Keywords
radiation-induced meningioma - spontaneous meningioma - pituitary adenoma - fungal
sinusitis
Introduction
The evolution of radiotherapy and radiosurgery has greatly reduced the radiation exposure
of nontarget tissues. But radiation-induced tumors remain an important complication
of this treatment modality. The overall cumulative risks for patients to develop radiation-induced
cranial neoplasms are 2.0% at 5 years and 8.9% at 10 years,[1]
[2] of which meningiomas are the most common.[2]
We present a case of grade III papillary meningioma following high-dose cranial radiotherapy
for recurrent pituitary adenoma. To the best of our knowledge, this is the second
case in the literature of radiation-induced grade III papillary meningioma.[2]
Case History
A 69-year-old male presented with clinical features of pituitary adenoma and was operated
twice for the same. Postoperative cranial stereotactic radiotherapy (SRT) was given.
He subsequently developed a temporal meningioma, which was excised. The sequence of
events is as follows.
-
1. Patient presented in January 2015 with generalized fatigue, bitemporal hemianopia,
and panhypopituitarism secondary to pituitary macroadenoma which was excised by endoscopic
transnasal transsphenoidal approach ([Fig. 1]). Histopathological examination (HPE) confirmed a gonadotroph adenoma positive for
follicle-stimulating hormone (FSH) and luteinizing hormone. Patient's vision improved
significantly after surgery.
-
2. In May 2016, he presented with bitemporal hemianopia. Magnetic resonance imaging
(MRI) revealed a recurrent pituitary macroadenoma. Reoperation through transnasal
approach revealed frank pus in the sphenoid sinus, hence tumor surgery was abandoned
([Fig. 2]). Pus for culture and sensitivity grew Klebsiella pneumoniae and was treated with
susceptible antibiotics. Six weeks later patient underwent functional endoscopic sinus
surgery (FESS) with posterior septectomy. Tissue in sphenoid sinus on HPE showed aspergilloma.
He was treated with antifungal (Itraconazole).
Fig. 1 Magnetic resonance imaging (MRI) brain contrast pituitary macroadenoma with suprasellar
extension.
Fig. 2 Magnetic resonance imaging (MRI) brain contrast in April 2016 recurrence of pituitary
macroadenoma and hyperintensity in sphenoid sinus suggestive of sinusitis.
Three months after FESS, in October 2016, patient presented with deterioration in
vision. He could perceive only hand movements in both eyes in bilateral inferior nasal
field. Color vision was impaired to red and green. This time the tumor was approached
through a right pterional craniotomy and internal decompression of recurrent pituitary
macroadenoma was done. Postoperatively, patient's vision improved. HPE of the tumor
was gonadotroph adenoma, positive for FSH. Postoperatively, he underwent external
beam radiotherapy for the residual lesion by SRT technique—6 MV photons to a dose
of 54 Gy in 30 fractions at 1.8 Gy/fraction, 5 days/week, completed in December 2016.
MRI done in October 2018 showed a static small residual pituitary adenoma. No other
lesion was noted ([Fig. 3]).
-
3. In December 2020 patient presented with 4 months' duration of progressively worsening
speech, memory disturbances, and right-sided weakness. Patient had poor attention
span, global dysphasia, and right hemiparesis with 4/5 power. MRI brain revealed a
left temporoparietal convexity dural-based, irregular, heterogeneously enhancing space-occupying
lesion (4.9 × 4.5 × 4.3 cm) with disproportionate perilesional edema and significant
midline shift to right. A small residual pituitary adenoma was also noted with no
interval change ([Fig. 4]). Left temporoparietal craniotomy and Simpson's grade I excision of the lesion was
done. The tumor was extra-axial, dura-based, reddish in color, soft to firm in consistency,
moderately vascular, had multiple nubbins and pial breach noted at multiple places.
Postoperatively, patient's sensorium improved significantly. HPE showed tumor composed
of meningothelial cells arranged in sheets, nests, and pseudopapillary pattern, increased
nuclear cytoplasmic ratio with atypical mitosis 6/10 high power fields, Ki67 index
20%, epithelial membrane antigen negative, vimentin not contributory, suggestive of
papillary meningioma World Health Organization grade III ([Fig. 5]).
-
4. The following day (postoperative day [POD] 1), patient became drowsy. CT brain
revealed acute subdural hematoma and extradural hematoma in left temporoparietal region
with significant mass effect and midline shift. Recraniotomy and evacuation of hematomas
and bony decompression was done. Intraoperatively, there was no active source of bleed
from the tumor bed and following evacuation of hematoma the brain became lax. Postoperatively,
he was electively ventilated. CT brain showed significant reduction in midline shift,
hence patient was extubated on POD-2. On POD-3, patient's sensorium improved. He started
verbalizing, recognizing relatives, moving all four limbs, and was gradually made
ambulant. He tolerated oral feeds. Repeat CT brain done on POD-10 showed postop changes
with no fresh tumor bed bleed or infarcts.
-
5. On POD-11, patient developed fever, one episode of right focal seizure involving
face only and rapid deterioration in sensorium. CT brain showed fresh tumor bed bleed
with edema and significant midline shift. The coagulation profile, platelet count,
bleeding time, and clotting time were within normal limits. Emergency evacuation of
tumor bed bleed was done. No source of bleed was noted in tumor bed. Following the
surgery patient became hemodynamically unstable, continued to deteriorate, and succumbed
to the disease on POD-14.
