SEER estimates an average of 3,260 people were newly diagnosed with cancer of the bones and joints, excluding myeloma, lymphoma, and leukemias, in 2017. During the same year, an estimated 1,550 people died from cancer of the bone and joints. The number of new cases of bone and joint cancers was estimated to be 1.0 per 100,000 people per year during the years 2012-2016.1  However, death rates from bone and joint cancers have declined slightly (0.2% per year) since 1982-2016, following a 9.9% decline from 1975-1982.2 Approximately 40% of bone cancers are diagnosed at a localized stage, for which the 5-year relative survival is 85%.3 The overall 5-year relative survival rate in the 2004-2015 NCDB Database set for Bone and Joint cancers was 65% but is higher for all combined chondrosarcomas (74%) than all combined osteosarcomas (60%). (Reference Table 6A.A.1.0 PDF [8] CSV [9] and Table 6A.A.1.5.1 PDF [30] CSV [31]. See Table 6A.B.1.1 PDF [16] CSV [17] and Table 6A.B.1.2 PDF [18] CSV [19] for the NCDB database data regarding the two- and five-year survivorship of all bone and joint sarcomas.)

Myeloma occurs up to ten times more frequently than bone and joint cancers and is not defined as a rare cancer as the incidence is just over the 6/100,000 rare cancer definition. In 2019, myeloma was estimated to be diagnosed in 32,110 persons per year, an incidence rate of 6.9 per 100,000 persons per year. An estimated 12,960 persons will die of myeloma in 20194, with a death rate of 3.3 per 100,000 persons. (Reference Table 6A.A.1.2.1 PDF [34] CSV [35] and Table 6A.A.1.2.2 PDF [36] CSV [37])

• 1. National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program. SEER *Explorer. Bones and Joints Cancer 5-Year Age-Adjusted Incidence Rates, 2012-2016 (Recent Rates). https://seer.cancer.gov/explorer  [38] Accessed July 30, 2019.
• 2. National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program. SEER *Explorer. Bones and Joints Cancer Long-Term Trends in U.S. Mortality Rates, 1975-2016 (Long-Term Trends).  https://seer.cancer.gov/explorer [39] Accessed July 30, 2019.
• 3. American Cancer Society. Cancer Facts & Figures 2017. Special section: rare cancers in adults, p 36. Atlanta: American Cancer Society; 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-... [40] Accessed January 22, 2018.
• 4. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). Cancer Stat Facts: Myeloma. https://seer.cancer.gov/statfacts/html/mulmy.html [41] Accessed August 5, 2019.

Gender and Race

Most bone cancers and soft tissue sarcomas are found more frequently in males than females and more frequently among whites than those of any other race, although there are exceptions or outliers to these generalizations for certain subtypes of bone and soft tissue tumors. However, reported rates have varied slightly for both genders and by race for the past decade. The average annual incidence of bone and joint cancers between 2012 and 2016 was 1 in 100,000, a slightly higher rate than reported in the first decade of the 21st century. The rate among white males was 1.2 in 100,000, while, among white females it was 0.9 in 100,000. The lowest reported rate, 0.6/100,000 was found for females of the Asian or Pacific Islander race. The incidence of cancer of the bones and joints in the United States is comparable to several site-specific oral cancers (i.e., lip, salivary gland, floor of the mouth), cancers of the bile duct, cancers of the eye, and Kaposi's sarcoma, which affects the skin and mucous membranes and is often associated with immunodeficient individuals with AIDS. (Reference Table 6A.A.1.1.1 PDF [42] CSV [43] and Table 6A.A.1.3.1 PDF [10] CSV [11])

As with bone and joint cancers, males have a higher incidence of myeloma than do females, with an average of 8.1 cases in 100,000 white males to 4.9 cases in 100,000 white females for the years 2012-2016. Blacks have a much higher incidence rate of myeloma than whites, with 16.3 cases in 100,000 black males to 11.9 cases in 100,000 black females for the years 2012-2016 while American Indians/Alaska Natives and Asian/pacific islanders have lower incidence rates. The incidence of myeloma in the United States is comparable to the incidence of esophageal, liver, cervical, ovarian, brain, and lymphocytic leukemia cancers. Death rates reflect incidence. (Reference Table 6A.A.1.2.1 PDF [34] CSV [35] and Table 6A.A.1.2.2 PDF [36] CSV [37])

The gender make-up of bone and joint cancers from the most recent NCDB (2004-2015) cohort also shows a male predominance for most of the bone and joint cancers and cancer subtypes, with parosteal osteosarcoma showing the major break from this generalization with 34% male and 66% female patients with this cancer. (Reference Table 6A.B.1.6 PDF [48] CSV [49] and Table 6A.B.1.7 PDF [50] CSV [51])

Age

The median age for cancers of the bones and joints has risen slightly, to age 43 years, in recent years. However, it remains the leading cause of cancer in young persons under the age of 20 years. More than one in four (26%) diagnoses of bone and joints cancer is in children and youth under the age of 20 years, with 42% of cases diagnosed in persons younger than 35 years. Death from bone and joints cancer also affects children and youth at a high rate, with 12% of deaths occurring in those under 20 years of age and one fourth (27%) in those younger than 35 years. Males are typically diagnosed with bone cancers, and die from bone cancer, at an age several years younger than females. (Reference Table 6A.A.1.3.1 PDF [10] CSV [11]; Table 6A.A.1.4.1 PDF [12] CSV [13]; Table 6A.A.1.7 PDF [52] CSV [53]; and Table 6A.A.1.8 PDF [54] CSV [55]).

Younger patients have a higher likelihood of surviving bone cancers. For example, the 5-year survivorship for classic osteosarcoma is 67% in 10 to 20-year-old patients, compared to 34% in patients in their 60s, 19% for patients in their 70s, and only 7% in patients in their 80s and older. Similar declining survivorship is noted with increasing age for Ewing Sarcoma and chondrosarcoma (unpublished NCDB current data analysis).

