J Neurosurg 108:1014–1017, 2008

Metastatic choriocarcinoma with multiple neoplastic
intracranial microaneurysms
Case report
IN BOK CHANG, M.D.,1 BYUNG MOON CHO, M.D., PH.D.,1 SE HYUCK PARK, M.D., PH.D.,1
DAE YOUNG YOON, M.D., PH.D.,2 AND SAE MOON OH, M.D., PH.D. 1
Departments of 1Neurosurgery and 2Radiology, Hallym University, College of Medicine, Seoul, Korea

PThe authors report on a case of a metastatic choriocarcinoma that mimicked systemic necrotizing vasculitis on a cerebral angiogram. A 35-year-old woman presented with right hemiplegia and a drowsy mental state. A computed tomography (CT) scan revealed an intracerebral hemorrhage in the left frontal region. A cerebral angiogram showed multiple
microaneurysms arising from the bilateral anterior cerebral arteries and middle cerebral arteries, and the renal angiogram
showed multiple microaneurysms arising from the left distal renal artery. A chest CT scan revealed multiple metastatic
lesions in the left lower lung field. The hematoma and microaneurysms were surgically removed. Choriocarcinoma was
diagnosed after histological examination. Despite receiving postoperative chemotherapy, the patient died 1 month after
the operation. (DOI: 10.3171/JNS/2008/108/5/1014)
KEY WORDS • choriocarcinoma • intracerebral hematoma • neoplastic aneurysm •
polyarteritis nodosa

C

HORIOCARCINOMA is the malignant form of gesta-

tional trophoblastic disease, which includes a clinical spectrum consisting of the benign hydatidiform
mole, the invasive mole, and the highly malignant choriocarcinoma.15 It usually disseminates hematogenously to the
lungs, vagina, brain, kidney, and ovaries.13 Cerebral metastases occur in 10–20% of patients with choriocarcinoma.1
Choriocarcinoma with cerebral metastases has been associated with intracerebral hematoma, embolic vascular occlusion, subdural hematomas, arterial aneurysms, and a spinal
epidural hematoma.1,15 Even though there have been some
reports of metastatic choriocarcinomas with single cerebral
neoplastic aneurysms, reports of multiple cerebral neoplastic aneurysms with metastatic choriocarcinoma confirmed
by preoperative angiograms are rare.5,10 Many aneurysms
might have remained undiscovered on angiograms or necropsies due to compression from a hematoma. Although
rare, similar findings have been reported in patients with
polyarteritis nodosa.9 We report a case of metastatic choriocarcinoma associated with multiple intracranial microaneurysms and ICH.
Case Report
Presentation and Examination. This 35-year-old woman
Abbreviations used in this paper: ACA = anterior cerebral artery;
b-HCG = beta–human chorionic gonadotropin; CT = computed tomography; EMACO = etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine; ICH = intracerebral hemorrhage;
MCA = middle cerebral artery; MR = magnetic resonance.

1014

was admitted to the Department of Neurosurgery complaining of severe headache, nausea, vomiting, and progressive somnolence. She had delivered a normal full-term
infant 7 years ago and had a history of artificial (intentional) abortion at a local clinic 2 years ago. Her mental status was drowsy, and her pupils were promptly reactive to
light. She had right hemiplegia and hyperesthesia on admission. Because she was of childbearing age, her urine
was checked for b-HCG, which was positive. A CT scan of
the brain revealed a 3 3 5–cm hemorrhagic mass in the left
upper-frontal region with vasogenic edema. An MR image
of the brain showed a hematoma with multiple enhancing
nodular lesions in the left frontal and right parietal regions
(Fig. 1). The cerebral angiograms revealed multiple microaneurysms arising from the bilateral ACAs and MCAs
(Fig. 2). A renal angiogram was performed to rule out simultaneous systemic vasculitis, and it also showed multiple microaneurysms arising from the left distal renal artery.
The patient’s serum b-HCG level on admission was at an
elevated level of 9354.5 mIU/ml, leading to suspicion of an
ectopic pregnancy, but her pelvic CT scan, transvaginal ultrasonography, and endometrial biopsy specimen were negative for ectopic pregnancy or other diseases. Furthermore,
a pelvic MR image revealed no definitive primary lesion in
the uterus. The patient was in a high-risk group (. 8) according to the World Health Organization classification of
gestational trophoblastic disease.12
Operation. Emergency stereotactic aspiration of the hematoma was performed, resulting in a reversal of her neurological deterioration. Due to rebleeding, however, a craJ. Neurosurg. / Volume 108 / May 2008

Cerebral metastatic choriocarcinoma

FIG. 1. Preoperative CT scan (left) showing ICH in the left parietal region and coronal Gd-enhanced T1-weighted MR
image (right) demonstrating enhancing nodular lesions.

niotomy and removal of a hematoma (along with a biopsy
procedure) was performed. In the operative field, neoplastic microaneurysms were exposed on the cortex of the left
frontal region, which was coagulated and resected, and the
intracerebral hematoma was evacuated (Fig. 3). The cerebrospinal fluid b-HCG level obtained after hematoma
evacuation remained elevated at 134.1 mIU/ml.
Histological Examination. Histological examination of
the hematoma was compatible with a diagnosis of choriocarcinoma. The specimens showed several atypical pleomorphic trophoblastic cells on a necrotic background and
some scattered trophoblasts in the hematoma and invading
the vessel wall. Immunohistochemical study revealed positive staining for b-HCG in the tumor cells (Fig. 4), but the
endometrial biopsy specimen showed no evidence of chorionic villi, trophoblasts, or decidual reaction.

