What is Undifferentiated Pleomorphic Sarcoma?
Undifferentiated Pleomorphic Sarcoma (UPS), previously known as malignant fibrous histiocytoma, is a severe type of cancer that grows in soft tissues. It’s thought to originate from a type of stem cell rather than some kinds of immune cells as previously believed. The cancer can spread from soft tissues to bones and other organs. Early findings suggested that it was the most common type of soft tissue cancer in adults. However, more recent research using more advanced testing methods found that many of these cases were actually other types of sarcoma, a kind of cancer that starts in bones or soft tissues.
In the past, this type of cancer was divided into several subtypes, but those classifications are rarely used now. The definition of this type of cancer has been debated for over fifty years, so it’s not always easy to tell from older studies what they were referring to. At this moment, doctors diagnose UPS by ruling out other types of well-defined soft tissue sarcomas.
What Causes Undifferentiated Pleomorphic Sarcoma?
The exact causes of undifferentiated pleomorphic sarcoma (UPS), a type of cancer, are still unknown. Generally, soft tissue sarcomas (STSs), which include UPS, are made up of different types of cells that can come from simple or complex genetic changes. UPS falls into the category of complex genetic changes, with various types of cells, genetic mutations, and altered signaling pathways involved.
The development of UPS is thought to start with certain cells called “side population” (SP) cells. Tests can identify these cells, and researchers believe these cells can grow, multiply, and can form tumors. Studies show that two signaling pathways, Hedgehog and Notch, are notably increased at both the cellular and tissue levels.
The Hippo pathway, another signaling pathway, could also play a role in UPS. Certain genes, VGLL3 and YAP1, were found to be greatly increased in UPS. Also, there’s documented evidence of mutations resulting in loss or deletion of the PTEN gene and overproduction of the protein pAKT, both involved in the PIK3/PTEN/AKT/mTOR pathway.
Additionally, a protein called DKK1, which inhibits the Wnt/B-catenin signaling pathway, was found to be much more present in UPS than in other STSs. The study also found a significant link between the gene pattern of human mesenchymal stem cells (hMSC) and UPS and confirmed that Dkk1 is necessary for hMSC differentiation (change and specialization into different types of cells).
UPS has also been associated with mutations in several genes such as TP53, CDKN2A, RB1, and ATRX, and gene fusions have been identified in others like PRDM10 and TRIO.
Aside from genetic changes, radiation therapy has been identified as a risk factor for developing STS, including UPS. According to one study, one to three percent of all sarcoma diagnoses are associated with previous radiation treatment. In a study of 1,068 UPS patients, 5.1% had a history of radiation therapy.
Risk Factors and Frequency for Undifferentiated Pleomorphic Sarcoma
The World Health Organization in 2020 placed undifferentiated pleomorphic sarcoma (UPS), a type of soft tissue tumor, under the classification of malignant tumors of uncertain differentiation. According to data by the Surveillance, Epidemiology and End Results (SEER) program, amongst 26,758 cases, UPS made up 17.1% of them, making it the second most common diagnosis after leiomyosarcoma. It also highlighted certain trends in who gets affected by UPS.
- There are more males who are affected with UPS than females.
- Within the male population, white males are more commonly affected than black males.
- The incidence of UPS tends to increase with age, being more common in people who are in their sixth decade of life or older.
Signs and Symptoms of Undifferentiated Pleomorphic Sarcoma
Undifferentiated pleomorphic sarcoma (UPS) usually shows up as a painless, rapidly growing lump under the skin or on the surface of the skin without any visible skin changes. If UPS forms inside the body, in the chest, or in the stomach area, it might cause symptoms due to the growing mass. There might also be general body symptoms like fever or weight loss. In a recent review of 100 UPS cases, most tumors were found in the arms or legs (55%), followed by the torso or trunk (35%), behind the stomach area (9%), and in the left upper chamber of the heart (1%). In another review of 266 cases, the average tumor size was approximately 8.8 cm. If UPS is related to previous radiation therapy, it usually takes about 9.33 years for the tumor to develop after the radiation treatment.
