Laboratory Studies
Similar to most cancers of mesenchymal origin, little or nothing is demonstrated by blood work, although the sudden development of profound thrombocytopenia in patients with angiosarcoma may either suggest rapid growth of the primary tumor or herald the development of metastatic disease.
Imaging Studies
The choice of imaging studies for angiosarcoma varies somewhat, depending on whether the lesion is located in soft tissue, bone, or skin.
Soft tissue angiosarcoma
For angiosarcoma of the extremities, retroperitoneum, or abdominal wall, magnetic resonance imaging (MRI) provides more accurate delineation of the extent of local disease than computed tomography (CT). MRI provides sagittal and coronal views and better distinction between bone, vascular structures, and tumor than CT scanning. MRI or plain radiographs should address the possibility of bone invasion by the tumor.
MRI is the imaging modality of choice to evaluate the tumor response to preoperative radiation or chemotherapy. It can detect changes in tumor size and in the relationship of the mass to adjacent vital structures and can identify areas of intratumoral necrosis or hemorrhage, especially with the use of static or dynamic gadolinium-enhanced imaging techniques.
Chest CT scan is useful in the detection of lung, pleural, and mediastinal metastasis. Searches for bone and brain metastasis rarely are indicated unless the patient has clinical manifestations suggesting involvement of these organs.
Bone angiosarcoma
Plain radiographic assessment is paramount to characterize lesions of bone angiosarcoma and confirm their multiplicity. [21] However, the radiographic presentation of bone angiosarcoma is not specific. A solitary lesion (60% of cases) appears as a destructive lytic mass with irregular borders or a mixed lytic-sclerotic pattern and occasional bony expansion. High-grade lesions exhibit features of complete cortical destruction and extension into soft tissue. The vascular nature of the neoplasm can be suggested if synchronous multicentric involvement of several bones of one extremity or anatomic region is present (40% of cases).
Plain film of the tibia demonstrates small lucencies without internal matrix production in keeping with the diagnosis of a vascular lesion.
Bone angiosarcoma can present a distinctive pattern of soap-bubble lesions because it frequently extends up and down the bone. When the spine is involved, the most common pattern is regional involvement in several contiguous vertebral bodies.
CT scan confirms the permeative, invasive character of the radiographic lesions and their multiplicity.
MRI shows a nonspecific decreased or variable signal intensity in T1 and an increased signal in T2. The lesions enhance with gadolinium. MRI is especially helpful in the characterization of the soft tissue extension and involvement of neurovascular structures and joints.
Coronal T1 magnetic resonance imaging (MRI) study reveals a lesion of the diaphysis with cortical breakthrough.
Coronal T2 magnetic resonance image shows a diaphyseal lesion with intense surrounding edema (high signal intensity).
Axial T2 magnetic resonance image shows a heterogeneous signal lesion with cortical destruction.
Delayed whole-body bone scintigraphy shows marked radioisotope uptake, although findings can be negative in aggressive destructive lesions. Radionuclide-tagged red blood cell scanning is helpful in the differential diagnosis with other multifocal vascular processes of bone and multiple myeloma or Langerhans cell histiocytosis.
Cutaneous sarcoma
Both CT scan of the head and neck and MRI help in the preoperative planning to evaluate the extent of bone and soft tissue involvement, respectively. These studies help in identifying cervical lymph node involvement.
Biopsy
Early detection by means of biopsy offers the only realistic chance of a cure. Diagnosis is based on the microscopic features of the biopsy or specimen and the ultrastructural and histochemical markers.
The gross appearance of angiosarcoma is that of soft, dark red tissue that may have a spongy consistency (see the image below). [23] Solid gray areas may be interspersed with embedded bone fragments if the cortex has been breached.
Appropriate biopsy of an extremity lesion requires avoiding several potential pitfalls. Core-needle biopsies and fine-needle aspiration (FNA) are accurate tools; however, larger samples of tissue may be necessary to obtain sections of viable tissue adequate for determination of grade and histologic type.
Orient the biopsy incision along the long axis of an extremity or parallel to the dominant underlying muscle group on the trunk. An improper biopsy incision may result in a significantly larger surgical defect than otherwise would be necessary to excise the biopsy cavity appropriately. In turn, this may result in significantly larger postoperative radiotherapy fields to encompass all tissues at risk. A poorly oriented biopsy tract can even challenge the planned limb salvage procedure.
The need for adequate hemostasis after a biopsy cannot be overemphasized. Extravasation of blood allows dissemination of tumor cells and therefore increases the volume of tissue requiring treatment.
