All About Soft Tissue Sarcoma

OncoLink Team
Last Modified: April 24, 2018

What is sarcoma?

Sarcoma is a cancer of the soft tissue or bone. Soft tissues include muscles, tendons, fibrous tissues, fat, blood vessels, nerves, and synovial tissues (found in joints). Sarcomas are more specifically named by the tissues they affect. For example, sarcoma that arises from the bone is called osteosarcoma (although there are other types that form in the bone), and a sarcoma of the fat cells is called liposarcoma. (See list in appendix for types of soft tissue sarcomas). Soft tissue sarcomas encompass a group of 50 different types of tumors, with most types considered extremely rare. Sarcomas account for 0.7% of all adult cancer diagnoses with close to 13,000 new cases annually in the soft tissues. Soft tissue sarcomas can develop from any site in the body, but the majority form in the extremities (about 50%), most commonly in the thigh. The remaining cases are evenly distributed throughout the rest of the body (10-15% in the trunk, <10% in the head & neck and 15% in the retroperitoneum).

What causes soft tissue sarcoma and am I at risk?

Soft tissue sarcomas (STS) can develop in people of all ages, with approximately 20% of cases in people under age 40, 30% in people from 40-60 years of age, and 50% in people older than 60. In most cases of sarcoma, no specific cause is known. Sarcomas can develop secondary to radiation therapy for another cancer, but these are most often osteosarcomas. There is thought to be an increased risk with exposure to chemicals used in certain industries, but research of these chemicals has produced mixed results, and a clear-cut association has not been found. The agents in question include: phenoxyacetic acids (forestry workers), TCDD (tetrachlorodibenzo-p-dioxin), Agent Orange (Vietnam veterans), chlorophenols (sawmill workers), thorotrast (formerly used as radiology contrast), vinyl chloride, and arsenic (vineyard workers). There is also thought to be a link between chronic lymphedema (induced by surgery, radiation, or congenital abnormalities) and a type of sarcoma called lymphangiosarcoma. Lastly, there are a few genetic syndromes that are linked to STS; these include Li-Fraumeni syndrome, neurofibromatosis, and familial retinoblastoma.

Given the lack of a clear-cut cause, one cannot really prevent sarcoma from developing, aside from maybe avoiding the chemicals listed above.

What screening tests are used for soft tissue sarcoma?

Unfortunately, there are no screening tests for STS. Screening tests are developed for the early detection of common or very deadly diseases. Given how rare STS are, they would be difficult to screen for in the general population. In addition, the number of different types of STS would make it very difficult to develop one single screening test that could detect all types.

What are the signs of soft tissue sarcoma?

The signs of STS are dependent on where the tumor has formed. As the majority of STS form in the extremities, those patients will most likely present with the complaint of a mass or lump found in the extremity, with or without swelling. Depending on its location and size, the mass may or may not cause pain. If the tumor arises in the abdomen, it may reach considerable size before it is detected or leads to abdominal or back pain. Tumors arising in the gastrointestinal tract may cause diarrhea, constipation, blood in the stool, or abdominal pain. A uterine sarcoma may cause bleeding, swelling, or pain in the pelvic area.

How is soft tissue sarcoma diagnosed?

In general, blood tests are normal in patients with STS. Initial imaging studies depend on the location of the tumor. For STS located in the extremities or in the pelvic region, magnetic resonance imaging (MRI) is the study of choice. For STS located in the abdomen, CT scan is the preferred study.

Given how rare sarcomas are, many physicians have never seen or cared for a patient with sarcoma. When sarcoma is suspected, it is important to seek out a healthcare team familiar with sarcoma. A biopsy is critical for diagnosis and to determine the exact type of sarcoma. Successful biopsy requires knowledge of sarcomas and their treatment, and is best done by a surgeon familiar with sarcoma, followed by examination of the sample by a pathologist who has experience with sarcoma specimens. Biopsies can be performed as an open (surgical) procedure or a closed (percutaneous) procedure (using a large needle to remove the tissue). In general, the preferred method is the least invasive technique required that still allows the pathologist to give a definitive diagnosis.

How is soft tissue sarcoma staged?

Most tumor types are staged using a system developed by experts, but this has been difficult to develop for STS given the number of types and the varying locations. The most widely used system has been developed by the American Joint Committee on Cancer (AJCC) (7th edition). It incorporates tumor size, histologic grade (how different the cells look under the microscope when compared to normal cells), and spread to lymph nodes or other body sites in determining the stage. The "T stage" represents the extent of the primary tumor itself. The "N stage" represents the degree of involvement of the lymph nodes. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. STS staging also includes histologic grade, “G” which describes how the cells looks under a microscope. The “G” is determined by three different factors, cell differentiation, mitotic count and tumor necrosis. The T, N, M and G ratings are combined to assign a stage, from I (one) denoting more limited disease, to IV (four) denoting more advanced disease.

