BJR|case reports https://doi.org/10.1259/bjrcr.

20150092

Received: Revised: Accepted:

04 March 2015 12 December 2016 15 December 2016

Cite this article as:

Thomas RZ, Dalal I. Extracranial metastases of anaplastic meningioma. BJR Case Rep 2017; 2: 20150092.

CASE REPORT

Extracranial metastases of anaplastic meningioma

ROBBIN ZACHERY THOMAS, MD and ISHANI DALAL, MD

Radiology, Henry Ford Hospital, Detroit, MI, Michigan

Address correspondence to: Dr Robbin Zachery Thomas
E-mail: robt@rad.hfh.edu

ABSTRACT
Anaplastic meningioma is a World Health Organization (WHO) Class III lesion representing 2–3% of all meningiomas, with
more aggressive spread, increased mortality and increased likelihood of recurrence. Metastases outside the blood–brain
barrier are uncommon but can occur to the lungs, liver, bone and skin.Definitive diagnosis is obtained with pathological
analysis. The World Health Organization classifies meningiomas into benign (Grade I), atypical (Grade II) and anaplastic/
malignant (Grade III) based on histological findings including number of mitoses, cellularity, nucleus to cytoplasm etc.
This case presents a 58-year-old female with history of treated anaplastic meningioma with new onset headache, nausea
and vomiting. Workup demonstrated multiple new bilateral pulmonary nodules, which subsequent biopsy proved to be
metastasis from recurrent anaplastic meningioma, with extensive intrathoracic involvement.

CLINICAL VIGNETTE large pleural and parenchymal metastatic disease. Subse-

The patient is a 58-year-old female with past medical his- quent positron emission tomography/CT confirmed lung,
tory of left breast cancer status post resection and chemo- chest wall, pleural, chest and upper abdomen lymph node
therapy (2000), basal cell carcinoma of the forehead (1997) and osseous involvement of a thoracic vertebral body and
and pathology proven anaplastic intracranial meningioma right iliac bone. The patient transitioned to palliative care
(9/2012) status post three surgical resections, radiation and has since passed.
therapy and radiosurgery with ongoing antiangiogenic
therapy with bevacizumab, who presented to the emer- BACKGROUND
gency department in mid-2014 with headache, nausea and Meningiomas arise from arachnoid cap cells of the menin-
vomiting. Acute abdominal series demonstrated multiple ges and represent approximately 13–26% of intracranial
new bilateral pulmonary nodules. Subsequent CT revealed tumours.1 They are often found incidentally and can pres-
both pulmonary and pleural components, and MRI of the ent with symptoms relating to size and location such as
brain demonstrated recurrent brain mass in area of previ- headache, nausea, vomiting, seizure, visual deficits, hearing
ous surgical resection (fFigure 1). Whole body positron loss or weakness. Anaplastic meningiomas represent 2–3%
emission tomography/CT demonstrated avid of all meningiomas and demonstrate more aggressive char-
fludeoxyglucose uptake with significant SVU within nod- acteristics with increased mortality and likelihood of recur-
ules involving the lungs, pleura and epiphrenic/retrocrural rence. Metastases outside the blood–brain barrier are
lymph nodes (Figure 2). Subsequent left pleural biopsy uncommon but can occur to the lungs, liver, bone and
revealed spindle cell neoplasm with pathology similar to skin.1,2 Atypical and anaplastic meningiomas have been
findings from previous intracranial resection specimen. suggested in some studies to represent a malignant pro-
Immunohistochemical staining results included focal dot- gression of benign meningiomas, with some series suggest-
like positive epithelial membrane antigen (EMA) stain, ing up to 28.5% of recurrent benign meningiomas
high MIB-1 (Mindbomb E3 ubiquitin protein ligase 1) pro- demonstrating atypical or anaplastic pathology.2,3
liferation index up to 45% in more active areas, glial fibril-
lary acidic protein (GFAP) staining suggestive of EPIDEMIOLOGY AND PROGNOSIS
multifocal areas of invasion of the brain, negative CD34 The annual prevalence rate for meningiomas is approxi-
ruling out the possibility of solitary fibrous tumour and mately 6 per 100,000. The majority of meningiomas
negative S-100 staining (Figures 3 and 4). Octreotide was occurs in middle aged or elderly patients but can also
added to the patient's regimen at that time. Several months be seen in younger populations with syndromes such as
later, the patient again presented with left rib pain and neurofibromatosis Type 2.2 Benign meningiomas are
shortness of breath with CT demonstrating progression of more prevalent in females, whereas atypical and

