Introduction

Undifferentiated Pleomorphic Sarcoma (UPS), earlier known as malignant fibrous histiocytoma (MFH),¹ is a rare type of cancer that primarily affects soft tissues in the body. Soft tissues are fundamental for optimal body function since they connect, support, and surround other body structures.²

This article aims to provide a comprehensive overview of UPS, from its definition and causes to its diagnosis, treatment options, and prognosis. Upon conclusion, we hope to have broadened your understanding of this challenging condition and the importance of early detection and intervention, in order to help not only those affected but also their relatives.

Overview of soft tissue sarcomas

Undifferentiated Pleomorphic Sarcomas belong to a group of rare cancers known as soft tissue sarcomas. These sarcomas affect the tissues that connect, support, and surround other body structures and organs, which include muscles, tendons, fat, blood vessels, and cartilage.³

Causes and risk factors of UPS

The exact cause of UPS remains unclear, however, due to the characteristics of undifferentiated pleomorphic sarcomas some information regarding its potential causes can be derived. For example, the distinct feature of UPS is its heterogeneous population of cells with mesenchymal features which can result from both simple or complex genetic modifications.

These cells have been shown to have an increased capacity for self-renewal, growth, proliferation (rapid growth or reproduction), and recapitulate tumour formation.¹ Given this information, it is believed that undifferentiated pleomorphic sarcomas might have a genetic derivative. Despite this uncertainty regarding the origin of the cause of UPS, there are two common risk factors that may increase the likelihood of developing the condition:

• Age - it is more common for adults over 50 years of age to acquire this condition, however, it can occur at any age
• Radiation therapy - although unlikely, if the individual has had previous radiation therapy, the cancer might develop in the area of the treatment²

The incidence of UPS in patients with a prior history of radiation therapy was reported as 5.1% in a series of 1068 cases.⁹ 

Signs and symptoms 

Frequently, tumours do not provoke any immediate symptoms as they develop. Symptoms only start developing after a long period of time, giving enough time for the tumour to grow. However, despite the lack of primary symptoms, there are some signs that can potentially be identified; these include:

• The growth of a lump
• Experiencing pain, especially if the tumour applies pressure on nearby nerve
• Feeling a pressure sensation in the surrounding muscle

In addition to these signs, there are some other symptoms that individuals may experience. These may vary depending on the location of the tumour. Some other symptoms may include:

• Swelling
• Fever
• Loss of appetite
• Feeling discomfort or uneasiness (malaise)
• Weight loss
• Constipation
• Feeling pain, tingling, and numbness in limbs^2,4

Diagnosis process 

The diagnosis of undifferentiated pleomorphic sarcoma typically commences with a thorough evaluation of symptoms and a physical examination. Often, this type of cancer is identified once other cancer possibilities have been eliminated.

The diagnostic process involves the following steps:

Physical examination

This is when the healthcare professional will inquire about the onset of your symptoms and any changes they may have undergone over time. The tumour most often involves the arms and the legs, however, other organs may also be involved. A physical examination will also be conducted to assess various aspects, including the size and depth of the growth, its relationship with nearby tissues, and the presence of any signs of swelling or nerve damage.

Imaging tests

This might be requested after physical examination, as imaging tests generate detailed images of the affected area, further enhancing the understanding of the condition. These imaging tests may encompass X-rays, computerised tomography (CT) scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans.

Tissue biopsy

To establish a definitive diagnosis, it might be required to collect a sample of the tumour tissue and send it to a laboratory for thorough analysis. The method of collecting the tissue sample may vary based on your specific situation and may involve a needle inserted through your skin or a surgical procedure.

Within the laboratory, specialised medical professionals, known as pathologists, meticulously examine the tissue sample to determine the cell types involved and assess their potential aggressiveness. This critical information serves to rule out other types of cancer and plays a pivotal role in shaping the treatment plan.⁵

Treatment 

Treatment strategies for undifferentiated pleomorphic sarcoma are multifaceted, with the primary goal of eliminating cancer cells and preventing their regrowth. The choice of treatment modalities depends on various factors, including the size and location of the cancer.