Postoperative Course. After the surgery, a chest CT scan
revealed multiple metastatic lesions in the left lower lung
field. The patient underwent combination chemotherapy
with EMACO. Despite aggressive therapy, recurrent bleeding occurred and the patient died 1 month after her initial
presentation.

Discussion
The incidence of choriocarcinoma after a normal pregnancy is 1 in 50,000 live births, whereas the development
of this tumor after a nonmolar abortion is unknown.14 Tidy
and colleagues14 reported that choriocarcinoma after nonmolar pregnancies represents 17% of the total gestational
trophoblastic tumors requiring treatment.12 In our case, the
patient had delivered a normal full-term infant 7 years pre-

FIG. 2. Cerebral angiograms showing multiple microaneurysms. A right internal carotid artery angiogram (left) showing microaneurysms in the MCA and both ACAs (arrows) and a left internal carotid artery angiogram (right) showing a
microaneurysm in the left MCA (arrow).

J. Neurosurg. / Volume 108 / May 2008

1015

I. B. Chang et al.

FIG. 3. Intraoperative photograph showing a neoplastic microaneurysm on the cortex of the brain (arrowheads).

viously and had had an artificial abortion at a local clinic 2
years ago; however, the type of abortion (molar or nonmolar) was unclear.
Choriocarcinoma has a tendency to rapidly and hematogenously spread to the lungs, vagina, brain, liver, kidney,
and ovaries.13 Cerebral metastases occur in 10–20% of patients with choriocarcinoma. In these patients, however, cerebral metastasis is the major cause of death.1 Choriocarcinomas with cerebral metastases have been associated
with intracerebral hematoma, embolic vascular occlusion,
subdural hematoma, arterial aneurysm, and a spinal epidural hematoma.1,13 The trapped neoplastic cells, with a form
of emboli in the cerebral circulation, have a predilection for
invading the vessel wall, which can result in a hemorrhage
within the tumor, or partial disruption of the vessel wall that
can lead to aneurysm formation and subsequent hemorrhage.3,15 There are 2 mechanisms for neoplastic aneurysm
formation. First, after tumor embolization in the distal cerebral vessels, focal destruction of the intima, internal elastic
lamina, and media layers may cause a true neoplastic aneu-

rysm. Second, lodging of the tumor embolus in the vasa vasorum and involvement of the internal elastic lamina may
lead to aneurysm formation in the final stage.5 Neoplastic
aneurysm and pseudoaneurysm formation may be the most
common cause of ICH in choriocarcinoma.6
Fewer than 20 cases of neoplastic cerebral aneurysm
with metastatic choriocarcinoma have been reported, and
only 3 cases of multiple neoplastic cerebral aneurysms
have been reported. Most reported aneurysms were solitary
and located on one of the terminal branches of the MCA. In
our case, the multiple microaneurysms were located in the
bilateral ACAs and MCAs.
This case was uniquely rare for several reasons. First, the
patient had no history of molar pregnancy (gestational trophoblastic disease). Second, no primary focus was found.
According to the scientific literature, metastatic choriocarcinomas were reported without evidence of choriocarcinomas in the pelvic cavity, suggesting that pelvic choriocarcinomas can regress after metastasis. Third, the patient had
metastases to the brain, lung, and kidney with microaneurysms visible on angiograms. These angiographic findings
are rare, but similar angiographic findings have been found
in patients with polyarteritis nodosa, a form of systemic
necrotizing vasculitis.8
Treatment of metastatic choriocarcinoma using chemotherapy and/or radiotherapy produces long-term survival
rates of as high as 80%.1 Patients with a low risk have been
treated with single-agent chemotherapy using methotrexate
or actinomycin D, but EMACO therapy has been considered the most effective treatment regimen for patients in
the high-risk group.7 Our patient belonged to the high-risk
group because she had multiple metastases as well as a high
serum b-HCG level. She died 1 month after the initial presentation in spite of the hematoma evacuation and intensive
chemotherapy.
The effectiveness of surgical treatment for cerebral metastases has been reported. Surgery is indicated in patients
with significant mass effect due to intracranial hemorrhage
or tumor mass, cerebral aneurysms that have been angiographically proven to be the source of bleeding, or chemotherapy-resistant intracranial metastatic deposits.11

FIG. 4. Photomicrographs of the hematoma specimen showing some scattered trophoblasts in the hemorrhage and invasion of the vessel wall (left, arrows) and positive immunoreactivity for b-HCG (right). H & E, original magnification 3
400 (left) and 3 200 (right).

