Soft tissue tumors, which, like bone tumors, are also called sarcomas, are encountered more frequently than bone and joint tumors. These tumors originate in connective or non-glandular tissue, and can develop in any part of the body that contains fat, muscle, nerve, blood vessels, fibrous tissues, and in any deep tissues, including tissues surrounding joints, bones, or deep subcutaneous tissues. More than half of soft tissue sarcomas develop in the arms or legs. About one in five (20%) are found in the abdominal cavity and present with symptoms similar to other abdominal-based health problems. The rest begin in the head and neck area (about 10%), and in and on the chest or abdomen (about 10%).1
There also are a vast number of non-malignant soft tissue neoplasms and tumors such as lipomas. Also typically included are cystic lesions of the deep tissues. The differentiating feature of soft tissue tumors (sarcomas) is that they arise from these connective tissues and do not arise from organs such as kidneys lungs, intestines, breasts, or thyroid glands.
Additional information on soft tissue sarcomas can be found in Weiss and Goldblum’s Enzinger and Weiss’s Soft Tissue Tumors, 5th ed.2
There are multiple soft tissue sarcomas with varying degrees of aggressive behavior, but virtually all have the capacity to metastasize and cause death. Treatment for high-grade soft tissue sarcomas is typically resection (removal) and radiation. Chemotherapy is playing an ever-increasing role, especially in high-grade (fast-growing) and metastatic cases.
The most common types of soft tissue sarcomas are described below.1 Cancer cells are often referred to as differentiated versus undifferentiated. Differentiation describes how much or how little tumor tissue looks like the normal tissue it came from. Well-differentiated cancer cells look more like normal cells and tend to grow and spread more slowly than poorly differentiated or undifferentiated cancer cells. Differentiation is used in tumor grading systems, which are different for each type of cancer.2
Malignant Fibrous Histiocytomas (MFH)/Pleomorphic Sarcomas (PS) Not Otherwise Specified (NOS)
The most commonly encountered soft tissue sarcoma is malignant fibrous histiocytoma, a tumor of the fibrous tissue most often occurring in the arms or legs. The least differentiated of the sarcomas, in many cases it represents a poorly defined, high-grade soft tissue sarcoma that cannot be further defined pathologically (histologically). A recent trend is to classify these poorly differentiated sarcomas as pleomorphic sarcomas or spindle cell sarcomas not otherwise specified, (NOS) rather than the previous designation as malignant fibrous histiocytoma. Poorly differentiated sarcomas typically affect older individuals. Analysis of annual rates of MFH and PS reflect this evolving diagnostic trend.
Liposarcomas
The next most commonly encountered and reported soft tissue sarcoma is liposarcoma, which is a malignant tumor of the fatty (adipose) tissues. This sarcoma also is more common in older persons. There are several subtypes ranging from the low-grade lipoma-like liposarcoma that rarely metastasizes to high-grade pleomorphic liposarcomas and round cell liposarcomas, which have a prognosis similar to malignant fibrous histiocytoma. Liposarcomas can develop anywhere in the body, but they most often develop in the thigh, around the knee, and inside the back of the abdomen. Seen in a wide range of patient ages, liposarcomas occur most frequently in adults between 50 years and 65 years old. Some liposarcomas grow very slowly, whereas others can grow quickly.
Synovial Sarcomas
The third most commonly encountered soft tissue sarcoma is synovial sarcoma, which is more likely to affect younger adults than previously mentioned sarcomas. The most common location is the thigh. Despite the name synovial sarcoma, most do not occur in joints or in the synovium of joints. It tends to occur mostly in young adults, but can also occur in children and in older people. Many of these cases respond very favorably to chemotherapy with significant shrinkage of the tumor, although resection (surgical removal) and radiation remain the cornerstones of current therapy. The prognosis is similar to malignant fibrous histiocytoma and the other high-grade soft tissue sarcomas mentioned above.