For example, it might be necessary to have a surgical intervention. This is often the preferred approach for UPS, aiming to completely excise the sarcoma while minimising damage to surrounding healthy tissue. Surgeons strive to employ limb-sparing procedures whenever feasible, particularly when the sarcoma affects the arms or legs. These operations aim to remove the cancer while preserving the affected limb's functionality.

In certain cases, when the sarcoma's size or location poses challenges, amputation of the affected limb may be necessary. In such instances, other therapeutic modalities, including radiation therapy and chemotherapy, may be recommended before surgery to reduce the tumour's size and facilitate its subsequent surgical removal without amputation.

Another potential treatment is the use of radiation therapy, which employs high-energy beams, such as X-rays or protons, to target and eradicate cancer cells. It can be delivered in two primary forms:

• External beam radiation: This approach involves a machine that orbits around the patient as they lie on a treatment table. The machine precisely directs radiation to specific points on the body
• Intraoperative radiation therapy (IORT): IORT is administered during surgery, immediately after the cancer's removal. The radiation is directed at the area previously occupied by the tumour. IORT is recommended when the sarcoma's location complicates complete surgical removal

Chemotherapy is another potential course of treatment. This is a drug-based approach that employs chemicals to target and destroy cancer cells. It can be administered orally, intravenously, or through a combination of both methods. Additionally, chemotherapy may be combined with radiation therapy to enhance its therapeutic efficacy.

Moreover, targeted drug therapies might also be suggested. These are designed to address specific abnormalities within cancer cells, effectively causing these cells to undergo programmed cell death (apoptosis). For UPS, targeted therapy drugs may be combined with chemotherapy for a more comprehensive approach. It's important to note that the effectiveness of certain targeted therapies may depend on the presence of specific genetic mutations within the cancer cells, which can be determined through laboratory testing.

Another type of treatment is immunotherapy, which harnesses the body's immune system to combat cancer. In cases of advanced cancer, where the immune system may not naturally target the cancer due to its ability to evade detection, immunotherapy can be a viable option. It operates by interfering with the mechanisms that allow cancer cells to hide from the immune system.

However, it is important to note that immunotherapy is generally reserved for individuals with advanced-stage UPS as the treatment works by disrupting the cancer cell's ability to evade immune system surveillance, ultimately mobilising the body's immune defenses to attack the cancer cells.^5,6

Prognosis

The key to enhancing the overall prognosis in undifferentiated pleomorphic sarcoma (UPS) lies in the early recognition of the disease and the implementation of an appropriate treatment strategy. A recent retrospective study involving 319 patients from three tertiary care centres indicated that recurrences occurred in 14.1% of cases, with 7.8% experiencing metastases.⁷

Moreover, in a specific report focusing on UPS, post-treatment local recurrence (15%) was statistically linked to advanced age and inadequate surgical margins. In comparison, post-treatment metastatic disease (37.6%) was significantly associated with tumours larger than or equal to 5 cm.⁸ However, the 5- and 10-year overall survival rates were 60% and 48%, respectively.¹ 

Summary

To summarise, undifferentiated pleomorphic sarcoma (UPS), or malignant fibrous histiocytoma (MFH), is a rare soft tissue cancer. UPS is characterised by its impact on connective tissues, where whilst the exact cause remains uncertain, age and prior radiation therapy are common risk factors.

Diagnosis entails physical examinations, imaging tests, and biopsies fundamental to not only confirm the diagnosis but also to devise the appropriate treatment course to be undertaken. The potential treatments offered include surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapy.

However, as the studies mentioned demonstrated, early detection and proper treatment are crucial for improving prognosis. Moreover, continuous research might provide a more hopeful outcome for both the affected individuals and their families.