Testing for Undifferentiated Pleomorphic Sarcoma
After diagnosing a tumor using tests like histopathology and immunohistochemistry, the next steps involve taking pictures of the tumor, the lymph nodes, and any spread of the cancer to other parts of the body. This is known as “staging the cancer,” and the specifics of this can change depending on where the tumor is located.
According to the NCCN guidelines, getting an MRI with contrast is recommended. MRI is a type of scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body. The contrast is a special dye injected into the veins to make the images clearer. This test can help determine the size of the tumor, whether it has invaded nearby tissues or structures, and whether it’s affecting blood vessels or nerves.
In cases where the tumor is suspected to involve internal organs or the area behind the abdomen, performing a CT scan of the chest, abdomen, and pelvis without contrast is considered. A CT scan is a type of X-ray that takes detailed images from different angles to create a three-dimensional picture of the inside of the body.
In some instances, an MRI or CT of the total spine, head, and neck may be required. Moreover, while tests like a sentinel lymph node biopsy or a PET scan aren’t typically recommended for this disease, recent research studies have suggested that a certain type of PET scan called an (18)F-fluorodeoxyglucose PET scan may be useful in predicting outcomes in patients with soft tissue and bone sarcomas.
Research efforts are ongoing to determine the role of molecular diagnosis in this disease for better understanding, prognostic prediction, and treatment planning.
Treatment Options for Undifferentiated Pleomorphic Sarcoma
The go-to treatment for UPS (Undifferentiated Pleomorphic Sarcoma), a form of cancer, in the head, neck, trunk, and extremities is a type of surgery called en bloc excision, particularly for stage I tumors. In simpler terms, this surgery involves removing the tumor along with some surrounding healthy tissue to ensure no cancer cells are left behind. This method is usually achieved by removing the tumor with a 2 cm margin of healthy tissue. In some cases, this can be challenging due to the presence of important nerves and blood vessels near the tumor.
After surgery, radiotherapy, which is the use of high-energy rays to destroy cancer cells, is recommended if the tumor is very close to the healthy tissue margin, if any cancer cells are found in the margins, or if the tumor involves important structures like bones, major blood vessels, or nerves. Radiotherapy, which covers a 5 cm margin, can be given through different methods, like the use of an external device (external beam RT), during surgery (intraoperative RT) or by placing radioactive materials inside the body (brachytherapy).
People who had cancer remaining in the margins after surgery showed a 1.82 times higher death rate compared to those who had a proper removal of the tumor. Moreover, radiotherapy after the surgery reduced the death rate and spread of cancer in 68% and 66% of UPS patients, respectively. In some instances, Mohs micrographic surgery, a precise surgical technique used to treat skin cancer, was utilized to conserve healthy tissue. Amputation or removal of the affected limb is the last resort, as it does not necessarily have superior results compared to surgeries that save the limb.
Chemotherapy, which uses drugs to kill cancer cells, is utilized for advanced stages of the disease or if the tumor cannot be removed surgically. When a patient is at stage II or III, there needs to be a collaborative effort to discuss whether it is best to administer chemotherapy and radiation therapy before or after surgery. If the tumor can’t be removed, the options could include using chemotherapy alone, combining it with radiotherapy, or a special regional limb therapy. For stage IV patients, there aren’t enough research findings to suggest a clear plan, so expert cancer doctors must be consulted.
In one study, it was shown that tailored chemotherapy was not more effective than the standard chemotherapy regime. Indeed, in the case of UPS, patients showed better chances of being free from the disease after receiving standard chemotherapy compared to those treated with a tailored regime.
Experiments are currently being conducted on using therapies that work on the immune system such as pembrolizumab, nivolumab, and ipilimumab for treating UPS.
The same principles apply when it comes to treating UPS found inside the body. If the disease can be removed, the treatment of choice is excision with negative margins, with or without intraoperative radiotherapy. For unremovable cases, chemotherapy, chemoradiation, or HDR brachytherapy (a specialized form of radiotherapy) are generally the preferred treatments.