The staging system is very complex, and the entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed.

In addition to the staging, doctors consider a few characteristics that point to a higher likelihood of relapse when deciding on treatment options. Patients with these characteristics are considered "high risk" and may be treated more aggressively. Some high-risk factors include: high grade (appearance under the microscope), deep location, size > 10cm, age > 50, or presenting with a recurrence in the area of the original tumor. CT scan of the lungs may be performed to assess for spread of the tumor to the lungs, as this is the most common place to which STS metastasizes (spreads). If the particular tumor type can spread to bone, a bone scan may also be performed to look for metastasis.

How is Soft Tissue Sarcoma treated?

Given the rarity of STS, these patients are best served at a specialty treatment center. Treatment of STS requires complex multi-modality therapy (surgery, radiation, and chemotherapy). Specific treatment is dependent upon the size and location of the tumor, the grade (aggressiveness) of the tumor, and whether or not it has spread. The following is a general review of current treatments, but specific cases should be discussed with your healthcare team.

Surgery

Surgery is the primary means of treatment in STS, with the goal of complete tumor removal. Given that most tumors arise in the extremities, in the past this has typically required amputation of the affected limb. Through great surgical advances and the use of radiation therapy after surgery, only 10% of patients require amputation today, an overwhelming improvement from previous years. In addition to the tumor, the surgeon typically removes a 2 cm area of normal tissue around the tumor whenever possible. There is a low risk of spread to lymph nodes, therefore lymph node dissection is not routinely performed. However, in certain subtypes, lymph node involvement is more common (angiosarcoma and embryonal rhabdomyosarcoma). In these patients, if lymph node involvement is suspected, removal of these nodes can be curative. For patients with small, low risk tumors, surgery can be curative. However, most patients will also require radiation therapy.

Radiation Therapy

Radiation therapy can be performed before or after surgery, or during surgery through the use of brachytherapy. Studies have clearly shown that treatment with radiation prevents recurrence in the area of the original tumor more so than surgery alone. In addition, radiation in conjunction with limb-sparing surgery allows patients with STS in an extremity to avoid amputation.

There is no consensus on when to give radiation to achieve the best outcomes. Pre-operative radiation may allow smaller doses of radiation with smaller, better-defined treatment areas and result in a smaller surgery by shrinking the tumor before surgery. But, preoperative radiation can make precise staging more difficult and can result in poorer wound healing after surgery.

Chemotherapy

Chemotherapy can be given before surgery (called neoadjuvant), in an effort to shrink the tumor enough to allow for a better resection, or after surgery (called adjuvant). Surgery and radiation can only act on a small area around the tumor site, whereas the main goal behind adjuvant chemotherapy is to kill any cancer cells floating undetected elsewhere in the body. It is these cells that can plant themselves and start to grow in other organs, most commonly the lungs.

Seventy-five percent of patients will be cured with surgery and radiation alone, so it is important to limit chemotherapy treatment to those patients at highest risk for relapse, as chemotherapy carries with it the downside of significant toxicity. Commonly used chemotherapeutic medications used in the treatment of STS are: doxorubicinifosfamideepirubicingemcitabinemesnavinorelbinedocetaxel, and dacarbazine. These medications can be used in combination or as single agents. The medications used are dependent on the subtype of soft tissue sarcoma being treated.

Some STS subtypes may be treated with targeted therapies that focus on specific gene mutations or proteins present in that tumor. Targeted therapies work by targeting something specific to a cancer cell, which allow the medication to kill cancer cells while preserving the health of most normal cells. Sometimes the “target” is found on a certain type of healthy cells and side effects occur as a result. These medications include olaratumab, pazopanibimatinib, palbociclib, crizotinib, ceritinib, sunitinib, and sorafenib. Other targeted and immune therapies are being studied in the treatment of soft tissue sarcomas.

Hyperthermic Isolated Limb Perfusion (HILP) is a technique that is used to treat STS in the extremities (legs or arms). The circulation to that limb is basically isolated and chemotherapy is infused directly into it, all while the limb's temperature is heated above normal temperatures. This technique makes the chemotherapy far more potent than administering it through a regular IV. HILP is being studied in patients who would otherwise require amputation or those who have a localized area of recurrence.

