Angiosarcoma |
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Dysplastic blood vessels are seen within a fibrous stroma. |
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Quick Review for Patients
| The angiosarcoma is a malignancy of vascular channels and half of the skin angiosarcomas occur in the head and neck region, usually affecting the scalp of elderly men. It is very uncommon in the oral cavity but when occurring there it usually involves the mandible or the maxilla. It appears as a painless, rounded, sometimes ulcerated mass submucosal mass which may have a bluish hue. Growth may be rapid and treatment is radical surgical excision. Half of the affected individuals die within 15 months of the diagnosis and the 5-year survival is only 12%. Smaller lesions at diagnosis have a better prognosis than larger ones. |
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The term angiosarcoma is still used to designate the vascular neoplasm with a definitively aggressive, malignant clinical course and an histopathologic appearance which is more atypical than the low-grade lesion called hemangioendothelioma. It is a decidedly rare entity, representing 1-2% of all soft tissue sarcomas in humans, and there is often so little microscopic evidence for the vessels of origin, i.e. blood or lymphatic vessels, that it seems best to use the rather generic term, angiosarcoma, rather than hemangiosarcoma or lymphangiosarcoma. More than half of all skin/mucosal cases are found in the head and neck region, and in this area the scalp and facial skin are the most commonly affected sites; less than 8% of head and neck lesions arise from oral cavity sites. Trauma, long-standing lymphedema, and irradiation of benign vascular lesions appear to be contributory factors in the onset of some cases but most cases present with no obvious etiology.
Clinical Features
Angiosarcoma of the oral region is a disease of older individuals, averaging more than 65 years of age, but it has been reported in infancy. There is no gender predilection and the tumor is typically a solitary or multifocal submucosal nodule which may be bosselated, may be ulcerated, and may bleed spontaneously (Figure 1). The clinical appearance may be indistinguishable from that of oral pyogenic granuloma. Most cases have involved the mandible, but other less frequent sites of involvement have included the maxilla, parotid glands, lips, tongue, floor of mouth, cheek, palate and antrum.
The lesion is rather painless and is fixed to surrounding soft tissues and adjacent bony structures; margins are difficult to define. Some tumors grow rapidly while others take many months to reach a size of 4-5 cm. Occasional lesions will be deceptively small at clinical examination, only to reveal deep and widespread submucosal extension at surgery. The clinical differential diagnosis includes: hemangioma, pyogenic granuloma, Kaposi's sarcoma, melanoma and metastatic disease. When bone is involved, of course, the differential diagnosis is expanded to include several primary and metastatic malignancies of bone.
Pathology and Differential Diagnosis
The histopathologic appearance of this neoplasm varies greatly, depending on the degree of cellular differentiation although, by definition, the lesional cells must show some degree of vascular differentiation, either at the light microscopic level or in immunohistochemical studies. The well-differentiated lesions may be quite similar to hemangioendothelioma, with distinct, endothelium-lined vascular channels with relatively flattened endothelial nuclei (Figures 2-4). There is, however, a tendency for the channels in angiosarcoma to anastomose with one another and to produced dilated sinusoids. The sarcoma, moreover, has a more infiltrative, dissecting pattern at its interface with the normal surrounding tissues. Overall, there are three main patterns of growth: an angiomatous pattern with epithelioid features, a spindle cell pattern, and an undifferentiated or solid pattern. These patterns can be mixed within the same tumor.
Occasional proliferation of lesional cells will produce islands and sheets of tumor endothelial cells with large, hyperchromatic nuclei. These proliferations often protrude into the vascular lumina to form papulations similar to those found in intravascular papillary endothelial hyperplasia. Chronic inflammatory cells may be seen in small numbers at the periphery of the lesion.
The less-differentiated angiosarcoma may have scattered areas of well-differentiated lesional tissues, but it is usually comprised of pleomorphic and hyperchromatic epithelioid cells with abundant mitotic activity (Figures 3 & 4). It may resemble a carcinoma or poorly differentiated fibrosarcoma, in which case a reticulin stain will often demonstrate the vascular channels with tumor cells lying on the luminal side of the vessel. Ulex europaeus staining for endothelial cells is also helpful, although it must be remembered that it is also positive in some examples of synovial sarcoma and epithelioid sarcoma.
