Sarcoma: Types, Symptoms & Treatment Guide

What Is Sarcoma and How Does It Develop?

Sarcoma is a rare type of cancer that originates in the body's connective tissues, including bones, muscles, fat, blood vessels, nerves, tendons, and cartilage. Unlike carcinomas (which arise from epithelial cells), sarcomas develop from mesenchymal cells and can occur anywhere in the body. There are over 70 distinct subtypes, broadly categorized as soft tissue sarcomas and bone sarcomas.

The term "sarcoma" comes from the Greek word "sarx" meaning flesh, reflecting these cancers' origin in the body's supportive and connective tissues. These tissues, collectively called mesenchymal or stromal tissues, form the structural framework of the body and include the skeleton, muscles, fat, and blood vessels. When cells in these tissues undergo malignant transformation, they can develop into sarcomas.

Understanding sarcoma requires recognizing its fundamental difference from more common cancers. While breast cancer, lung cancer, and colon cancer arise from epithelial cells that line organs and body surfaces, sarcomas originate from the mesodermal layer of embryonic development. This distinct cellular origin influences how sarcomas behave, spread, and respond to treatment.

Sarcomas are relatively rare, accounting for approximately 1% of all adult cancers but representing about 15% of childhood cancers. In the United States, approximately 13,000 new soft tissue sarcomas and 3,600 bone sarcomas are diagnosed annually. Despite their rarity, sarcomas represent a significant clinical challenge due to their diverse subtypes, variable locations, and the specialized expertise required for optimal treatment.

The development of sarcoma, like other cancers, involves genetic mutations that cause cells to grow uncontrollably. Some sarcomas are associated with specific genetic alterations that can now be detected through molecular testing, helping guide treatment decisions. These mutations may be inherited (as in Li-Fraumeni syndrome) or acquired during a person's lifetime due to various factors including previous radiation exposure.

Why Sarcomas Are Different from Other Cancers

Several characteristics distinguish sarcomas from more common epithelial cancers (carcinomas). Sarcomas typically spread through the bloodstream rather than the lymphatic system, which is why they most commonly metastasize to the lungs rather than lymph nodes. This pattern influences staging systems, treatment approaches, and surveillance strategies.

Sarcomas also tend to grow along tissue planes and can infiltrate surrounding structures, making surgical planning complex. The goal of surgery is complete removal with adequate margins of normal tissue, which requires specialized expertise. Inadequate initial surgery significantly impacts long-term outcomes, emphasizing the importance of treatment at specialized sarcoma centers.

What Are the Different Types of Sarcoma?

Sarcomas are broadly divided into soft tissue sarcomas (developing in muscles, fat, blood vessels, and nerves) and bone sarcomas (developing in bone and cartilage). Soft tissue sarcomas include over 50 subtypes such as liposarcoma, leiomyosarcoma, and rhabdomyosarcoma. Bone sarcomas include osteosarcoma, Ewing sarcoma, and chondrosarcoma, each with distinct characteristics and treatment approaches.

The classification of sarcomas has evolved significantly with advances in molecular pathology. The 2020 WHO Classification of Tumours of Soft Tissue and Bone recognizes over 70 distinct sarcoma subtypes, each with specific histological features, molecular characteristics, and clinical behaviors. This detailed classification is crucial because different sarcoma types may require fundamentally different treatment strategies.

Soft Tissue Sarcomas

Soft tissue sarcomas arise from non-bony connective tissues and represent the larger category of sarcomas. They can develop virtually anywhere in the body but most commonly occur in the extremities (arms and legs), followed by the trunk and retroperitoneum (the space behind the abdominal organs). The behavior and prognosis of soft tissue sarcomas vary dramatically based on the specific subtype, grade, size, and location.

Common types of soft tissue sarcomas include:

• Liposarcoma: Arises from fat cells and is among the most common soft tissue sarcomas in adults. Subtypes range from well-differentiated (low grade, good prognosis) to dedifferentiated and pleomorphic (high grade, more aggressive).
• Leiomyosarcoma: Develops from smooth muscle cells, commonly occurring in the uterus, retroperitoneum, or blood vessels. It represents about 15-25% of soft tissue sarcomas.
• Undifferentiated pleomorphic sarcoma (UPS): Previously called malignant fibrous histiocytoma, this is a high-grade sarcoma without a specific line of differentiation.
• Synovial sarcoma: Despite its name, it doesn't arise from synovial tissue. It commonly affects young adults and is characterized by a specific genetic translocation.
• Rhabdomyosarcoma: The most common soft tissue sarcoma in children, arising from skeletal muscle precursor cells. It has several subtypes including embryonal and alveolar forms.
• Gastrointestinal stromal tumor (GIST): Arises from specialized cells in the digestive tract wall. GISTs are notable for responding to targeted therapy with tyrosine kinase inhibitors like imatinib.
• Angiosarcoma: A rare, aggressive sarcoma arising from blood vessel or lymphatic vessel cells. It can develop in any location but has associations with prior radiation and chronic lymphedema.