Fig. 3 Magnetic resonance imaging (MRI) brain contrast in October 2018 residual pituitary
adenoma with no other lesion noted.
Fig. 4 Magnetic resonance imaging (MRI) brain contrast in November 2020 left temporal convexity
meningioma with midline shift to right.
Fig. 5 Histopathological examination (HPE). (A) On low power lesion showing papillary structures, surrounding fibrovascular core
appears cellular with nuclear atypia. (B) On high power atypical cells with focal meningothelial features suggestive of papillary
meningioma.
Discussion
The most common brain neoplasm caused by ionizing radiation is radiation induced meningioma
(RIM).[2] Harrison et al have divided RIMs into three groups based on dose of radiation exposure:
those due to low-dose (< 10 Gy), intermediate-dose (10–20 Gy), and high-dose (> 20
Gy) radiation.[3] Our patient falls in the high-dose radiation exposure group.
Criteria for diagnosis of radiation-induced brain tumors was established by Cahan
et al based on the following parameters: (1) the tumor must occur within the irradiated
field; (2) a sufficient latency period must exist between irradiation and tumor development;
(3) the radiation-induced tumor must be proven to be of a different histological type
than the original neoplasm; and (4) the patient must not have any pathology favoring
the development of tumors such as von Recklinghausen's disease, Li-Fraumeni disease,
tuberous sclerosis, xeroderma pigmentosum, retinoblastoma, or neurofibromatosis.[4]
The latency period from radiotherapy to the development of meningioma was shorter
in the high-dose radiation group than in the low-dose radiation group. The mean overall
latency period between radiation exposure and diagnosis of meningioma is 36.3 years
(range 34–48 years).[5] In one of the recent studies, exposure to higher doses of radiation shortens the
length of the latency period to a mean of 19.5 years (range 4–50 years).[5]
Our patient satisfies the above criteria as he developed a temporal meningioma after
a sufficient latency period of 4 years after radiation to recurrent pituitary macroadenoma
and did not have any phakomatoses.
In RIM, the males were more commonly affected or at least the female predominance
was lesser when compared with spontaneous meningioma (SM).[2]
[5]
There is a higher incidence of calvarial meningiomas in radiation-induced group when
compared with the SM which may be related to the higher dose delivered to the calvaria.[2]
On histological grading, RIMs have a higher incidence of grade II and III meningiomas
than in those with SMs.[2]
[5] Yamanaka et al in their extensive literature search had reported an incidence of
13.3% grade II and III RIM following irradiation for pituitary adenomas[6] and also reported 33.9% of aggressive meningiomas (atypical 21 cases, anaplastic
9 cases, and papillary meningioma 1 case) in the high-dose radiation group than in
the low-dose group.[2] To the best of our knowledge, this is the second case in the literature of radiation-induced
grade III meningioma.
On the whole Louis et al had concluded that aggressive meningiomas with high proliferation
indices, or atypical, or multifocal tumors are more frequent in the radiation-induced
group than SMs.[7]
Because of the invasive nature of aggressive RIM, radical excision may not be always
possible and thus adjuvant treatment and clinical long-term follow-up are required.
Management
The main treatment modality for most cases of RIM is surgical excision.
In RIM, in view of higher incidence of calvarial meningiomas, parasagittal and falcine
meningiomas, assessment of superior sagittal sinus is needed preoperatively. In few
cases, the tumor's vascular anatomy may be visualized by preoperative angiography
and preoperative embolization may be helpful in highly vascular tumors.[8]
Complete surgical resection is an important component of treatment of RIM. For aggressive
RIM involving dura matter wide resection margin is vital to prevent recurrence.[8] Also, radical removal of the tumor involving the under- or overlying bone is significant
in determining the tumor recurrence.[8] However, for tumors which involve a major cranial sinus or skull base, it becomes
difficult to excise with wide resection margin and hence higher recurrence rates have
been reported.[8]
[9]
Despite the radiation-related origin of these tumors, stereotactic radiosurgery or
fractionated stereotactic radiosurgery can provide as an alternative or adjunctive
treatment option in some patients.[8]
[9]
Despite radical surgery and radiotherapy treatment for RIMs, they have a higher recurrence
rates than SM due to their aggressive clinical behavior.[10]
In our reported case, following the first surgical excision of pituitary adenoma patient's
vision improved. As he developed a recurrence with visual deterioration he was reoperated.
Fearing further recurrence cranial radiotherapy was advised for residual pituitary
tumor after second surgery.
We could not explain the reason for repeated postoperative hematoma which occurred
after 10 days and resulted in poor outcome. We feel bleeding from the fragile pial
vasculature may be the cause for the postoperative hematoma.
Conclusion
RIM is the most common secondary cranial tumor caused by ionizing radiation exposure
to brain. The incidence of higher-grade lesions is more common in the RIM group, especially
in patients exposed to higher dose of radiation. RIMs have a clinically aggressive
behavior and are difficult to treat. The treatment modality of choice is surgical
resection with wide resection margin. Radiotherapy can be given to residual/recurrence
of tumor. Despite aggressive treatment provided for RIMs, there are high recurrence
rates and higher risks of morbidity and mortality.
