Liposarcoma

Liposarcoma is a type of soft tissue sarcoma that encompasses five distinct subtypes, each varying in behavior from almost benign to high-grade malignant. The most common subtype is well-differentiated liposarcoma. This tumor is also known as atypical lipomatous tumor when it occurs in the extremities. (There is a difference in naming primarily based on location: when located in deep soft tissues like the retroperitoneum, it is named well-differentiated liposarcoma (WDL), and when located in extremities or superficial soft tissues, it is named atypical lipomatous tumor (ALT) despite both tumors sharing the same histology.) WDL and ALT behave in a way that is often described as “low-grade malignant” or even “borderline malignant,” meaning they do not typically metastasize. Nonetheless, both well-differentiated liposarcoma and ALT have a significant risk of subsequent malignant transformation. This subtype is described in detail in the “Atypical Lipomatous Tumors” chapter. The other four forms are myxoid liposarcoma; round cell liposarcoma; pleomorphic liposarcoma; and dedifferentiated liposarcoma. Lesions with both myxoid and round cell components are commonly seen. Pleomorphic and dedifferentiated liposarcomas as well as those with greater than 5% round cells are aggressive and high-grade. While treatment options can vary depending on the specific subtype, surgical resection with wide margins accompanied by local radiation remains the mainstay of treatment across all subtypes.

Epidemiology

Myxoid and Round Cell Liposarcoma subtypes tend to develop in patients aged 20 to 45 years and are the second most common forms of liposarcoma, accounting for 30-40% of all cases. Since they are often seen together in the same specimen, the round cell component is typically reported as a percentage of the total specimen (i.e., “myxoid liposarcoma with X% round cell component”). When the round cell component is found to comprise more than five percent of the tumor, the tumor is high-grade. Myxoid and round cell liposarcomas have an extraordinary tendency to metastasize to the spine and as such staging studies for these tumors should include an MRI scan of the entire spine.

Pleomorphic Liposarcoma tends to be found in patients aged 50 to 70 years and accounts for 5-10% of all liposarcomas.

Dedifferentiated Liposarcoma usually develops from a well-differentiated liposarcoma or atypical lipomatous tumor and accounts for 5-7% of all liposarcomas.

Clinical Features

Liposarcoma typically presents as a painless, enlarging mass. The rate of growth can vary from slow progression over years to more rapid enlargement. In rare cases, it can cause compressive neuropathy. In the extremities, the mass often becomes palpable and visible, prompting patients to seek medical evaluation. The size of the presenting tumor can range from a few centimeters to a much larger mass. In the retroperitoneum, the tumor can grow substantially before being discovered, often during the examination of nonspecific abdominal or pelvic symptoms, such as constipation, early satiety, or pain.

Radiologic Features

Liposarcoma does not have a pathognomonic radiographic finding, although it can rarely exhibit soft-tissue calcifications on X-ray. Magnetic resonance imaging is usually needed for characterization and biopsy is needed for histologic diagnosis.

Myxoid and Round Cell Liposarcomas are soft-tissue sarcomas with little to no fat preservation within the mass, despite their names. As a result, they do not “follow fat” on MRI sequences, appearing hypointense on T1 sequences and hyperintense on fluid-sensitive sequences (e.g., T2 fat-saturated, T2 fat-suppressed, and short tau inversion recovery (STIR) sequences). Myxoid tissue has a high water content and can appear very bright on water sensitive sequences. Administration of contrast demonstrates internal enhancement. When wisps of fatty tissue are present, small areas of hyperintensity on T1 sequences and hypointensity on T2 fat-suppressed sequences can be seen (Figure 1A-B). A “tail sign,” namely, that the tumor appears to extend along fascial planes, may be observed occasionally on MRI but is not diagnostic.

Figure 1A and B: T1 axial (A) and PD fat-saturated axial (B) MRI sequences of left buttock myxoid liposarcoma. Note the small amount of high T1 signal in Figure 1A, representing the small amount of residual fat that remains in this liposarcoma. The tumor is otherwise hypointense on T1 sequences and hyperintense on fluid-sensitive sequences.

Pleomorphic Liposarcoma has a nonspecific appearance on MRI due to the loss of fat signal. However, the tumor is frequently associated with necrosis so it may exhibit a partially cystic and heterogeneous enhancement pattern on contrast-enhanced studies.

