrating inter-
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trabecular bone and adjacent fibro-connective tissue with associated desmoplasia. Although mostly patternless, the presence of a few minute meningothelial whorls, cytologic features including nuclear pseudo-inclusions, and interspersed collagen in strands and pockets; along with EMA immunopositivity in the absence of any other histologic differentiation and negative
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AE1/AE3 staining indicated an infiltrating meningothelial neoplasm. The combination of a few mitoses (about 3/10 HPF in variably cauterized tissue), mild to moderate nuclear pleomorphism, frequently detectable nucleoli, focal minute necrosis; along with an elevated Ki67 labeling index
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up to about 12% were diagnostic of an atypical meningioma (WHO grade 2). [Fig. 3-7].
Post-Operative Course
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Gamma knife therapy (15 Gy) to the tentorial leaflet margins was given in February of 2018. Follow up since procedure has shown stable decrease in size of tumor, and resolution of peripheral neurologic deficits associated with spinal metastasis.
Discussion
Meningiomas are primarily benign tumors of meningothelial cells, which most
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commonly present as intracranial masses. Depending on the WHO histologic classification, Grade II and Grade III have the highest rate of local recurrence, and distant metastasis. While metastasis of a meningioma is a relatively rare event, it generally affects the lungs, liver, and lymph nodes14,15,17,18. Spinal metastasis of intracranial meningioma is an exceedingly rare
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occurrence, and there is a small body of literature characterizing these cases. Thus,
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documentation is key in elucidating the common factors between patients.
Primary intracranial meningiomas with spinal metastases (PIMSM) have been described at the cervical (C1, C2), thoracic (T1, T5, T7, T10, T11), lumbar (L1-5), and sacral spine as demonstrated in Table 110,18-24. However, this is the first such reported case of a C-7 metastasis. To date, there is a paucity of reported cases of PIMSM in the literature. The oddity of this case is the fact that the patient had almost simultaneous recurrence of the intracranial meningioma adjacent to prior surgical site combined with metastasis to the C-7 vertebral body. While there is no definitive mechanism of metastasis, it had been postulated that extension can be precipitated by CSF, lymphatics, and the venous drainage of the brain parenchyma11. These common avenues
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of seeding lend themselves to the most common extracranial areas of recurrence, such as the lungs, liver, lymph nodes, and bones. There is concern that iatrogenic seeding due to prior intracranial surgery may increase the risk of metastasis, however cases have been reported that demonstrated metastasis of Grade II or III meningiomas in the absence of prior surgical removal.
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While the majority of meningiomas tend to metastasize to one organ, about 31% cases can metastasize to multiple organs 25.
Follow up imaging is the primary mode of identification and histopathology the gold standard of
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diagnosing both recurrence and metastasis of meningiomas. WHO histologic tumor grading provides three grades of tissue classification, of which Grade II and Grade III meningiomas
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typically have a higher rate of recurrence and metastasis than Grade I. While WHO histologic evaluation provides definitive diagnosis and grading that in turn is predictive of the risk of recurrence and metastasis, well-timed follow up imaging is crucial in the identification and establishment of the location of tumor recurrence and metastasis. Moreover, even though classified as atypical, WHO grade II meningiomas can also be rarely associated with metastasis to spine (Table I). Clinically, larger tumor size is associated with a higher likelihood of WHO
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grade II meningioma independent of other risk factors including parasagittal tumor location and male sex.26 Moreover, in addition to the WHO histologic criteria described in introduction section, Ki67 labeling index of >4% is reportedly associated with recurrence similar to atypical and >20% with mortality similar to anaplastic meningioma.2 In an illustrative case, a 68-year-old
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patient who presented with left sided motor weakness and dysarthria who was treated with a Simson’s Grade I surgical excision of the mass.10 Histopathological diagnosis was of an atypical
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Grade II meningioma, however Ki-67 labeling index was 20% (closer to grade III) . The patient subsequently developed recurrence of the primary lesion in multiple sites both intracranially and in the spine. In a recent study, favorable prognostic factors for local tumor progression in atypical meningiomas included gross total resection, adjuvant radiation therapy and MIB labeling index of ≤7%, whereas favorable prognostic factors from mortality included gross total resection and MIB labeling index of ≤7%.27 Thus both the histologic features of atypical meningioma WHO grade II, and elevated ki67 labeling index of 12% in the current case in tumor from spine were predictive of higher rate of recurrence and unfavorable outcome.