Myeloma, on the other hand, is primarily a cancer found among elderly persons, with a median age of 69 at the time of diagnosis and 75 at time of death from myeloma. Sixty-two percent (62%) of new myeloma cases are diagnosed in persons age 65 years and older, with more than three in four (78%) of deaths due to myeloma occurring in those 65 and older. Again, males are typically diagnosed with myeloma at ages a few years younger than females. (Reference Table 6A.A.1.3.1 PDF [10] CSV [11]; Table 6A.A.1.4.1 PDF [12] CSV [13]; Table 6A.A.1.7 PDF [52] CSV [53]; and Table 6A.A.1.8 PDF [54] CSV [55])

Race and Ethnicity

The incidence of bone and joints cancers is higher among non-Hispanic whites than found in other race/ethnicity groups, while myeloma is higher in non-Hispanic blacks. Death rates follow the same race/ethnic lines. (Reference Table 6A.A.1.1.1 PDF [42] CSV [43]; Table 6A.A.1.1.2 PDF [58] CSV [59]; Table 6A.A.1.2.1 PDF [34] CSV [35]; and Table 6A.A.1.2.2 PDF [36] CSV [37])

Causes of health disparities are complex and can include interrelated social, economic, cultural, environmental, and health system factors, and may arise, at least in part, from inequities in work, wealth, education, housing, and overall standard of living, as well as social barriers to high-quality cancer prevention, early detection, and treatment services.1

• 1. American Cancer Society. Cancer Facts & Figures 2017. Cancer disparities, p 49.  https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-... [40] Accessed January 22, 2018.

Annual population-based mortality rates due to cancers of bones and joints are low, averaging four deaths per one million people since the early 1990s.1 While the mortality rate from bone and joint cancer dropped by approximately 50% from that of the late 1970s, no significant improvement in this rate has been observed over the past 20 years.2 Males have a higher mortality rate than females for all race/ethnic groups. (Reference Table 6A.A.1.1.2 PDF [58] CSV [59])

Because bone and joint cancers affect younger populations more than other types of cancers, the median age at death, 61 years of age, is younger than any other type of cancer. There is a higher death rate in older individuals, but a higher incidence rate in younger individuals.  At 0.1% risk, bone and joints cancer also has one of lowest life-time risks. This compares to 12% risk for breast and prostate cancer, the two highest risk cancers. (Reference Table 6A.A.1.5.1 PDF [30] CSV [31] and Table 6A.A.1.6.1 PDF [60] CSV [61]; and Table 6A.A.1.6.2 PDF [62] CSV [63])

The overall 5-year survival rate in 2009-2015 for bone and joint cancers was 66.2%, placing it roughly in the middle of all cancers for 5-year survival and comparable to several more common cancers such as rectal, cervical, and soft tissue cancers.3 This is a survival rate increase of 27% since 1975, when the 5-year survival rate was 52%. (Reference Table 6A.A.1.5.2 PDF [64] CSV [65])

By extrapolation from median age at diagnosis and median age at death, one could estimate a median survival rate. However, this extrapolated survival time is misleading and inaccurate as younger patients, who typically are healthier and can tolerate more aggressive treatments, have improved survival compared to older individuals, who cannot tolerate such aggressive treatments and have poorer survival, greatly affecting this derived or extrapolated estimate of survivorship.

The overall 5-year survival rate for the primary types of bone and joint cancers varies by type and subtype of cancer, how it responds to treatment, and the degree to which the cancer has spread. Osteosarcoma diagnosed and treated before it has spread has a reported general survival rate between 60% and 80%; if it has already spread at the time of diagnosis, the 5-year survival rate is reported to be between 15% and 30%.4   

If Ewing sarcoma is found before it metastasizes, the 5-year survival rate for children and youth is about 70%, with a survival rate of 78% reported for children under age 5, dropping to around 60% survival for adolescents age 15 to 19. However, if already metastasized when found, the 5-year survival rate drops to 15% to 30%.5

The annual population-based mortality rate of myeloma has been an average of 33 persons per one million population between 2001 and 2016. The mortality rate from myeloma has remained relatively constant since the mid-1970s. The 5-year survival rate for myeloma, 50%, is one of the lowest for all cancers; however, due to being primarily a cancer of older persons, this age-relatedness may, in part, reflect survival regardless of the presence or absence of myeloma. The median calculated rate of survival after diagnosis of myeloma is only 6 years. (Reference Table 6A.A.1.2.2 PDF [36] CSV [37] and Table 6A.A.1.5.1 PDF [30] CSV [31])

Within the NCDB, no change in the overall survival rates for patients diagnosed and treated in the years 1985 to 1988 compared to patients between 1994 and 1998 was found. There have been no substantial changes in therapies utilized for osteosarcoma since 1998, and the overall 1998-2010 NCDB data reveals no significant improvement, with an approximate 50% 5-year overall survival. However, the survival rate varies greatly with the histologic subtype of sarcoma. For instance, the 5-year relative survival rate is 56% for classic high-grade osteosarcoma, 89% for parosteal osteosarcoma, and 37% for osteosarcoma associated with Paget's disease of the bone. The most recent NCDB database investigation the three primary authors have performed, which covered patients diagnosed between 2004-2015, inclusive, is summarized in the data tables attached to this chapter. These data provide the analysis of the numbers of cases reported during these years, along with the Kaplan-Meier survivorship of the major diagnostic groupings, as well as of the subgroups and age-based for the various primary bone and joint tumors reported and treated 2004-2015. (Reference Table 6A.B.1.1 PDF [16] CSV [17]; Table 6A.B.1.2 PDF [18] CSV [19]; Table 6A.B.1.3 PDF [20] CSV [21]; and Table 6A.B.1.4 PDF [22] CSV [23])

The above and all other reported survivorships in this chapter were generated using SAS/STAT software, Version14.2 for Windows 3. Copyright 2002-2012, SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. As stated previously, the NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used in this study and this report are derived from a de-identified NCDB file comprising more than 1,500 Commission-accredited cancer programs. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed or the conclusions drawn from these data by the investigator and authors of this chapter.

