Soft Tissue Sarcomas – Causes, Symptoms, Treatment

Soft Tissue Sarcomas (STS) are a rare and heterogeneous group of tumors, arising in connective tissues embryologically derived from the mesenchyme. There are dozens of subtypes arising from cartilage, muscle, blood vessels, nerves, and fat.^[rx] Sarcoma make up <1% of all neoplasms, which often results in a delay in diagnosis.^[rx]Sarcoma are best managed at specialist referral centers, and suspected cases are recommended to be referred promptly, allowing for further investigation and review by a multidisciplinary team (MDT). Surgery remains the mainstay of treatment, supported by advancing multimodal therapies including chemotherapy and radiotherapy. This review discusses the diagnosis and management of sarcomas, along with the clinical challenges faced in orthopedic oncology.

Soft-tissue sarcomas largely comprise tumors arising from the extraskeletal connective tissues of the body that connect, support, and surround other discrete anatomical structures. Most of these structures are derived from the embryonic mesoderm. They include muscles and tendons, fibrous tissue, fat and synovial tissue. These tumors demonstrate similarities in pathological appearance, clinical presentation and biological behaviour. Tumors that arise in Schwann cells are also included in tSoft Tissue Sarcomashe category of soft-tissue sarcoma.

Subdivisions of Soft Tissue Sarcoma

• angiosarcoma
• clear cell sarcoma
• dermatofibrosarcoma protuberans
• desmoplastic small round cell tumor
• epithelioid sarcoma
• malignant peripheral nerve sheath tumors
• myxofibrosarcoma
• rhabdomyosarcoma
• solitary fibrous tumor
• synovial sarcoma
• undifferentiated pleomorphic sarcoma

Types of Soft Tissue Sarcomas

A few entities that were found to most likely represent morphologic variants of other tumors were deleted from the current classification or subsumed into other sections.[rx]

1. Adipocytic tumors.

   1. Benign.

      • Lipoma.
      • Lipomatosis.
      • Lipomatosis of nerve.
      • Lipoblastoma/lipoblastomatosis.
      • Angiolipoma.
      • Myolipoma.
      • Chondroid lipoma.
      • Extra-renal angiomyolipoma.
      • Extra-adrenal myelolipoma.
      • Spindle cell/pleomorphic lipoma.
      • Hibernoma.

   2. Intermediate (locally aggressive).

      • Atypical lipomatous tumor/well-differentiated liposarcoma.

   3. Malignant.

      • Dedifferentiated liposarcoma.
      • Myxoid liposarcoma.
      • Pleomorphic liposarcoma.
      • Liposarcoma, not otherwise specified (NOS).

2. Chondro-osseous tumors.

   • Soft tissue chondroma.
   • Extraskeletal mesenchymal chondrosarcoma.[rx]
   • Extraskeletal osteosarcoma.

3. Fibroblastic/myofibroblastic tumors.

   1. Benign.

      • Nodular fasciitis.
      • Proliferative fasciitis.
      • Proliferative myositis.
      • Myositis ossificans.
      • Fibro-osseous pseudotumor of digits.
      • Ischemic fasciitis.
      • Elastofibroma.
      • Fibrous hamartoma of infancy.
      • Fibromatosis colli.
      • Juvenile hyaline fibromatosis.
      • Inclusion body fibromatosis.
      • Fibroma of tendon sheath.
      • Desmoplastic fibroblastoma.
      • Mammary-type myofibroblastoma.
      • Calcifying aponeurotic fibroma.
      • Angiomyofibroblastoma.
      • Cellular angiofibroma.
      • Nuchal-type fibroma.
      • Gardner fibroma.
      • Calcifying fibrous tumor.