Clinical Trials

There are clinical research trials for most types of cancer and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow Up Care and Survivorship

After initial treatment, patients should be seen and examined every 3-6 months for the first 3 years, then annually (may be less frequent for stage I cases). Periodic CT scans or MRIs of the original tumor site may allow detection of a recurrence before symptoms arise. Abdominal sarcomas should be scanned every 3-6 months for the first 2-3 years, then every six months for two years, then annually, as recurrence is more difficult to detect in the abdomen using physical examination alone. Chest x-ray or CT scan of the chest can be performed every 6-12 months to monitor for lung metastases.

Fear of recurrence, relationships challenges, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by soft tissue sarcoma survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Sarcoma Foundation of America

The SFA raises money for sarcoma research and aims to raise awareness of sarcoma. The site has information for patients as well.

http://www.curesarcoma.org/

Sarcoma Alliance

This website, started by a sarcoma survivor, is based on the mantra "guidance, education, and support". They also maintain a list of specialty centers.

http://www.sarcomaalliance.org

Appendix: World Health Organization Classification of Tumors of Soft Tissues and Bone, Fourth Edition, 2013.

  • Adipocytic Tumors
    • Atypical lipomatous tumor
    • Well-differentiated liposarcoma
    • Liposarcoma, NOS
    • Dedifferentiated liposarcoma
    • Myxoid/round cell liposarcoma
    • Pleomorphic liposarcoma
  • Fibroblastic/Myofibroplastic Tumors
    • Dermatofibrosarcoma protuberans
    • Fibrosarcomatous dermatofibrosarcoma protuberans
    • Pigmented dermatofibrosarcoma protuberans
    • Solitary fibrous tumor, malignant
    • Inflammatory myofibroblastic tumor
    • Low-grade myofibroblastic sarcoma
    • Adult fibrosarcoma
    • Myxofibrosarcoma (formerly myxoid malignant fibrous histiocytoma [myxoid MFH])
    • Low-grade fibromyxoid sarcoma
    • Sclerosing epithelioid fibrosarcoma
  • So-called Fibrohistiocytic Tumors
    • Giant cell tumor of soft tissues
  • Smooth Muscle Tumors
    • Leiomyosarcoma (excluding skin)
  • Pericytic (Perivascular) Tumors
    • Malignant glomus tumor
  • Skeletal Muscle Tumors
    • Embryonal rhabdomyosarcoma (including botryoid, anaplastic)
    • Alveolar rhabdomyosarcoma (including solid, anaplastic)
    • Pleomorphic rhabdomyosarcoma
    • Spindle cell/sclerosing rhabdomyosarcom
  • Vascular Tumors
    • Retiform hemangioendothelioma
    • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma
    • Epitheliod hemangioendothelioma
    • Angiosarcoma of soft tissues
  • Chondro-osseous Tumor
    • Extraskeletal osteosarcoma
  • Gastrointestinal Stromal Tumors
    • Gastrointestinal stromal tumor, malignant
  • Nerve Sheath Tumors
    • Malignant peripheral nerve sheath tumor
    • Epithelioid malignant peripheral nerve sheat tumor
    • Malignant Triton tumor
    • Malignant granular cell tumor
  • Tumors of Uncertain Differentiation
    • Ossifying fibromyxoid tumor, malignant
    • Myoepithelial carcinoma
    • Phosphaturic mesenchymal tumor, malignant
    • Synovial sarcoma (NOS, spindle cell, biphasic)
    • Epithelioid sarcoma
    • Alveolar soft part sarcoma
    • Clear cell sarcoma of soft tissue
    • Extraskeletal myxoid chondrosarcoma
    • Extraskeletal Ewing sarcoma
    • Desmoplastic small round cell tumor
    • Extrarenal rhabdoid tumorPerivascular epithelioid cell tumor (PEComa), NOSIntimal sarcoma
  • Undifferentiated/Unclassified Sarcoma
    • Undifferentiated (spindle cell sarcoma, pleomorphic sarcoma, round cell sarcoma, epithelioid sarcoma, NOS)

Appendix: AJCC Complete Soft Tissue Sarcoma Staging, 8th Edition, 2016

Soft Tissue Sarcoma of the Trunk and Extremities

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1

Tumor 5 cm or less in greatest dimension

T2

Tumor more than 5 cm and less than or equal to 10 cm in greatest dimension

T3

Tumor more than 10 cm and less than or equal to 15 cm in greatest dimension

T4

Tumor more than 15 cm in greatest dimension

 

Regional Lymph Nodes (N)

