doi:10.1111/j.1750-3639.2009.00302.
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COM FEBRUARY 2009 CASE 2 b pa _ 3 0 2
64-YEAR-OLD MAN WITH MULTIPLE CEREBRAL LESIONS
Nicolas Dea MD2; Manuela Pelmus MD1; David Mathieu MD2; François Belzile MD3; Denis Bergeron MD3;
Sylvie Gosselin MD4; Ana-Maria Tsanaclis MD1
1
Department of Pathology, 2 Service of Neurosurgery, 3 Department of Neuroadiology, 4 Department of Neurology, Centre Hospitalier Universitaire de
Sherbrooke, Sherbrooke, Québec, Canada.
CLINICAL HISTORY
A 64 year-old man presented with multiple transient cerebral
ischemic attacks progressing for a week consisting of right-sided
hemiparesis. The patient had a history of squamous cell cancer of
the pharynx managed by chemotherapy and radiotherapy 10 years
earlier. Six years ago, he had a lingual recurrence of his cancer,
for which he underwent a partial glossectomy with left cervical
dissection.
Radiologic investigation revealed a subtotal stenosis of the left
internal carotid artery without cerebral infarction (Figure 1 and 2).
In view of his prior history of surgery and radiation in the left
cervical area, he was treated by percutaneous angioplasty and
stenting. He was then asymptomatic for about 8 months when
ischemic episodes began to recur. Repeat percutaneous left carotid
Figure 1.
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535..538
bpa_302 535..538
angioplasty was performed for progression of the stenosis in the
left common carotid artery, proximal to the initial stenotic stented
area. After an additional seven months of being asymptomatic, he
presented, once again, with right hemiparesis. A head CT scan
revealed multiple hyperdense lesions in the left carotid artery terri-
tory. Contrast-enhanced MRI confirmed the presence of 15 hemor-
rhagic lesions restricted to that vascular territory (Figure 3). These
lesions were hypointense on T1WI and T2WI with mild focal gado-
linium enhancement and showed no diffusion restriction. A carotid
angiogram showed the patency of the left carotid axis. A FDG PET
scan revealed no active systemic neoplasm and hypometabolic
cerebral lesions.
A left frontal open biopsy was performed and 3 grouped lesions
were removed and submitted for pathology.
PATHOLOGY
Gross examination of the specimen revealed dark brown fragments
of intermediate consistency. Histopathological examination
revealed a necrotic and hemorrhagic lesion formed by an irregular
set of vascular channels (Figure 4). These channels were lined by
highly anaplastic cells with marked pleomorphism and numerous
mitoses (Figure 5). The chromatin content of the nucleus was
Figure 2.
535
Correspondence
Figure 3.
highly variable. There was a voluminous vessel with endoluminal
proliferation of neoplastic cells (Figure 6). The tumor cells rested
on a conjunctive tissue stroma. In addition, there were macroph-
ages with hemosiderin-filled cytoplasm, indicating remote bleed-
ing. The interface with the adjacent cerebral tissue was sharply
demarcated and this tissue showed a mild hypercellularity in the
form of a significant reactive gemistocytic astrocytosis.
Figure 4.
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Tumor cells revealed a strong positive reaction for CD31 and
CD34. The reaction for factor VIII was positive but more
delicate. Reticulin surrounded vascular channels and some actin
positivity was noted in the vessels walls. Immunostaining for
GFAP, EMA, Melan-A and HMB-45 did not elicit any reaction. A
positive reaction for GFAP was noted in the peripheral reactive
astrocytosis.
Brain Pathology 19 (2009) 535–538
 Correspondence

Figure 5.

Figure 6.

