Journal of Neuro-Oncology 53: 51–54, 2001.

© 2001 Kluwer Academic Publishers. Printed in the Netherlands.

Clinical Study

Multiple cysts in the cerebral white matter: a rare complication of

whole brain radiation therapy

Dieta Brandsma1 , René van Helvoirt2 and Martin J.B. Taphoorn1

1
Department of Neurology, 2 Department of Radiotherapy, University Medical Center Utrecht,
Utrecht, The Netherlands

Key words: cysts, white matter changes, whole brain radiation therapy

Summary

We describe a patient with multiple cysts in the cerebral white matter, several years after whole brain radiation
therapy (WBRT) for a solitary cerebellar metastasis of a lung carcinoma. MR images of the brain show diffuse white
matter changes, 1 year after radiation, and cyst formation in the white matter, starting 3.5 years later. We conclude
that cysts in the cerebral white matter can be a late stage of white matter damage after whole brain radiation therapy
in long-term survivors with brain metastases.

Introduction Radiation necrosis, but not cyst formation has been

Radiation necrosis is a serious complication of high
dose radiation therapy to the brain. The risk of radia-
tion necrosis increases with increasing total dose and
if daily fractions of more than 2.0 Gy are applied [1].
Lee et al. [2] reported an incidence of temporal lobe
necrosis of 1% in a series of 9606 patients treated with
radical radiation therapy (50–60 Gy) for a nasopharyn-
geal carcinoma. Marks et al. [3] found that 5% of the
patients with primary brain or pituitary tumors who
received more than 45 Gy to the brain, developed radi-
ation necrosis. Onset of symptoms of this complica-
tion ranges from 1.5 to 11 years after completion of
radiation therapy [2,3]. Cyst formation in necrotic brain
is a rare and often late stage of radiation necrosis. Early
cystic/necrotic changes have only been reported after
hyperfractionated radiation therapy in children with
brain stem gliomas. Fifteen percent of these children
developed cysts within in the brainstem during the first
eight weeks after treatment (1 Gy twice daily; total
dose 72 Gy) [4]. Delayed cyst formation in the tem-
poral lobes was found in 0.17% of the patients in the
series reported by Lee et al. [2], 7 years following high
dose radiation therapy. Furthermore, delayed cyst for-
mation was observed in 7.9% of patients with cerebral
arteriovenous malformations treated with gamma knife
radiosurgery, more than 5 years after treatment [5].
described in patients treated with gamma knife radio-
surgery for brain metastases or malignant gliomas
[6,7]. In patients treated with whole brain radiation
therapy (WBRT) (total dose 30–50 Gy), focal radia-
tion necrosis is seldomly seen, but diffuse white matter
changes occur frequently [8,9]. To our knowledge, cyst
formation in the white matter after WBRT has not been
reported. We describe a patient who developed multi-
ple cysts in the cerebral white matter, 4.5 years after
WBRT for a solitary cerebellar metastasis of a lung
carcinoma.
Case report
A 44-year-old woman underwent a total strumectomy
for a papillary thyroid carcinoma in 1979. Ten years
later metastases of this carcinoma were found in the
cervical lymph nodes. The patient was treated with
I-131 ablation therapy (3700 MBq). In January 1991
a routine chest X-ray showed a density in the upper
lobe of the right lung. A lobectomy was performed and
pathological examination showed an adenocarcinoma
of the lung. No adjuvant radiation or chemotherapy
was given. One month later, she complained of dizzi-
ness and a tendency to fall. A CT brain scan demon-
strated a contrast enhancing lesion in the vermis and
52

Figure 1. (A) CT brain scan (February 1991): contrast enhancing lesion in the vermis and left cerebellar hemisphere with edema and mass
effect. (B) CT brain scan (February 1991): normal differentation of the supratentorial grey and white matter. (C) CT brain scan (April
1992): no tumor recurrence after contrast enhancement. (D) CT brain scan (April 1992, as compared to Figure 1B): diffuse white matter
changes. (E) Gadolinium enhanced T1 MR brain image (August 1995): cyst formation in the left cerebellum, but no tumor recurrence.