• 1. SEER Cancer Stat Facts: Bone and Joint Cancer. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/statfacts/html/bones.html [70] . Accessed January 25, 2018.
• 2. Damron TA , Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing sarcoma: National Cancer Center Data Base Report. Clin Orthop Relat Res 2007;459·40-47.
• 3. National Institutes of Health. National Cancer Institute, Division of Cancer Control & Population Sciences., Surveillance Research Program. Table 1.4: Age-Adjusted SEER Incidence and U.S. Death Rates and 5-Year Relative Survival (Percent) By Primary Cancer Site, Sex and Time Period. https://surveillance.cancer.gov/statistics/types/survival.html  [71] Accessed October 29, 2019.
• 4. Cancer.net. Osteosarcoma-Childhood Statistics. Available at: https://www.cancer.net/cancer-types/osteosarcoma-childhood/statistics [72]. Accessed January 25, 2018.
• 5. Cancer.net. Ewing Sarcoma-Childhood Statistics. Available at: https://www.cancer.net/cancer-types/ewing-sarcoma-childhood-and-adolesce... [73] . Accessed January 25, 2018.

The economic burden of bone cancers can be great. The more advanced the disease, the worse the prognosis and, accordingly, the more expensive the treatments. It is likely that early detection, and, certainly, prevention if possible, could drastically reduce costs. Several expensive treatments are required to address these tumors. In the 2007 report by Damron, Ward, and Stewart,1 it was noted that the most frequent initial treatments varied widely based on the type of sarcoma and, although not reported, also on the stage of the disease as well.

Collectively, they reported surgery alone was the most common initial treatment for chondrosarcomas (69%), whereas Ewing sarcoma treatments were divided between surgery and chemotherapy (24% of cases), radiation and chemotherapy (23%), and chemotherapy alone (18%). With osteosarcoma, when initial treatment was known, the largest group received surgery and chemotherapy (46%). Surgery was reported as part of the initial treatment in 71% of osteosarcoma patients, 83% of chondrosarcoma patients, and 47% of Ewing sarcoma patients. The most frequent operations performed were limb-sparing radical resections and excisions. When the type of surgery was defined and known, limb-preservation surgery was performed in 69% of osteosarcomas, 79% of chondrosarcomas, and 81% of Ewing sarcomas.1

The frequencies of the various treatment modalities employed in the latest reported (2004-2015) NCDB cohort are shown in the data tables attached to this section for bone and joint cancers and soft tissue cancers. As shown in the table, for Osteosarcoma NOS 76% had surgery, 74% had chemotherapy, and only 8% had radiation. For Ewing Sarcoma, the numbers were 51%, 85%, and 45%, respectively. For Chondrosarcoma NOS, the numbers were 85%, 3%, and 10%. These distributions reflect the widely different treatments of these three major categories of bone and joint cancers. (Reference Table 6A.B.1.9 PDF [74] CSV [75] and Table 6A.B.2.6 PDF [76] CSV [77])

In Dr. Ward's personal series of more than 100 osteosarcomas, amputation has been required in only 17% of patients, but almost all remaining patients have had surgical resection, limb reconstruction, and chemotherapy.1 The authors believe Dr Ward’s series is a reasonable approximation of treatments employed by most orthopedic oncologists in the US today.

Multiple therapies may be needed throughout the course of the patient's disease, especially in more advanced cases. In later stages of the disease for those not cured with surgery alone, significant costs will accumulate as patients develop pulmonary disease and ultimately die. Hormone therapy, immunotherapy, bone marrow transplant, and endocrine treatments each accounted for 1% or less of initial treatments. However, in severely affected individuals in whom standard treatments fail, these alternative treatments may be tried more frequently. Currently, the authors are not aware of any data source that reports the rate of utilization of such late treatments.

All these treatments are costly to administer. Per-patient cost will vary widely depending on the treatments utilized, and the number and intensity of treatments. Overall, treatment for bone and joint cancers can easily exceed $100,000 for a single patient. This is particularly true if a patient receives surgery, chemotherapy, and radiation therapy. If one includes bone-replacing endoprostheses or artificial limbs used in cases requiring amputation, the cost will be much higher. In addition to the direct medical cost, there are extensive indirect and social costs from lost work time and disability. For some patients, healthcare costs associated with their bone and joint cancers will be ongoing.

Analysis of the most recent NCDB insurance data, which covers all ages and covers the years 2004-2015 inclusive,  available for 18,881 reported bone and joint cancer cases show Medicare and Medicaid covering 16.76% and 14.71%, respectively,  with private insurance covering 57.33%, other government payors covering 1.9% with 5.05% uninsured and 4.24% with unknown insurance status. (Reference Table 6A.B.1.11 PDF [80] CSV [81]) 

 

• 1. a. b. c. Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma and Ewing sarcoma National Cancer Data Base Report. Clin Orthop Relat Res 2007:(459)·40-47.

Almost all cancers have preferential sites to which they spread or metastasize, resulting in secondary cancers. Secondary bone cancer is much more common than primary bone cancer and results in great morbidity and pain. The three most common sites to which cancers metastasize are lung, liver, and bone. The skeleton is the most common organ affected by metastatic cancer, and the site of disease that produces the greatest morbidity. The most commonly encountered cancers that readily and frequently spread to bone are cancers of the breast, lung, kidney, prostate, gastrointestinal tract, and thyroid gland. The incidence of bone metastases in lung cancer patients is approximately 30% to 40%, with the median survival time (MST) of patients with such metastases 6 to 7 months.1 At postmortem examination, 70% of patients dying of breast and prostate cancer have evidence of metastatic bone disease. Cancers of the thyroid, kidney, and bronchus also commonly give rise to bone metastases, with an incidence at postmortem examination of 30% to 40%.2 Brain and ovarian cancers rarely spread to bone. Many other cancers have intermediate rates of spread to bones.

