Malignant fibrous histiocytoma is a type of cancerous tumor that can develop in soft tissues or bones, most commonly affecting the arms and legs. Now more frequently called undifferentiated pleomorphic sarcoma, this rare condition has historically been recognized as one of the most common soft tissue cancers in older adults, though it can occur at any age.
Epidemiology
Malignant fibrous histiocytoma, now more accurately referred to as undifferentiated pleomorphic sarcoma, represents approximately 1% of all adult cancer diagnoses each year. Despite its rarity in the general population, it stands as the most common type of soft tissue cancer in late adulthood, particularly among people over the age of 50.[3]
The disease typically peaks around age 50, with the average age of diagnosis being approximately 59 years. Men are affected about twice as often as women, with a male-to-female ratio of approximately 1.5 to 1. This pattern of occurrence differs significantly from most cancers, which tend to show more equal gender distribution.[3][20]
While malignant fibrous histiocytoma is among the most common soft tissue tumors found in adults, it is rarely found in children. However, cases have been documented in young people, including rare instances in patients as young as 11 years old. When the disease does occur in children, it presents with similar characteristics to adult cases but is considered extremely unusual.[1][4]
The tumor accounts for approximately 20 to 30% of all soft tissue sarcomas diagnosed each year. Although it can develop anywhere in the body, the vast majority of cases occur in specific regions. About 70 to 75% of tumors develop in the extremities, with the lower extremities accounting for roughly 59% of all cases. The arms, legs, and abdomen are the most frequently affected areas.[1][3]
Causes
The exact cause of malignant fibrous histiocytoma remains unknown, though researchers have identified several factors that may contribute to its development. The tumor is believed to originate from primitive mesenchymal cells, which are basic cells that can develop into various types of connective tissue. This understanding has led to the reclassification of the disease, as earlier scientists incorrectly believed the tumor stemmed from histiocyte cells.[3]
Genetic abnormalities appear to play a role in the development of this cancer. Some people may be genetically predisposed to developing malignant fibrous histiocytoma, though specific genetic mutations responsible for the disease have not been definitively identified. The cause has been linked to genetics, though the precise mechanisms remain under investigation.[4][20]
Exposure to certain chemicals has been suspected as a potential cause. The list of chemicals under suspicion includes arsenic, vinyl chloride, wood preservatives containing chlorophenols, and some herbicides. However, the connection between these chemical exposures and tumor development has not been conclusively proven.[20]
The disease is not believed to be caused by physical trauma, despite many patients recalling an injury near the tumor site. It is common for people with this condition to mistakenly assume that a bump or accident caused the growth. In reality, the pain or swelling following an injury is often coincidental with the tumor’s progression rather than its cause.[23]
Risk Factors
Previous radiation therapy represents the most significant known risk factor for developing malignant fibrous histiocytoma. The disease is recognized as the most common radiation-induced sarcoma. Patients who have undergone radiation treatment for other cancers are at elevated risk, with tumors typically developing seven to twenty years after the initial radiation exposure. Most patients who develop radiation-associated sarcomas have received a radiation dose of 50 Gray or more.[3][5]
Chronic conditions affecting the bones may increase risk when the tumor develops in bone rather than soft tissue. These include Paget disease, a condition that disrupts normal bone renewal processes. Certain chemotherapy treatments have also been linked to an increased likelihood of developing this type of cancer, though the specific drugs and mechanisms are still being studied.[9][16]
People with a history of retinoblastoma, a type of eye cancer that primarily affects children, may develop malignant fibrous histiocytoma as a second cancer later in life. This connection suggests that some inherited disease patterns or genetic factors may predispose certain individuals to multiple cancer types over their lifetime.[3]
Symptoms
The most common initial symptom of malignant fibrous histiocytoma is a noticeable mass or lump on the body. In most cases, this mass appears as a painless, soft tissue growth that gradually increases in size over a period of weeks or months. The tumor typically measures between 5 and 10 centimeters in diameter by the time it is diagnosed, though some cases report tumors reaching approximately 9 centimeters in width before detection.[3][5]
When the tumor develops in the extremities, which is the most common location, patients may experience symptoms that affect movement and function of the affected limb. These can include restricted movement of an arm or leg, difficulty walking or a noticeable limp, and progressive enlargement of the affected area. The mass may appear reddish in color with a smooth overlying surface, particularly when it affects areas close to the skin.[1][22]
Pain is not always present in the early stages of the disease. When pain does occur, it typically develops later as the tumor grows larger and begins compressing nearby nerves or muscles. This delayed onset of pain is one reason why the disease often goes undetected until it has reached a more advanced stage. The tenderness or discomfort may be dull and aching rather than sharp or severe.[22][23]
When malignant fibrous histiocytoma develops in bone rather than soft tissue, symptoms typically include pain at the tumor site that persists over several months. This may be accompanied by swelling over a bone or joint, and in approximately 20% of cases involving bone, the affected bone may break without clear cause, a condition known as pathologic fracture.[9][16]
In cases where the tumor develops in the retroperitoneum (the back of the abdominal cavity), symptoms may be quite different and more general. Patients may experience fatigue, unintended weight loss, abdominal pressure or discomfort, fever, and a general feeling of being unwell (malaise). These vague symptoms can make diagnosis more challenging, as they could be attributed to many different conditions.[3][5]
Prevention
Because the exact cause of malignant fibrous histiocytoma remains unknown, specific prevention strategies have not been established. However, awareness of risk factors can help individuals and their healthcare providers maintain appropriate vigilance for early detection.