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Different avenues exist for the treatment of intracranial meningiomas, however there is no consensus on a treatment paradigm that would decrease incidence of metastasis in grades II and III menigiomas. The general treatment strategy has been surgical excision, radiation including gamma knife, or a combination of radiosurgery and cold knife for high grade meningiomas28.
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The current standard of care consists of maximally safe gross total resection (GTR) and
radiotherapy for WHO grade III meningiomas, whereas radiotherapy is optional for WHO grade II meningiomas.1 A recent analysis of the National Cancer Database (NCDB) showed marginal survival benefit of adjuvant radiation in patients <55 and >75 years, while survival improved
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with surgery alone patients between 55 and 75 years29. Recently, Kessler et al. reviewed 6 cases of recurrent diffusely metastatic meningiomas treated with some combination of resection, chemotherapy, and radiation therapy. However, the patients did not show any noteworthy benefit
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or marked clinical improvement from differential therapy.1 Of note, in another recent study, the use of post-operative RT in atypical meningiomas was associated with improved PFS even after GTR, and authors recommend early RT for patients with residual tumor volume >8.76 cm3 having an increased risk of disease progression30.
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Conclusion
Extracranial metastasis is mainly a feature of WHO grade III meningiomas, and is only rarely reported in grade II meningiomas. Intra-osseous spinal metastasis of intracranial
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meningioma is even rarer. Post-operative follow-up imaging, and histopathological evaluation are key to their diagnosis. While treatment for grades II and III meningioma generally utilize multiple modalities, no specific treatment consensus has been reached in regard to the rare cases
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of extracranial metastasis. Larger studies are required to determine the most likely risk factors, pathogenesis and effective treatment of these metastatic meningiomas. Funding Sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No portion of this work has been presented or published in any form prior to this submission
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Figure legends:
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1. MRI, T1 weighted, demonstrating nodular enhancement of the left tentorial leaflet with marked nodularity and dural tail. A) Axial View. B) Sagittal View. C) Coronal View. 2. MRI, T2 weighted, sagittal view, demonstrating complete replacement of the C7 vertebral body marrow with a soft tissue component extending posteriorly through the vertebral body into the epidural space. 3. Meningioma infiltrating bone (H&Ex40) 4. Meningioma with hypercellular areas (A; H&Ex40), and focal necrosis (B; H&Ex100). 5. Meningioma with tiny meningothelial whorls (A; H&Ex200), and other areas of syncytial growth (B; H&Ex100). 6. Meningioma with mild to moderate nuclear pleomorphism, occasional prominent nucleoli (arrowheads) and mitosis (arrow) (H&Ex400). 7. Meningioma with patchy membranous and cytoplasmic EMA immunopositivity (A; EMAx100), and increased ki67 nuclear labeling in tumor cells (B; Ki67x200).
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Table 1: Reported cases of WHO grade II atypical meningioma with extracranial vertebral metastasis.