A tumor formed by metastatic cancer cells is called a metastatic tumor or a metastasis. The cancer cells in their new metastatic site closely resemble the original or primary cancer from which the cancer initially arose. For example, breast cancer that spreads to the bone and forms a metastatic tumor is still considered metastatic breast cancer, not true bone cancer. The cancerous tissues in the bone will still exhibit the microscopic appearance of breast tissue and breast cancer when it is inspected or viewed under a microscope. Many lay people will now refer to it as bone cancer, but to the physician, bone cancer implies a cancer that started or originated in the bone, such as osteosarcoma, Ewing sarcoma, or myeloma, as discussed previously.

Metastatic bone disease complications are termed skeletal related events (SREs). SREs include pain, pathologic fracture, vertebral deformity and collapse, spinal cord compression, and hypercalcemia (overabundance of calcium in the blood) of malignancy. These complications result in impaired mobility and reduced quality of life (QOL) and have a significant negative impact on survival.2  In addition, metastatic disease may remain confined to the skeleton, with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment.

The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Survival rates for secondary bone cancer depend on patient factors such as age, overall health, treatment, and response to treatment. However, due to the advanced stage of cancer that has spread to the bone, survival rates are much lower than for primary cancer without such spread.

The fundamental treatment for disease control for bone metastasis from advanced cancer is systemic chemotherapy and radiation of the bone lesions. Prevention and treatment of bone metastases is highly dependent on an effective treatment being employed against the primary cancer. As a direct treatment for bone metastases themselves, radiation therapy, surgery, and bisphosphonates are the mainstays of treatment. Intravenous bisphosphonate, such as zoledronic acid, have been shown to prevent or reduce pathologic fractures and may reduce these costs.3 With the 1995 FDA approval of the use of bisphosphonate medications to prevent such fractures, the incidence of fractures in treated patients with bone metastasis has significantly decreased. Fracture rates reported in cases of metastatic disease and myeloma have been demonstrated in multiple studies to be diminished by roughly 50%. The bisphosphonate medications work by interrupting a biochemical pathway required for bone breakdown by osteoclasts, the cells that normally remove bone in the process of bone remodeling. This bone breakdown step is overactivated in the presence of bony metastases, causing bone loss, bone destruction, and ultimately fractures from the weakening of the bone. Thus, the introduction of bisphosphonate medication has been a major advance during the past 20 years, with significant impact on the health of those with myeloma and metastatic cancer to the bone. Most pathologic fractures encountered currently are in patients with newly diagnosed metastatic cancer who have not received prophylactic treatments because the cancer had not been diagnosed.

Dr. Ward has had several anecdotal cases in the last year (2018-2019) with metastatic lung and other cancers that have metastasized to bone in whom the cancer elsewhere in the body is responding favorably to newer targeted chemotherapy and immunotherapy regimens, but the bone metastasis for some reason is not responding favorably, requiring more extensive surgical treatment of the unresponsive bone metastatic lesion. Whether or not this will become a more common challenge in the future is anyone’s guess, but with several cases seen by one physician in a short time, it raises the possibility that more extensive bone resection treatments may become more necessary for metastatic bone lesions as these individualized systemic targeted treatments are employed in greater numbers and are capable of controlling the disease in the rest of the body.

• 1. Tsuya A, Kurata T, Tamura K, Fukuoka M. Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer 2007:57.229-232.
• 2. a. b. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006: 12 ;624s-6249s.
• 3. Capalbo S, Delia M, Diomede D. et al. Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy: Paradoxical complication or treatment of bone lesions in multiple myeloma patients. Int J Hematol 2006;83·439-442.

The economic burden of SREs in patients with bone metastases is substantial. Several recent studies show that the estimated lifetime SRE-related cost per patient suffering from bone metastatic disease (BMD) resulted in medical costs more than twice the treatment cost for cancer in patients without BMD.1^,2 Finding cures and effective treatments for all types of cancer can help reduce the prevalence and costs associated with bone and joint cancer.

Overall, cancers metastatic to bone cause significant pain and morbidity. Approximately 50% of patients with metastatic cancer of lung, breast, prostate, and kidney develop bony metastases prior to death. Untreated, these metastases can lead to pathological fractures and cause great pain and disability. Thus, the elucidation of the biochemical steps involved in bone destruction and the development of drugs to combat such steps, have been an example of tremendous scientific advancement and achievement in the field of cancer research and treatment.

 

• 1. Decroisette C, Monnet I, Berard H, et al. Epidemiology and treatment costs of bone metastases from lung cancer: a French perspective, observational, multicenter study. Journal of Thoracic Oncology 2001;6(3):576-582.
• 2. Hagiwara M, Oglesby A, Chung K, Zilber S. The impact of bone metastases and skeletal-related events on healthcare costs in prostate cancer patients receiving hormonal therapy. MDedge:Hematology & Oncology. https://www.mdedge.com/hematology-oncology/article/47005/genitourinary-c... [84] Accessed August 14, 2019.

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.

Cancer cells are often referred to as differentiated versus undifferentiated. Differentiation describes how much or how little the tumor tissue microscopically resembles the normal tissue from which it originated. Well-differentiated cancer cells look much 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.1 The most common types of soft tissue sarcomas are described below.2

Malignant Fibrous Histiocvtomas (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, 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. Synovial sarcomas tend 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. Prognosis is similar to malignant fibrous histiocytoma and the other high-grade soft tissue sarcomas mentioned above.

