Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma is a rare and aggressive type of cancer that affects soft tissues or bones, most commonly appearing as a painless mass in the arms or legs of older adults, though it can occur in children and throughout the body.

Table of contents

• What is Malignant Fibrous Histiocytoma?
• Alternative Names and Classification
• Who is Affected?
• Where Does It Occur?
• Signs and Symptoms
• Causes and Risk Factors
• Diagnosis
• Treatment Options
• Prognosis and Outcomes

What is Malignant Fibrous Histiocytoma?

undifferentiated pleomorphic sarcoma, UPS, pleomorphic sarcoma, MFH, soft tissue sarcoma

Malignant fibrous histiocytoma is a type of sarcoma, which is cancer that develops in connective tissues of the body^[1]. A sarcoma gets its name from a Greek word meaning fleshy growth and can form in bones, fat, muscles, blood vessels, cartilage, and deep skin tissues^[20]. Malignant fibrous histiocytoma can start in either bone or, most often, in the soft tissues that connect, support, or surround organs and other body parts^[4].

This condition is the most common soft tissue sarcoma of late adult life^[1]. Although relatively rare, accounting for around 1 percent of adult cancer diagnoses each year, it is considered the most common primary malignant soft tissue tumor of adulthood^[3]. The tumors typically arise in deep fascia or skeletal muscle^[1].

Alternative Names and Classification

The medical understanding of this disease has changed over time. Malignant fibrous histiocytoma was first described as a new malignant tumor by O’Brian and Stout in the 1960s^[1]. The original name was assigned because scientists thought the tumor stemmed from histiocyte cells, which are normal immune cells found in various parts of the body^[3].

However, further research revealed that mesenchymal stem cells are the most likely source of the disease^[3]. Because of this discovery, the condition is now more accurately referred to as undifferentiated pleomorphic sarcoma, or UPS^[3]. The majority of tumors within the old classification did not show any evidence of histiocytotic differentiation, and many were found to be other types of poorly differentiated tumors^[5].

Who is Affected?

Malignant fibrous histiocytoma typically occurs in late adulthood, particularly peaking around the age of fifty^[3]. The mean age of patients is 59 years^[20]. Men are twice as likely to receive a diagnosis as women^[20]. Formation in bone is more frequent in White patients, with a male-to-female ratio of 1.5:1^[3].

While this cancer most commonly affects older adults, it can occur at any age^[9]. Unlike other kinds of sarcoma, malignant fibrous histiocytoma in children is relatively rare^[1]. However, cases have been reported in children as young as 11 years old^[1]. Malignant fibrous histiocytoma is among the most common types of soft tissue tumors found in adults but is rarely found in children^[4].

Where Does It Occur?

Malignant fibrous histiocytoma occurs most commonly in the extremities, which include the arms and legs. Between 70 and 75 percent of cases develop in these areas, with lower extremities accounting for 59 percent of cases^[1]. The thighs are especially common sites^[5]. After the extremities, the retroperitoneum (the back of the abdomen) is the next most common location^[1].

Although malignant fibrous histiocytoma can occur anywhere in the body, it is relatively uncommon in the head and neck area^[1]. In the head and neck, the nasal cavity and the paranasal sinuses are the most commonly affected sites, accounting for 54.3 percent of cases, and can lead to subsequent involvement of the maxillary alveolar bone^[1].

The tumor has been reported to occur in many other parts of the body, including the lung, kidney, bladder, scrotum, vas deferens, heart, aorta, stomach, small intestine, orbit, central nervous system, paraspinal area, dura mater, facial sinuses, and oral cavity^[1].

Signs and Symptoms

One of the challenging aspects of malignant fibrous histiocytoma is that it can grow for a long time virtually unnoticed, especially because it doesn’t cause much, if any, pain at first^[20]. The fact that it usually targets soft tissue allows it to grow virtually undetected initially^[20].

The most common clinical presentation is an enlarging painless soft tissue mass, typically measuring 5 to 10 centimeters in diameter^[5]. Soft tissue malignant fibrous histiocytoma usually presents as a painless soft tissue mass with progressive enlargement over months^[3]. Most tumors are diagnosed when they reach around nine centimeters wide^[3].