© 2017 The Authors. Published by the British Institute of Radiology. This is an open access article under the terms of the Creative Commons Attribution
4.0 International License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are
credited.
 BJR|case reports Thomas and Dalal

Figure 1. MRI with and without contrast of the brain, top row left to right sagittal T1, axial T2, fluid-attenuated inversion-recovery and
bottom row left to right axial T1 precontrast, axial T2 postcontrast, coronal T1 postcontrast. MRI demonstrates recurrent multilobu-
lated heterogeneous mass with associated oedema and avid enhancement. There is extension into the falx-tentorial region and likely
involvement of the superior sagittal and straight sinuses. There is mass effect on the corpus callosum posteriorly.

anaplastic meningiomas are more commonly seen in men.2 multiple sites, to recur early after excision and have a higher
There are some reports of atypical meningiomas after cranial tendency to involve osseous structures.5
irradiation in younger populations with intracranial tumours
as well as implication of dental x-rays or past low-dose A tumour suppressor gene on chromosome 22q12 has been
experimental treatments for issues such as tinea capitas.4 implicated in the initiation of meningioma formation and is
Radiation-induced meningiomas are more likely to involve seen in up to 70% of surgical specimens.6 Factors such as male

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 Case report: Extracranial metastases of anaplastic meningioma BJR|case reports

Figure 2. Positron emission tomography-CT obtained within 1 year of figure 1 demonstrates multiple foci of abnormal fludeoxyglucose
uptake in both lungs and pleura, which correspond to conglomerate masses on concurrent CT. Maximum SUV = 11.1. Also noted is exten-
sive involvement of hilar, mediastinal, retrocrural and upper abdomen lymph nodes as well as partially visualized T12 vertebral body
involvement. Right iliac bone involvement is not seen on provided images. Left pleural biopsy resulted in spindle cell neoplasm with
pathology similar to intracranial tumour resection specimen and previous intracranial tumour resection specimen
(not included).

sex, age less than 40 years and meningioma location at the skull number of mitoses, cellularity, nucleus-to-cytoplasm ratio etc.
base or parasagittal-falcine area are believed to be associated Criteria for anaplastic meningioma includes “>/=mitotic fig-
with increased recurrence rate after subtotal resection in ana- ures/10 HPF or focal or diffuse loss of meningothelial differen-
plastic meningiomas.1,7 Prognosis is poor after development of tiation resulting in carcinoma-, sarcoma-, or melanoma –like
recurrent disease as there is high likelihood of treatment failure.4 appearance”.12
Median survival time for benign meningiomas with brain inva-
Immunohistochemical findings that can help differentiate
sion is between 10 and 14 years with a 5 year mortality rate of
meningioma from other central nervous system neoplasms
25%. Median survival time for anaplastic lesions without brain
such as hemangiopericytoma and schwannoma include posi-
invasion is 1.5 years with a 5-year mortality rate of 68%, but
tive EMA, weakly positive S-100 staining and strong vimen-
median survival time is reduced to 1.4 years with a 5-year mor-
tin staining, which often stays positive through the various
tality rate of 83% in the presence of brain invasion.8
WHO grades.13 Decreased EMA positivity, as seen with the
presented case, can occur with recurrence or malignant pro-
IMAGING gression to Grade III anaplastic meningioma.11 S-100 immu-
CT characteristics such as heterogeneous precontrast examina- noreactivity is not universally seen with meningiomas, as
tion with homogenous bright enhancement after contrast injec- with our case, but when present, is often less reactive than
tion, associated bone destruction, lack of calcification, indistinct would be expected
margins and nodular contours are not unique to more aggressive when sampling schwannoma or solitary fibrous tumour.13
variants and may also be seen in benign meningiomas. Similar Ki-67/MIB-1 is used as an indication of cellular proliferation,
remarks can be made about MRI findings such as indistinct and was found to be up to 45% in the more active areas of
margins on T1 weighted images or post-contrast T1 enhance- the presented case specimen. Ki-67-MIB-1 proliferative index
ment pattern.2 A future role for apparent diffusion coefficient has been found to increase from Grade I to Grade III
(ADC) mapping and diffusion tensor imaging may be consid- meningiomas in a large retrospective study performed by
ered in non-invasive differentiation between benign and atypical Roser et al,14 with mean values of 3.88%, 9.95% and
and anaplastic meningioma with studies showing significantly 12.18%, respectively.
higher ADC values and more disorganized water motion in
Studies by Perry et al7,8 found microscopic brain invasion to be
benign meningiomas. Other studies suggest a role of magnetic
the most powerful predictive tool for disease recurrence. Inde-
resonance spectroscopy in differentiating higher grade meningi-
pendently, maximal mitotic rate of >/=4/10 HPF was found to
omas by their increases in choline/creatinine ratio, lactate
increase the chance of recurrence. Frank histologic anaplasia,
and methylene.9,10
defined by the Mayo Clinic scheme as >/=20 mitotic figures/10
HPF or loss of meningothelial differentiation with or without
PATHOLOGY brain invasion, is noted as the worst prognostic finding.
Anaplastic meningiomas are thought to be formed either de
novo or via transformation of a pre-existing meningioma.11 TREATMENT
The World Health Organization (WHO) classifies meningio- Surgical resection is the primary treatment for all grades of
mas into benign (Grade I), atypical (Grade II) and anaplastic/ meningioma, with complete excision associated with decreased
malignant (Grade III) based on histological findings including recurrence and increased survival.8 Anaplastic tumours are often