Tumors of Muscle Tissue

Leiomyosarcomas

Smooth muscle (involuntary 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 (benign version of similar tumor) 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 the smooth muscle cells in the walls of arteries, resection of extremity leiomyosarcomas frequently requires a concomitant 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 [86].“

Malignant Peripheral Nerve Sheath Tumors

Malignant schwannomas, neurofibrosarcomas, and neurogenic sarcomas are malignant tumors of the protective lining that surrounds nerves. The currently favored name for these sarcomas is malignant peripheral nerve sheath tumor. A rare form of cancer, it often has an association with neurofibromatosis and thus may possess a genetic component.

Tumors of Blood Vessels and Lymph Vessels

Angiosarcomas (Hemangiosarcomas)

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, tending to recur where they started, even after surgery, unless widely excised. Following recent research and further histologic, genetic, and clinical evaluations, hemangiopericytomas have recently been reclassified as one end of the spectrum of malignant solitary fibrous tumors or possibly identical to malignant solitary fibrous tumors.

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 metastasizes 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). It also develops 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 in the introduction section of soft tissue cancers.

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 between fibrosarcomas and benign tumors, such as fibromas and superficial fibrous diseases like Dupytren's disease. They tend to grow slowly, but steadily. These tumors are often referred to as desmoid tumors. Although they are benign and do not metastasize, they do form in response to genetic alterations similar 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 them as benign but locally aggressive tumors. Certain hormones, particularly estrogen, may increase the growth of some desmoid tumors. There has been a very recent evolution in the thinking about this disease, with an evolution toward a greater role for careful observation after diagnosis, with surgical intervention being less enthusiastically employed, reserving such for more painful and/or aggressively growing tumors. Antiestrogen drugs are sometimes useful in treating desmoids that cannot be completely removed by surgery. Radiation therapy plays a role in treatment, especially when the tumor cannot be resected or in recurrent cases. There are ongoing chemotherapeutic trials in place with newer agents that interrupt the various biological processes in the growth of these tumors that hold 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 normal 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. One of the most vascular (many tumor-contained and tumor-associated blood vessels) of all sarcomas, 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 soft tissue sarcomas, including survival curves, the 2- and 5-year survivorship rate, and various demographic data.4

• 1. National Cancer Institute. NCI Dictionary of Cancer Terms: differentiation. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms?expand=D [87] . Accessed January 28, 2018.
• 2. Weiss SW, Goldblum JR, Folpe AL. Enzinger and Weiss's Soft Tissue Tumors. 5th ed., 2008. Mosby, Inc., an affiliate of Elsevier.
• 3. Weiss SW, Goldblum JR, Folpe AL. “Malignant Mesenchymoma.” Enzinger and Weiss's Soft Tissue Tumors. 5th ed., 2008. Mosby, Inc., an affiliate of Elsevier. PP 1213-14.
• 4. Corey RM, Swett K, Ward WG. Epidemiology and survivorship of soft tissue sarcomas in adults: a national cancer database report. Cancer Med. 2014 Oct;3(5);1404-15. doi: 10.1002/cam4.288.

Soft tissue sarcomas account for less than 1% of all cancer cases diagnosed each year, and for a similar proportion of cancer deaths in any given year.

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 2010 to 2014, the annual average number of soft tissue neoplasms, including the heart, approximated 15,500 cases/year in the SEER database. Estimated new cases for 2018 by the American Cancer Society are 13,040.1 Soft tissue sarcomas come in a wide variety of forms that affect different age groups, but the most frequently encountered soft tissue sarcomas affect adults age 45 and older. (Reference Table 6A.A.1.3.1 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 72% of the cancers treated in the United States.2 It should be noted this percentage varies from year to year based on the participation and reporting by hospitals to this voluntary database.

A 2014 report by Corey, Swett, and Ward examined the adult cases reported to the NCDB of soft tissue sarcomas during 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.3 However the NCDB is not an incidence or prevalence based database, and the number can simply reflect a change in makeup of the reporting member institutions.

• 1. American Cancer Society. Cancer A-Z. Key Statistics for Soft Tissue Sarcoma. Available at https://www.cancer.org/cancer/soft-tissue-sarcoma/about/key-statistics.html [88] . Accessed January 29, 2018.
• 2. Mallin K, Browner A, Palis B, et al. Incident cases captured in the National Cancer Database compared with those in U.S. population based Central Cancer Registries in 2012-2014. Ann Surg Oncol 2019 Jun;26(6):1604-1612. doi: 10.1245/s10434-019-07213-1. Epub 2019 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/30737668 [4] Accessed December 27, 2019.
• 3. Corey RM, Swett K, Ward WG. Epidemiology and survivorship of soft tissue sarcomas in adults: a national cancer database report. Cancer Med. 2014 Oct;3(5);1404-15. doi: 10.1002/cam4.288.

Soft tissue sarcomas can be found among all ages, with the risk of developing soft tissue cancer very small, ranging from 0.33% at 20 years to 0.17% at 75 years of age. However, due to the smaller population count in older cohorts, the share of cases diagnosed after the age of 55 is larger than in younger cohorts. (Reference Table 6A.A.1.3.1 PDF [10] CSV [11], Table 6A.A.1.3.2 PDF [89] CSV [90], and Table 6A.A.1.6.2 PDF [62] CSV [63])

The rate at which males are diagnosed with soft tissue sarcomas has historically been higher than for females, with corresponding increases or decreases found in both sexes. The most recent rates from the NCI are for the year 2014 and are 4.1/100,000 for males and 2.9/100,000 for females. Males are diagnosed with soft tissue sarcomas at a slightly higher age than females. (Reference Table 6A.A.1.1.3 PDF [93] CSV [94] and Table 6A.A.1.7 PDF [52] CSV [53])

Blacks are diagnosed an average of eight years earlier than those who are white. In the 1970s and 1980s, the incidence rates for soft tissue sarcomas was slightly higher among the black population than for the white population. However, in the early 1990s a shift was observed and today incidence rates are higher among whites. In 2014, the rates were 3.5 and 3.3 per 100,000 persons, respectively, for whites and blacks. (Reference Table 6A.A.1.7 PDF [52] CSV [53] and Table 6A.A.1.1.4 PDF [95] CSV [96])