Histologic Findings
All angiosarcomas have similar microscopic findings, with vascular spaces more or less obvious and lined by tumor cells showing atypia. Low-grade lesions have vascular spaces lined by large plump endothelial cells that penetrate the stroma and papillary fronds of cells that project into the lumen. Higher-grade lesions are more cellular, with atypical cells and abnormal mitoses.
Foci of angiosarcomas can show well-formed vascular channels that aid in the diagnosis. These channels can be difficult to find in a large number of tumors.
Atypical cells in solid sheets or nests are typical of this tumor and can make diagnosis on hematoxylin and eosin (H&E) sections difficult, necessitating the use of immunohistochemistry.
The main challenge in the diagnosis of angiosarcoma is histopathologic recognition. Angiosarcoma may be confused with vascular tumors of intermediate malignancy (eg, epithelioid and spindle cell hemangioendotheliomas, histioid hemangioma, and malignant endovascular papillary angioendothelioma). In its more benign form, angiosarcoma may be confused with hemangiomas. In its more aggressive form, irregular sheets of anaplastic cells may have only poorly defined vascular channels and may be difficult to differentiate from anaplastic melanomas and carcinomas.
These tumors also are distinct from other malignant vasoformative tumors, including Kaposi sarcoma and malignant hemangiopericytoma. The diagnosis of angiosarcoma can be confirmed by immunohistochemical staining, described as follows [20] :
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The ultrastructure of tumor cells includes intercellular and intracellular lumina with or without red cells.
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In their cytoplasm, tumor cells contain intermediate filaments (vimentin, occasional tonofilaments [keratin]) and pinocytotic vesicles.
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Weibel-Palade bodies, a marker of endothelial differentiation, may be seen in some cases.
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The vast majority of lesions express vimentin and focally factor VIII–related antigen. Also expressed are CD34 (74%), BNH9 (an endothelial marker, 72%), and cytokeratins (35%).
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CD34 immunohistochemistry highlights the vascular nature of angiosarcomas and aids in the diagnosis.
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Some of the tumors show actin expression, demonstrating a prominent pericytic component. Epithelial membrane antigen is not expressed, which helps to rule out a carcinoma.
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S100 protein and gp100 (HMB-45 antigen, both melanocytic markers) also are not expressed; this helps to rule out melanoma.
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Researchers have shown that anti-CD31 antibodies are one of the most specific endothelial cell markers. However, several other immunohistochemical markers (against factor VIII–associated antigen or the nonimmunologic binding to Ulex Europeans) should be used to avoid misdiagnosis.
Staging
The characteristics of the primary tumor (T), spread to regional lymph nodes (N), and the involvement by the tumor of distant lymph nodes and other distant organs and tissues (metastasis, ie, M), form the basis of the American Joint Committee on Cancer (AJCC) staging of cancer and are used widely in the United States. [24] The T, N, and M are further divided into Tx, T0, T1, T2, T3, T4; Nx, N0, N1, N2, N3; and Mx, M0, and M1. Tx indicates that the primary tumor cannot be assessed. This indicates carcinoma in situ, and stage IV indicates metastasis. Stages are as follows:
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Stage I: Localized and resectable tumor is found at one site in the liver and could be treated surgically
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Stage II: Localized and possibly resectable primary tumor is found at one or more locations in the organ and may be treated surgically. The decision to treat the disease surgically depends on the experience of the physician.
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Stage III: Advanced cancer has spread to more than one location in the organ and/or to other parts of the body. Frequently these tumors require multiple treatment modalities for maximum benefit. Often, surgical resection does not provide benefit to the patient.
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Stage IV: Disseminated cancer involves multiple sites throughout the body. Frequently, surgery is not indicated, and chemotherapy is the best option.
For bone and soft tissue sarcomas in adults, [13] the two most commonly used staging systems are those developed by the AJCC and by Enneking. In children, the Intergroup Rhabdomyosarcoma Study and the International Union Against Cancer describe the systems used most commonly. These systems for soft tissue sarcomas rely on an ability to determine accurately both the local and distant extent of disease. The stages are as follows:
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Ia - Low grade, intracompartmental G1/T1/M0
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Ib - Low grade, extracompartmental G1/T2/M0
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IIa - High grade, intracompartmental G2/T1/M0
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IIb - High grade, extracompartmental G2/T2/M0
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IIIa - Low or high grade, intracompartmental G1-G2/T1/M1 with metastases
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IIIb - Low or high grade, extracompartmental G1-2/T2/M1 with metastases
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This is a classic example of angiosarcoma associated with chronic lymphedema after lymphadenectomy and radiotherapy. The patient is a 33-year-old woman who presented with a recurrent grade 2 angiosarcoma of the soft tissue after an attempt at wide excision and skin graft. Two weeks following this procedure, she developed multiple subcutaneous erythematous nodules involving the back and overlying the right scapula region, the supraclavicular fossa, the right breast, and arm. The window shows a microphotograph of the tissue obtained from the biopsy (hematoxylin and eosin stain, original magnification X160). Histologic preparation reveals neoplastic endothelial cells showing a solid pattern with occasional mitotic figures and sporadic protruding growth into the vascular lumens.