Bone Sarcomas

Bone sarcomas, also called primary bone cancers, arise directly from bone or cartilage tissue. They are distinct from cancer that has spread to bone from another site (bone metastases), which is far more common but not classified as bone cancer. Bone sarcomas tend to occur at specific ages and in specific locations, which helps guide diagnosis.

The main types of bone sarcomas include:

• Osteosarcoma: The most common primary bone cancer, typically affecting adolescents and young adults during periods of rapid bone growth. It most commonly occurs around the knee (distal femur, proximal tibia) and in the upper arm (proximal humerus). A second peak occurs in adults over 60, often associated with Paget's disease.
• Ewing sarcoma: The second most common bone cancer in children and adolescents, characterized by a specific genetic translocation (EWSR1-FLI1 in most cases). It can also occur in soft tissues (extraosseous Ewing sarcoma). It responds to chemotherapy and radiation in addition to surgery.
• Chondrosarcoma: Arises from cartilage cells and typically affects adults, with increasing incidence after age 40. It ranges from low-grade (slow-growing, good prognosis) to high-grade (aggressive). Unlike other bone sarcomas, chondrosarcoma is typically resistant to chemotherapy and radiation, making surgery the primary treatment.

What Are the Symptoms of Sarcoma?

The most common symptom of sarcoma is a painless lump or mass that grows over weeks to months. For soft tissue sarcomas, this typically appears in the arms, legs, or abdomen. Bone sarcomas often cause deep, persistent bone pain that may worsen at night or with activity. Other symptoms include swelling, limited range of motion, abdominal discomfort, and in some cases, pathological fractures.

Sarcoma symptoms vary significantly depending on the tumor's location, size, and type. Many sarcomas are discovered incidentally during imaging for other reasons, while others present with symptoms that prompt medical evaluation. Understanding the warning signs is crucial for early detection, which significantly impacts treatment outcomes.

The insidious nature of sarcomas often leads to diagnostic delays. Soft tissue sarcomas, in particular, may grow for months before causing noticeable symptoms because they often develop deep in the muscle tissue. By the time they become palpable, they may already be quite large. Healthcare providers and patients alike should maintain a high index of suspicion for any growing mass, particularly those larger than 5 cm or located deep to the muscle fascia.

Symptoms of Soft Tissue Sarcoma

Soft tissue sarcomas most commonly present as a painless mass that progressively enlarges. The characteristics that should raise concern include:

• Growing lump: A mass that increases in size over weeks to months, particularly if larger than 5 cm (about the size of a golf ball)
• Deep location: Masses located deep to the muscle fascia are more concerning than superficial lumps
• Pain or tenderness: While often painless initially, larger tumors may cause pain as they compress surrounding structures
• Limited movement: Tumors near joints may restrict range of motion
• Neurological symptoms: Numbness, tingling, or weakness if the tumor affects nearby nerves

Retroperitoneal sarcomas (those growing behind the abdominal organs) may present differently, with symptoms including abdominal fullness, early satiety, back pain, or symptoms related to compression of nearby organs. These tumors can grow very large before causing symptoms, sometimes reaching 20 cm or more before detection.

Symptoms of Bone Sarcoma

Bone sarcomas typically present with symptoms distinct from soft tissue sarcomas:

• Bone pain: Deep, persistent pain in a bone that may initially be attributed to injury or "growing pains." The pain often worsens at night and may not respond to typical pain relievers.
• Swelling: Visible or palpable swelling over the affected bone, which may develop weeks after pain begins
• Pathological fracture: In some cases, the first sign is a fracture from minimal trauma, occurring because the tumor has weakened the bone
• Limping: Changes in gait if the tumor affects the lower extremity
• Limited joint movement: Stiffness or decreased range of motion near the affected area

What Causes Sarcoma and Who Is at Risk?

In most cases, the exact cause of sarcoma is unknown. However, identified risk factors include previous radiation therapy, certain genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis, familial adenomatous polyposis), chronic lymphedema, and exposure to certain chemicals. Most sarcomas occur sporadically without identifiable risk factors, making prevention challenging.