Lee et al. 2009 10
68 M
Intraventric ular (Rt. Lateral)
Pinsker et al. 200531
76 M
R. Frontal Lobe
58 F
L. middle cranial fossa
Singh et al. 2016 11
Initial grade
Metastasis
I, II (recurrence)
Spine: T5, T10, L1, L3, L4, S1, S2, T7 Retroperitoneum, both lungs
II
C3-4
II
57, F
R. frontal lobe
I to II
Olson et al. 1994 11 Palmer et al. 1994 11
70, M 43, M
L. frontal lobe R. posterior fossa
II
Paix et al. 2017 32
43, F
R. parietal
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Singh et al. 2016 11
II
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II
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L. frontal, L. hemisphere extending to calvarium, multiple meningeal masses in entire L hemisphere, falx
Kessler et al. 2017 1
65, M
II, III
Treatment
T7-T10, L4 vertebra, S2
Multiple vertebrae, clavicle, humerus T6, T11 vertebra L5 vertebra, Lung T8, T10, L1, L4 vertebra, 8th rib, coccyx, Lungs
Liver, spine
Outcome
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Initial location
Surgery, radiation
Died several months later
Surgery, RT
Alive with metastasis
Surgery, RT
Died 45 months after diagnosis
Surgery, RT
Died 84 months after diagnosis
NA
NA
Surgery, RT
-
Surgery, RT
Alive with metastasis
Surgery, RT, Hydroxyurea
Died 10 years after diagnosis
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Age / sex
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CSF – Cerebrospinal Fluid EMA – Epithelial Membrane Antigen GTR – Gross Total Resection HPF – High Powered Field Ki-67 – Aniten KI67 MIB-1 – E3 unbiquitin-protein ligase MIB 1 N:C Ratio: Nucleus to Cytoplasm Ratio PIMSM - Primary intracranial meningiomas with spinal metastases RT - Radiotherapy WHO – World Health Organization
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Abbreviations
S1878-8750(18)32614-7
DOI:
https://doi.org/10.1016/j.wneu.2018.11.067
Reference:
WNEU 10751
To appear in:
World Neurosurgery
Received Date: 13 September 2018 Revised Date:
6 November 2018
Accepted Date: 8 November 2018
Please cite this article as: Ward A, Risman A, Segar S, Sharma S, Vender J, Atypical Intracranial Meningioma with Metastasis to C-7 Vertebral Body: A Case Report, World Neurosurgery (2018), doi: https://doi.org/10.1016/j.wneu.2018.11.067. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Atypical Intracranial Meningioma with Metastasis to C-7 Vertebral Body: A Case Report
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Authors Ayobami Ward1, Aida Risman1, Sharmila Segar1, Suash Sharma M.D.,2 John Vender M.D.1
Affiliations Department of Neurosurgery, Medical College of Georgia at Augusta University 2. Department of Pathology, Medical College of Georgia at Augusta University
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Corresponding Author John Vender, M.D. Interim Chair Department of Neurosurgery Medical College of Georgia at Augusta University Medical College of Georgia BI-3088; 1120 15th Street August, GA 30912 | Email: [email protected]
Key Words meningioma, metastatic, spine, atypical, radiosurgery, resection
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Funding Sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No portion of this work has been presented or published in any form prior to this submission
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Abstract Extracranial metastasis, mainly a feature of WHO grade III meningiomas, is only rarely reported in grade II meningiomas. We report a case of a 48-year-old man who was initially
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diagnosed in 2010 with an occipital convexity meningioma based on CT/MRI and treated with surgical therapy + gamma knife. The first operation achieved a macroscopically complete
resection. The tumor was histologically classified as an atypical meningioma. Patient had a recurrence in 2014 on the left tentorial leaflet as noted on post-contrast MRI. Patient was
asymptomatic, without focal neurological deficits. In 2016, patient reported new onset pain in the
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neck and left upper extremity. MRI indicated complete replacement of the C7 vertebral marrow, with a soft tissue component extending posteriorly into the epidural space that appeared to be
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flattening the thecal sac but without evidence of abnormal cord signal. Histopathology of resection confirmed atypical meningioma. This case represents a rare instance of intra-osseous spine as the first site of metastasis of WHO grade II atypical meningioma, and is the first reported case of extracranial metastasis of a meningioma to the C-7 vertebral body.
