- Author: Belen Carsi, MD, PhD, FRCS; Chief Editor: Dirk M Elston, MD more...
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.
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 more sensitive, although less specific, than conventional tomography 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.
Plain radiographic assessment is paramount to characterize lesions of bone angiosarcoma and confirm their multiplicity. However, the radiographic presentation of bone angiosarcoma is not specific. A solitary lesion (60% of cases) presents 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).
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.
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.
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 affectation.
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.
The main problem 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:
The ultrastructure of tumor cells includes intercellular and intracellular lumina with or without red cells.
In their cytoplasm, tumor cells contain intermediate filaments (vimentin, occasional tonofilaments [keratin]) and pinocytotic vesicles.
Weibel-Palade bodies, a marker of endothelial differentiation, may be seen in some cases.
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%).
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.
S100 protein and gp100 (HMB-45 antigen, both melanocytic markers) also are not expressed; this helps to rule out melanoma.
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.
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. 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:
Stage I: Localized and resectable tumor is found at one site in the liver and could be treated surgically
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.
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.
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, 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:
Ia - Low grade, intracompartmental G1/T1/M0
Ib - Low grade, extracompartmental G1/T2/M0
IIa - High grade, intracompartmental G2/T1/M0
IIb - High grade, extracompartmental G2/T2/M0
IIIa - Low or high grade, intracompartmental G1-G2/T1/M1 with metastases
IIIb - Low or high grade, extracompartmental G1-2/T2/M1 with metastases
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.
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.
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