Tumors of Muscle Tissue
Leiomyosarcomas
Smooth muscle cells are found in internal organs such as stomach, intestines, blood vessels, or uterus. This muscle tissue gives these organs the ability to contract involuntarily. Leiomyosarcomas are malignant tumors of involuntary muscle tissue. They can occur almost anywhere in the body, but most often are found in the uterus. A second common site is the retroperitoneum (back of the abdomen) and in the internal organs and blood vessels where leiomyomas also arise. Less often, they develop in the deep soft tissues of the legs or arms. They tend to occur in adults, particularly the elderly. Since they often arise from arteries, resection of these tumors frequently requires an immediate vascular reconstruction.
Rhabdomyosarcomas
Skeletal muscles are the voluntary muscles that control and allow movement of arms and legs and other body parts. Rhabdomyosarcomas are malignant tumors of skeletal muscle. These tumors commonly grow in the arms or legs, but they can also begin in the head and neck area and in reproductive and urinary organs, such as the vagina or bladder. Rhabdomyosarcomas are primarily tumors of children. Clinically and behaviorally, they are in a class by themselves. They are treated with aggressive chemotherapy, as well as surgery and/or radiation in many cases. The aggressive treatments often cause permanent life-altering disability, even in survivors. For more information, see the American Cancer Society document "Rhabdomyosarcoma. [2]”
Malignant Peripheral Nerve Sheath Tumors
Malignant schwannomas, neurofibrosarcomas, or neurogenic sarcomas are malignant tumors of the cells that surround a nerve. The currently favored name for these sarcomas is malignant peripheral nerve sheath tumor.
Tumors of Blood Vessels and Lymph Vessels
Angiosarcomas
Malignant tumors can develop either from blood vessels (hemangiosarcomas) or from lymph vessels (lymphangiosarcomas). These tumors often develop in a part of the body that has been exposed to radiation. Angiosarcomas are sometimes seen in the breast after radiation therapy for breast cancer or in the arm on the same side as a breast that has been irradiated or removed by mastectomy. They are difficult to cure as they spread through the bloodstream to other parts of the body and often spread extensively through the local tissues.
Hemangiopericytoma
These are tumors of perivascular tissue (tissue around blood vessels). They most often develop in the legs, pelvis, and retroperitoneum (the back of the abdominal cavity) and are most common in adults. These can be either benign or malignant. They do not often spread to distant sites, but tend to recur where they started, even after surgery, unless widely excised. Following recent research and further histologic, genetic, and clinical evaluations, these have recently been reclassified as one end of the spectrum of malignant solitary fibrous tumors, or possibly identical to malignant solitary fibrous tumors.1
Hemangioendothelioma
This is a less aggressive blood vessel tumor than Hemangiosarcoma, but still considered a low-grade cancer. It usually invades nearby tissues, and sometimes can metastasize to distant parts of the body. It may develop in soft tissues or in internal organs, such as the liver or lungs.
Kaposi Sarcoma
These cancers are composed of cells similar to those lining blood or lymph vessels. In the past, Kaposi’s sarcoma was an uncommon cancer mostly seen in older people with no apparent immune system problems. It is now most common in people with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), but can also develop in organ transplant patients who are taking medication to suppress their immune system. It is probably related to infection with a virus called human herpesvirus-8 (HHV-8).
Tumors of Fibrous Tissue
Fibrous tissue forms tendons and ligaments and covers bones, muscles and joint capsules, as well as other organs in the body.
Malignant fibrous histiocytoma (MFH)
MFH is found most often in the arms or legs. Less often, it can develop inside the back of the abdomen. This sarcoma is most common in older adults. Although it mostly tends to grow locally, it can spread to distant sites. It is the most commonly diagnosed soft tissue sarcoma, although now these are more often classified as pleomorphic sarcoma, not otherwise specified (NOS), as discussed above.
Fibrosarcoma
Fibrosarcomas are cancers of fibrous tissue. They have a characteristic herringbone cloth pattern when viewed under the microscope. Fibrosarcomas most commonly affect the legs, arms, or trunk. They are most common between the ages of 20 years and 60 years, but can occur at any age, even in infancy.
