Malignant fibrous histiocytoma
Now referred to as undifferentiated pleomorphic sarcoma
The following case study is inspired by patient data taken directly from the Soft-tissue-Sarcoma Collection within The Cancer Imaging Archive (TCIA), a service that hosts an archive of publicly accessible de-identified cancer medical images.
- Name: Bernie Saxophone
- Gender: M
- Age: 49
- Cancer: Sarcoma
- Type: Soft tissue sarcoma (STS)
- Histology: Malignant fibrous histiocytoma
- Grade: High
- Site of primary STS: Right thigh
- Treatment: Surgery + radiotherapy + chemotherapy
- Outcome: Metastasis to lung
Bernie is a 49 year old man who noticed as he was walking up the stairs a dull aching pain in his right thigh. When he reached the top of the stairs, he saw that part of his right thigh was swollen and recalled that he had in fact bumped his right leg into the kitchen table a few days ago. He read some advice columns online that for muscle strain-like pain, icing the affected area would help. He did this for a couple days, but the tenderness did not go away. After five weeks, his wife brought to Bernie’s attention that not only was the mass still there, but had enlarged noticeably. After some persistent nagging from the wife, he finally made a trip to the doctor’s office.
At the doctor’s office, Bernie insisted that the enlarging lump was due to his injury over the kitchen table, and that over time the affected area would naturally heal on its own. The physician was not convinced after observing the rather large mass in his right thigh, and asked Bernie a few standard questions based on his complaints:
Physician: When did the pain start?
Bernie: About five weeks ago after bumping into the corner of the kitchen table.
Physician: Whendid you first notice this mass?
Bernie: While climbing a set of stairs, maybe a few days afterbumping into the kitchen table.
Physician: Has the mass been increasing in size?
Bernie: Yes, it does seem bigger than before.
Physician: Is the pain getting worse?
Bernie: Yes, but it’s probably part of the healing process. I’m not concerned.
Physician: Have you taken any medication for this?
Bernie: Occasionally a pain reliever here and there. I made sure to ice the area like articles on the Internet instructed.
With these answers and information gathered from the patient history, Bernie’s physician ordered a set of imaging tests including an X-ray, magnetic resonance (MR), computed tomography (CT) and positron emission tomography (PET) scans for better visualization of the right thigh. A biopsy was also arranged to extract tissue from the enlarged area on the thigh to evaluate whether there was cancerous activity, and if so, the aggressiveness of the tumor, i.e., pace of spread or tendency to recur.
The pathology report returned with a histology finding of high grade malignant fibrous histiocytoma, now referred to as undifferentiated pleomorphic sarcoma, on the right thigh. Taking into account all information collected, the physician concluded that the mass in Bernie’s right thigh was not swollen due to injury, but soft tissue sarcoma.
It is not uncommon for patients with this particular type of soft tissue sarcoma, particularly malignant fibrous histiocytoma, to assume that a newly formed lump was caused by a physical accident such as bumping into a table or a sharp corner. However, trauma is not known to cause malignant fibrous histiocytoma.1 Some patients with malignant fibrous histiocytoma also incorrectly assume that a swollen mass on the body, such as on the leg, is caused by muscle strain. The physician explained that the tenderness in Bernie’s leg following the kitchen table injury was coincidental with progression of his soft tissue sarcoma, and along those lines, icing the affected area would not have helped.
The tumor grade describes a tumor based on how its cells appear under a microscope and gives an indication of the tumor’s aggressiveness, i.e., how quickly the tumor is likely to grow and spread. The grade can help to guide practitioners in making treatment decisions.
- High grade tumors tend to be more aggressive and thus have higher tendency to recur and spread
- Low grade tumors tend to be less aggressive and thus have lower tendency to recur and spread2
SOFT TISSUE SARCOMA
Soft tissue sarcoma is a group of cancers that forms in soft tissues of the body, such as muscle, fat, nerves, blood vessels, lymph vessels, fibrous tissues, tendons and the lining of joints.3 These sarcomas which are rare and constitute less than 1% of all cancer cases can begin in any part of the body, with the most common primary sites including the arms or legs (60%), torso or abdomen (30%), and head and neck (10%).4 For metastatic soft tissue sarcoma, the most common site of metastasis is the lungs. There are more than 50 histologic types of soft tissue sarcomas, with the more common types including malignant fibrous histiocytoma (more recently called “undifferentiated pleomorphic sarcoma”), liposarcoma, and leiomyosarcoma.5 While the most common treatment involves surgical removal, depending on the size, type, location and aggressiveness of the tumor, radiation and chemotherapy may also be recommended.
What is Malignant fibrous histiocytoma?
Malignant fibrous histiocytoma, also referred to as undifferentiated pleomorphic sarcoma, is an aggressive tumor considered in many studies as the most common type of soft tissue sarcoma, accounting for 25-40% of all adult soft tissue sarcoma cases6 , though some more current studies rank it as the fourth most common soft tissue sarcoma7.
Following the site distribution trend found for soft tissue sarcoma in general, common sites of involvement for malignant fibrous histiocytoma, particularly of localization on the body regions is as follows: greater than 70% of cases located in the extremities (50% of cases in lower extremities and 25% in upper extremities), 15% of cases in the retroperitoneum, and 3-10% of cases in the head and neck region.8
The image of the legs (with emphasis on the right thigh) is taken from the Bodymap VR application.