the left cerebellar hemisphere (Figure 1, panel A).
Resection was performed and pathological examina-
tion revealed a poorly differentiated adenocarcinoma,
similar to the lung carcinoma. Postoperative WBRT
(30 Gy, 10 fractions, 4 fractions per week) was given
without adjuvant chemotherapy. During the following
years, the patient complained of intermittent headache
and dizziness, but no tumor recurrence was seen on
repeated CT/MR images of the brain (Figure 1, panels
C, E, G). Diffuse white matter changes were noted on
a CT brain scan in April 1992, 1 year after WBRT
(Figure 1, panel D as compared to panel B). In August
1995, 4.5 years after WBRT, a MR brain image with
gadolinium showed multiple, non-contrast enhancing,
cystic lesions in the white matter (Figure 1, panel F).
Since May 1998 the patient had short-term memory
difficulties. A MR brain image (FLAIR sequence) in
November 1998 showed an increase in both the size
and number of the cystic lesions (Figure 1, panel H).
The patient did not consent to a lumbar puncture. No
surgery was performed or corticosteroids were given.
At present the patient’s short-term memory problems
worsen and she is lacking in initiative. No metastatic
activity of either the thyroid carcinoma or the lung car-
cinoma could be detected up till now (Figure 1).
Discussion
Diffuse white matter changes are well known side
effects of WBRT and were seen in our patient on a
CT brain scan 1 year after radiotherapy. Multiple cys-
tic lesions developed 3.5 years later in the cerebral
white matter. From the subsequent MRI findings we
conclude that the cysts in the cerebral white matter
are a late stage of white matter damage due to WBRT,
although we have no histologic evidence of that. Recur-
rent tumor could be excluded because there was no
contrast enhancement or mass effect of the cysts. More-
over, the slow evolution of the radiological abnormal-
ities does not fit in with the diagnosis of recurrent
tumor. Encephalitis was highly unlikely because the
cysts evolved over many years and no clinical or lab-
oratory signs of infection were present. Formation of
(F) Gadolinium enhanced T1 MR brain image (August 1995): non-contrast enhancing, cystic lesions in the cerebral white matter with one
large cyst, right frontal. (G) MR brain image, FLAIR sequence (October 1998): progressive atrophy of the brain and cyst formation in the left
cerebellar hemisphere. (H) MR brain image, FLAIR sequence (October 1998): increase in both size and number of the cysts in the white matter
as compared to Figure 1F.
53
cysts after this relatively low dose of radiation was
not to be expected. The patient received WBRT of
30 Gy in 10 fractions without adjuvant chemother-
apy. Two years before WBRT, she was treated with
I-131 ablation therapy for lymph node metastases of
a papillary thyroid carcinoma. We do not believe that
the I-131 ablation therapy contributed to cyst forma-
tion since the radiation absorbed dose of the brain
after 3700 mBq I-131 therapy is estimated to be only
0.3 Gy [10]. Furthermore, there were no risk factors
for small vessel disease like hypertension or diabetes
mellitus in this patient, which could additionally dam-
age the white matter. Our patient had progressive
memory changes, which could be due to both cyst
formation and progressive brain atrophy. We assume
that the cerebral white matter cysts are seen in this
particular patient because of her long survival time
after WBRT. Median survival of patients with brain
metastases treated with WBRT is 3–6 months with
a 10–15% 1-year survival rate [11]. Our patient sur-
vived for more than 8 years without tumor recur-
rence. Cysts in the white matter were first noted on
MR brain scans, 4.5 years after WBRT, when most
patients with brain metastases have already died. We
conclude from this case study that cysts in the cere-
bral white matter can be a late stage of white matter
damage after WBRT in long-term survivors with brain
metastases.
Acknowledgements
We thank Dr. ThD. Witkamp, M.D., radiologist, for
valuable advice and Dr. J.E.C. Bromberg, M.D.,
neurologist, for critically reading the manuscript.
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Address for offprints: D. Brandsma, Department of Neurology,
G03.228, University Medical Center Utrecht, PO Box 85500,
3584 CX Utrecht, The Netherlands; Tel.: (31)(30)2507939;
Fax: (31)(30)2542100; E-mail: d.brandsma@neuro.azu.nl