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Key Words: meningioma, metastatic, spine, atypical, radiosurgery, resection
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Introduction Meningiomas are mostly benign slow-growing neoplasms derived from arachnoid meningothelial cells that represent the most common central nervous system neoplasms in adults, constituting about 36% of all intracranial tumors.1,2 Meningiomas are typically solitary (>90%),
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appear more commonly in women than in men, and are subclassified by location, type, and histological characteristics3. Majority of meningiomas are benign, and classified as World Health Organization (WHO) Grade I. About 20-25% meningiomas are WHO grade II, and 1-6% are WHO Grade III2,4; these are more commonly seen in men. WHO Grade II meningiomas are
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subclassified into atypical (most common), clear cell and chordoid meningiomas. Grade III meningiomas are subclassified into anaplastic, papillary and rhabdoid subtypes.2 Atypical
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meningiomas are characterized by either frequent mitoses (≥4 per 10 HPF), brain invasion on histology, or three or more of the following: Sheeting architecture, hypercellularity, prominent nucleoli, small cells with high N:C ratio, and foci of spontaneous necrosis2,5. Grade II (29-52%) and Grade III (50-94%) meningiomas typically have a more aggressive behavior and higher rate of recurrence than Grade I (7-25%), even after gross total resection.1,2,6-8 With gross total resection and radiotherapy, WHO grade II meningiomas show 74-100% 5-year progression-free
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survival, whereas WHO grade III meningiomas show 47-61% 5-year overall survival rates.1
Extracranial metastasis in meningiomas is exceedingly rare, estimated to appear in 0.1% of intracranial cases1,9-12. While incidence of distant metastases in malignant/WHO grade III
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meningioma is approximately 43%, rare cases of metastasis of grade II meningiomas have also been reported.1,13 The most frequent site of extracranial metastasis is the lung (60%), with other
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sites such as the liver, lymph nodes, and bone being less common14-16. Given the rarity and consequent lack of standardized management of extracranial metastasis of meningioma, documentation of such cases is of the utmost importance. We report a rare instance of intraosseous spine as the first site of metastasis of WHO grade II atypical meningioma, and the first known case of a metastatic meningioma to the C-7 vertebral body in the literature.
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Case Report History A 48-year-old man was self-referred to our outpatient service in June 2010 with a past clinical history of atypical meningioma of the right occipital convexity. Patient was previously
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treated in August 2009 with craniotomy and resection, intensity-modulated radiation therapy (IMRT), and stereotactic radiosurgery with gamma knife (15 Gray) to the margin at an outside hospital. Patient remained free of any focal neurological deficits, seizures, headaches, or visual difficulties. Contrast enhanced MRI indicated post-radiation changes. Follow up scans from
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2010-2014 showed no interval change.
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Examination
In November 2014, routine follow up MRI indicated a more conspicuous enhancement of the left tentorial leaflet with mild nodularity, consistent with a small tentorial leaflet meningioma without mass effect. The meningioma showed no growth over the course of 2 years serial MRI monitoring. In August of 2016, routine MRI indicated that the left tentorial leaflet meningioma had marginally increased in size (5.4 x 14.3 x 8.1 mm in 2015, 7.3 x 15.6 x 8.3 mm in 2016)
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[Fig. 1A-C]. Over the following 6 months, the patient began to complain of neck pain localized to the mid/lower cervical area associated with left upper extremity pain and digital paresthesia in the ulnar nerve distribution. This pain and paresthesia was refractory to conservative management. MRI of the brain indicated stable characteristics of the tentorial meningioma, but
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cervical spine MRI indicated a complete replacement of the C7 vertebral body marrow with a soft tissue component extending posteriorly through the posterior cortical buttress of the
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vertebral body into the epidural space [Fig. 2]. This lesion appeared to be flattening the thecal sac without evidence of abnormal cord signal.
Operation and Pathologic Findings Patient underwent CT guided biopsy of the vertebral lesion. The pathology report found scant crushed cells with weak EMA staining but lacking CD138 and CD79a markers, consistent with features (although not definitive) of meningioma rather than plasma cell neoplasm. Patient underwent complete removal of the lesion and stabilization of the spine after removal. Histopathology of tumor resection showed a meningothelial neoplasm infiltrating inter-
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trabecular bone and adjacent fibro-connective tissue with associated desmoplasia. Although mostly patternless, the presence of a few minute meningothelial whorls, cytologic features including nuclear pseudo-inclusions, and interspersed collagen in strands and pockets; along with EMA immunopositivity in the absence of any other histologic differentiation and negative
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AE1/AE3 staining indicated an infiltrating meningothelial neoplasm. The combination of a few mitoses (about 3/10 HPF in variably cauterized tissue), mild to moderate nuclear pleomorphism, frequently detectable nucleoli, focal minute necrosis; along with an elevated Ki67 labeling index
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up to about 12% were diagnostic of an atypical meningioma (WHO grade 2). [Fig. 3-7].
Post-Operative Course
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Gamma knife therapy (15 Gy) to the tentorial leaflet margins was given in February of 2018. Follow up since procedure has shown stable decrease in size of tumor, and resolution of peripheral neurologic deficits associated with spinal metastasis.