   2. Intermediate (locally aggressive).

      • Palmar/plantar fibromatosis.
      • Desmoid-type fibromatosis (previously called desmoid tumor or aggressive fibromatoses).
      • Lipofibromatosis.
      • Giant cell fibroblastoma.
   3. Intermediate (rarely metastasizing).
      • Dermatofibrosarcoma protuberans.
      • Fibrosarcomatous dermatofibrosarcoma protuberans.
      • Pigmented dermatofibrosarcoma protuberans.
      • Solitary fibrous tumor.
      • Solitary fibrous tumor, malignant.
      • Inflammatory myofibroblastic tumor.
      • Low-grade myofibroblastic sarcoma.
      • Myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor.
      • Infantile fibrosarcoma.[rx]

   4. Malignant.

      • Adult fibrosarcoma.
      • Myxofibrosarcoma.
      • Low-grade fibromyxoid sarcoma.[rx]
      • Sclerosing epithelioid fibrosarcoma.

4. Skeletal muscle tumors.

   • Rhabdomyoma.
   • Rhabdomyosarcoma (embryonal, spindle cell/sclerosing, alveolar, and pleomorphic forms). (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.)

5. Smooth muscle tumors.

   1. Benign.

      • Deep leiomyoma.

   2. Malignant.

      • Leiomyosarcoma (excluding skin).
      Angioleiomyoma was reclassified under perivascular tumors.

6. So-called fibrohistiocytic tumors.

   1. Benign.

      • Tenosynovial giant cell tumor.
      • Localized type.
      • Diffuse type.
      • Malignant.
      • Deep benign fibrous histiocytoma.

   2. Intermediate (rarely metastasizing).

      • Plexiform fibrohistiocytic tumor.
      • Giant cell tumor of soft tissue.
      The malignant counterpart of so-called fibrohistiocytic tumors, formerly known as malignant fibrous histiocytoma and its subtypes was renamed undifferentiated sarcoma and was previously classified under the undifferentiated/unclassified sarcomas section.

7. Nerve sheath tumors.

   1. Benign.
      • Schwannoma (including variants).
      • Melanotic schwannoma.
      • Neurofibroma (including variants).
      • Plexiform neurofibroma.
      • Perineurioma.
      • Malignant perineurioma.
      • Granular cell tumor.
      • Dermal nerve sheath myxoma.
      • Solitary circumscribed neuroma.
      • Ectopic meningioma.
      • Nasal glial heterotopia.
      • Benign Triton tumor.
      • Hybrid nerve sheath tumor.

   2. Malignant.

      • Malignant peripheral nerve sheath tumor.
      • Epithelioid malignant peripheral nerve sheath tumor.
      • Malignant Triton tumor.
      • Malignant granular cell tumor.
      • Ectomesenchymoma.

8. Pericytic (perivascular) tumors.

   • Glomus tumor (and variants).
   •  Glomangiomatosis.
   • Malignant glomus tumor.
   • Myopericytoma.
   • Myofibroma (hemangiopericytoma are now included in recent WHO classification).
   •  Myofibromatosis.
   • Infantile myofibromatosis.
   • Angioleiomyoma.

9. Tumors of uncertain differentiation.

   1. Benign.

      • Acral fibromyxoma.
      • Intramuscular myxoma (including cellular variant).
      • Juxta-articular myxoma.
      • Deep (aggressive) angiomyxoma.
      • Pleomorphic hyalinizing angiectatic tumor.
      • Ectopic hamartomatous thymoma.

   2. Intermediate (locally aggressive).

      • Hemosiderotic fibrolipomatous tumor.
   3. Intermediate (rarely metastasizing).
      • Atypical fibroxanthoma.
      • Angiomatoid fibrous histiocytoma.
      • Ossifying fibromyxoid tumor.
      • Ossifying fibromyxoid tumor, malignant.
      • Mixed tumor NOS.
      • Mixed tumor NOS, malignant.
      • Myoepithelioma.
      • Myoepithelial carcinoma.
      • Phosphaturic mesenchymal tumor, benign.
      • Phosphaturic mesenchymal tumor, malignant.
   4. Malignant.
      • Synovial sarcoma NOS.
      • Synovial sarcoma, spindle cell.
      • Synovial sarcoma, biphasic.
      • Epithelioid sarcoma.
      • Alveolar soft part sarcoma.
      • Clear cell sarcoma of soft tissue.
      • Extraskeletal myxoid chondrosarcoma.
      • Extraskeletal Ewing sarcoma. (Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)
      • Desmoplastic small round cell tumor.
      • Extra-renal rhabdoid tumor.
      • Neoplasms with perivascular epithelioid cell differentiation (PEComa).
      • PEComa NOS, benign.
      • PEComa NOS, malignant.
      • Intimal sarcoma.