Unlike some cancers with well-established lifestyle risk factors (such as smoking for lung cancer), most sarcomas develop without clear preventable causes. This makes prevention difficult but underscores the importance of awareness, early detection, and prompt evaluation of suspicious symptoms.

Research into sarcoma causes has identified several factors that increase risk, though most patients diagnosed with sarcoma have none of these risk factors. The sporadic nature of most sarcomas highlights the role of random genetic mutations that accumulate over time or occur during cell division.

Known Risk Factors

• Previous radiation therapy: Radiation-induced sarcomas can develop years or decades after radiation treatment for other cancers. The risk increases with higher radiation doses and longer follow-up periods. These typically occur within the radiation field and are often high-grade tumors.
• Genetic syndromes:
  • Li-Fraumeni syndrome: Caused by TP53 gene mutations, significantly increases lifetime risk of sarcomas and other cancers
  • Neurofibromatosis type 1: Associated with malignant peripheral nerve sheath tumors (MPNST)
  • Familial adenomatous polyposis: Increases risk of desmoid tumors
  • Retinoblastoma: Survivors have increased osteosarcoma risk
• Chronic lymphedema: Long-standing lymphedema, particularly following breast cancer treatment, is associated with lymphangiosarcoma (Stewart-Treves syndrome)
• Chemical exposures: Historical exposure to certain chemicals including vinyl chloride (linked to hepatic angiosarcoma) and some herbicides
• Viral infections: Human herpesvirus 8 (HHV-8) is associated with Kaposi sarcoma, particularly in immunocompromised individuals
• Bone conditions: Paget's disease of bone and bone infarcts may predispose to osteosarcoma development

Age and Sarcoma Risk

Different sarcoma types show distinct age patterns. Osteosarcoma and Ewing sarcoma most commonly affect children, adolescents, and young adults, with osteosarcoma showing a second peak in older adults. Soft tissue sarcomas can occur at any age but become more common with advancing age, with about half of cases occurring in people over 60. Rhabdomyosarcoma primarily affects young children, while chondrosarcoma typically develops in middle-aged and older adults.

How Is Sarcoma Diagnosed?

Sarcoma diagnosis requires a systematic approach including imaging studies (MRI for soft tissue tumors, X-ray and CT for bone tumors) followed by biopsy for definitive diagnosis. Core needle biopsy or surgical biopsy provides tissue for pathological examination, which determines the exact sarcoma subtype through histology, immunohistochemistry, and molecular testing. Staging studies evaluate whether the cancer has spread.

Accurate diagnosis of sarcoma is fundamental to treatment planning and prognosis. Given the rarity and diversity of sarcomas, diagnosis should ideally be performed at or in consultation with specialized sarcoma centers with experienced pathologists. Misdiagnosis or incorrect subtyping can lead to inappropriate treatment with potentially serious consequences.

The diagnostic process typically begins when a patient presents with symptoms or when an abnormality is found incidentally on imaging. A careful clinical history and physical examination guide initial evaluation, followed by imaging studies and ultimately biopsy for tissue diagnosis.

Imaging Studies

Different imaging modalities serve specific purposes in sarcoma evaluation:

• X-ray: Often the first study for bone lesions, showing characteristic patterns that may suggest specific diagnoses
• MRI (Magnetic Resonance Imaging): The preferred imaging modality for soft tissue tumors, providing excellent soft tissue contrast and demonstrating the tumor's relationship to surrounding structures
• CT (Computed Tomography): Useful for bone tumors, evaluating cortical destruction, and staging (particularly chest CT for lung metastases)
• PET scan: May help assess tumor activity, staging, and monitoring treatment response in some sarcomas
• Bone scan: Can detect bone involvement and metastases in bone sarcomas

Biopsy: The Essential Step

Biopsy is absolutely essential for sarcoma diagnosis—treatment should never be initiated based on imaging alone. The biopsy provides tissue for pathological examination, which determines the exact tumor type and guides treatment decisions.

Core needle biopsy is the preferred approach for most suspected sarcomas. Performed under image guidance (ultrasound or CT), it provides tissue cores for analysis while minimizing disruption to surrounding tissues. The biopsy tract must be carefully planned so it can be removed during subsequent surgery.

Incisional biopsy (surgical removal of a portion of the tumor) may be necessary when core needle biopsy is insufficient or technically difficult. Open biopsies should be performed by surgeons experienced in sarcoma surgery, as poorly placed incisions can compromise subsequent definitive surgery.

