64‐YEAR‐OLD MAN WITH MULTIPLE CEREBRAL LESIONS

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 (1, 2).

Figure 1.

Figure 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 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 territory. Contrast‐enhanced MRI confirmed the presence of 15 hemorrhagic lesions restricted to that vascular territory (Figure 3). These lesions were hypointense on T1WI and T2WI with mild focal gadolinium 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.

Figure 3.

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 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 macrophages with hemosiderin‐filled cytoplasm, indicating remote bleeding. 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.

Figure 5.

Figure 6.

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.

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 metastatic 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, placenta 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 insertion 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 confirms 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.

ABSTRACT

A 64 year‐old man, previously treated with radiotherapy for a pharyngeal 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.