1016

J. Neurosurg. / Volume 108 / May 2008

Cerebral metastatic choriocarcinoma
The usefulness of radiation therapy for cerebral metastases has also been reported.4,16 In the study of Yordan and
associates,16 in the patients who received combined chemotherapy and radiation therapy, the survival rate was higher
than that of the patients who received only chemotherapy.
Ghaemmaghami et al.4 reported that they had no patient
complications after treatment with the combination of
chemotherapy and whole-brain radiotherapy. Combination
chemotherapy with whole-brain radiotherapy might be effective for choriocarcinoma with multiple cerebral metastases.
Despite such improvements in treatment, the prognosis
in patients with cerebral metastasis is still poor.2 Because
these patients generally have a poor outcome within a few
weeks after initiating presentation, the earlier recognition
of choriocarcinoma might enable the treating physician to
reduce the mortality rate and make an earlier diagnosis.6,14
Conclusions
The authors suggest that metastatic choriocarcinoma
should be considered as a cause of bleeding when intracranial hemorrhagic lesions in unusual locations occur in
women of childbearing age. Use of hematoma biopsy specimens and b-HCG levels are mandatory for making an accurate diagnosis.
References
1. Athanassiou A, Begent RH, Newlands ES, Parker D, Rustin GJ,
Bagshawe KD: Central nervous system metastases of choriocarcinoma. 23 years’ experience at Charing Cross Hospital. Cancer
52:1728–1735, 1983
2. Buckley JD: The epidemiology of molar pregnancy and choriocarcinoma. Clin Obstet Gynecol 27:153–159, 1984
3. Fujiwara T, Mino S, Nagao S, Ohmoto T: Metastatic choriocarcinoma with neoplastic aneurysms cured by aneurysm resection and
chemotherapy. Case report. J Neurosurg 76:148–151, 1992
4. Ghaemmaghami F, Behtash N, Memarpour N, Soleimani K, Hanjani P, Hashemi FA: Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors. Int
J Gynecol Cancer 14:966–971, 2004
5. Giannakopoulos G, Nair S, Snider C, Amenta PS: Implications for

J. Neurosurg. / Volume 108 / May 2008

the pathogenesis of aneurysm formation: metastatic choriocarcinoma with spontaneous splenic rupture. Case report and a review.
Surg Neurol 38:236–240, 1992
6. Kalafut M, Vinuela F, Saver JL, Martin N, Vespa P, Verity MA:
Multiple cerebral pseudoaneurysms and hemorrhages: the expanding spectrum of metastatic cerebral choriocarcinoma. J Neuroimaging 8:44–47, 1998
7. McDonald TW, Ruffolo EH: Modern management of gestational
trophoblastic disease. Obstet Gynecol Surv 38:67–83, 1983
8. Newlands ES, Bagshawe KD, Begent RH, Rustin GJ, Holden L,
Dent J: Developments in chemotherapy for medium- and highrisk patients with gestational trophoblastic tumours (1979-1984).
Br J Obstet Gynaecol 93:63–69, 1986
9. Oran I, Memis A, Parildar M, Yunten N: Multiple intracranial aneurysms in polyarteritis nodosa: MRI and angiography. Neuroradiology 41:436–439, 1999
10. Seigle JM, Caputy AJ, Manz HJ, Wheeler C, Fox JL: Multiple
oncotic intracranial aneurysms and cardiac metastasis from choriocarcinoma: case report and review of the literature. Neurosurgery 20:39–42, 1987
11. Semple PL, Denny L, Coughlan M, Soeters R, Van Wijk L: The
role of neurosurgery in the treatment of cerebral metastases from
choriocarcinoma: a report of two cases. Int J Gynecol Cancer
14:157–161, 2004
12. Smith DB, O’Reilly SM, Newlands ES: Current approaches to
diagnosis and treatment of gestational trophoblastic disease. Curr
Opin Obstet Gynecol 5:84–91, 1993
13. Tai KS, Chan FL, Ngan HY: Renal metastasis from choriocarcinoma: MRI appearance. Abdom Imaging 23:536–538, 1998
14. Tidy JA, Rustin GJ, Newlands ES, Foskett M, Fuller S, Short D,
et al: Presentation and management of choriocarcinoma after nonmolar pregnancy. Br J Obstet Gynaecol 102:715–719, 1995
15. Weir B, MacDonald N, Mielke B: Intracranial vascular complications of choriocarcinoma. Neurosurgery 2:138–142, 1978
16. Yordan EL Jr, Schlaerth J, Gaddis O, Morrow CP: Radiation therapy in the management of gestational choriocarcinoma metastatic
to the central nervous system. Obstet Gynecol 69:627–630, 1987

Manuscript submitted June 7, 2007.
Accepted August 16, 2007.
Address correspondence to: Byung Moon Cho, M.D., Ph.D., Department of Neurosurgery, Kangdong Sacred Heart Hospital, Hallym University, College of Medicine, 445 Gil-dong, Gangdong-gu,
Seoul 134-701, Korea. email: nschbm@hanmail.net.

1017