Keywords
meningioma - intraosseous - anaplastic - extensive invasion - genetic analysis
Introduction
Primary intraosseous meningioma (PIM) is a rare tumor and a subset of primary extradural
meningioma (PEM). The majority of meningiomas are located in the subdural space. In
contrast, PEM is located at sites other than the dura, such as the skin, skull, nasopharynx,
and lung.[1] PEM accounts for less than 2% of all meningiomas, and PIM makes up only 14% of PEMs.[1]
[2]
[3] While only a handful of case reports have mentioned PIM, there are even fewer on
anaplastic cases. We report an older patient with anaplastic PIM, who was successfully
treated with surgical resection and radiation therapy.
Case Report
A 78-year-old man, presenting with a growing hard mass in the right frontoparietal
bone, was admitted. He had a history of head injury 7 months previously and the mass
had appeared 4 months before admission. He did not demonstrate abnormality on a bedside
examination. Past medical history, occupational history, and family history were unremarkable.
There was no history of weight loss. Routine blood tests were within the normal range.
An X-ray photograph of the skull showed a 6 × 5 cm osteolytic lesion in the right
frontoparietal bone, just across the coronal suture ([Fig. 1A]). Bone window computed tomography (CT) scan showed a large osteolytic lesion with
bone destruction in the same area ([Fig. 1B]). Magnetic resonance imaging (MRI) using gadolinium–diethylenetriamine penta-acetic
acid showed heterogeneous enhancement of the intraosseous mass and homogeneous enhancement
of the dura mater ([Fig. 2D–F]). Brain invasion was not definitively revealed. Whole-body contrast-enhanced CT
and positron emission tomography (PET) contrast-enhanced CT revealed no solid malignancy
except for in the skull. Perfusion CT showed an increase in tumor blood volume, which
indicated high vascularity ([Fig. 3B]). Given the unusual radiological findings, meningioma, osteosarcoma, metastatic
tumor, malignant lymphoma, and epidermoid tumor were listed as possible differential
diagnoses.[2]
[4]
Fig. 1 (A) X-ray photograph showing a 6 × 5 cm osteolytic lesion in the right frontoparietal
bone. (B) CT scan showing a large osteolytic lesion with bone destruction. CT, computed tomography.
Fig. 2 (A) T1-weighted MRI showing isointensity. (B) T2-weighted MRI showing isointensity. (C) FLAIR images showing heterogeneous high intensity. (D–F) T1-weighted MRI with gadolinium showing heterogeneous enhancement of the intraosseous
mass and homogeneous enhancement of the dura mater. FLAIR, fluid attenuated inversion
recovery; MRI, magnetic resonance imaging.
Fig. 3 (A) PET-CT demonstrating a mass lesion with intermediate uptake. (B) Perfusion CT demonstrating an increase in CBV. Note the high vascularity. CBV, cerebral
blood volume; CT, computed tomography; PET-CT, positron emission tomography–computed
tomography.
The patient underwent surgery to obtain a pathological diagnosis and for complete
removal of the mass. Tumor invasion was seen subcutaneously, subdurally, and at the
surface of the brain ([Fig. 4A, C]). The subcutaneous tumor was dissected from the pericranium and removed under the
galea. A right frontoparietal craniotomy was performed with multiple burr holes ([Fig. 4B]). A round dural incision was made around the tumor invasion. Intraoperative findings
showed that the tumor had invaded the brain ([Fig. 4C]). Since the cortical vein adhered tightly to the tumor, a small portion of the tumor
was not able to be removed. As a result, gross total resection of the extracranial
tumor and partial resection of the intracranial tumor were performed. Cranioplasty
with a titanium mesh plate was performed. Postoperative MRI confirmed subtotal removal
of the tumor ([Fig. 5]).
Fig. 4 Intraoperative findings with ORBEYE. (A) The tumor was exposed outside of the skull. (B) A right frontoparietal craniotomy was performed with multiple burr holes. (C) The tumor had invaded subdurally and into the brain and adhered tightly to the cortical
vein.
Fig. 5 Postoperative T1-weighted MRI with gadolinium showing subtotal removal of contrast-enhanced
lesions. MRI, magnetic resonance imaging
Histopathological diagnosis was a World Health Organization (WHO) grade 3 anaplastic
meningioma. Immunohistochemistry showed positivity for CAM5.2 ([Fig. 6D]), AE1/AE3, vimentin, and claudin-1, and negativity for CD34 and signal transducer
and activator of transcription 6 (STAT-6). Ki-67 expression was found in approximately
64% of cells ([Fig. 6E]) and increased mitotic activity (>20 mitoses/10 high-power fields) was revealed
([Fig. 6C]). The tumor cells focally expressed epithelial membrane antigen (EMA), which is
one of the diagnostic markers of meningioma. However, only the Golgi apparatus showed
EMA staining, not the membrane. CAM 5.2 and AE1/3 are reliable markers of epithelial
content, and metastatic lesions also show immunopositivity for them. Since whole-body
PET-CT and contrast-enhanced CT ruled out metastases from any solid malignancy, the
histopathological diagnosis was meningioma.
Fig. 6 (A) Hematoxylin and eosin (H&E) stain showing infiltration of atypical cells into and
outside of the skull (×0.4). (B) H&E stain showing proliferation of atypical cells (×20). (C) H&E stain showing increased mitotic activity (>20 mitoses/10 high-power fields)
(×40). (D) CAM 5.2 stain showing strong positivity (×40). (E) Ki-67 expression is found in ∼64% of cells (×40). Note the high proliferative ability.