As noted, dedifferentiated liposarcoma usually develops from the transformation of a well-differentiated liposarcoma or atypical lipomatous tumor. Thus, on MRI, this subtype will demonstrate both areas of the original (more benign) tumor and focal, nodular areas corresponding to dedifferentiated cells that no longer express the adipocyte phenotype and appear similar to most soft tissue sarcomas, which are dark on T1 images and bright on fat-suppressed T2 images. (Figure 2A-B).

Figure 2A and B: MRI T1 sagittal (A) and STIR sagittal (B) sequences demonstrating a dedifferentiated liposarcoma of the anterolateral left thigh. There is an area of plain lipoma (hyperintense on T1 and hypointense on STIR) immediately above the sarcoma, which is hypointense on T1 and hyperintense on STIR.

Pathology

In Myxoid and Round Cell Liposarcomas, the myxoid tissue surrounding the malignant spindle cells has a gelatinous, mucus-like appearance. Signet ring lipoblasts are seen, with their nucleus pushed to the side of the cell. The cells are typically bland and spindle-shaped, and a delicate arborizing capillary “fisherman’s net” network is usually present (Figure 3). Areas of densely packed small round blue cells comprise the round cell component of the tumor. In a mixed lesion, the percentage of round cells present correlates with the grade of the tumor, such that greater than 5% of round cells constitutes a high grade tumor (Figure 4). Ninety percent of cases are characterized by a t(12;16) or t(12;22) translocation, which results in the formation of the TLS-CHOP or EWS-CHOP fusion protein, respectively.

Figure 3: Myxoid/round cell liposarcoma, composed of signet ring lipoblasts (arrowhead), monomorphic round cells, myxoid stroma and arborizing capillary network (arrow). (Courtesy of Dr. Gord Zhu)

Figure 4: Round cell component of myxoid/round cell liposarcoma showing hypercellular areas of round blue cells with sparse cytoplasm, resembling other round blue cell tumors. (Courtesy of Dr. Gord Zhu)

Pleomorphic Liposarcoma is characterized by significant atypia, pleomorphism, and bizarre-appearing lipoblasts.

Dedifferentiated Liposarcoma is characterized by an area of well-differentiated liposarcoma/atypical lipomatous tumor immediately adjacent to an area of high-grade atypical spindle cell sarcoma. This latter region bears little histologic resemblance to the adjacent well-differentiated component tumor (see Figure 5).

Figure 5: Dedifferentiated liposarcoma, non-lipogenic area composed of pleomorphic spindle cells which was only confirmed by MDM2 amplification by FISH. (Courtesy of Dr. Gord Zhu)

Differential Diagnosis

Lipoma
Lipoma variants
Undifferentiated pleomorphic sarcoma

Disease Course: Treatment and Prognosis

Myxoid and Round Cell Liposarcomas subtypes are treated with preoperative or postoperative radiation and wide surgical resection. If the round cell component exceeds 5% of the tumor, it is high grade and chemotherapy, in addition to radiation and surgery, is considered. Despite this additional treatment, these tumors which are higher-grade carry a higher risk of metastasis and a less favorable long-term outcome as the data supporting the efficacy of this chemotherapy is limited. Myxoid and Round Cell Liposarcomas has a high incidence of spinal metastasis. As such, the staging work-up of this lesion should include either a PET scan or an MRI of the entire spine.

Pleomorphic Liposarcoma is an aggressive tumor, with a high propensity to metastasize (40% of cases) and a poor 5-year prognosis (less than 60% survival rate). It is treated with radiotherapy and wide surgical resection. The use of chemotherapy is controversial but can be considered for large, deep tumors which are greater than 5 cm in diameter.

Dedifferentiated Liposarcoma in the appendicular skeleton is treated with wide surgical resection aiming for clear margins, usually combined with pre- or postoperative radiation therapy. Metastases occur in approximately 10-20% of cases. When found in the retroperitoneum, dedifferentiated liposarcoma is characterized by very high rates of local recurrence and mortality, partly due to the challenges of achieving complete resection in this location. The use of systemic chemotherapy is controversial but generally indicated for unresectable, recurrent, or metastatic tumors.

Key Test Topics

Well-differentiated liposarcoma and atypical lipomatous tumors demonstrate fat with stranding on MRI. Atypical cells with large nuclei are found primarily in the strands of fibrous tissue.
Myxoid liposarcoma has a significant tendency to metastasize to the spine.
Myxoid and round cell liposarcoma is associated with a t(12;16) or t(12;22) translocation.
Dedifferentiated liposarcoma is characterized by a high-grade spindle cell component adjacent to a low-grade tumor such as atypical lipomatous tumor.