Discussion
Meningiomas are primarily benign tumors of meningothelial cells, which most
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commonly present as intracranial masses. Depending on the WHO histologic classification, Grade II and Grade III have the highest rate of local recurrence, and distant metastasis. While metastasis of a meningioma is a relatively rare event, it generally affects the lungs, liver, and lymph nodes14,15,17,18. Spinal metastasis of intracranial meningioma is an exceedingly rare
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occurrence, and there is a small body of literature characterizing these cases. Thus,
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documentation is key in elucidating the common factors between patients.
Primary intracranial meningiomas with spinal metastases (PIMSM) have been described at the cervical (C1, C2), thoracic (T1, T5, T7, T10, T11), lumbar (L1-5), and sacral spine as demonstrated in Table 110,18-24. However, this is the first such reported case of a C-7 metastasis. To date, there is a paucity of reported cases of PIMSM in the literature. The oddity of this case is the fact that the patient had almost simultaneous recurrence of the intracranial meningioma adjacent to prior surgical site combined with metastasis to the C-7 vertebral body. While there is no definitive mechanism of metastasis, it had been postulated that extension can be precipitated by CSF, lymphatics, and the venous drainage of the brain parenchyma11. These common avenues
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of seeding lend themselves to the most common extracranial areas of recurrence, such as the lungs, liver, lymph nodes, and bones. There is concern that iatrogenic seeding due to prior intracranial surgery may increase the risk of metastasis, however cases have been reported that demonstrated metastasis of Grade II or III meningiomas in the absence of prior surgical removal.
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While the majority of meningiomas tend to metastasize to one organ, about 31% cases can metastasize to multiple organs 25.
Follow up imaging is the primary mode of identification and histopathology the gold standard of
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diagnosing both recurrence and metastasis of meningiomas. WHO histologic tumor grading provides three grades of tissue classification, of which Grade II and Grade III meningiomas
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typically have a higher rate of recurrence and metastasis than Grade I. While WHO histologic evaluation provides definitive diagnosis and grading that in turn is predictive of the risk of recurrence and metastasis, well-timed follow up imaging is crucial in the identification and establishment of the location of tumor recurrence and metastasis. Moreover, even though classified as atypical, WHO grade II meningiomas can also be rarely associated with metastasis to spine (Table I). Clinically, larger tumor size is associated with a higher likelihood of WHO
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grade II meningioma independent of other risk factors including parasagittal tumor location and male sex.26 Moreover, in addition to the WHO histologic criteria described in introduction section, Ki67 labeling index of >4% is reportedly associated with recurrence similar to atypical and >20% with mortality similar to anaplastic meningioma.2 In an illustrative case, a 68-year-old
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patient who presented with left sided motor weakness and dysarthria who was treated with a Simson’s Grade I surgical excision of the mass.10 Histopathological diagnosis was of an atypical
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Grade II meningioma, however Ki-67 labeling index was 20% (closer to grade III) . The patient subsequently developed recurrence of the primary lesion in multiple sites both intracranially and in the spine. In a recent study, favorable prognostic factors for local tumor progression in atypical meningiomas included gross total resection, adjuvant radiation therapy and MIB labeling index of ≤7%, whereas favorable prognostic factors from mortality included gross total resection and MIB labeling index of ≤7%.27 Thus both the histologic features of atypical meningioma WHO grade II, and elevated ki67 labeling index of 12% in the current case in tumor from spine were predictive of higher rate of recurrence and unfavorable outcome.
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Different avenues exist for the treatment of intracranial meningiomas, however there is no consensus on a treatment paradigm that would decrease incidence of metastasis in grades II and III menigiomas. The general treatment strategy has been surgical excision, radiation including gamma knife, or a combination of radiosurgery and cold knife for high grade meningiomas28.