We also performed whole-genome analysis with specimens, as part of the HOPE project.[5]
NF2 was amplified and loss of CDKN2A/B was detected ([Fig. 7]). NF2 amplification is frequently seen in meningiomas.
Fig. 7 In the whole-genome analysis with specimens, NF2 was amplified and loss of CDKN2A/B was detected.
The postoperative course was uneventful and the patient was discharged home 2 weeks
after the surgery. One month after the surgery, the patient underwent intensity-modulated
radiotherapy (IMRT) with a total dose of 60 Gy in 30 fractions for the residual tumor.
Follow-up MRI 9 months after the radiation therapy showed no recurrence of the tumor.
Discussion
According to the 2021 WHO classification, anaplastic meningiomas are diagnosed with
increased mitotic activity (>20 mitoses/10 high-power fields), loss of CDKN2A/B, or TERT promoter mutation.[6] WHO grade 3 PIM is extremely rare. Omofoye et al reviewed 111 cases of PIM and found
that only two of them were WHO grade [3]
[7]
[8] ([Table 1]). In our case, the tumor component was localized mainly in the skull. The histopathological
diagnosis was anaplastic intraosseous meningioma, but undifferentiated sarcoma of
intraosseous origin was also considered. However, since NF2 was amplified, undifferentiated sarcoma was unlikely. Finally, based on the extensive
immunohistochemistry panel and review by pathologists, the diagnosis of anaplastic
intraosseous meningioma was reached.
Table 1
The reported cases of primary intraosseous meningioma, World Health Organization grade
3
|
Case
|
Age
|
Sex
|
Symptom
|
Tumor location
|
Cranial suture
involved
|
EOR
|
Pathology
|
Time to
recurrence
|
Publication year
|
|
1
|
42
|
Male
|
Facial nerve paresis
|
Rt temporal
|
Yes
|
STR
|
Anaplastic
|
1.3 y
|
1993[7]
|
|
2
|
70
|
Female
|
Scalp mass
|
Lt parietal
|
No
|
GTR
|
Anaplastic
|
2.5 y
|
2006[8]
|
|
Present case
|
78
|
Male
|
Scalp mass
|
Rt frontoparietal
|
Yes
|
STR
|
Anaplastic
|
N/A
|
N/A
|
Abbreviations: EOR, extent of resection; GTR, gross total resection; Lt, left; N/A,
not available; Rt, right; STR, subtotal resection.
Grade 3 meningiomas generally exhibit high rates of recurrence and mortality. In one
report, grade 3 meningiomas and one-third of grade 2 meningiomas recur within 20 months.[3] The recurrence rate was found to be significantly associated with the WHO tumor
grade. In another report, aggressive atypical or anaplastic meningiomas were reported
to have high mortality of 29%.[9] As for molecular analysis, several studies have shown that CDKN2A/B alteration is correlated with recurrence.[10] In grade 3 meningiomas, deletion of CDKN2A/B appears to have prognostic value.[11]
Histopathological diagnosis without molecular classification has been established
for meningiomas. Meanwhile, molecular diagnostics have also been incorporated that.
Meningioma is classified as a benign tumor and can be completely treated by surgical
removal, if gross total resection is achieved. However, in cases of repeated recurrence
and those where the tumor is difficult to remove, such as skull base meningioma, the
value of genomic diagnosis, and the possibility of subsequent molecular-targeted therapy
are considered.
In general, meningiomas arise from arachnoid cap cells, most of which occur in the
subdural space. Meningiomas that occur in the epidural space are rare due to the result
of the ectopic arachnoid cap cells.[1]
[3] Lang et al. collectively defined them as PEM.[12] In our case, the tumor that initially developed inside the skull extensively invaded
outside the skull. Intraoperatively, a high proportion of the tumor component was
clearly present in the skull, and we made a diagnosis of PIM. Several theories have
been proposed on the exact origin of PIM.[13]
[14]
[15] First, it was suggested that these cases originate from arachnoid cap cells that
get trapped in the cranial sutures during embryogenesis or molding of the cranium
at birth. Another theory proposed that they originate from arachnoid cap cells through
blood vessels or nerves that cross the skull.[13]
[14]
[15] Trauma with skull fracture has also been proposed as a causative factor. In this
case, part of the dura mater would be taken into the fracture at the time of trauma,
subsequently forming a tumor over time.[16]
[17] The cause of our case is unclear, although there are several theories.
We successfully treated the presented case with tumor resection, followed by IMRT.
Preoperatively, the tumor grew larger in a short period of time and imaging findings
suggested an atypical or anaplastic meningioma. Therefore, early diagnosis, total
removal, and subsequent radiotherapy were required. Cranioplasty with a titanium plate
was also required. Generally, anaplastic meningioma portends a high likelihood of
recurrence and the possibility of extracranial metastasis, most commonly involving
the lung, liver, and bones.[18] Not only MRI of the surgical site but also radiological follow-up for metastases
to other organs is needed to ensure meticulous care. In addition, calvarial meningioma
often develops as a painless tumor, which exerts less pressure on the brain.[16] Neurological signs are often rare and the diagnosis may be delayed. When encountering
these cases in a clinical context, care is required.
Conclusion
We experienced a rare case of primary intraosseous anaplastic meningioma with extensive
invasion inside and outside the skull. As for the origin of such cases, several theories
have been proposed. Early diagnosis, total removal, and subsequent radiotherapy may
contribute to an improved outcome. In addition, meticulous care is needed in such
cases because of the high recurrence rate and the possibility of extracranial metastasis.