Pathological examination includes standard histology (examining tissue under the microscope), immunohistochemistry (using antibodies to identify specific proteins), and increasingly, molecular testing to identify characteristic genetic alterations. Many sarcomas have specific translocations or mutations that aid diagnosis and may predict response to targeted therapies.

Staging

Once sarcoma is diagnosed, staging determines the extent of disease and guides treatment planning. Staging typically includes:

• Assessment of tumor size and local extent
• Chest CT to evaluate for lung metastases (the most common site of spread)
• Additional imaging as indicated by specific sarcoma type
• Assessment of tumor grade (how abnormal cells appear under microscope)

How Is Sarcoma Treated?

Sarcoma treatment is highly individualized based on tumor type, location, size, grade, and stage. Surgery is the cornerstone of treatment for localized sarcomas, aiming for complete removal with adequate margins. Radiation therapy is commonly used for soft tissue sarcomas. Chemotherapy is standard for bone sarcomas (osteosarcoma, Ewing sarcoma) and some high-risk soft tissue sarcomas. Targeted therapies benefit specific subtypes like GIST.

Effective sarcoma treatment requires a multidisciplinary approach involving oncologic surgeons, medical oncologists, radiation oncologists, pathologists, and radiologists working together. Treatment at specialized sarcoma centers improves outcomes due to greater experience and access to clinical trials testing new treatments.

The treatment approach varies significantly based on sarcoma type, illustrating why accurate diagnosis is so critical. What works for one sarcoma type may be ineffective or even inappropriate for another. Treatment plans must be individualized based on the specific circumstances of each case.

Surgery

Surgical resection remains the primary treatment for most localized sarcomas. The goal is complete tumor removal with adequate margins of normal tissue—a concept called "wide excision" or "R0 resection." Achieving adequate margins while preserving function requires specialized surgical expertise.

Key principles of sarcoma surgery include:

• Wide margins: Removing tumor with a cuff of normal tissue to reduce local recurrence risk
• Limb-sparing surgery: Modern surgical techniques often allow tumor removal while preserving the limb, avoiding amputation in most cases
• Reconstruction: When significant tissue removal is necessary, reconstructive procedures (skin grafts, muscle flaps, prostheses) may restore function
• Biopsy tract removal: The biopsy tract should be included in the surgical specimen

Amputation is rarely necessary today but may be required when limb-sparing surgery cannot achieve adequate margins or would result in a non-functional limb. When amputation is necessary, prosthetic rehabilitation can help restore mobility and function.

Radiation Therapy

Radiation therapy plays an important role in soft tissue sarcoma treatment, typically used in combination with surgery to reduce local recurrence risk. Radiation may be given before surgery (neoadjuvant), after surgery (adjuvant), or in some cases, both.

Preoperative radiation advantages include smaller treatment volumes and lower doses, but increases wound healing complications. Postoperative radiation allows for pathological assessment before radiation but requires larger treatment fields and higher doses.

For bone sarcomas, radiation sensitivity varies by type. Ewing sarcoma is radiation-sensitive, and radiation therapy is an important treatment component. Osteosarcoma and chondrosarcoma are generally radiation-resistant, so radiation plays a limited role in these diseases.

Chemotherapy

The role of chemotherapy varies dramatically among sarcoma types:

Bone sarcomas: Chemotherapy is a standard component of treatment for osteosarcoma and Ewing sarcoma. For osteosarcoma, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy has significantly improved survival. Ewing sarcoma is highly chemosensitive, and intensive multiagent chemotherapy is essential.

Soft tissue sarcomas: The role of chemotherapy is more limited. It may be considered for high-grade tumors at high risk of metastasis, large tumors, or certain chemosensitive subtypes like rhabdomyosarcoma and synovial sarcoma. For many soft tissue sarcomas, the benefit of adjuvant chemotherapy remains uncertain.

Chemotherapy regimens typically include doxorubicin (often the most active single agent) and ifosfamide. Specific regimens vary based on sarcoma type and treatment setting (neoadjuvant, adjuvant, or metastatic disease).

Targeted Therapy

Advances in understanding sarcoma biology have led to effective targeted therapies for specific subtypes:

• GIST: Tyrosine kinase inhibitors (imatinib, sunitinib, regorafenib) have transformed GIST treatment by blocking specific molecular pathways driving tumor growth
• Dermatofibrosarcoma protuberans: Imatinib is effective due to a characteristic PDGFB translocation
• Other sarcomas: Pazopanib is approved for certain soft tissue sarcomas, and clinical trials continue to evaluate new targeted agents

What Is the Prognosis for Sarcoma?