When symptoms do develop, they may include:

• A large, palpable mass on the body, often on the legs or arms^[20]
• Restricted movement with an arm or leg^[22]
• Pain from compressed nerves or muscles^[22]
• Limping^[1]
• A reddish, bilobulated swelling with smooth overlying surface^[1]

When the tumor occurs in bone, symptoms might include pain at the tumor site, swelling over a bone or joint, a lump that can be felt, or a bone that breaks for no clear reason^[9]. When malignant fibrous histiocytoma affects bone, it usually presents with pain over several months with or without swelling and can be associated with pathologic fracture (a break in weakened bone) in approximately 20 percent of cases^[3].

Patients with retroperitoneal malignant fibrous histiocytoma may have symptoms of fatigue, weight loss, abdominal pressure, fever, and malaise^[3].

Causes and Risk Factors

The cause of malignant fibrous histiocytoma is unknown but has been linked to genetics, radiation treatment, and inherited diseases^[4]. No one really knows what causes it, but there are three likely possibilities many in the medical profession believe are probably responsible^[20].

First, there is genetics. Some genetic abnormality could be at the heart of this type of sarcoma, and some people may be genetically predisposed to certain forms of cancer including malignant fibrous histiocytoma^[20].

Second, this cancer could be caused by exposure to certain chemicals. On the list of suspected chemicals are arsenic, vinyl chloride, wood preservatives with chlorophenols, and some herbicides^[20].

Lastly, and most likely, there is radiation. Malignant fibrous histiocytoma is the most common radiation-induced sarcoma^[3]. Patients who receive radiation therapy are believed to be the most common type from the three groups^[20]. Anywhere a patient who previously received radiation therapy is vulnerable to this cancer, which usually develops seven to twenty years after the therapy^[3]. Sadly, those who go in for radiation therapy because of one form of cancer may end up with this second type too^[20].

These tumors may also be linked to other medical conditions such as Paget disease, certain chemotherapy treatments, or past radiation treatments^[9]. Patients with retinoblastoma (a type of eye cancer) may develop malignant fibrous histiocytoma as a second cancer^[3].

It’s important to note that trauma is not known to cause malignant fibrous histiocytoma^[23]. It is not uncommon for patients with this particular type of soft tissue sarcoma to assume that a newly formed lump was caused by a physical accident such as bumping into a table or a sharp corner, but this is coincidental^[23].

Diagnosis

Due to the nature of malignant fibrous histiocytoma, these tumors are often mistaken for hematomas (when blood collects outside of the blood vessels) or hemangiomas (bright red birthmarks)^[4]. Any time you notice a large growth on your body, you should seek medical attention as soon as possible^[20].

Doctors generally diagnose malignant fibrous histiocytoma through several steps. Your doctor will do a physical exam and ask you about your health history and the changes or problems you’ve noticed^[9].

An X-ray can show these tumors^[9]. Soft tissue malignant fibrous histiocytoma is best diagnosed with magnetic resonance imaging (MRI) with gadolinium contrast^[3]. This tumor usually appears as a well-defined hypervascular heterogeneous soft tissue mass with areas of hemorrhage and necrosis^[3]. You may also get a CT scan or MRI to show more details and how much of your bone is affected^[9]. Your doctor may also use a bone scan or PET scan to see if it has spread^[9].

When this type of cancer spreads, it tends to go to the lungs. So you may also get a chest X-ray or chest CT scan^[9]. The condition most commonly spreads (metastasizes) to the lungs but can also invade the lymph nodes and bone^[4]. Cancer cells grow and spread quickly, impacting the lungs or other organs in 40 percent of cases^[3].

The only way to know for sure that it’s cancer is to do a biopsy. A small piece of the tumor is taken out and checked to see if there are cancer cells in it^[9]. If your healthcare provider suspects malignant fibrous histiocytoma, they’ll likely have all or part of the tumor removed (biopsied) and examined under a microscope^[4]. A biopsy was also arranged to extract tissue from the enlarged area to evaluate whether there was cancerous activity, and if so, the aggressiveness of the tumor, meaning the pace of spread or tendency to recur^[23].