 

The 5-year survival rate in 2010-2014 for soft tissue sarcomas is reported at 64% by the SEER database and an overall relative survival rate of 50% by the American Cancer Society.1 This rate is similar to that for leukemia, colon and rectum, and non-Hodgkin lymphoma cancers. Average length of survival after diagnosis is 5 years, similar to that of breast, colon, and bladder cancers. White women have a slightly higher 5-year survival rate than do men and live an average of 1 year longer after diagnosis. Black women are diagnosed at about the same  average age as black men with soft tissue sarcomas but live an average of two years longer after diagnosis. (Reference Table 6A.A.1.5.1 PDF [30] CSV [31]; Table 6A.A.1.7 PDF [52] CSV [53]; and Table 6A.A.1.8 PDF [54] CSV [55])

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 staging criteria of soft tissue sarcoma of the National Cancer Institute groups sarcomas by whether they are still confined to the primary site (called localized); have spread to nearby lymph nodes or tissues (called regional); or have spread (metastasized) to sites away from the main tumor (called distant). The 5-year survival rates for soft tissue sarcomas have not changed much for many years. The corresponding 5-year relative survival rates were:
•    83% for localized sarcomas (56% of soft tissue sarcomas were localized when they were diagnosed)
•    54% for regional stage sarcomas; (19% were in this stage)
•    16% for sarcomas with distant spread (16% were in this stage)
The 10-year relative survival rate is only slightly worse for these stages, meaning that most people who survive 5 years are probably cured.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.

• 1. a. b. American Cancer Society. Survival by Stage of Soft Tissue Sarcoma. Based on data from the National Cancer Institute. Available at: https://www.cancer.org/cancer/soft-tissue-sarcoma/detection-diagnosis-st... [101] . Accessed January 30, 2018.

From 2004-2015 inclusive, information on insurance coverage was available for roughly 65,015 patients treated with soft tissue sarcomas. The largest insurance payer was private insurance (51.0%), followed by Medicare and Medicaid (30.9% and 8.9%) respectively. Other government payors covered 1.4%, while 4.8% were uninsured and payor status was unknown in 3.0%. (Reference Table 6A.B.2.8 PDF [102] CSV [103])

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 during the course of the patient's disease, especially in more advanced cases. In later stages of the disease in those not cured with surgery alone, significant costs will accumulate as patients typically develop pulmonary disease and ultimately die. Chemotherapy, and subsequently hormone therapy, immunotherapy, bone marrow transplant, and 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. (Reference Table 6A.B.2.6 PDF [76] CSV [77])

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 compared to $44,770 for 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.1

This analysis confirms that proper work-up, evaluation, and treatment are key to maintain costs, as well as improve 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.

• 1. Alamanda VK, Delisca GO, Mathis SL, et al. The financial burden of re-excising incompletely excised soft tissue sarcomas: a cost analysis. Ann Surg Oncol 2013; (9): 2808-2814.

The majority of sarcomas develop in people with no known risk factors, and there is currently no known way to prevent these cases. Whereas future developments in genomic research may allow genetic testing to identify persons with increased risk of developing 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.

Whenever physicians examine a patient presenting with a new mass in the leg, thigh, muscles, and deep tissue of the body, particularly if the patient has a previous history of cancer, metastatic cancers in the soft tissues should be considered. The most likely cancers to metastasize to soft tissue are cancers of the lung and kidney.

Osteochondroma

The most commonly encountered benign tumor of bone is osteochondroma, which typically arises near the long ends of bones. Osteochondromas are often painful because of formation of bursae (small fluid-filled sac) overlying the lesion and/or tenting and irritation of overlying soft tissues. They can cause interference with neurovascular function due to tenting of such structures over the osteochondroma surface, and they have the potential for causing growth deformity in the involved and adjacent bones. Long-term complications are uncommon except for rare cases of dedifferentiation into chondrosarcoma. There is no estimate of the number of patients seen with nonoperatively managed osteochondromas due to lack of records. An annual US prevalence of >1,500 surgical cases is based on records kept by Dr. Ward; this is believed to be clearly underestimated. This estimate would not include cases treated by general orthopedic surgeons and pediatric orthopedic surgeons, who, in addition to orthopedic oncologists, provide medical and surgical treatment of many osteochondromas.

Unicameral Bone Cysts

Unicameral bone cysts (simple bone cysts) are the second most commonly encountered benign bone lesions, with an estimated annual prevalence of more than 1,250 surgical cases. The etiology of these fluid-filled bone cysts, usually found in the growing ends of children’s long bones such as the proximal humerus or femur, is unclear. Because they never metastasize and are usually quite characteristic on radiographs, many of these are treated by other orthopedic surgeons, especially pediatric orthopedic surgeons. The true incidence, therefore, is probably significantly higher than that estimated by extrapolation from Dr. Ward's practice experience. These cystic lesions cause weakening of the bone and the patients may require multiple surgeries to rebuild the bone with bone grafts, injections, and other techniques. They occur in children, and typically recur multiple times until skeletal maturity is achieved.

Giant Cell Tumor of Bone

Giant cell tumor of bone, with an estimated annual prevalence of more than 750 cases, is the third most commonly encountered benign bone neoplasm and accounts for significant disability and dysfunction. This typically occurs near the end of the long bones, most commonly the lower femur or upper tibia, and causes destruction of the bone. The tumor may extend through the cortex of the bone into the soft tissues and, if large enough prior to treatment, can be associated with pathologic fracture of the involved bone. Smaller tumors can be treated with bone resection and reconstruction with bone grafts or cement filler. Cases that are more complicated require sophisticated reconstruction with massive joint replacements and/or massive allografts which can cause severe long-term disability. On rare occasions, giant cell tumors metastasize to the lungs. In such cases, they typically respond poorly to chemotherapy and may cause death. These tumors are rarely treated by general orthopedic surgeons. Although currently not considered the standard of care, many patients' tumors have had excellent responses to denosumab treatment, a monoclonal antibody directed against RANK ligand, the activator of osteoclasts (giant cells). This is very similar to the mechanism of action of bisphosphonates. Initial studies with denosumab have shown a very favorable response in many tumors so treated but presently, even with denosumab pretreatment, surgical resection appears to be ultimately required. Current research continues and with enhanced understanding of the underlying pathogenic mechanisms, nonsurgical management may become possible in the future.