Dermatofibrosarcoma protuberans (DFSP)
These tumors are slow-growing cancers of the fibrous tissue beneath the skin, usually noted in the trunk or limbs. They invade nearby tissues but rarely metastasize. They primarily affect young adults. Due to their slow, insidious growth; their uncommon occurrence; and their innocuous appearance, diagnosis is often delayed. The local recurrence rate is higher than many sarcomas, and has been reported to be as high as 50% in some studies. While death due to disease is uncommon (<5%), the local recurrences can cause significant local morbidity.
Fibromatosis/Desmoid tumors
Fibromatosis is one of the names given to neoplastic tumors with features in between fibrosarcomas and benign tumors, such as fibromas and superficial fibrous diseases like Dupytren's disease. They tend to grow slowly, but often steadily. These tumors are often referred to as desmoid tumors. Although they do not metastasize, they do form in response to genetic alterations identical to many cancers and can cause great disability and even death. These tumors can invade nearby tissues, causing great havoc and occasionally even death. Some doctors may consider these to be a type of low-grade fibrosarcomas; most, however, regard these as benign but locally aggressive. Certain hormones, particularly estrogen, may increase the growth of some desmoid tumors. Antiestrogen drugs are sometimes useful in treating desmoids that cannot be completely removed by surgery. Radiation therapy plays a role in treatment, especially in unresectable or recurrent cases. There are ongoing chemotherapeutic trials in place with newer agents that interrupt the various biological processes in the growth of these tumors; these hold great promise for future patients. Additional research into the biology and treatment of these and virtually all tumors is clearly indicated.
Tumors of Uncertain Tissue Type
Through microscopic examination and other laboratory tests, doctors can usually find similarities between most sarcomas and certain types of normal soft tissues, thus, allowing them to be classified based on this histologic appearance. However, some sarcomas have not been linked to a specific type of normal soft tissue due to their unique appearance that does not closely resemble any single tissue type.
Malignant mesenchymoma
These very uncommon sarcomas contain areas showing features of at least two types of sarcoma, including fibrosarcomatous tissue per the original description. Since all connective tissue derive from undifferentiated mesenchymal tissues in an embryologic sense, it has been termed Mesenchymoma. The term has fallen out of favor and it is now thought that many cases may be better classified as one of the subtypes of sarcomas based on the tissue type contained within the tumor.3
Alveolar soft-part sarcoma
This rare cancer primarily affects young adults. The legs are the most common location of these tumors. This is one of the most vascular (blood vessels) sarcomas because it induces an extensive network of vessels to grow in and around the tumor. Because of their very slow growth rate, a delay in diagnosis can occur. Unfortunately, it ultimately has a high mortality rate and can lead to death years after diagnosis. The rate of progression can be quite slow; late metastases are common.
Epithelioid sarcoma
This sarcoma often develops in tissues under the skin of the hands, forearms, feet, or lower legs. Adolescents and young adults are often affected. These are often misdiagnosed as infections and chronic infectious ulcers because of their innocuous appearance and uncommon occurrence. This sarcoma has a much higher propensity for lymph node metastasis than most sarcomas, which usually preferentially metastasize to the lung.
Clear cell sarcoma
This rare cancer often develops in tissues of the arms or legs. It recently has been determined to be a variant of malignant melanoma, a type of cancer that develops from pigment-producing skin cells. How cancers with these features develop in parts of the body other than the skin is not known. As a melanoma, it behaves differently than sarcomas. It has a propensity to spread through the lymphatic system. Local recurrence is common; therefore wide resections are required for complete local eradication.
Other Types of Sarcoma
There are other types of soft tissue sarcomas, but they are less commonly encountered and not included in this discussion.