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© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Correspondence
DIAGNOSIS
Cerebral angiosarcoma.
DISCUSSION
Angiosarcoma is a rare tumor accounting for less than one percent
of all sarcomas (10). It occurs typically in the skin and soft tissues
of the head and neck. It is a very malignant neoplastic proliferation
arising from vascular endothelial cells. Systemic metastasis at the
time of diagnosis is reported to be as high as 80% (4). Central
nervous system (CNS) involvement has been described, but is quite
unusual. Only 17 cases of cerebral angiosarcoma primary to the
CNS have been reported in the English literature (5, 6). Cerebral
metastases are also rare; only 21 cases have been described (for
references please go to: http://path.upmc.edu/divisions/neuropath/
bpath/cases/case181/dx.html ). The typical primary site for meta-
static cerebral angiosarcoma is the heart, accounting for 57% of
cases. Other primary sites have been described, such as Dacron
aortic vascular grafts, aorta, pleura, skin, liver, penis, bone, pla-
centa and the orbit. Cerebral metastases are multiple in 57.9% of
the cases. The described risk factors for the development of
angiosarcomas are radiation therapy, foreign object (8), chronic
lymphedema associated with radical mastectomy, A-V fistulas and
certain environmental carcinogens like vinyl chloride, arsenic and
Thorotrast.
In a series of 53 post-radiation sarcomas (3), Laskin and al.
reported that the most frequent radiation-induced sarcoma was
malignant fibrous histiocytoma (68%) and that an angiosarcoma
represented only one case (2%), on the thoracic wall. Another
series (9) of 2500 patients treated for ENT cancer reported only 5
sarcomas in the irradiated zone. None were angiosarcoma.
Vascular prostheses, especially Dacron prostheses, also have the
potential to induce malignant mesenchymatous changes (1, 2, 7,
11). We, however, did not find any cases that occurred after inser-
tion of a vascular endoprosthesis.
The histologic examination of this case shows typical features
of angiosarcoma: atypical cells forming an irregular vascular
network. The positivity of these cells for endothelial markers con-
firms the diagnosis. Immunohistochemistry for factor VIII was
slightly positive but cases with poorly differentiated tumors are
reported with equivocal positivity for this marker.
We believe this patient had an angiosarcoma of the carotid artery
with distal tumor embolisms since all the lesions were restricted to
this vascular territory, and presented as stroke-like episodes. The
carotid stent might have contributed to the development of the
tumor in tissues already sensitized by the prior irradiation. The
brain tumors may also be primary angiosarcomas, but in view of
the multiplicity of the lesions and the restriction to the vascular
territory of the left internal carotid artery, this hypothesis seems
less likely. Investigations did not reveal any other possible primary
source. Unfortunately, even though a mass of tumoral cells was
identified inside one of the specimen’s vascular channels, we are
not able to ascertain that the primary site is the carotid artery, as the
family of the patient refused the proposed autopsy.
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REFERENCES
1. Ben-Izhak O, Vlodavsky E, Ofer A, Engel A, Nitecky S, Hoffman A
(1999) Epithelioid angiosarcoma associated with a Dacron vascular
graft. Am J Surg Pathol 23(11):1418–1422.
2. Fehrenbacher JW, Bowers W, Strate R, Pittman J (1981)
Angiosarcoma of the aorta associated with a Dacron graft. Ann
Thorac Surg 32(3):297–301.
3. Laskin WB, Silverman TA, Enzinger FM (1988) Postradiation soft
tissue sarcomas, an analysis of 53 cases. Cancer 62:2330–2340.
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10. Weiss SW, Goldblum JR (1995) Malignant Vascular Tumors. In: Soft
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ABSTRACT
A 64 year-old man, previously treated with radiotherapy for a pha-
ryngeal carcinoma, presented with multiple transient cerebral
ischemic attacks. Investigations revealed subtotal stenosis of the
left internal carotid artery, for which he underwent angioplasty.
Several months later he presented with multiple cerebral lesions
confined to the vascular territory of the stented carotid artery.
Histopathological examination of these lesions revealed highly
anaplastic cells forming irregular sets of vascular channels with
endoluminal proliferation. Positive reaction for CD31 and CD34
confirmed the diagnosis of metastatic angiosarcoma. Considering
the past history of radiation to the cervical area and the fact that
these lesions were all confined to a single vascular territory, we
believe this patient developed an angiosarcoma of the carotid
artery with distal tumor embolism. No other primary sources were
found despite extensive investigation. Angiosarcoma is a rare
tumor with cerebral involvement being even more unusual. Only 17
cases of primary cerebral angiosarcoma are described and only 21
cases of cerebral metastases from other sites have been reported,
the heart being the single most often cited primary site. Radiation
therapy is a well known risk factor for this type of tumor. We
found no cases of post-radiotherapy carotid angiosarcoma in the
literature.
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