Description

N0

No regional lymph node metastasis or unknown lymph node status

N1

Regional lymph node metastasis

 

Distant Metastasis (M)

Description

M0

No distant metastasis

M1

Distant metastasis

 

FNCLCC Histologic Grade (G)

Description

GX

Grade cannot be assessed

G1

Total differentiation, mitotic count and necrosis score or 2 or 3

G2

Total differentiation, mitotic count and necrosis score of 4 or 5

G3

Total differentiation, mitotic count and necrosis score of 6,7,or 8

 

Anatomic Stage/Prognostic Groups

T

N

M

G

Stage IA

T1

N0

M0

G1, GX

Stage IB

T2

N0

M0

G1, GX

 

T3

N0

M0

G1, GX

 

T4

N0

M0

G1, GX

Stage II

T1

N0

M0

G2, G3

Stage IIIA

T2

N0

M0

G2, G3

Stage IIIB

T3

N0

M0

G2, G3

 

T4

N0

M0

G2, G3

Stage IV

Any T

N1

M0

Any G

 

Any T

Any N

M1

Any G

 

Soft Tissue Sarcoma of the Retroperitoneum

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1

Tumor 5 cm or less in greatest dimension

T2

Tumor more than 5 cm and less than or equal to 10 cm in greatest dimension

T3

Tumor more than 10 cm and less than or equal to 15 cm in greatest dimension

T4

Tumor more than 15 cm in greatest dimension

 

Regional Lymph Nodes (N)

Description

N0

No regional lymph node metastasis or unknown lymph node status

N1

Regional lymph node metastasis

 

Distant Metastasis (M)

Description

M0

No distant metastasis

M1

Distant metastasis

 

FNCLCC Histologic Grade (G)

Description

GX

Grade cannot be assessed

G1

Total differentiation, mitotic count and necrosis score of 2 or 3

G2

Total differentiation, mitotic count and necrosis score of 4 or 5

G3

Total differentiation, mitotic count and necrosis score of 6, 7 or 8

 

Anatomic Stage/Prognostic Groups

T

N

M

G

Stage IA

T1

N0

M0

G1, GX

Stage IB

T2

N0

M0

G1, GX

 

T3

N0

M0

G1, GX

 

T4

N0

M0

G1, GX

Stage II

T1

N0

M0

G2, G3

Stage IIIA

T2

N0

M0

G2, G3

Stage IIIB

T3

N0

M0

G2, G3

 

T4

N0

M0

G2, G3

 

Any T

N1

M0

Any G

Stage IV

Any T

Any N

M1

Any G

 

Soft Tissue Sarcoma of the Abdomen and Thoracic Visceral Organs*

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T1

Organ Confined

T2

Tumor extension into tissue beyond organ

T2a

Invades serosa or visceral peritoneum

T2b

Extension beyond serosa (mesentery)

T3

Invades another organ

T4

Multifocal involvement

T4a

Multifocal (2 sites)

T4b

Multifocal (3-5 sites)

T4c

Multifocal (>5 sites)

 

Regional Lymph Nodes (N)

Description

N0

No lymph node involvement or unknown lymph node status

N1

Lymph node involvement present

 

Distant Metastasis (M)

Description

M0

No metastasis

M1

Metastases present

 

FNCLCC Histologic Grade (G)

Description

GX

Grade cannot be assessed

G1

Total differentiation, mitotic count and necrosis score of 2 or 3

G2

Total differentiation, mitotic count and necrosis score of 4 or 5

G3

Total differentiation, mitotic count and necrosis score of 6, 7 or 8

 

Soft Tissue Sarcoma of the Head and Neck*

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T1

Tumor < 2 cm

T2

Tumor > 2 to < 4 cm

T3

Tumor > 4 cm

T4

Tumor with invasion of adjoining structures

T4a

Tumor with orbital invasion, skull base/dural invasion, invasion of central compartment viscera, involvement of facial skeleton, or invasion of pterygoid muscles

T4b

Tumor with brain parenchymal invasion, carotid artery encasement, prevertebral muscle invasions, or central nervous system involvement via perineural spread

 

Regional Lymph Nodes (N)

Description

N0

No regional lymph nodes metastasis or unknown lymph node status

N1

Regional lymph node metastasis

 

Distant Metastasis (M)

Description

M0

No distant metastasis

M1

Distant metastasis

 

Definition of Grade (G)

Description

GX

Grade cannot be assessed

G1

Total differentiation, mitotic count and necrosis score of 2 or 3

G2

Total differentiation, mitotic count and necrosis score of 4 or 5

G3

Total differentiation, mitotic count and necrosis score of 6,7, or 8

 

*Anatomic stage/prognostic groupings for Head and Neck and Abdomen and Thoracic Soft Tissue Sarcomas are being studied and are not available at this time from the AJCC.

