Keywords
radiation-induced meningioma - atypical meningioma - craniotomy
Introduction
In the recent years, improvements in the survival rate of medulloblastoma and other
pediatric brain tumors have been recognized due to improved surgical resection rates,
the development of new agents, and advances in radiation techniques.[1]
[2]
[3]
[4] On the other hand, there is an increasing concern about the occurrence of radiation-induced
brain tumors as well as recurrence and higher brain dysfunction in long-term survivors
after childhood radiotherapy.[1]
[2]
[3]
[4] In this report, we describe a relatively rare case of radiation-induced meningioma
(RIM) that developed with the consciousness disturbance and the right hemiplegia 36
years after radiotherapy for suprasellar germ cell tumor. RIM should be kept in mind
when treating children who have received childhood radiotherapy. We report this case
because we believe it was informative.
Case Presentation
Present Medical History
A 46-year-old woman was admitted to our department as an emergency because of a sudden
loss of consciousness and right hemiplegia. At the age of 10, she underwent craniotomy
for suprasellar germ cell tumor. He received postoperative radiotherapy (24 Gy whole
brain, 30 Gy local, 30 Gy whole spine). Since then, the patient had been doing well.
History of hyperlipidemia, diabetes, osteoporosis, no family history of note. One
year earlier, a brain MRI was performed by another clinic, and a tumor of 1 cm in
diameter was observed in the left middle cranial fossa, but it was left unattended.
On admission, neurological examination showed the immediate improvement in the consciousness
disturbance and the right hemiplegia after admission, and the patient became alert.
There were no other abnormal neurological findings. Blood and biochemical tests, chest
X-ray, and electrocardiogram showed no abnormal findings.
Neuroimaging
Brain MRI demonstrated a mass lesion (3.5 × 3.4 × 4.5 cm) with brain edema in the
left middle cranial fossa with an equal signal on T1-weighted imaging (T1WI) ([Fig. 1A]) and a high signal on T2WI ([Fig. 1B]), which was highly enhanced by gadolinium ([Fig. 1C, D]). In addition, a dural enhancement around the tumor, which was a dural tail sign
([Fig. 1D]), was observed, and meningioma was suspected. Based on the rapid growth rate of
the tumor, which was 1 cm in diameter a year earlier, it was considered to be a RIM
of high malignant potential, and it was decided to perform a craniotomy to remove
the tumor after embolization of the feeding artery of the tumor.
Fig. 1 Preoperative magnetic resonance imaging. The preoperative T1-weighted image shows
a well-defined, hypointense mass lesion in the left middle fossa (A). The T2-weighted image shows hyperintensity (B). The gadolinium-enhanced image shows an enhancement effect (C, axial section; D, coronal section). The dural tail sign was observed (D; arrow).
Intervention
The embolization of feeding artery of the tumor was performed 2 days before craniotomy
([Fig. 2A, B]). The approach included puncturing the right femoral artery. The tumor was mainly
fed by the middle meningeal artery (MMA) and the accessory meningeal artery (AMA).
The stain was stained intensely. First, N-butyl cyanoacrylate (NBCA) 12.5% and Embosphere
were injected from the MMA, and then a coil was implanted proximally. About 12.5%
NBCA was similarly injected into the AMA, and then a coil was implanted proximally.
External carotid angiography confirmed the disappearance of the tumor stain. Tumor
resection was performed by left frontotemporal craniotomy. There was no adhesion between
the dura mater and the scalp, and no bone thickening was observed. At the sphenoid
ridge, the tumor was partially exposed outside the dura. After the dural incision,
the sphenoid ridge dura was coagulated with a bipolar, and the tumor was removed.
The tumor was elastic hard and did not show significant hemorrhage. Although there
was some adhesion between the brain surface and the tumor, we were able to separate
the tumor from the brain surface with minimal damage to the brain surface. After removal
of the tumor, the dura was incised and removed as much as possible, and the remaining
portion was coagulated with a bipolar, and duraplasty was performed with periosteum.
As for the removal rate, the surgery was completed at Simpson grade II.
Fig. 2 Preoperative external carotid artery angiogram (A, before embolization of the feeding artery of the tumor; B, postembolization of the feeding artery). (A) The tumor is fed by the middle meningeal (arrowhead) and accessory meningeal (arrow) arteries. (B) After embolization of the feeding artery, tumor stain disappeared.
Histopathological Examination
Cells with short spindle-shaped to round nuclei were densely proliferated in a flowing
manner ([Fig. 3A, B]). Immunostaining was negative for S100 protein and positive for epithelial membrane
antigen ([Fig. 3C, D]). The diagnosis was made as World Health Organization (WHO) grade II.
Fig. 3 Histopathological examination. Hematoxylin–eosin staining (A and B) shows dense cell proliferation with spindle- to round-shaped nuclei. Proliferating
cells are stained with an epithelial membrane antigen (C). The labeling rate of Ki-67 is 20% at the highest lesion, with an average of approximately 5 to 10% (D). EMA, epithelial membrane antigen.
Postoperative Course
The postoperative course was uneventful with no new neurological deficits, and the
patient was discharged from the hospital on the 8th postoperative day. Postoperative
MRI showed that the tumor had been completely removed ([Fig. 4A, B]). She has been followed up on an outpatient clinic since then, and there has been
no apparent recurrence of the tumor as of 3 years after the surgery.
Fig. 4 Postoperative magnetic resonance imaging (A, axial section; B, coronal section). The gadolinium-enhanced T1-weighted image shows tumor resolution.