10. Undifferentiated/unclassified sarcomas.

    • Undifferentiated spindle cell sarcoma.
    • Undifferentiated pleomorphic sarcoma.
    • Undifferentiated round cell sarcoma.
    • Undifferentiated epithelioid sarcoma.
    • Undifferentiated sarcoma NOS.[rx]

    Genetic subgroups are emerging within this family and this work is ongoing:

    • Undifferentiated round cell and spindle cell sarcoma.
    • Undifferentiated pleomorphic sarcoma.

11. Vascular tumors.

    1. Benign.
       • Hemangioma. (Refer to the PDQ summary on Childhood Vascular Tumors Treatment for more information.)
       •  Synovial.
       •  Venous.
       • Arteriovenous hemangioma/malformation.
       • Intramuscular.
       • Epithelioid hemangioma.
       • Angiomatosis.
       • Lymphangioma.

    2. Intermediate (locally aggressive).

       • Kaposiform hemangioendothelioma.

    3. Intermediate (rarely metastasizing).

       • Retiform hemangioendothelioma.
       • Papillary intralymphatic hemangioendothelioma.
       • Composite hemangioendothelioma.
       • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma.
       • Kaposi sarcoma.

    4. Malignant.

       • Epithelioid hemangioendothelioma.
       • Angiosarcoma of the soft tissue.

The World Health Organization lists the following cell types in its classification of soft tissue sarcomas:[rx,rx]

• Adipocytic tumors.
• Atypical lipomatous tumor.
• Well-differentiated liposarcoma.
• Liposarcoma, not otherwise specified.
• Dedifferentiated liposarcoma.
• Myxoid/round cell liposarcoma.
• Pleomorphic liposarcoma.
• Fibroblastic/myofibroblastic tumors.
• Dermatofibrosarcoma protuberans.
• Fibrosarcomatous dermatofibrosarcoma protuberans.
• Pigmented dermofibrosarcoma protuberans.
• Solitary fibrous tumor, malignant.
• Inflammatory myofibroblastic tumor.
• Low-grade myofibroblastic sarcoma.
• Adult fibrosarcoma.
•  Myxofibrosarcoma.
• 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 rhabdomyosarcoma.
• Vascular tumors of soft tissue.
• Retiform hemangioendothelioma.
• Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma.
• Epithelioid hemangioendothelioma.
• Angiosarcoma of soft tissue.
• Chondro-osseous tumors.
• Extraskeletal osteosarcoma.
• Nerve sheath tumors.
  • Malignant peripheral nerve sheath tumor.
  • Epithelioid malignant peripheral nerve sheath tumor.
  • Malignant Triton tumor.
  • Malignant granular cell tumor.