Individuals with malignant fibrous histiocytoma often complain of a mass or lump, such as a lump on the thigh, that occurred over a short period of time (usually over the course of weeks to months). The mass is also usually found to have enlarged over time. Some patients mistake the lump to be caused by some sort of trauma to the affected area, such as an injury caused by “running into the corner of a table.”9
Bernie has many characteristics consistent with the profile of an individual with soft tissue sarcoma of the malignant fibrous histiocytoma histological type: he is male, Caucasian, middle-aged, and presents with a tumor in the lower extremity. His clinical presentation of a mass in the affected area being rapidly enlarging also resembles that of an individual with malignant fibrous histiocytoma. More details on these characteristics:
- Male: there is a slight male predilection for malignant fibrous histiocytoma with a male-to-female ratio of 1.2:110
- Caucasian: malignant fibrous histiocytoma is more common in the Caucasian race11
- Age: some reports state that malignant fibrous histiocytoma tends to arise most frequently during the sixth and seventh decades of life12 while others suggest this average range is younger at 50 to 70 years of age13. There is also literature suggesting that the range falls between 32 to 80 with a mean age of 59 at diagnosis14.
- Extremities: over 70% of malignant fibrous histiocytoma cases are located in the extremities, with 50% in the lower extremities15
Malignant fibrous histiocytoma presents as a rapidly enlarging mass, with reports of dull aching pain or tenderness from 30% of patients. Some patients complain of trauma to the affected area, hematoma, or muscle strain, but in actuality, trauma does not cause malignant fibrous histiocytoma, and systemic symptoms are not typically expected.16
After evaluating Bernie’s symptoms and results from diagnostic tests and scans, Bernie’s multidisciplinary healthcare team formulated a plan integrating treatment modalities including surgery, irradiation, and systemic therapy.
Surgical management is the cornerstone of treatment for malignant fibrous histiocytoma. 17 The aim of surgery is to achieve wide surgical resection with clear resection margins.18 In some cases, amputation may be required to ensure that the lesion is completely removed.
Wide surgical resection:
With wide excision, the surgeon cuts out the tumor area with a wide margin to make sure that only healthy tissue remains. A “wide” surgical margin suggests there is a considerable distance between the tumor and the cut, whereas that distance is much less with a “narrow” surgical margin.19 In other words, if the excision does not achieve wide margins around the abnormal tissue, then some of the disease may be left behind.
Radiotherapy is often recommended as a supplement to surgery, and is useful in malignant fibrous histiocytoma cases where the tumor is classified as high-grade, large, deep-seated, affecting the extremities, and where negative (“clean”) margins are not obtained.20,21
Radiation therapy is administered by a radiation oncologist to minimize probability of local recurrence and metastasis of the cancer. The radiation dose typically ranges from 40 Gy to 65 Gy and depends on how much of the tumor was completely removed by surgical treatment and whether there are residual microscopic or macroscopic tumor cells.22
The Cancer Library VR in-app view above shows a snapshot of Bernie’s soft tissue sarcoma of malignant fibrous histiocytoma histological subtype in the right thigh with tumor segmentation displaying the general area to which radiotherapy treatment would be targeted. Cancer Library VR app users can select the segmentations they wish to visualize alongside other anatomical structures. The image is taken from the Cancer Library VR, and contains de-identified patient image and clinical data obtained from The Cancer Imaging Archive (TCIA), Soft-tissue-Sarcoma Collection (TCIA subject ID: STS_021).
Post-operative chemotherapy was indicated as part of Bernie’s treatment plan in order to minimize chances of recurrence. Treatment protocol is dependent on size of the primary lesion, whether metastasis is present, and patient age, to name a few factors. 23
The role of chemotherapy in treatment of malignant fibrous histiocytoma or even soft tissue sarcoma in general is not clearly understood. Studies have shown only a modest improvement of less than 10% in overall survival for soft tissue sarcoma patients from the addition of chemotherapy as a treatment modality, though this percentage was higher in individuals with tumors in the extremities as opposed to those with axial or retroperitoneal tumors.24
After completing the series of treatments, Bernie returned to his life and went about his normal routine. During a follow-up session with his physician two years later, it was discovered that the original tumor had spread beyond the initial site of the right thigh. The cancer had metastasized to his lungs.
While this was upsetting news, Bernie was fully aware of this possibility as his physician had already forewarned him when explaining the different treatment options that metastasis was a likely outcome given his initial diagnosis and test results. Bernie’s malignant fibrous histiocytoma was designated as high grade at diagnosis, and studies indicate that most malignant fibrous histiocytomas are high grade, aggressive in biological behavior, and frequently metastasize despite aggressive treatment.25 It is estimated that 35% to 45% of these patients will develop metastasis.
In fact, studies show that not only is distant metastasis common with malignant fibrous histiocytoma, but the most common site of metastasis in individuals with malignant fibrous histiocytoma is the lungs.26
Even though Bernie was unable to achieve disease-free status, he is thankful to be alive given the statistics provided to him by his physician that overall 5-year survival of individuals with malignant fibrous histiocytoma is between 25-70%.27
Bernie is currently receiving treatment for his condition which has progressed from malignant fibrous histiocytoma to include cancer that is metastatic to the lung. His words of advice to anyone facing a similar situation would be to seek medical attention as soon as something feels “off” or perhaps more than just coincidental. Getting something as unsuspecting as a lump on the leg checked out may just save a life.
Special acknowledgement to the researchers and institutions that provided the Soft-tissue-Sarcoma collection datasets on TCIA:
Vallières, Martin, Freeman, Carolyn R., Skamene, Sonia R., & El Naqa, Issam. (2015). A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. The Cancer Imaging Archive.28
Vallières, M., Freeman, C. R., Skamene, S. R., & Naqa, I. El. (2015, June 29). A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. Physics in Medicine and Biology. IOP Publishing.29
Clark K, Vendt B, Smith K, Freymann J, Kirby J, Koppel P, Moore S, Phillips S, Maffitt D, Pringle M, Tarbox L, Prior F. The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository, Journal of Digital Imaging, Volume 26, Number 6, December, 2013, pp 1045-1057.