What else can Undifferentiated Pleomorphic Sarcoma be?
When diagnosing UPS, or undifferentiated pleomorphic sarcoma, doctors consider a variety of other conditions that can show similar symptoms. These conditions are identified through details from the patient’s medical history, a physical examination, and specific lab tests known as immunohistochemistry markers.
- Atypical fibroxanthoma
- Liposarcoma
- Leiomyosarcoma
- Angiosarcoma
- Fibrosarcoma
- Myxofibrosarcoma
- Dermatofibrosarcoma protuberans
- Osteosarcoma
- Malignant peripheral nerve sheath tumor
- Metastases
- Desmoplastic melanoma
- Spindle-cell squamous cell carcinoma
In other words, UPS can exhibit similar characteristics to other types of soft tissue sarcomas (STSs), metastatic cancer, and some forms of melanoma and skin cancer, hence the need to broadly investigate these possibilities.
What to expect with Undifferentiated Pleomorphic Sarcoma
Identifying the disease early and forming the right treatment strategy are both vital to improve the overall outlook. In a recent examination of 319 patients from three major care facilities, 14.1% and 7.8% of the cases saw recurrence and spread of the disease, respectively. The risk of recurrence was notably higher in cases where the preoperative tumors were larger than 5 cm, there was invasion beyond the fat just beneath the skin, and the American Joint Committee on Cancer (AJCC) staging was advanced. In addition to these, the risk of the disease spreading was high for tumors ranging from 2-5 cm and those that have invaded the lymph or blood vessels.
However, an essential point to note from this study is that the diagnoses were pooled together with a different kind of tumor, atypical fibroxanthoma, which could limit the results. In a study focused purely on UPS (your specific kind of tumor), recurrence of the disease after treatment (15%) was significantly tied to older age and insufficient surgical margins, while post-treatment spread of the disease (37.6%) was found to be significant in tumors 5 cm or larger.
In terms of survival, 60% of patients survived at least five years, and 48% made it to ten years. Interestingly, another study showed that the 5-year survival and recurrence rates were significantly worse in patients with UPS linked to radiation therapy, suggesting the disease might behave differently based on its cause.
Continuous follow-up visits are important to check for local recurrence or spread of the disease. Physical check-ups for stage I tumors should occur every 3-to-6-months for the first two years, then annually thereafter. Imaging tests, like MRIs or CT scans, are not typically needed unless the patient is showing specific signs and symptoms. However, for stages II to IV, check-ups should be every two to six months for the first two to three years, then every six months for the next two years, and then annually. Post-surgery, MRI with and without contrast, or contrast CT, is recommended to assess the site of the primary tumor. Further imaging of affected and distant areas may be needed depending on the individual’s risk of recurrence.
Possible Complications When Diagnosed with Undifferentiated Pleomorphic Sarcoma
Like many serious soft tissue sarcomas (STSs), the usual complications are local reappearances of the disease, spread of the disease to other parts of the body, and death. Depending on the area affected, there may also be complications related to treatment, such as disability from limb amputation, organ damage consequences, problems with wound healing, and issues with nerves and blood vessels.
Common Complications:
- Local reappearances of the disease
- Spread of the disease to other parts of the body
- Death
- Disability from limb amputation
- Organ damage consequences
- Problems with wound healing
- Issues with nerves and blood vessels
Preventing Undifferentiated Pleomorphic Sarcoma
It’s crucial for patients to be educated about UPS (Undifferentiated Pleomorphic Sarcoma, a type of cancer) as it helps them to feel reassured, follow their treatment plans and attend follow-up appointments properly. One study found that nearly half of the people newly diagnosed with sarcoma, another type of cancer, experienced signs of mental distress. This turmoil often affects patient’s daily life activities and financial situation. Furthermore, they pointed out the lack of accessible information, the need for supportive groups and the complexity of navigating the healthcare system as major concerns. Being well-informed about this disease can help manage these concerns better.