Causes of Soft Tissue Sarcomas

• A genetic predisposition – clearly exists in a minority of these tumors, such as Gardner’s syndrome. Retinoblastoma is also associated with osteosarcomas, and this fact has led to the discovery that many sarcomas display structural defects of the RBI gene. Multiple endocrine neoplasia 2B syndrome includes ganglioneuromas, and patients with neurofibromatosis, or von Recklinghausen’s disease, carry a 7% to 10% lifetime risk of developing malignant neurofibrosarcoma. Li-Fraumeni cancer family syndrome includes an increased susceptibility to a variety of sarcomas. Many patients with Li-Fraumeni syndrome have a defect in the p53 gene, and this tumor suppressor gene is defective in some types of sarcoma as well [rx].
• Ionizing radiation – is associated with sarcoma and acts as both a tumor initiator and a promoter. Of the radiation-induced sarcomas, approximately 70% are malignant fibrous histiocytoma, which tends to be an aggressive type of tumor. The latency period is 7 to 25 years, and these patients typically have a poor prognosis. In one series of 53 patients, a 5-year survival rate of 26% was reported [rx].
• Chemical carcinogens – have been reported to be etiologic agents. Although the effects of these carcinogens are much better described in experimental animals, the best human example is probably the dioxin-containing herbicide TDCC, or Agent Orange, a defoliant that was widely used in the Vietnam War. Agent Orange was implicated to such an extent that the Department of Veterans Affairs has agreed to compensate veterans who were exposed to it and developed sarcomas. Follow-up studies on the subject have yielded mixed results. Collins and coworkers found no causal relationship between dioxin exposure in factory workers and the incidence of sarcoma[rx]. However, Fingerhut et al [rx and Suruda et al [rx]demonstrated a significant increase in the risk of death from sarcoma among exposed factory workers.
  Immunologic factors – are implicated as well. Immunosuppression is associated with an increased risk of all kinds of neoplasms, typically those that are epithelial in origin (e.g., squamous cell carcinoma of the skin) and lymphomas. Sarcomas, however, also have been described.
• Viral factors – are clearly at play. In 1911, Peyton Rous demonstrated a transmissible avian sarcoma virus, named the Rous virus, and later won the Nobel Prize for this discovery. HIV is probably the best-known example in humans, being implicated in Kaposi’s sarcoma. It is unclear, however, whether Kaposi’s sarcoma is caused by the virus alone or by a combination of viral effect and immunologic suppression (probably the latter).
• Other environmental factors are also to blame – The link between mesothelioma and asbestos is well known, as is the link between Stewart-Treves syndrome (postmastectomy lymphangiosarcoma) and long-standing lymphedema of the extremities. Interestingly, a risk of lymphangiosarcoma exists after mastectomy and radiation therapy even when the upper extremity appears grossly normal, and the tumor may not be in the irradiated field.

The link between foreign bodies and sarcoma has been described since the 1880s and has been well studied in rats. Rare human cases have also been described, involving surgical implants, plastic, bullets, surgical sponges, bone wax, or Teflon-Dacron prostheses. The largest study was done by Engel and colleagues, who looked at the rate of sarcoma in thousands of women with breast implants but did not find a statistically significant increase [rx].

Risk Factors

Some genetic factors and external exposures have been associated with the development of nonrhabdomyosarcomatous soft tissue sarcoma, including the following:

Genetic factors

• Li-Fraumeni syndrome – Patients with Li-Fraumeni syndrome (usually due to heritable cancer-associated changes of the TP53 tumor suppressor gene) have an increased risk of developing soft tissue tumors (mostly nonrhabdomyosarcomatous soft tissue sarcomas), bone sarcomas, breast cancer, brain tumors, and acute leukemia.[rx,rx]
• Familial adenomatous polyposis – Patients with familial adenomatous polyposis are at increased risk of developing desmoid-type fibromatosis.[rx]
• RB1 gene – Germline mutations of the RB1 gene have been associated with an increased risk of developing soft tissue sarcoma, particularly leiomyosarcoma, and the risk appears higher among those younger than 1 year who were treated with alkylating agents.[rx,rx]
• SMARCB1 gene – Germline mutations or deletions of the SMARCB1 (INI1) gene are associated with an increased risk of developing extrarenal rhabdoid tumors.[rx]
• Neurofibromatosis type 1 – Approximately 4% of patients with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors, which usually develop after a long latency; some patients develop multiple lesions.[rx–rxrx]
• Werner syndrome – Werner syndrome is characterized by spontaneous chromosomal instability, resulting in increased susceptibility to cancer and premature aging. An excess of soft tissue sarcomas has been reported in patients with Werner syndrome.[rx]
• Tuberous sclerosis complex – Tuberous sclerosis complex is associated with the development of various tumors showing perivascular epithelioid cell differentiation (PEComas), including lymphangioleiomyomatosis and hepatic and renal angiomyolipomas.[rx–rx]
• Adenosine deaminase-deficient severe combined immunodeficiency – Patients with adenosine deaminase-deficient severe combined immunodeficiency have been reported to be at increased risk of developing multicentric dermatofibrosarcoma protuberans, which usually presents at an average age of 8.9 years.[rx]

