Angiosarcoma is an uncommon malignancy that arises from endothelial cells, which form the inner lining of blood and lymphatic vessels. This cancer represents a small fraction of all soft tissue sarcomas and can develop in any part of the body, though it most often appears in the skin, soft tissue, breast, and liver. The study of its microscopic anatomy, known as histology, is fundamental to its diagnosis, as examining the tissue structure provides the definitive evidence needed for identification.
What Angiosarcoma Looks Like Under the Microscope
When a pathologist examines a suspected angiosarcoma, they observe a wide spectrum of appearances. In some cases, the tumor is well-differentiated, meaning it still forms recognizable, albeit irregular and disorganized, vascular channels. These channels are lined by atypical endothelial cells that interconnect and weave through the body’s normal tissues. This infiltrative growth pattern is a hallmark of the malignancy, showing how the tumor invades surrounding structures.
The endothelial cells themselves may be plump, elongated like spindles, or epithelioid, which means they are large and round. Their nuclei often show significant atypia, including pleomorphism (a notable variation in nuclear size and shape) and hyperchromasia, where the nuclei stain darker than normal because of excess DNA. Prominent nucleoli within the nucleus are another common feature.
The overall architecture of the tumor can vary significantly, even within the same lesion. Besides infiltrating channels, angiosarcomas can form papillary tufts, which are small projections of cells that extend into a vessel lumen. In other areas, the tumor may be poorly differentiated, growing as solid sheets of malignant cells with little to no vessel formation. Pathologists also assess mitotic activity by counting the number of dividing cells to determine the tumor’s proliferation rate.
Using Special Stains to Confirm Angiosarcoma
When angiosarcomas do not form obvious vessels, pathologists use immunohistochemistry (IHC) to confirm the endothelial origin of the tumor cells. This method uses antibodies designed to detect specific proteins, or antigens, that are characteristic of certain cell types. When the antibody binds to its target protein in the tissue sample, a chemical reaction creates a visible stain, effectively tagging the malignant cells.
Several IHC markers are reliably used to identify endothelial differentiation in a suspected angiosarcoma. A panel of these stains is important when the microscopic appearance is ambiguous.
- CD31 is a widely used and specific marker found on the surface of most endothelial cells.
- ERG is a protein found in the nucleus of endothelial cells and is considered highly sensitive and specific.
- CD34 is another endothelial marker, though it is less specific than CD31 and ERG.
- FLI1 is a nuclear transcription factor that is consistently expressed in vascular tumors.
Different Faces of Angiosarcoma: Variants and Grades
Angiosarcomas can present in several different forms known as histological variants. These variants are defined by the dominant type of cell and architectural pattern observed under the microscope. Recognizing these different faces is important because they can sometimes mimic other types of cancer, creating diagnostic challenges.
One of the most recognized variants is epithelioid angiosarcoma. This type is characterized by large, rounded cells with abundant pink-staining cytoplasm, making them resemble epithelial cells found in carcinomas. This variant can sometimes co-express proteins called cytokeratins, which are markers for carcinomas, further complicating the diagnostic picture. Another common form is spindle cell angiosarcoma, which is composed of elongated, spindle-shaped cells that can be mistaken for other sarcomas.
Beyond identifying variants, pathologists also assign a histological grade to the tumor. Grading is a system used to classify the cancer’s aggressiveness based on its microscopic features. This assessment evaluates the degree of cellular atypia, the mitotic rate (how fast the cells are dividing), and the extent of necrosis, which is the death of tissue within the tumor. A higher grade indicates a more aggressive clinical course.
How Microscopic Details Influence Outlook and Diagnosis
The collective information gathered from the microscopic examination directly informs the patient’s prognosis and guides treatment planning. Features such as a high histological grade, the presence of necrosis, and a high mitotic rate are associated with more aggressive tumor behavior and a poorer outlook. Certain histological variants, particularly the epithelioid type, have also been linked to a higher likelihood of metastasis. The depth of tumor invasion into surrounding tissues is another factor that helps predict its potential to spread.
These histological findings help medical teams make decisions about treatment. For instance, evidence of a highly aggressive, deeply invasive tumor might lead to recommendations for more extensive surgery or the inclusion of radiation therapy. The detailed pathological report provides a roadmap for oncologists as they consider different therapeutic strategies.
Despite advances in diagnostic techniques, identifying angiosarcoma can still pose challenges. One issue is tumor heterogeneity, where a single tumor may show different patterns and grades in different areas. A small biopsy might only capture a well-differentiated portion, underestimating the tumor’s true aggressiveness. Additionally, distinguishing a low-grade angiosarcoma from benign or atypical vascular lesions requires careful evaluation.