For individuals who have previously received radiation therapy for cancer treatment, long-term monitoring is advisable. Since radiation-induced sarcomas typically develop seven to twenty years after radiation exposure, patients with a history of radiation treatment should remain alert to any unusual growths or masses, particularly in areas that received radiation. Regular follow-up appointments with healthcare providers can facilitate early detection if a tumor develops.[3][5]
Minimizing exposure to potentially harmful chemicals may reduce risk, though the connection has not been definitively proven. This includes taking appropriate safety precautions when working with arsenic, vinyl chloride, wood preservatives containing chlorophenols, or certain herbicides. Following workplace safety guidelines and using proper protective equipment when handling such substances is prudent.[20]
Early detection through self-awareness represents the most practical approach to addressing this disease. Individuals should pay attention to any unusual lumps or masses on their body, particularly those that persist for more than a few weeks, continue to grow, or develop without an obvious cause. Seeking medical evaluation promptly when such changes are noticed can lead to earlier diagnosis and potentially better outcomes.
For people with certain inherited conditions, such as retinoblastoma, discussing cancer surveillance strategies with healthcare providers may be beneficial. These individuals face elevated risks for secondary cancers and may benefit from more frequent medical monitoring throughout their lives.[3]
Pathophysiology
Malignant fibrous histiocytoma develops when certain cells in the body begin to grow and divide in an uncontrolled manner. The tumor cells are believed to derive from primitive mesenchymal stem cells, which are basic cells capable of developing into various types of connective tissue. Rather than differentiating into normal, specialized cells, these cells remain in an immature state and multiply rapidly.[3]
The tumor is characterized by the presence of four main cell types: storiform/pleomorphic, myxoid, giant cell, and inflammatory. The term “pleomorphic” refers to the variable appearance of the tumor cells under a microscope, indicating that the cells can take on many different shapes and sizes. This variability in cell appearance is one reason the tumor can be difficult to distinguish from other types of cancers.[3]
Tumors typically arise in deep structures within the body, most commonly in deep fascia (the tissue that surrounds muscles) or within skeletal muscle itself. As the tumor grows, it forms a mass that may appear well-defined on imaging studies. However, at the microscopic level, the tumor often spreads beyond its visible borders, with cancer cells extending along muscle fibers and fascial planes. This microscopic spread is one reason why surgical removal must include a margin of healthy tissue around the visible tumor.[1][5]
When examined during surgery or at gross pathologic examination, the tumor typically appears multilobulated with areas of necrosis (dead tissue), degeneration, or hemorrhage (bleeding) visible on the cut surface. Some tumors show extensive internal bleeding. Despite often appearing well-defined at this level of examination, the microscopic reality is that tumor cells frequently extend beyond these apparent boundaries.[5]
The cancer cells grow and spread quickly, demonstrating aggressive behavior. In approximately 40% of cases, the disease metastasizes, or spreads to distant organs. The lungs are the most common site of metastasis, though the cancer can also spread to lymph nodes, bone, and other organs. This tendency to spread makes the disease particularly dangerous and contributes to its poor prognosis.[3][10]
When malignant fibrous histiocytoma develops in bone, the cancer cells progressively destroy normal bone tissue. This destruction weakens the bone structure, which explains why pathologic fractures occur in approximately 20% of bone cases. The tumor causes the bone to lose its normal strength and integrity, making it susceptible to breaking even without significant trauma.[9]
The tumor grade, which describes how abnormal the cells appear under a microscope, provides important information about the tumor’s behavior. High-grade tumors, which make up the majority of cases, contain cells that look very different from normal cells and tend to be more aggressive. These tumors grow rapidly, are more likely to invade surrounding tissues, and have a higher tendency to spread to other parts of the body. Lower-grade tumors, while less common, tend to grow more slowly and are less likely to spread.[3]