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Figure 3. Haematoxylin and eosin stained histologic slides of left pleural soft tissue nodule biopsy sample, with top row left to right
4, 10, and 40 magnification of resected intracranial mass demonstrating proliferation of spindled meningothelial cells with an
excess of 35 mitoses per 10 HPF (high power field), compatible with anaplastic meningioma (WHO 3). Bottom row left to right 4,
10 and 40 magnification of left pleural nodule biopsy consistent with low to intermediate grade malignant spindle cell neoplasm
with similar morphological appearance to resected intracranial meningioma.

found to adhere to cortical vessels, making resection difficult Stereotactic radiosurgery is considered for lesions <3 cm follow-
and increasing the risk of postoperative complications (e.g. ing subtotal resection, recurrent disease, asymptomatic disease
infarction, oedema). Hypervascular tumours not supplied by the or in otherwise non-operative cases.16 Newer antiangiogenic
internal carotid artery may be treated with embolization prior to therapies targeting vascular endothelial growth factor and recep-
surgical resection to shrink tumour volume and potentially tors take advantage of a 10-fold increased expression of vascular
lower blood loss.15 Repeat surgical resection is commonly per- endothelial growth factor in anaplastic meningiomas, with
formed with disease recurrence. Early postsurgical adjunct ther- reports suggesting some delay in disease progression.17
apy with conventional radiation has been shown to slow or halt Hydroxyurea has been shown to inhibit in vitro meningioma
disease progression, increase disease-free survival and increase cell growth, with some response in benign meningiomas but
overall survival in atypical and anaplastic meningiomas.1 equivocal response in anaplastic tumours. Therapies targeting

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Figure 4. Immunohistochemical staining of left pleural nodule LEARNING POINTS

biopsy sample with epithelial membrane antigen (top left) 1. Anaplastic meningioma is a WHO Class III lesion
demonstrates focal weak dot-like positive stain. Epithelial representing 2–3% of all meningiomas, with more
membrane antigen stain is a typical marker of meningioma, aggressive spread, increased mortality and increased
with decreased expression often seen with anaplastic meningi- likelihood of recurrence.1,2
oma and recurrent meningioma. Staining with S-100 (bottom 2. Metastases outside the blood–brain barrier are
right) is negative, consistent with meningioma. uncommon but can occur to the lungs, liver, bone
and skin.1,2
3. CT characteristics such as heterogeneous precontrast
examination with homogeneous bright enhancement
after contrast injection, associated bone destruction, lack
of calcification, indistinct margins and nodular contours,
are not unique to more aggressive variants and may also
be seen in benign meningiomas.2
4. Pathological criteria for anaplastic meningioma includes
“>/=mitotic figures/10 HPF or focal or diffuse loss of
meningothelial differentiation resulting in carcinoma-,
the platelet-derived growth factor receptors are currently being
sarcoma-, or melanoma –like appearance”.12
investigated as these receptors are significantly increased in
5. Surgical resection is the primary treatment for
atypical and anaplastic meningiomas.8
all grades of meningioma with adjunct therapy
with conventional radiation shown to slow or halt
SUMMARY
disease progression, increase disease-free survival
Anaplastic meningioma is a WHO Class III lesion with worse
and increase overall survival in atypical and
prognosis and increased recurrence rate after treatment as com-
anaplastic meningiomas.1,8
pared to Class I and Class II lesions. Definitive diagnosis is
obtained with pathological analysis with ADC and diffusion ten-
sor imaging characteristics on MRI showing promise in non- CONSENT
invasive differentiation.9,10 The case presented demonstrates a
rare complication of anaplastic meningioma with extracranial Written informed consent for the case to be published
metastatic disease. Extracranial metastasis most commonly (including images, case history and data) was obtained from the
spreads to the lungs, but can also be seen in the liver, bone patient(s) for publication of this case report, including
and skin.1,2 accompanying images.

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