A recently published study, based on the National Cancer Database NCDB of the American College of Surgeons Commission on Cancers, reports the 13-year experience (1998–2010) with 34 of the most commonly encountered soft tissue sarcomas. This report provides a good overview of the US experience with these, including survival curves, the 2- and 5-year survivorship rate, and various demographic data. A current NCDB analysis of soft tissue sarcomas, including demographic data and survivorships are shown in Table 9A.9.1 to Table 9A.9.3. (Reference Table 8A.9.1 PDF [3] CSV [4], Table 8A.9.2 PDF [5] CSV [6], and Table 8A.9.3 PDF [7] CSV [8])
Soft tissue sarcomas account for less than 1% of all cancer cases diagnosed each year, and for a similar proportion of cancer deaths in a given year. Over the past decade, the overall incidence of soft tissue sarcomas showed a 31% increase in new cases diagnosed annually in the NCDB data, a slightly higher rate of increase than found for all the top 73 cancer sites reported. (Reference Table 8A.3.1 PDF [10] CSV [11] and Table 8A.5.2 PDF [12] CSV [13])
In terms of case numbers, the musculoskeletal health burden in the United States from soft tissue sarcomas is three to four times greater than that of bone and joint sarcomas. For the period from 2006 to 2010, the annual average number of soft tissue neoplasms, including the heart, approximated 14,000 cases/year in the SEER database, a number similar to those for Hodgkin lymphoma.1 Estimated new cases for 2014 by the American Cancer Society are 12,000.2 Soft tissue sarcomas come in a wide variety of forms that affect different age groups, but the most frequently encountered soft tissue sarcomas affect older adults. (Reference Table 8A.3.1 PDF [10] CSV [11])
As previously noted, the National Cancer Data Base (NCDB), a joint program of the Commission on Cancer and the American College of Surgeons, maintains the most thorough database on patients diagnosed with soft tissue sarcomas. Although the NCDB was not created to serve as an incidence-based registry, it currently gathers data on approximately 71% of the cancers treated in the United States. It should be noted this percentage varies from year to year based on the participation and reporting by hospitals to this voluntary database.
Over the 18-year period, 1985 to 2003, 86,355 soft tissue sarcomas of the extremities, shoulders ,and pelvic girdles and trunk were reported. This number excludes approximately 32,250 soft tissue sarcomas of the head and neck, thoracic, and abdominal areas; these patients are generally cared for by non-musculoskeletal specialists. Using a 20-year average and assuming 70% of the annual US cases are included in NCDB, more than 5,700 new cases of soft tissue sarcoma would have occurred annually. This compares to the estimated 12,020 cases predicted for 2014 by the American Cancer Society.2
A 2014 report by Corey, Swett, and Ward examined the adult cases reported to the NCDB of soft tissue sarcomas over a 13-year interval (1998–2010). In 2010, 5,070 soft tissue sarcomas were reported to the NCDB. While the numbers of soft tissue sarcomas reported to the NCDB increased by 19% over this 13-year period, the number of bone sarcomas reported to the NCDB increased by only 10.7% during this same time period.3
While soft tissue sarcomas can be found among all ages, the incidence increases after the age of 55 years. Once a person reaches age 85 years or older, the incidence of diagnosis drops sharply. Males are diagnosed with soft tissue sarcomas at a slightly higher age than females. Blacks are diagnosed an average of 10 years earlier than those who are White. (Reference Table 8A.3.1 PDF [10] CSV [11], Table 8A.3.2 PDF [16] CSV [17], and Table 8A.2.1 PDF [18] CSV [19])
The age distribution at time of death for persons diagnosed with soft tissue sarcomas reflects a relative survival rate that favors younger persons. (Reference Table 8A.3.4 PDF [20] CSV [21])
The 5-year survival rate for soft tissue sarcomas is reported at 66% by both the SEER database and the National Cancer Institute (NCI). This is a rate similar to that for bone and joint, uterine/ovarian, and non-Hodgkin lymphoma cancers. Average length of survival after diagnosis is 7 years, similar to that of breast, urinary, and nervous system cancers. White women have a slightly higher 5-year survival rate than do men, and live an average of 1 year longer after diagnosis. However, the reverse is true for Black women, who die an average of 2 years sooner than Black men diagnosed with soft tissue sarcoma. (Reference Table 8A.4.1 PDF [22] CSV [23], Table 8A.4.2 PDF [24] CSV [25], and Table 8A.4.3 PDF [26] CSV [27])
For high-grade soft tissue sarcomas, the most important prognostic factor is the stage at which the tumor is identified. Staging criteria for soft tissue sarcomas are primarily determined by whether the tumor has metastasized or spread elsewhere in the body. Size is highly correlated with risk of metastasis and survival. In general, the prognosis for a soft tissue sarcoma is poorer if the sarcoma is large. As a general rule, high-grade soft tissue sarcomas over 10 cm in diameter have an approximate 50% mortality rate and those over 15 cm in diameter have an approximate 75% mortality rate.