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The current standard of care consists of maximally safe gross total resection (GTR) and
radiotherapy for WHO grade III meningiomas, whereas radiotherapy is optional for WHO grade II meningiomas.1 A recent analysis of the National Cancer Database (NCDB) showed marginal survival benefit of adjuvant radiation in patients <55 and >75 years, while survival improved
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with surgery alone patients between 55 and 75 years29. Recently, Kessler et al. reviewed 6 cases of recurrent diffusely metastatic meningiomas treated with some combination of resection, chemotherapy, and radiation therapy. However, the patients did not show any noteworthy benefit
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or marked clinical improvement from differential therapy.1 Of note, in another recent study, the use of post-operative RT in atypical meningiomas was associated with improved PFS even after GTR, and authors recommend early RT for patients with residual tumor volume >8.76 cm3 having an increased risk of disease progression30.
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Conclusion
Extracranial metastasis is mainly a feature of WHO grade III meningiomas, and is only rarely reported in grade II meningiomas. Intra-osseous spinal metastasis of intracranial
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meningioma is even rarer. Post-operative follow-up imaging, and histopathological evaluation are key to their diagnosis. While treatment for grades II and III meningioma generally utilize multiple modalities, no specific treatment consensus has been reached in regard to the rare cases
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of extracranial metastasis. Larger studies are required to determine the most likely risk factors, pathogenesis and effective treatment of these metastatic meningiomas. Funding Sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No portion of this work has been presented or published in any form prior to this submission
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Figure legends:
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1. MRI, T1 weighted, demonstrating nodular enhancement of the left tentorial leaflet with marked nodularity and dural tail. A) Axial View. B) Sagittal View. C) Coronal View. 2. MRI, T2 weighted, sagittal view, demonstrating complete replacement of the C7 vertebral body marrow with a soft tissue component extending posteriorly through the vertebral body into the epidural space. 3. Meningioma infiltrating bone (H&Ex40) 4. Meningioma with hypercellular areas (A; H&Ex40), and focal necrosis (B; H&Ex100). 5. Meningioma with tiny meningothelial whorls (A; H&Ex200), and other areas of syncytial growth (B; H&Ex100). 6. Meningioma with mild to moderate nuclear pleomorphism, occasional prominent nucleoli (arrowheads) and mitosis (arrow) (H&Ex400). 7. Meningioma with patchy membranous and cytoplasmic EMA immunopositivity (A; EMAx100), and increased ki67 nuclear labeling in tumor cells (B; Ki67x200).
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Table 1: Reported cases of WHO grade II atypical meningioma with extracranial vertebral metastasis.
Lee et al. 2009 10
68 M
Intraventric ular (Rt. Lateral)
Pinsker et al. 200531
76 M
R. Frontal Lobe
58 F
L. middle cranial fossa
Singh et al. 2016 11
Initial grade
Metastasis
I, II (recurrence)
Spine: T5, T10, L1, L3, L4, S1, S2, T7 Retroperitoneum, both lungs
II
C3-4
II
57, F
R. frontal lobe
I to II
Olson et al. 1994 11 Palmer et al. 1994 11
70, M 43, M
L. frontal lobe R. posterior fossa
II
Paix et al. 2017 32
43, F
R. parietal
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Singh et al. 2016 11
II
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II
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L. frontal, L. hemisphere extending to calvarium, multiple meningeal masses in entire L hemisphere, falx
Kessler et al. 2017 1
65, M
II, III
Treatment
T7-T10, L4 vertebra, S2
Multiple vertebrae, clavicle, humerus T6, T11 vertebra L5 vertebra, Lung T8, T10, L1, L4 vertebra, 8th rib, coccyx, Lungs
Liver, spine
Outcome
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Initial location
Surgery, radiation
Died several months later
Surgery, RT
Alive with metastasis
Surgery, RT
Died 45 months after diagnosis
Surgery, RT
Died 84 months after diagnosis
NA
NA
Surgery, RT
-
Surgery, RT
Alive with metastasis
Surgery, RT, Hydroxyurea
Died 10 years after diagnosis
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Age / sex
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CSF – Cerebrospinal Fluid EMA – Epithelial Membrane Antigen GTR – Gross Total Resection HPF – High Powered Field Ki-67 – Aniten KI67 MIB-1 – E3 unbiquitin-protein ligase MIB 1 N:C Ratio: Nucleus to Cytoplasm Ratio PIMSM - Primary intracranial meningiomas with spinal metastases RT - Radiotherapy WHO – World Health Organization
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Abbreviations