Laboratory Studies
Although Stewart-Treves syndrome is also known as lymphangiosarcoma, ultrastructural and immunohistologic studies show that this malignancy arises from blood vessels rather than lymphatic vessels.
The following immunohistologic and ultrastructural findings can be used to confirm that the tumor originates from blood vessels:
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Antibodies against factor VIII–related antigen are markers for endothelial cells. Although malignant endothelial cells may not always show positive staining with this marker, a more sensitive endothelial marker, lectin Ulex europaeus-I, is more likely to react with hemangiosarcoma tumor cells. However, the specificity of this marker is reduced in people with blood group O because normal epithelial cells and carcinomas also bind this lectin in these individuals.
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CD34 antigen is a marker of vascular endothelial cells and does not react with the lymphatic endothelium.
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Antikeratin antibodies show no evidence of keratin in this malignancy; this finding confirms that the tumor cells are nonepithelial in origin.
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Positive staining for laminin, CD31, collagen IV, and vimentin can aid in diagnosing the tumors as angiosarcomas.
Imaging Studies
Magnetic resonance imaging (MRI) is recommended to evaluate the local extent of angiosarcomas. However, its true value is in question because of poor results in delineating the margin of the tumor. It may be low in signal intensity on T2-weighting and short-tau inversion recovery (STIR) imaging, reflecting the densely cellular, fibrous stroma and sparsely vascularized tumor histology. [36, 37] Additional administration of intravenous contrast medium may reveal significant enhancement of the tumorous lesions. However, in patients with chronic lymphedema, nodules detected by MRI within the lymphedema should be evaluated for Stewart-Treves syndrome. [38, 39]
Chest CT scanning should be performed to rule out metastatic disease to the lungs before the patient undergoes extensive surgery.
Chest radiography can help in identifying pulmonary metastases and pleural effusion. A positron-emission tomographic (PET) scan may document the extent of subcutaneous spread and aid in planning surgical management. [40] Fluorodeoxyglucose (FDG) PET/CT scanning may delineate tumor spread, including metastases, and detect the possible malignant transformation in patients with chronic lymphedema. [41]
Procedures
Analysis of a biopsy specimen is essential to the diagnosis of lymphangiosarcoma. Fine-needle aspiration is inadequate for diagnosis of Stewart-Treves syndrome.
Histologic Findings
Histologically, angiosarcomas in Stewart-Treves syndrome are indistinguishable from angiosarcomas in nonlymphedematous sites. Postlymphedema angiosarcomas are characterized by proliferating vascular channels, which dissect the dermal collagen and, often, the obliterate appendages. Tumor endothelial cells lining these channels show marked hyperchromatism and pleomorphism. Mitoses are commonly seen in these tumor cells. The vascular endothelial cells appear round or oval, and they are protuberant and often project into the lumen. Erythrocytes can be seen inside these vascular channels. The overlying epidermis may be hyperkeratotic and acanthotic, or it may be atrophic. Prominent proliferation of reticular fibers can be seen in association with this malignancy.
At electron microscopic examination, lymphangiosarcoma cells are surrounded by a complete basal lamina. In some tumor cells, pinocytosis, intercellular junctions, and cytoplasmic intermediate filaments are observed. In addition, Weibel-Palade bodies and erythrophagocytosis are often present. These ultrastructural findings suggest a vascular endothelial origin rather than a lymphatic endothelial origin.
Staging
In 1959, McConnell and Haslam divided the course of development of lymphangiosarcoma into 3 stages. [42] This staging system lacks universal application.
Stage 1 (prolonged lymphedema) is as follows:
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This stage is characterized by extensive edema that causes the degeneration of fat and collagen mainly in the deep part of the dermis.
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Edema separates the collagen bands, creating a misperception of an increased amount of fibrous tissue in the area.
Stage 2 (premalignant angiomatosis) is as follows:
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This stage involves multiple foci of small, proliferating channels in the dermis and subdermis. These vessels are lined by hyperplastic endothelial cells, as well as normal, flattened cells.
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The areas of angiomatosis vary in size, ranging from 100 µm to a couple of centimeters in diameter.
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Superficial areas can be seen as bruises or vesicles, whereas deeper areas are seen as areas of induration and hemorrhage.
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Early lesions show little evidence of malignancy, but more advanced lesions reveal early malignant transformation with an increased number of mitotic figures and pleomorphic cells.
Stage 3 (frankly malignant angiosarcoma) is as follows:
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These aggressive tumors develop from areas of premalignant angiomatosis.
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The histologic features of this malignancy are described above in stage 2.
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Classic example of angiosarcoma associated with chronic lymphedema after lymphadenectomy and radiation therapy.