External exposures

• Radiation – Some nonrhabdomyosarcomatous soft tissue sarcomas (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site.[rx,rx–rx]
• Epstein-Barr virus infection in patients with AIDS – Some nonrhabdomyosarcomatous soft tissue sarcomas (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with AIDS.[rx,rx]

Symptoms of Soft Tissue Sarcomas

The soft tissue sarcomas commonly present as a painless, slow-growing mass. While sarcomas in the extremities may present earlier, the diagnosis of sarcomas involving the pelvic cavity may be delayed as their location deep within the body precludes palpation of the tumor mass early in the course of the disease. Consequently, these tumors often attain large size prior to diagnosis without causing overt symptoms. Any soft tissue lump exhibiting any of the following four clinical features should be considered to be malignant until proved otherwise: (i) increasing in size, (ii) size >5 cm, (iii) location deep to the deep fascia, or (iv) pain. The more the number of these clinical features present, the greater the risk of malignancy, with increasing size being the best individual indicator.^[rx]

• swelling under the skin may cause a painless lump that cannot easily be moved around and gets bigger over time
• swelling in the tummy (abdomen) may cause abdominal pain, a persistent feeling of fullness and constipation
• swelling near the lungs may cause a cough or breathlessness

Early-stage symptoms

In their early stages soft tissue sarcomas do not usually cause symptoms. As sarcomas can grow anywhere in the body, the symptoms will depend on where the cancer is. The main symptoms can include:

• a lump that’s painless at first
• pain or soreness as the lump grows and presses against nerves and muscles

Lumps

You should see your doctor if you have an unexplained lump. Many people get lumps and bumps and most of them will not be cancer. But its best to get it checked.

A lump is more likely to be a sarcoma if it:

• is big (for example, more than 5 cm across) or getting bigger
• is deep in the body tissues
• is painful
• occurs when you are older
• has come back after previous surgery to remove sarcoma

Diagnosis of Soft Tissue Sarcomas

When a suspicious lesion is identified, it is crucial that a complete workup, followed by adequate biopsy be performed. The lesion is imaged before initiating any intervention using the following procedures:

• Physical exam and health history – An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Chest x-ray – An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. Plain films can be used to rule out bone involvement and detect calcifications that may be seen in soft tissue tumors such as extraskeletal osteosarcoma or synovial sarcoma.
• Blood chemistry studies – A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.

• Complete blood count (CBC) – A procedure in which a sample of blood is drawn and checked for the following:

  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made up of red blood cells.
• CT scan (CAT scan) – A procedure that makes a series of detailed pictures of areas inside of the body, such as the lung and abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging) – A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• PET scan (positron emission tomography scan) – A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Chest computed tomography (CT) – Chest CT is essential to assess the presence of metastases.
• Abdominal CT or magnetic resonance imaging (MRI) – Abdominal CT or MRI can be used to image intra-abdominal tumors, such as liposarcoma.
• Extremity MRI – MRI is essential for extremity lesions.
• Positron emission tomography (PET) scan and bone scan.
  Immunohistochemistry – A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Light and electron microscopy – A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
• Cytogenetic analysis – A laboratory test in which the chromosomes of cells in a sample of tissue are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• FISH (fluorescence in situ hybridization) – A laboratory test used to look at and count genes or chromosomes in cells and tissues. Pieces of DNA that contain fluorescent dyes are made in the laboratory and added to a sample of a patient’s cells or tissues. When these dyed pieces of DNA attach to certain genes or areas of chromosomes in the sample, they light up when viewed under a fluorescent microscope. The FISH test is used to help diagnose cancer and help plan treatment.
• Flow cytometry – A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of the cells, such as size, shape, and the presence of tumor (or other) markers on the cell surface. The cells from a sample of a patient’s blood, bone marrow, or other tissue are stained with a fluorescent dye, placed in a fluid, and then passed one at a time through a beam of light. The test results are based on how the cells that were stained with the fluorescent dye react to the beam of light.
• Biopsy – If your doctor thinks you may have a soft tissue sarcoma, a biopsy will be done. The type of biopsy will be based on the size of the tumor and where it is in the body. There are three types of biopsy that may be used:
  • Incisional biopsy: The removal of part of a lump or a sample of tissue.
  • Core biopsy: The removal of tissue using a wide needle.
  • Excisional biopsy: The removal of an entire lump or area of tissue that doesn’t look normal.