Enchondroma

A fourth commonly encountered tumor that may require surgery is enchondroma, estimated at more than 725 annual surgical cases. Bones typically form as cartilage during the embryo stage of human development, and this cartilage model ultimately converts into bone structure. The cartilage-based growth plates add length to the bones from bone growth. Enchondromas are tumors derived from remnants of these cartilaginous tissues that abnormally remain in the skeleton as remnants or nodules from the normal pattern of maturation and development. If these achieve sufficient size, they can cause cortical bone erosion and pain or fracture and may present diagnostic challenges requiring biopsy. They often require treatment by curettage and bone grafting. These lesions can dedifferentiate into malignant cartilage tumors called chondrosarcomas. Many small enchondromas are seen incidentally, cause no symptoms, and are treated with simple observation, thus, total incidence of enchondromas is much higher than calculated from extrapolation of the surgical data. In addition, the burden of enchondromas requiring surgical treatment is very conservatively estimated, as many are treated by general orthopedic surgeons, pediatric orthopedic surgeons, and hand surgeons.

Other Benign Bone Tumors

Multiple other benign tumors are commonly encountered.

• Aneurysmal/ bone cysts (ABCs) are aggressive cystic lesions similar to unicameral bone cysts. However, ABCs are more destructive, expanding and weakening the bone and causing greater bone destruction. They tend to fill with blood and tissue, not simple fluid. Usually, ABCs respond favorably to curettage and bone grafting, but recur in at least 20% of cases. Some ABCs arise secondarily in other bone lesions and conditions such as fibrous dysplasia.
• Metaphyseal fibrous defects (non-ossifying fibromas) are focal defects in normal bone that are filled with soft tissue. These occur in 2% to 3% of children. Most resolve without ever causing symptoms and may never be detected unless the child receives an X-ray or MRI scan for another problem. Large ones may require surgery, such as bone grafting to prevent fracture and for surgery to treat completed fractures that have already occurred.
• Osteoid osteoma is a small tumor typically occurring in children that is associated with severe, unrelenting night pain. It usually requires resection or radio frequency ablation and occasionally may require bone grafting. When located in the spine, it can cause a painful scoliosis. Recently, successful treatment with radio frequency ablation under radiographic guidance has become the treatment of choice for accessible lesions.
• Chondroblastoma is an unusual neoplasm that occurs in the ends of growing bones in teenagers and young adults. This requires resection of the lesion and bone grafting. If untreated, it can cause collapse and degenerative arthritis in the associated joint and, on rare occasion, can metastasize to the lung. Chondroblastomas are usually referred to orthopedic oncologists.
• Numerous other less common benign bone tumors often are treated similarly to giant cell tumors, ABCs, or chondroblastomas with curettage, resection, and bone grafting. Most cause some degree of disability and dysfunction of the involved extremity.

As with the benign bone tumors, there is no national registry of benign soft tissue tumors. By comparing Dr. Ward's 13 years of practice history from 1991 to 2004 and computing an incidence index relative to that of osteosarcoma, some estimate of the minimal prevalence of surgically treated lesions may be obtained.

From this index estimate, a baseline estimated extrapolation of the national incidence can be calculated. However, benign soft tissue tumors are the most likely category of tumors to be treated by other surgeons, such as general orthopedic surgeons, plastic surgeons, and general surgeons; therefore, this national estimate is extremely conservative. The prevalence and burden In the United States from benign soft tissue tumors is significantly higher than estimated herein. (Reference Table 6A.C.1 PDF [125] CSV [126])

Benign soft tissue tumors are usually detected as asymptomatic masses. Treatment typically requires resection. Benign lesions rarely cause death, and it is rare that an amputation is necessary. However, depending on the site of involvement and size of the lesion, significant disability of the involved extremity and/or joint can occur. The true cost of these otherwise benign neoplasms can be high for healthcare costs, lost worktime, morbidity, emotional cost, and disability expenses.

Tumors of Fat Tissue

Lipomas: Benign tumors of fat tissue

Lipomas are the most common benign soft tissue tumor. Most are found under the skin, but they can develop anywhere in the body. Many lipomas are present for years and inactive, but those that are growing lesions are probably the most commonly resected soft tissue benign tumor. Resection of small growing lesions is usually performed in local community settings by multiple surgical specialists and even by primary care practitioners. Only patients with larger, more concerning lesions are typically referred to surgeons with a focus in surgical oncology. Not infrequently, a slow-growing sarcoma is mistakenly diagnosed as a lipoma, leading to a delay in the diagnosis of soft tissue sarcoma. This misdiagnosis can lead to an original suboptimal resection of the unappreciated sarcoma by the unsuspecting community surgeon.

Lipoblastomas

Lipoblastomas are benign fat tumors that occur in infants and young children.

Hibernomas

Hibernomas are benign fat tissue tumors that behave similarly to lipomas. They are so named because of their brownish coloration that resembles the appearance of the fatty tissue of bears, hence the name hibernomas. They are much less common than lipomas.

Tumors of Muscle Tissue

Leiomyomas (Smooth Muscle Benign Tumors)

Smooth muscle is found in internal organs such as stomach, intestines, blood vessels, or uterus. Unlike skeletal muscle that contracts voluntarily, smooth muscle contracts involuntarily. Leiomyomas are benign tumors of smooth, or involuntary muscle. Leiomyomas can arise almost anywhere in the body in either men or women because they start in widespread tissues such as blood vessels or intestine. The most common leiomyomas is the fibroid tumor that often develops in the uterus.

