What is undifferentiated pleomorphic sarcoma?

Undifferentiated pleomorphic sarcoma (UPS) is a rare type of cancer that arises in soft tissues.  It was previously known as malignant fibrous histiocytoma and was recently renamed by the World Health Organization.  Its name reflects the way the tumor appears microscopically.  Undifferentiated cells do not have any obvious characteristics of the tissues from which they develop.  They are termed pleomorphic, indicating that these cells are not uniform or similar to one another, but rather take on different sizes and shapes.   UPS represent around 10% of all adult soft-tissue sarcomas, making it one of the most common subtypes.  It frequently develops in the thigh and hip region but can occur in other extremity locations as well as in deeper anatomic regions such as the retroperitoneum.  These tumors are generally considered high-grade, which are true cancers and which have a substantial likelihood of metastasizing.  They typically develop in older adult patients, and are relatively rare in the pediatric population.

What causes undifferentiated pleomorphic sarcoma?

Several specific genetic mutations have been linked to undifferentiated pleomorphic sarcoma.  These mutations include genes such as TP53 and RB1, which are important tumor suppressors as well as ATRX, a regulatory gene thought to manage chromatin remodeling.  In some instances, genes may be amplified while in other cases certain genes may be deleted or lost.  There is no evidence that environmental, social, dietary or other external factors contribute to its development. 

What are the symptoms?

Oftentimes patients will note a sizable, growing, though painless lump.  Pain is sometimes reported, but often these are not particularly uncomfortable, prompting some patients to delay medical attention.  These tumors can rapidly grow and often reach sizes between 5 and 15 cm in diameter, or larger.  As they enlarge, the overlying skin can appear taught or stretched.  Deeper structures or organs can be compressed, leading to a constellation of symptoms, depending upon what is being impacted.

How is undifferentiated pleomorphic sarcoma diagnosed?

Undifferentiated pleomorphic sarcoma is diagnosed using imaging studies, such as plain x-rays and MRI.  A CT scan of the chest, a PET scan or a PET CT is often obtained as well to detect the extent of the disease.  Ultimately, a biopsy is required to sample the tumor and review its microscopic appearance. 

How is undifferentiated pleomorphic sarcoma treated?

  • Treatment for undifferentiated pleomorphic sarcoma generally involves surgery.  When the tumor is small and localized to only one part of the body, surgery is sometimes curative alone, without the addition of other treatment modalities. 
  • If the tumor is larger than 5 cm, the combined use of surgery and radiation therapy offers patients better control of their disease, meaning a lower risk of local recurrence.  There are a variety of radiation techniques and often the exact method of delivery is tailored to a patient’s individual circumstances and clinical needs.
  • If the tumor is large, or if the tumor has metastasized, treatment will often also include chemotherapy. Cytotoxic chemotherapy has been historically utilized and while it can be helpful in some instances, this is not always the case. The addition or use of cytotoxic chemotherapy requires a thorough discussion with a medical oncologist who specializes in sarcoma care, to fully outline the value added and the inherent risks of systemic therapy.
  • Novel therapies are being explored, often within the context of ongoing clinical trials.  These include a wide variety of targeted agents, designed to affect one or more specific pathways.  The role of immunotherapy is also being currently explored.
  • Following the completion of treatment, patients treated for undifferentiated pleomorphic sarcoma will require close surveillance for a period of 5 years.  This includes physical examinations and periodic imaging studies.  Many patients continue to follow up even after 5 years, albeit at a reduced frequency.