  Samples will be taken from the primary tumor, lymph nodes, and other suspicious areas. A pathologist views the tissue under a microscope to look for cancer cells and to find out the grade of the tumor. The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the cells are dividing. High-grade tumors usually grow and spread more quickly than low-grade tumors.

• Ultrasound scan – Ultrasound scan (USS) is commonly used for the investigation of superficial STS. It is readily accessible and is used to confirm the presence and evaluate the size and depth of a soft-tissue mass. USS may play a role in guidance for the core-biopsy sampling of superficial masses. However, if a malignancy is suspected, then magnetic resonance imaging (MRI) and computed tomography (CT) scans are required prior to biopsy sampling, allowing for assessment and staging to be completed using images that have not yet been altered by the intervention.^[rx] A note of caution – beware the chronic hematoma as USS can also be misinterpreted with a common USS misdiagnosis being chronic hematoma, which can lead to erroneous care.
• Immunohistochemistry – A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Light and electron microscopy – A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
• Cytogenetic analysis – A laboratory test in which the chromosomes of cells in a sample of tissue are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• FISH (fluorescence in situ hybridization) – A laboratory test used to look at and count genes or chromosomes in cells and tissues. Pieces of DNA that contain fluorescent dyes are made in the laboratory and added to a sample of a patient’s cells or tissues. When these dyed pieces of DNA attach to certain genes or areas of chromosomes in the sample, they light up when viewed under a fluorescent microscope. The FISH test is used to help diagnose cancer and help plan treatment.
• Flow cytometry – A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of the cells, such as size, shape, and the presence of tumor (or other) markers on the cell surface. The cells from a sample of a patient’s blood, bone marrow, or other tissue are stained with a fluorescent dye, placed in a fluid, and then passed one at a time through a beam of light. The test results are based on how the cells that were stained with the fluorescent dye react to the beam of light.

Treatment of Soft Tissue Sarcomas

Surgery

Surgery is the most common treatment for adult soft tissue sarcoma. For some soft-tissue sarcomas, removal of the tumor in surgery may be the only treatment needed. The following surgical procedures may be used:

Mohs microsurgery – A procedure in which the tumor is cut from the skin in thin layers. During surgery, the edges of the tumor and each layer of tumor removed are viewed through a microscope to check for cancer cells. Layers continue to be removed until no more cancer cells are seen. This type of surgery removes as little normal tissue as possible and is often used where appearance is important, such as on the skin.

• Mohs surgery – A surgical procedure to remove a visible lesion on the skin in several steps. First, a thin layer of cancerous tissue is removed. Then, a second thin layer of tissue is removed and viewed under a microscope to check for cancer cells. More layers are removed one at a time until the tissue viewed under a microscope shows no remaining cancer. This type of surgery is used to remove as little normal tissue as possible.
• Wide local excision – Removal of the tumor along with some normal tissue around it. For tumors of the head, neck, abdomen, and trunk, as little normal tissue as possible is removed.
• Limb-sparing surgery – Removal of the tumor in an arm or leg without amputation, so the use and appearance of the limb is saved. Radiation therapy or chemotherapy may be given first to shrink the tumor. The tumor is then removed in a wide local excision. Tissue and bone that are removed may be replaced with a graft using tissue and bone taken from another part of the patient’s body, or with an implant such as artificial bone.
• Amputation – Surgery to remove part or all of a limb or appendage, such as an arm or leg. Amputation is rarely used to treat soft tissue sarcoma of the arm or leg.
• Lymphadenectomy – A surgical procedure in which lymph nodes are removed and a sample of tissue is checked under a microscope for signs of cancer. This procedure is also called a lymph node dissection.