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This is a gross specimen from a proximal humerus bone angiosarcoma. These tumors generally are red and hemorrhagic. Although the tumor has not extended into the adjacent soft tissues, cortical erosion is evident. The patient was treated with wide excision and reconstruction with a humeral spacer. The patient's next oncologic recheck showed multiple lesions, including a large destructive lesion in the right ilium extending to the sacroiliac joint and the right sacral ala. Also noted was an upper thoracic vertebral lesion, multiple indeterminate pulmonary nodules, extensive hepatic metastases most marked in the left lobe, and an indeterminate left adnexal mass.
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This radiograph is from a 27-year-old woman who had preexisting mild pain in her left clavicle for a couple of weeks. She woke up one morning with severe pain. Radiographs showed a pathological fracture through a lytic lesion. The permanent section of the needle biopsy is shown in the window and was read as a grade 1 angiosarcoma. The cell morphology varied from epithelioid to spindle-shaped with indistinct borders. Most nuclei were large and vesicular, containing irregular large eosinophilic nucleoli and frequent mitoses. Physicians also found anastomosing vascular channels lined by pleomorphic malignant cells.
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CT scan, MRI, and bone scan from a 27-year-old woman with grade 1 angiosarcoma who presented with a pathological fracture through a lytic lesion on her left clavicle. Note the expansile lytic lesion in the left clavicle accompanied by a soft tissue mass visible on the MRI. No other lesions are identifiable. Regional lymph nodes are visible by MRI, and they do not appear involved. Lungs are clear. She was treated with wide resection of the clavicle, leaving both bony ends. No further reconstruction was attempted. Eighteen months after surgery, she is free of disease and has a full range of motion in the left shoulder. The residual aesthetic deformity is minimal.
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This 71-year-old man presented with a dark lesion on his scalp. The lesion was first treated with an excisional biopsy performed by his local physician; the lesion recurred quickly. He was treated with wide excision and adjuvant radiation therapy. The specimen (hematoxylin and eosin, original magnification X12.5) shows a well-differentiated cutaneous angiosarcoma composed of irregular vascular channels.
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This young woman presented with multicentric angiosarcoma. The images show several bones of the right foot, the right distal femur, and the right patella affected with the process. The microphotograph of the specimen revealed a grade 2 angiosarcoma (hematoxylin and eosin, original magnification X100). Most bone tumors are solitary lesions with a very low incidence of multicentricity. Vascular tumors are an exception and may involve multiple bones. Angiosarcoma presents in this case as multiple lytic lesions in the same extremity.
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This is a soft tissue angiosarcoma presenting as a rapidly growing mass in the calf. This 69-year-old woman was treated with wide resection of the mass followed by external beam radiotherapy. The full-thickness graft obtained from the ipsilateral thigh at the moment of surgery aided in the closure and prevented further wound complications during the adjuvant radiotherapy. The rapid growth of soft tissue angiosarcomas explains why they are often misdiagnosed as abscesses and tentatively treated with drainage. The drainage is sanguinous, with blood clots, and hemostasis may be challenging. To avoid this problem, fine-needle aspiration should precede any attempt at incisional or excisional biopsy of a soft tissue mass.
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This 45-year-old man presented with progressive pain in his left hip. Activity-related at first, the pain turned constant. The patient described it as a dull ache and a boring sensation, with occasional stubbing episodes. The pelvic bone involvement was extensive. The patient was treated with an external hemipelvectomy. The patient survived for 1.5 years.
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Plain film of the tibia demonstrates small lucencies without internal matrix production in keeping with the diagnosis of a vascular lesion.
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Coronal T1 magnetic resonance imaging (MRI) study reveals a lesion of the diaphysis with cortical breakthrough.
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Coronal T2 magnetic resonance image shows a diaphyseal lesion with intense surrounding edema (high signal intensity).
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Axial T2 magnetic resonance image shows a heterogeneous signal lesion with cortical destruction.
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Grossly, angiosarcomas show a reddish-brown color and solid patterns.
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Foci of angiosarcomas can show well-formed vascular channels that aid in the diagnosis. These channels can be difficult to find in a large number of tumors.
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Atypical cells in solid sheets or nests are typical of this tumor and can make diagnosis on hematoxylin and eosin (H&E) sections difficult, necessitating the use of immunohistochemistry.
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CD34 immunohistochemistry highlights the vascular nature of angiosarcomas and aids in the diagnosis.