Total resection is confirmed.
Discussion
A definitive diagnosis of RIM is difficult to make. In recent reports, RIMs have been
reported to have fewer mutations in neurofibromatosis type 2 than common meningiomas.[5] However, it must be mentioned that the true pathogenesis is unknown at this time.[1]
[2]
[3]
[4] There is no pathologic or biochemical method to definitively diagnose RIM. Based
on the clinical course and anatomical location of tumor, the currently accepted definition
of RIM[1]
[3] is as follows. This is not a specific diagnosis for meningiomas, but it is rather
an application of the general diagnostic methods for radiation-induced brain tumors.
(1) Tumor is located in the irradiated area. (2) Histological findings are different
from those of previously existing neoplasms. (3) There is a sufficient period of time
between the irradiation and the development of the meningioma (usually more than 5
years). (4) There is no family history of nevus disease. (5) The tumor is not recurrent
or metastatic, and (6) the tumor does not exist prior to treatment. In our case, it
is difficult to conclude that this is a definite diagnosis. In our case, all of the
above criteria are fulfilled and RIM was strongly suspected.
The incidence of RIM is reported to be higher in patients who received high doses
in childhood.[2] Based on the fact that chemotherapy presents an effect, a combination of stereotactic
radiotherapy and whole-brain irradiation to reduce the radiation dose has reported
good results.[6] Therefore, this method should be considered for reducing the irradiation dose. The
interval from irradiation to the onset of RIM is 18.7 to 24.0 years, with a maximum
of 40 years being observed, but very few cases were longer than 30 years.[3] In terms of the post-irradiation development period, irradiation at a younger age
is associated with an earlier onset of RIM, and high-dose irradiation is a factor
involved in the early onset of RIM.[2]
[3] In the present case, the patient received a high dose of 54 Gy of irradiation at
the age of 10, but it took 36 years for the development of the meningioma, which is
a relatively rare course. In RIMs, the higher the radiation dose, the higher the grade
II and grade III malignancy.[3]
[7] The postoperative recurrence rate of RIMs is also said to be higher than that of
spontaneous meningiomas.[7] On the other hand, a prospective study of 220 patients who developed meningiomas
after irradiation of tinea capitis in childhood showed a recurrence rate of 18.2%,
which was not significantly different from the 14.6% recurrence rate in the control
group of spontaneous meningiomas,[4] but this may be attributable to the fact that irradiation for tinea capitis is low-dose
and a relatively high percentage of the cases are benign.
A review of histopathological studies of RIM showed that 76% of the cases were WHO
grade I, 16% were grade II, and 8% were grade III, indicating a large number of grade
I cases.[8] RIMs are known to be highly malignant, and this result may be contradictory. This
result may be due to the large number of low-irradiation cases included. In present
case, the Ki-67 labeling index was 5 to 10%, indicating high proliferative potential. The cell
density was also high, and the diagnosis of WHO grade II atypical meningioma was made.
Because the irradiated skin is thin and blood flow is poor, it has been pointed out
that postoperative skin necrosis, lacerations, and spinal fluid leaks can occur more
frequently,[9] so it is important to observe the scalp preoperatively, consider the extent of the
skin incision, and carefully observe the scalp wound postoperatively. It is important
to observe the scalp preoperatively to determine the extent of the skin incision,
and to carefully observe the scalp wound postoperatively. Depending on the condition
of the scalp, joint surgery with a plastic surgery team should be considered. In this
case, we were concerned about postoperative ischemia of the scalp and carefully monitored
the wound.
Basically, RIM should be surgically removed as much as possible, with the aim of achieving
Simpson grade I. However, in cases involving the venous sinus, major blood vessels,
or cranial nerves, total removal may result in worsening of postoperative neurological
symptoms, suggesting the importance of adjuvant therapy.[5]
[7] There is a report[10] of tumor regression after 6 months of follow-up using bevacizumab, a monoclonal
vascular endothelial growth factor antibody, as chemotherapy; however, this has not
been established at this point, and further investigation is needed.
The embolization of tumor vasculature should be considered before craniotomy, if possible,
especially for large meningiomas. Not only will this reduce intraoperative bleeding,
but we believed that it will also make it easier to detect the dissected plane of
the tumor and surrounding tissues, thereby ensuring safe removal of the tumor. In
present case, although adhesion between the brain surface and the tumor was noted,
we could remove the tumor with minimal damage to the surface of the brain.
In cases where a residual tumor is unavoidable due to adhesions to major blood vessels,
stereotactic radiotherapy such as CyberKnife should be considered as an additional
therapy, even if high-dose radiotherapy has already been administered. Kondziolka
et al[11] reported that stereotactic radiotherapy with or without surgery for RIM was effective,
with a 5-year survival rate of 80.7%. An optimal dose of 13 Gy or higher was found
to be effective. In this case, the dura mater of the skull base was coagulated but
not removed. The patient requires close follow-up, and in the unlikely event of recurrence,
reoperation or stereotactic radiotherapy will be considered as soon as possible.
Conclusion
We report a case of RIM that developed 36 years after childhood irradiation. Although
reports of RIMs developing more than 30 years after radiotherapy are relatively rare,
they are quite longstanding and represent a blind spot in follow-up. Considering that
the prognosis of patients has been lengthening with advances in the treatment of brain
tumors, it is necessary to keep in mind not only recurrence and higher brain dysfunction
but also the occurrence of RIMs.