Malignant fibrous histiocytoma is commonly characterized by solid nests of histiocyte-like cells, cyst-like spaces, and masses of chronic inflammatory cells^[4]. The pathology report may return with a histology finding of high grade malignant fibrous histiocytoma^[23]. This tumor is difficult to distinguish histologically from other sarcomas and carcinomas^[1].

Treatment Options

Treatment plans are usually a combination of two or more methods, and an important part of treatment includes careful evaluation of both medical and personal factors including tumor location, tumor size and stage, patient’s age and medical history, patient lifestyle and physical condition, and whether this is a first diagnosis or recurrence^[22].

Surgery to take out the tumor is the main treatment^[9]. Surgery is the only treatment option according to some sources^[1]. Malignant fibrous histiocytoma treatment usually involves surgical removal of the tumor^[8]. Your surgeon removes the entire tumor, as well as some healthy tissue around it^[4]. This method reduces the risk of recurrence^[4]. Your doctors will try to keep as much of your normal bone as possible^[9].

Many times, doctors use chemotherapy first to try to shrink the tumor^[9]. When you have chemotherapy, you get drugs that kill cancer cells and help keep them from growing and spreading^[9]. You would then get surgery to take out the tumor^[9].

You may get chemotherapy or radiation after surgery^[9]. Treatment may include surgery along with radiation and/or chemotherapy^[4]. Radiation treatment uses high-powered radiation from X-rays and other sources to kill any cancer cells left in your body^[9]. If the tumor is located in an area that makes surgical removal challenging (such as your head or neck), radiation and/or chemotherapy may be considered^[4].

Palliative care is also important for anyone with a serious illness. It includes taking care of your pain and addressing any emotions you may be dealing with^[9].

You may also want to ask your doctor if there’s a clinical trial that would be a good fit for you. You can be part of one before, during, or after treatment^[9]. Recent clinical trials have investigated new treatment options including molecular targeted drugs and immune checkpoint inhibitors, which have shown superior outcomes compared to standard treatments for various types of malignancies^[13].

For advanced malignant fibrous histiocytoma, there have been reports of successful treatment with apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2^[10].

Prognosis and Outcomes

Prognosis is fairly poor, and recurrence and local metastasis (spread to other parts of the body) are common^[1]. The tumor can come back^[4]. These aggressive tumors tend to recur and metastasize^[3]. Unfortunately, approximately 40 percent of patients will develop local recurrences or distant metastases^[10].

The 5-year survival rate is 10 to 30 percent if malignant fibrous histiocytoma is only treated locally^[10]. In comparison with malignant fibrous histiocytoma of the extremities and the trunk, the 5-year survival rate for cases of this tumor in the head and neck is low^[1]. Larynx, maxillary sinus, and mandible have the worst prognosis in the head and neck lesion^[1].

Prognosis varies based on factors such as tumor size, depth, and metastasis, with a five-year survival rate ranging between 34 percent and 70 percent for advanced cases^[3]. For advanced malignant fibrous histiocytoma, the prognosis remains very poor, even with combined, multimodal therapy^[10].

It is important to consider malignant fibrous histiocytoma in differential diagnosis of tumors because of its poor prognosis^[1]. Awareness of this condition is important for timely diagnosis and intervention, as the disease poses significant health challenges^[3].

Finding out that you have cancer can be very hard to handle. You may find that it helps to join a support group, so you can talk with people who know what you’re going through^[9]. Counseling can also be a great way to manage the emotions that you feel^[9]. You can also let friends and family know how they can support you^[9].

Getting a cancer diagnosis is life-changing and catches us by surprise, no matter how well prepared we are. Medical centers recommend patients getting a second opinion and taking time to learn as much as they can about the disease and treatment options^[22]. Self-education is empowering and removes the feelings of helplessness that often comes with cancer^[22].