The grade of the tumor is also used to describe the cancer and plan treatment.

The grade of the tumor describes how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Low grade, mid grade, and high grade are used to describe soft tissue sarcoma:

• Low grade – In low-grade soft tissue sarcoma, the cancer cells look more like normal cells under a microscope and grow and spread more slowly than in mid-grade and high-grade soft tissue sarcoma.
• Mid-grade – In mid-grade soft tissue sarcoma, the cancer cells look more abnormal under a microscope and grow and spread more quickly than in low-grade soft tissue sarcoma.
• High grade – In high-grade soft tissue sarcoma, the cancer cells look more abnormal under a microscope and grow and spread more quickly than in low-grade and mid-grade soft tissue sarcoma.

For adult soft tissue sarcoma of the trunk, arms, and legs, the following stages are used:

Stage I

Stage I adult soft tissue sarcoma of the trunk, arms, and legs is divided into stages IA and IB:

• In stage IA, the tumor is 5 centimeters or smaller and is low grade or the grade is unknown.
• In stage IB, the tumor is larger than 5 centimeters and is low grade or the grade is unknown.

Stage II

In stage II adult soft tissue sarcoma of the trunk, arms, and legs, the tumor is 5 centimeters or smaller and is mid grade or high grade.

Stage III

Stage III adult soft tissue sarcoma of the trunk, arms, and legs is divided into stages IIIA and IIIB:

• In stage IIIA, the tumor is larger than 5 centimeters but not larger than 10 centimeters and is mid grade or high grade.
• In stage IIIB, the tumor is larger than 10 centimeters and is mid grade or high grade.

Stage IV

In stage IV adult soft tissue sarcoma of the trunk, arms, and legs, one of the following is found:

• the tumor is any size, any grade, and has spread to nearby lymph nodes; or
• the tumor is any size, any grade, and may have spread to nearby lymph nodes. Cancer has spread to other parts of the body, such as the lung.

For adult soft tissue sarcoma of the retroperitoneum, the following stages are used:

Stage I

Stage I adult soft tissue sarcoma of the retroperitoneum is divided into stages IA and IB:

• In stage IA, the tumor is 5 centimeters or smaller and is low grade or the grade is unknown.
• In stage IB, the tumor is larger than 5 centimeters and is low grade or the grade is unknown.

Stage II

In stage II adult soft tissue sarcoma of the retroperitoneum, the tumor is 5 centimeters or smaller and is mid grade or high grade.

Stage III

Stage III adult soft tissue sarcoma of the retroperitoneum is divided into stages IIIA and IIIB:

• In stage IIIA, the tumor is larger than 5 centimeters but not larger than 10 centimeters and is mid grade or high grade.
• In stage IIIB, one of the following is found:
  • the tumor is larger than 10 centimeters and is mid grade or high grade; or
  • the tumor is any size, any grade, and has spread to nearby lymph nodes.

Stage IV

In stage IV adult soft tissue sarcoma of the retroperitoneum, the tumor is any size, any grade, and may have spread to nearby lymph nodes. Cancer has spread to other parts of the body, such as the lung.

References

• https://www.ncbi.nlm.nih.gov/books/NBK65773/
• https://www.ncbi.nlm.nih.gov/books/NBK66046/
• https://www.ncbi.nlm.nih.gov/books/NBK534839/
• https://www.ncbi.nlm.nih.gov/books/NBK532911/
• https://www.ncbi.nlm.nih.gov/books/NBK538426/
• https://www.ncbi.nlm.nih.gov/books/NBK65923/
• https://www.ncbi.nlm.nih.gov/books/NBK66045/
• https://www.ncbi.nlm.nih.gov/books/NBK551667/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791230/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347369/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955018/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134013/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200782/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529718/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353406/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837937/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699380/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699380/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113522/
• https://www.ncbi.nlm.nih.gov/books/NBK6952/
• https://www.nhs.uk/conditions/soft-tissue-sarcoma/
• https://en.wikipedia.org/wiki/Soft-tissue_sarcoma
• https://rarediseases.org/rare-diseases/soft-tissue-sarcoma/

Show More