Sarcoma prognosis varies significantly based on type, grade, size, location, and stage at diagnosis. For localized soft tissue sarcomas treated with appropriate surgery, 5-year survival rates exceed 80%. Bone sarcomas (osteosarcoma, Ewing sarcoma) have 5-year survival rates of 60-70% for localized disease. Metastatic sarcoma has lower survival rates but long-term survival is possible for selected patients.

Predicting outcomes for individual patients is challenging due to the diversity of sarcoma types and the many factors influencing prognosis. Statistical survival rates describe populations, not individuals, and individual outcomes can vary significantly from average expectations.

Key prognostic factors include:

• Tumor grade: Higher-grade tumors are more aggressive with higher metastatic risk
• Size: Larger tumors (especially >5 cm) have worse prognosis
• Location: Deep tumors and certain locations (retroperitoneum) have higher recurrence rates
• Resection margins: Complete surgical removal with clear margins improves outcomes
• Stage: Localized disease has much better prognosis than metastatic disease
• Histological subtype: Different sarcoma types have different inherent prognoses
• Response to chemotherapy: For bone sarcomas, response to neoadjuvant chemotherapy predicts outcome

Long-term Follow-up

After treatment, regular follow-up is essential to monitor for recurrence. Follow-up typically includes physical examinations and imaging studies at regular intervals. The intensity and duration of surveillance depend on the specific sarcoma type and risk level.

For children and adolescents treated for sarcoma, long-term follow-up extends into adulthood to monitor for late effects of treatment, including potential cardiac effects from chemotherapy, radiation-related complications, and second cancers. Specialized survivorship programs help address these long-term needs.

What Happens If Sarcoma Returns?

Sarcoma can recur locally (at or near the original site) or as distant metastases (most commonly in the lungs). Local recurrences may be treated with surgery, sometimes combined with radiation. Pulmonary metastases from sarcoma can sometimes be surgically removed (metastasectomy) with potential for long-term survival. Treatment options for recurrent sarcoma include surgery, radiation, chemotherapy, and clinical trials.

The management of recurrent sarcoma requires careful multidisciplinary evaluation. Treatment decisions depend on the location and extent of recurrence, prior treatments, time since initial treatment, and the patient's overall condition. Even with recurrence, many patients can achieve meaningful disease control or cure.

Local recurrence occurs when sarcoma returns at or near the original tumor site. This is more common with inadequate surgical margins, high-grade tumors, or certain sarcoma types. Treatment typically involves surgery, often combined with radiation if not previously given.

Metastatic disease most commonly involves the lungs for most sarcoma types. Surgical removal of lung metastases (pulmonary metastasectomy) can result in long-term survival or cure for selected patients with limited metastatic disease, favorable histology, and adequate pulmonary reserve. This highlights the importance of surveillance imaging to detect metastases early when they may still be resectable.

How Does Sarcoma Affect Daily Life?

The impact of sarcoma on daily life depends on the tumor location, treatment required, and individual circumstances. Many patients successfully return to normal activities after treatment. Rehabilitation may be needed after surgery, particularly for limb sarcomas. Physical therapy helps restore function and strength. Psychological support addresses the emotional aspects of cancer diagnosis and treatment.

Sarcoma and its treatment inevitably impact patients' lives, but the extent varies greatly. Some patients with small, easily resected tumors experience minimal long-term effects, while others face more significant challenges. Comprehensive care addresses physical, emotional, and practical needs throughout the cancer journey.

Physical Rehabilitation

Physical rehabilitation is particularly important after surgery for extremity sarcomas. Physical and occupational therapists help patients regain strength, mobility, and function. For patients who require limb amputation, prosthetic rehabilitation enables return to many activities.

Emotional Support

Cancer diagnosis brings emotional challenges including fear, anxiety, and uncertainty. Professional counseling, support groups, and peer connections help patients and families cope. Sarcoma patient organizations provide valuable resources and connections with others facing similar challenges.

Fatigue Management

Cancer-related fatigue is common during and after treatment. Regular physical activity, adapted to individual capabilities, helps manage fatigue. Rest is important but prolonged inactivity can worsen fatigue. Energy conservation strategies and prioritizing activities help patients manage daily life.

Fertility Considerations

Chemotherapy and radiation can affect fertility. Patients of reproductive age should discuss fertility preservation options before treatment begins. Options include sperm banking for males and egg or embryo freezing for females. Pediatric patients may also have fertility preservation options that should be discussed with their oncology team.