Liposarcoma is a cancer that arises from the body’s fat cells within soft tissues. To diagnose it, doctors perform a biopsy, taking a small tissue sample for examination under a microscope. This microscopic analysis, known as histology, allows pathologists to confirm the presence of cancer and classify it into specific subtypes. The subtype of liposarcoma is important because it determines how the tumor is likely to behave, its potential to spread, and the most effective course of treatment.
The Hallmark Cell: The Lipoblast
When examining liposarcoma tissue, pathologists search for a lipoblast, which is a malignant, developing fat cell. A lipoblast contains one or more fat droplets, called vacuoles, that push against the cell’s nucleus, compressing and indenting it. This indentation often gives the nucleus a distinctive scalloped or crescent-like appearance. This visual cue is one of the primary features that helps pathologists distinguish liposarcoma from other soft tissue tumors.
While the lipoblast is a defining characteristic, its presence is not required to diagnose every subtype. In some forms of liposarcoma, these cells can be rare or difficult to identify. In these cases, pathologists rely on other microscopic features and genetic analysis to confirm the diagnosis.
Well-Differentiated and Dedifferentiated Subtypes
The most common form is well-differentiated liposarcoma (WDL), which can resemble normal, mature fat tissue. Pathologists look for subtle clues, such as variation in the size and shape of the fat cells (adipocytes). They also search for fibrous bands running through the tissue and scattered atypical cells with larger, darker nuclei.
When a WDL develops in the arms or legs, it is often called an Atypical Lipomatous Tumor (ALT). This name is used because these tumors do not metastasize, or spread to distant parts of the body. Their risk is primarily local recurrence, but they can progress into a more aggressive form if untreated.
Over time, a WDL can evolve into a dedifferentiated liposarcoma (DDL). DDL is defined by an abrupt transition where part of the tumor remains a WDL, while another section transforms into a high-grade, non-fatty sarcoma. This feature of two distinct tumor types existing side-by-side confirms a DDL diagnosis and signals a more aggressive cancer.
Myxoid Liposarcoma
Myxoid liposarcoma is the second most common subtype. Its most prominent feature is a large amount of myxoid stroma, a gelatinous substance filling the space between cancer cells. This material gives the tumor a pale, watery look on a histology slide.
Within this background, the tumor cells are uniform with a round or oval shape. Pathologists can find characteristic lipoblasts scattered throughout the tumor, which helps confirm the diagnosis.
Another defining feature of myxoid liposarcoma is its rich network of small blood vessels. These vessels form a distinct, branching pattern often described as a “chicken-wire” or plexiform network. This web of capillaries is a key histological clue for this subtype.
Pleomorphic Liposarcoma
Pleomorphic liposarcoma (PLS) is the rarest and most aggressive subtype. The term “pleomorphic” means “many shapes,” reflecting the tumor’s appearance, which is characterized by sheets of large, bizarre cells with extreme variation in size and shape.
The definitive diagnostic feature of PLS is the presence of numerous pleomorphic lipoblasts. These are not the typical lipoblasts of other subtypes; they are large, strange, and often contain multiple fat vacuoles. Their presence confirms the tumor’s nature.
Unlike dedifferentiated liposarcoma, PLS is a high-grade tumor from the outset and does not arise from a pre-existing well-differentiated component. The entire tumor exhibits aggressive features, including areas of necrosis and high mitotic activity, which are signs of rapid cell division.
The Role of Ancillary Studies in Diagnosis
Ancillary studies, including specialized staining and genetic analysis, provide objective data to support a diagnosis. These tests are helpful in challenging cases where histologic features are not definitive.
Immunohistochemistry (IHC) uses antibodies to detect specific proteins in tumor cells. For liposarcoma, IHC tests for MDM2 and CDK4 proteins, as their over-expression is a hallmark of well-differentiated and dedifferentiated subtypes. Staining for these proteins helps distinguish these tumors from benign growths or other sarcomas.
Molecular testing analyzes the tumor’s DNA for specific genetic abnormalities. For WDL and DDL, the finding is the amplification of the MDM2 gene. Myxoid liposarcomas are defined by a translocation where the FUS and DDIT3 genes fuse together. These genetic markers provide definitive proof of a specific subtype.