Less than one in four angiosarcomas will be immunoreactive for factor VIII-associated antigen. Antibodies to thrombomodulin are reactive in most cases, but have also been reactive in trophoblastic tumors and occasional carcinomas. CD34 is also expressed by most angiosarcomas, but may be seen in the occasional epithelioid sarcoma. Perhaps the most specific immunohistochemistry is reactivity to the CD31 antibody, the platelet-endothelial cell adhesion molecule. To date, nonvascular soft tissue tumors have been completely nonreactive to this antibody. Moreover, the CD31 antibodies label a higher percentage of angiosarcoma lesional cells than do antibodies directed against factor VIII-related antigen. When an epitheliod angiosarcoma mimics a carcinoma and possesses keratin positivity, the use of specific endothelial cell markers, such as CD31, becomes an invaluable part of the diagnosis.
The microscopic differential diagnosis should include: pyogenic granuloma, hemangioma, hemangioendothelioma, papillary endothelial hyperplasia, angiolymphoid hyperplasia with eosinophilia, Kaposi's sarcoma and malignant melanoma. The presence of a spindle cell component may suggest fibrosarcoma, malignant fibrous histiocytoma and other spindle cell sarcomas, while a large number of polygonal endothelial cells might suggest a carcinoma or lymphoma. Reactive papillary endothelial hyperplasia is a common process with a pattern of organized thrombus within a vessel. Sinusoidal hemangioma is a cavernous hemangioma variant with an array of dilated, thin-walled vessels. Spindle cell hemangioendothelioma exhibits cavernous spaces with associated thrombi and more solid spindle cell regions. Epithelioid hemangioendothelioma shows intracytoplasmic lumina in lesional cells, usually arranged in an angiocentric fashion. Kaposiform hemangioendothelioma presents as a lobular proliferation of spindle-shaped cells in addition to congested capillaries. The retiform hemangioendothelioma has a somewhat infiltrating pattern with protuberant, hobnail endothelial cells in a monolayer.
Treatment and Prognosis
Angiosarcoma of the
oral region is treated by wide local excision, although radiotherapy is
sometimes used for multifocal lesions. Some authorities favor the
combination of radiotherapy and surgery even for the single lesions. Treatment
is greatly complicated by the diffuse infiltration with which these tumors are
typically seen. It is not unusual for tumor
cells to be found more than a centimeter beyond the grossly evident lesional
periphery. Positive necks are treated by radical neck dissection. The prognosis
is very much dependent on two features: the degree of cellular differentiation
and the clinical size of the tumor. The overall survival is poor, only
10-15% after 5 years, with most recurrences and metastases occurring within 2
years of treatment. One half of patients die within 15 months of the diagnosis
and, in some series, no patients survived who had lesions with
diameters greater than 5 cm.
References (Chronologic Order)
Note: General references can be found by clicking on that topic to the left.
Bardwil JM, Mocega EE, Butler JJ, et al. Angiosarcomas of the head and neck region. Am J Surg 1968; 116:548-553.
Wesley RK, Mintz SM, Wertheimer FW. Primary malignant hemangioendothelioma of the gingiva. Report of a case and review of the literature. Oral Surg Oral Med Oral Pathol 1975; 39:103-112.
Cochran JH Jr, Fee WE Je. Angiosarcoma of the head and neck. Otolaryngol Head Neck Surg 1979; 87:409-416.
Frick WG, McDaniel RK. Angiosarcoma of the tongue. Report of a case. J Oral Maxillofac Surg 1988; 46:496-498.
Fletcher CD, Beham A, Bekir S, et al. Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm. Am J Surg Pathol 1991; 15:915-924.
Oliver AJ, et al. Primary angiosarcoma of the oral cavity. Br J Oral Maxillofac Surg 1991; 29:38-41.
Tosios K, Hkoutlas IG, Papanicolaou SI. Intravascular papillary endothelial hyperplasia of the oral soft tissues: report of 18 cases and review of the literature. J Oral Maxillofac Surg 1994; 52:1263-1268.
Mark RJ, Poen JC, Tran LM, et al. Angiosarcoma. A report of 67 patients and a review of the literature. Cancer 1996; 77:2400-2406.
Munoz M, et al. Oral angiosarcoma misdiagnosed as a pyogenic granuloma. J Oral Maxillofac Surg 1998; 56:488-491.
Loudon JA, Billy ML, DeYoung BR, Allen CM. Angiosarcoma of the mandible: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 89:471-476.