References

SEER Statistics, Soft Tissue Sarcoma, http://seer.cancer.gov/statfacts/html/soft.html

American Cancer Society, Soft Tissue Sarcoma, http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/index

NCCN Guidelines, Soft Tissue Sarcoma (registration required), www.nccn.org

Albertsmeier, M., Rauch, A., Roeder, F., Hasenhütl, S., Pratschke, S., Kirschneck, M., ... & Belka, C. (2018). External beam radiation therapy for resectable soft tissue sarcoma: a systematic review and meta-analysis. Annals of Surgical Oncology25(3), 754-767.

Andreou, D., Werner, M., Pink, D., Traub, F., Schuler, M. K., Gosheger, G., ... & Tunn, P. U. (2015). Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma. International Journal of Hyperthermia, 1-6.

Angelini, D. E., & Chugh, R. (2015). Soft Tissue Sarcoma. Tumor Board Review: Guideline and Case Reviews in Oncology, 265.

Beane, J. D., Yang, J. C., White, D., Steinberg, S. M., Rosenberg, S. A., & Rudloff, U. (2014). Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity: 20-year follow-up of a randomized prospective trial. Annals of Surgical Oncology21(8), 2484-2489.

Brennan, M. F., Antonescu, C. R., Moraco, N., & Singer, S. (2014). Lessons learned from the study of 10,000 patients with soft tissue sarcoma. Annals of Surgery260(3), 416-21.

Canter, R. J., Borys, D., Olusanya, A., Li, C. S., Lee, L. Y., Boutin, R. D., ... & Monjazeb, A. M. (2014). Phase I trial of neoadjuvant conformal radiotherapy plus sorafenib for patients with locally advanced soft tissue sarcoma of the extremity. Annals of Surgical Oncology21(5), 1616-1623.

Eastley, N., Green, P. N., & Ashford, R. U. (2016). Soft tissue sarcoma. BMJ352, i436.

Hohenberger, P. (2018). A start towards immunotherapy in sarcomas? The Lancet Oncology 19(3), 283-285.

Italiano, A., Cesne, A., Mendiboure, J., Blay, J. Y., Piperno, Neumann, S., Chevreau, C., ... & Lae, M. (2014). Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of soft?tissue sarcoma patients in the competing risks setting. Cancer120(21), 3361-3369.

Jakob, J., Tunn, P. U., Hayes, A. J., Pilz, L. R., Nowak, K., & Hohenberger, P. (2014). Oncological outcome of primary non?metastatic soft tissue sarcoma treated by neoadjuvant isolated limb perfusion and tumor resection. Journal of Surgical Oncology109(8), 786-790.

Linch, M., Miah, A. B., Thway, K., Judson, I. R., & Benson, C. (2014). Systemic treatment of soft-tissue sarcoma [mdash] gold standard and novel therapies. Nature reviews Clinical oncology11(4), 187-202.

Maki, R. G., Moraco, N., Antonescu, C. R., Hameed, M., Pinkhasik, A., Singer, S., & Brennan, M. F. (2013). Toward better soft tissue sarcoma staging: building on American Joint Committee on Cancer staging systems versions 6 and 7. Annals of Surgical Oncology20(11), 3377-3383.

Rastrelli, M., Campana, L. G., Valpione, S., Tropea, S., Zanon, A., & Rossi, C. R. (2015). Hyperthermic isolated limb perfusion in locally advanced limb soft tissue sarcoma: A 24-year single-centre experience. International Journal of Hyperthermia, 1-8.

Skafida, E., Kokkali, S., Nikolaou, M., & Digklia, A. (2017). Metastatic soft tissue sarcoma: current treatment landscape and future perspectives. Expert Review of Anticancer Therapy17(6), 537-543.

Tiwari, A., Gupta, V. G., & Bakhshi, S. (2017). Newer medical therapies for metastatic soft tissue sarcoma. Expert Review of Anticancer Therapy17(3), 257-270.

van der Graaf, W. T., Blay, J. Y., Chawla, S. P., Kim, D. W., Bui-Nguyen, B., Casali, P. G., ... & Le Cesne, A. (2012). Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet379(9829), 1879-1886.

Von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., ... & Gonzalez, R. J. (2014). Soft tissue sarcoma, version 2.2014. Journal of the National Comprehensive Cancer Network12(4), 473-483.

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