The NCI statistics staging classification of sarcomas is Stage 1, confined to the primary site (localized: 54% of sarcomas are diagnosed at this stage); Stage 2, spread to regional lymph nodes or directly beyond the primary site (regional: 22%); or Stage 3, metastasized (distant: 15%). For the remaining cases, the staging information was unknown. The corresponding 5-year relative survival rates reported are 84% for localized sarcomas, 62% for regional stage sarcomas, 16% for sarcomas with distant spread, and 54% for unstaged sarcomas. The 10-year relative survival rate is only slightly worse for these stages, meaning that most people who survive 5 years are cured.1
Using the staging criteria of soft tissue sarcomas of the American Joint Committee on Cancer (AJCC) produces similar results for sarcomas found in the limbs (arms or legs): 90% 5-year survival rate for Stage 1 sarcomas; 81% for Stage 2; and 56% for Stage 3. Sarcomas identified as Stage 4 have a very low 5-year survival rate. Sarcomas located in other than a limb also have lower survival rates.1
Sarcomas are often staged by orthopedic oncologists with a staging system established by Dr. William Enneking, and adopted and modified by surgical societies primarily consisting of orthopedic oncologists. That may have accounted for the lack of AJCC staging data in many cases of bone and soft tissue sarcomas reported to the NCDB. Nearly 40% of cases for 2000–2011 reported in the NCDB data have an unknown stage. This is a much higher proportion than found among other common cancer types, making it difficult to compare the severity of soft tissue sarcomas to other cancers. However, none of the cases was identified as Stage 1, with the majority at Stage 2 through Stage 4. (Reference Table 8A.5.1 PDF [28] CSV [29])
From 1998–2010, information on insurance coverage was available for roughly 96% of patients treated with soft tissue sarcomas. The largest insurance payer was managed care (33%), followed by Medicare with supplement (25%). Private insurance accounted for 14%, while Medicare (11%) accounted for a larger percentile than Medicaid (5%). Detailed NCDB insurance data for 7,684 of 7,878 cases of soft tissue sarcoma reported from the year 2010 showed private insurance paying just over 46%, while Medicare/Medicaid paid a slightly larger share of 47%.1
The total economic costs of malignant soft tissue sarcoma are unknown. Surgery is often the first line of treatment for soft tissue sarcoma. Multiple therapies may be needed later in the course of the patient’s disease, especially in the more advanced cases. In the later stages of the disease in those not cured with surgery alone, significant costs will accumulate as the patients develop pulmonary disease and ultimately die. Hormone therapy, immunotherapy, and bone marrow transplant/endocrine treatments are undertaken in a small number of cases that fail standard treatments. Overall, costs will vary with treatments utilized, number and intensity of treatments, and can easily top $100,000 for a single patient that receives surgery, chemotherapy, and radiation therapy.
