Dedifferentiated liposarcoma (DDLPS) is an aggressive and uncommon soft tissue cancer originating from fat cells. This cancer is characterized by its “dedifferentiated” nature, where cells lose specialized fat-cell characteristics and adopt a more aggressive, less mature appearance. DDLPS typically develops from a pre-existing, less aggressive fatty tumor called well-differentiated liposarcoma (WDLS), often in adults over 50. This transformation often occurs over time; about 90% of DDLPS cases arise spontaneously, with the rest developing from a recurrence of previously treated WDLS.
Causes and Symptoms
The exact cause of dedifferentiated liposarcoma is generally unknown. While genetic alterations, such as the amplification of genes on chromosome 12q (including MDM2 and CDK4), are consistently found in DDLPS, what triggers these changes remains unclear. Prior radiation therapy or specific genetic syndromes are rarely associated with an increased risk.
Symptoms of DDLPS vary significantly depending on the tumor’s location. When the tumor is in the retroperitoneum, the space behind the abdominal cavity, symptoms can include abdominal fullness, discomfort, bloating, or decreased appetite. These tumors can grow quite large before detection, sometimes found incidentally during imaging tests.
If DDLPS develops in the limbs, it typically presents as a growing lump. This lump is often painless, though it may cause swelling or numbness in the surrounding area as it expands. Less common symptoms can involve digestive issues like constipation, or general signs such as unintended weight loss, fever, or fatigue.
The Diagnostic Process
Confirming a diagnosis of dedifferentiated liposarcoma involves several steps, beginning with imaging tests. Doctors commonly use computed tomography (CT) scans or magnetic resonance imaging (MRI) to visualize the tumor. These scans help determine its precise size, location, and how it relates to nearby organs and tissues. Imaging can also show if the tumor has spread.
While imaging provides valuable information, a biopsy is the only way to definitively diagnose DDLPS. This procedure involves taking a small tissue sample from the tumor, often guided by imaging for accuracy. The sample is then sent to a pathologist, a doctor specializing in examining tissues and cells under a microscope.
The pathologist analyzes the tissue to identify the distinct characteristics of dedifferentiated cells, which appear less specialized than normal fat cells. The presence of both well-differentiated (fat-producing) and non-fat-producing sarcoma components confirms the diagnosis. Pathological examination includes genetic testing for MDM2 gene amplification, a molecular marker and defining feature of DDLPS. This specific genetic alteration helps distinguish DDLPS from other soft tissue tumors.
Standard Treatment Approaches
Surgery is the primary treatment for localized dedifferentiated liposarcoma. The goal of surgery is complete tumor removal, along with a surrounding border of healthy tissue, known as “negative” or “clear” margins. This approach aims to ensure no microscopic cancer cells are left behind, reducing the risk of cancer returning in the same area.
Radiation therapy is often used with surgery. It can be administered before surgery (neoadjuvant radiation) to shrink a large tumor, making it easier to remove. Alternatively, radiation may be given after surgery (adjuvant radiation) to destroy any remaining cancer cells not visible during the operation. This further lowers the chance of local recurrence, particularly when surgical margins are very close or positive.
Chemotherapy generally plays a limited role in the initial treatment of DDLPS. It is typically reserved for cases where cancer has spread (metastatic disease) or when the tumor cannot be completely removed surgically. While DDLPS can be modestly sensitive to chemotherapy, especially anthracycline-based regimens, the response varies. Receiving care from a multidisciplinary team at a specialized sarcoma center is beneficial, as these teams bring together various experts to develop a comprehensive and individualized treatment plan.
Prognosis and Recurrence
The outlook for individuals with dedifferentiated liposarcoma can vary, influenced by several factors. The tumor’s location plays a significant role, with retroperitoneal tumors often having a more challenging prognosis than those in the limbs. The tumor’s size at diagnosis and whether it was completely removed during surgery also affect the long-term outcome.
A notable characteristic of DDLPS is its high potential for local recurrence, where the cancer can reappear in the same area. Recurrence rates range from approximately 40% to 75%, and for retroperitoneal tumors, recurrence can be nearly 100% over a long follow-up period. While distant metastasis occurs in about 10% to 15% of cases, local effects of the tumor are often the primary cause of complications.
Given the high risk of local recurrence, consistent and long-term follow-up is standard care. This typically involves regular imaging scans to monitor for any signs of cancer returning. These follow-up appointments allow medical teams to detect any recurrence early and intervene promptly.