Rhabdomyomas (Skeletal Muscle Benign Tumors)

Skeletal muscle is the muscle that allows movement of arms and legs and other body parts. These are voluntary muscles. Rhabdomyomas are benign tumors of skeletal muscle and are very rare.

Benign Tumors of Peripheral Nerve Tissue (Benign Peripheral Nerve Sheath Tumors)

Neurofibromas, schwannomas (neurilemmomas), and neuromas are benign tumors of nerves. These tumors can occur almost anywhere in the body. An Inherited condition called neurofibromatosis, or Von Recklinghausen disease, causes people to develop many neurofibromas throughout their body. Some of these may dedifferentiate and become malignant. These dedifferentiated malignant tumors usually form from large neurofibromas in the upper arms, neck, pelvis, or thigh. Patients with the dedifferentiated neural sarcomas have a very poor prognosis and most ultimately succumb to the cancer.

Tumors of Joint Tissue

Joints are surrounded by tough tissue called synovium, which produces fluid that lubricates joint surfaces allowing them to move smoothly. Joint tissue tumors typically arise from the synovium.

Pigmented villonodular synovitis (PVNS) is a benign tumor of joint tissue. It is most common in its nodular form in the hands, and more common in women than in men. The nodular form rarely recurs following adequate and complete excision. PVNS also occurs in a diffuse form that typically will involve the entire joint lining and has a high recurrence rate after attempted resections. PVNS in its diffuse form is most commonly encountered in the knee joint, where it often causes recurrent bloody effusions (swollen knees filled with bloody fluid). It does not spread to other joints, but when recurrent or persistent, can destroy the involved joint.

Tumors of Blood Vessels and Lymph Vessels

Hemangiomas are benign tumors of blood vessels. They are rather common, are often present at birth, and can affect the skin or internal organs. They sometimes disappear without treatment, but when located in muscles and other deep tissues, can be quite problematic and may require surgical treatment.

Glomus tumors are benign perivascular (surrounding blood vessels) tumors. They usually are found under the skin and often under fingernails. They are usually small (<1 cm), but are exquisitely tender and painful. They may make the overlying skin sensitive to even light touch from clothing.

Hemangiopericytoma is a tumor of perivascular tissue. It most often develops in the legs, pelvis, and retroperitoneum (the back of the abdominal cavity) and is most common in adults. These can be either benign or malignant. They rarely spread to distant sites but tend to recur locally following surgical resection unless very widely excised. They may be multifocal.

Lymphangiomas are benign lymph vessel tumors that are usually present at birth. Lymph is a type of fluid that circulates in every tissue of the body. Lymph fluid is collected and routed back into the venous system by the lymphatic system. It contains waste products from tissues and immune system cells. Lymphangiosarcomas are the malignant lymph vessel equivalents of angiosarcomas.

Tumors of Fibrous Tissue

Fibrous tissue forms tendons and ligaments and covers bones as well as other organs in the body.

Fibromas, elastofibromas, extra-abdominal fibromatosis, and fibrous histiocytomas are all benign soft tissue tumors. Fibromatosis is the most problematic of these tumors. They frequently recur following resection, and may require additional treatment with repeat surgery, radiation therapy, chemotherapy, or other therapies. Although these tumors do not metastasize, they can be challenging. Fibromatoses (desmoid tumors) were discussed at length under the malignant soft tissue section above where they are often grouped due to their locally aggressive nature.

Tumors of Uncertain Tissue Type

Through microscopic examination and other laboratory tests, doctors can usually find similarities between most soft tissue tumors and certain types of normal soft tissues. This is how soft tissue tumors are classified. However, some soft tissue tumors have not been linked to a specific type of normal soft tissue.

Myxoma is a benign tumor that is usually located in muscles but does not develop from muscle cells. The cells of a myxoma produce mucus-like material in and around the cells, a distinguishing feature of this tumor. They are usually found in adults, and rarely recur after treatment. Myxoma must be differentiated from myxofibrosarcoma, a malignant neoplasm that can appear very similar under the microscope as well as in gross appearance. The challenge for the treating physician is to avoid overtreating myxomas and to avoid undertreating myxofibrosarcomas, in terms of the extent of normal tissue margin around the tumor to be resected with the tumor to minimize the risk of recurrence.

Granular cell tumors are very uncommon and are usually benign tumors of adults that can be found almost anywhere in the body. They are frequently multifocal.

Tumor-like Conditions of Soft Tissue

Some conditions of soft tissues are caused by inflammation or injury that forms a mass similar to a soft tissue tumor. Unlike a true tumor, they do not come from a single abnormal cell; they have limited capacity to grow or spread to nearby tissues, and never spread through the bloodstream or lymph system. Examples include nodular fasciitis and myositis ossificans, which involve tissues under the skin and muscle tissues, respectively.

There are also deposition diseases that are often grouped with tumors. The most commonly encountered ones are tophi, often seen in cases of poorly controlled gout. These tophi can achieve massive size and may be mistaken for true tumors. They can erode through the skin, causing skin breakdown and infection that may require surgical treatment and antibiotics. Calcium deposits are often seen in renal failure and poorly managed dialysis patients. They may be painful and may require difficult resection of deposits infiltrated into normal tissue. When not associated with diseases of abnormal calcium metabolism, such as renal failure and dialysis, the disease is termed tumoral calcinosis. It behaves essentially the same as the calcium deposition mentioned in association with renal disease. Amyloid deposition can rarely cause a soft tissue (or bony) mass. These are most often seen in poorly controlled dialysis patients. Rheumatoid nodules are soft tissue deposits of antibody-laden, inflammatory soft tissue masses that can be quite painful and may require resection for symptomatic relief. Adequate treatment of the underlying rheumatoid arthritis with current disease-modifying medications usually prevents the occurrence of such lesions.