Throughout the years 2005–2008, one study reported that the average professional charge for a primary excision was $9,700 and $12, 900 for re-excision. Although every 1-cm increase in size of the tumor results in an increase of $148 for a primary excision, size was not an independent factor affecting re-excision rates. The grade of the tumor was positively associated with professional charge, such that higher-grade tumors resulted in higher charges compared to lower-grade tumors. Analysis including professional technical and indirect charges revealed that, on average, patients undergoing definitive primary excision at their cancer treatment center were charged $40,230. This was compared to $44,770 for to patients receiving definitive re-excision of unsuccessful or incomplete previous resections at the same cancer treatment center. This higher cost did not include the charges and costs generated by their previous unsuccessful or incomplete previous attempt at resection.2
This analysis confirms that proper work-up, evaluation, and treatment are key to maintain costs, as well as, hopefully, improving the outcome for these patients. This cost analysis did not include the costs associated with chemotherapy or radiation therapy, or the costs of diagnostic and follow-up laboratory and radiographic studies, nor the actual costs of care.
The majority of sarcomas develop in people with no known risk factors: There is currently no known way to prevent these cases at this time. Whereas future developments in genomic research may allow genetic testing to identify persons with increased risk to develop soft tissue sarcomas, few such predictors are available at present. Reporting suspicious lumps and growths or unusual symptoms to a doctor, and appropriate evaluation of such abnormalities can help diagnose soft tissue cancer at an earlier stage. Treatment is thought to be more effective when detected early, as smaller-diameter sarcomas have been shown to have improved outcome compared to large sarcomas.
Cancers occasionally spread or metastasize to the soft tissues, such as the muscles and deep tissues of the body, including the thigh and leg. The most likely cancers to do so are cancers of the lung and kidney. As such, this fact must always be borne in mind whenever physicians examine a patient presenting with a new mass in the leg, thigh, or other soft tissues, especially if they have a history of a prior lung or kidney cancer.
Links:
[1] http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-soft-tissue-sarcoma
[2] http://www.cancer.org/cancer/rhabdomyosarcoma/detailedguide/rhabdomyosarcoma-detailed-guide-toc
[3] https://www.boneandjointburden.org/docs/T8A.9.1.pdf
[4] https://www.boneandjointburden.org/docs/T8A.9.1.csv
[5] https://www.boneandjointburden.org/docs/T8A.9.2.pdf
[6] https://www.boneandjointburden.org/docs/T8A.9.2.csv
[7] https://www.boneandjointburden.org/docs/T8A.9.3.pdf
[8] https://www.boneandjointburden.org/docs/T8A.9.3.csv
[9] http://www.cancer.gov/dictionary?cdrid=46445
[10] https://www.boneandjointburden.org/docs/T8A.3.1.pdf
[11] https://www.boneandjointburden.org/docs/T8A.3.1.csv
[12] https://www.boneandjointburden.org/docs/T8A.5.2.pdf
[13] https://www.boneandjointburden.org/docs/T8A.5.2.csv
[14] http://www.facs.org/cancer/ncdb/publicaccess.html
[15] http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-key-statistics
[16] https://www.boneandjointburden.org/docs/T8A.3.2.pdf
[17] https://www.boneandjointburden.org/docs/T8A.3.2.csv
[18] https://www.boneandjointburden.org/docs/T8A.2.1.pdf
[19] https://www.boneandjointburden.org/docs/T8A.2.1.csv
[20] https://www.boneandjointburden.org/docs/T8A.3.4.pdf
[21] https://www.boneandjointburden.org/docs/T8A.3.4.csv
[22] https://www.boneandjointburden.org/docs/T8A.4.1.pdf
[23] https://www.boneandjointburden.org/docs/T8A.4.1.csv
[24] https://www.boneandjointburden.org/docs/T8A.4.2.pdf
[25] https://www.boneandjointburden.org/docs/T8A.4.2.csv
[26] https://www.boneandjointburden.org/docs/T8A.4.3.pdf
[27] https://www.boneandjointburden.org/docs/T8A.4.3.csv
[28] https://www.boneandjointburden.org/docs/T8A.5.1.pdf
[29] https://www.boneandjointburden.org/docs/T8A.5.1.csv
[30] http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-staging