fbpx

Soft tissue sarcoma

Updated : February 23, 2024





Background

Soft tissue sarcoma are tumors that affect individuals of any age and originate from any body part. These tumors range in clinical presentation from benign lipomas to aggressive metastatic angiosarcomas.

They can affect skeletal muscle, blood, lymphatic system, adipose tissue, peripheral nerves, and connective tissue.

Epidemiology

Soft tissue sarcomas are rare, with 4740 fatalities and 12,020 new cases reported in the United States. They estimate about 1% of all cancer incidence and 2% of cancer-related fatalities in the United States.

In terms of the extremities, tumors occur more commonly in the proximal limb, particularly the thigh accounting for 44% of occurrences. Trunk sarcomas occur more frequently than retroperitoneal and intraperitoneal sarcomas.

Anatomy

Pathophysiology

Sarcomas are connective tissue tumors; thus, they develop in bone, cartilage, fat, muscle, or vascular or hematopoietic tissues. Sarcomas are substantially less common than carcinomas.

Most develop locally and infect neighboring tissues. Most patients report a hard mass or discomfort caused by pressure on adjacent nerves and soft tissues.

Etiology

There are several factors causative factors.

  • Radiation

The effects of radiation are dose-dependent and often occur near the radiation field’s periphery. Disease-specific survival is shorter as compared to spontaneous alternatives. Children acquire soft tissue sarcoma after radiation at 11.8 years later on average and in a dose-dependent manner.

  • Carcinogens

Patients exposed to Thorotrast, a thorium-IV-based contrast in the period 1930 to 1955, developed hepatic angiosarcoma after 20 to 30 years.

  • Von Recklinghausen Disease

Mutations in the NF1 gene, which codes for a protein known as neurofibromin, cause the autosomal dominant disorder.

Ras oncogene signaling pathway tumor suppressor

Multiple cutaneous neurofibromas are caused by mutations in the NF1 gene.

Genetics

Prognostic Factors

Curative excision for circumscribed and early-stage lesions is possible with acceptable long-term endurance; however, recurrences are prevalent. The risk of recurrence exists even after 10 to 15 years, and patients should be monitored for a prolonged time.

Most recurrences occur within the first five years of treatment. A cure is not achievable for patients with a severe condition, and the median survival time ranges from 12 to 18 months, based on the subtype.

Chemotherapy has a minimal response rate of about 10% to 50%. The response is also affected by the grade and histological subtype.

Clinical History

Age Group: 

  • Although they can happen to anyone at any age, adults are more likely to be diagnosed with soft tissue sarcomas. 
  • In the fifth and sixth decades of life, the incidence peaks. 

Associated Comorbidities or Activity: 

  • Soft tissue sarcomas can arise spontaneously or may be associated with certain genetic conditions, such as neurofibromatosis type 1 (NF1) or Li-Fraumeni syndrome. 
  • There is often no clear association with specific comorbidities, but some subtypes may be related to prior radiation therapy, exposure to certain chemicals, or genetic predisposition. 
  • Some soft tissue sarcomas may occur in areas of previous trauma or injury, but this is not a consistent finding. 

Acuity of Presentation: 

  • Soft tissue sarcomas often present as painless, enlarging masses or lumps. 
  • The growth of the tumor may be gradual, and patients may not seek medical attention until the tumor becomes large or causes symptoms. 
  • In some cases, there may be pain or tenderness associated with the mass, especially if it impinges on nerves or other structures. 
  • Superficial soft tissue sarcomas may present as a palpable mass, while deeper-seated tumors may not be evident until they reach a significant size. 

Physical Examination

Inspection: 

  • Skin Changes: Look for any skin changes overlying the mass, such as erythema, ulceration, or signs of inflammation. 
  • Surface Characteristics: Note the surface characteristics of the mass, including its size, shape, color, and any visible veins. 

Palpation: 

  • Texture and Consistency: Assess the texture and consistency of the mass. Soft tissue sarcomas are often firm or rubbery, and the consistency may vary. 
  • Tenderness: Check for tenderness, as soft tissue sarcomas are usually painless but may become tender as they grow and compress surrounding structures. 
  • Mobility: Evaluate the mobility of the mass in relation to underlying structures and surrounding tissues. 

Measurement: 

  • Size: Measure the dimensions of the mass, including length, width, and depth. This information is crucial for staging and monitoring changes over time. 

Regional Lymph Nodes: 

  • Palpate Lymph Nodes: Examine regional lymph nodes for enlargement or tenderness, which may suggest spread of the tumor. 

Neurological Examination: 

  • If the soft tissue sarcoma is located near nerves, assess neurological function in the affected area. Look for signs of nerve compression, such as weakness, sensory changes, or loss of function. 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Benign Soft Tissue Lesions: 

  • Lipoma: A common benign tumor composed of fat cells. It is usually soft and mobile. 
  • Fibroma: A benign tumor composed of fibrous tissue. 
  • Hemangioma: A vascular tumor that can present as a soft, compressible mass. 
  • Neurofibroma: Associated with neurofibromatosis, it is a benign nerve sheath tumor. 
  • Ganglion Cyst: A cystic lesion often arising from a joint or tendon sheath. 

Inflammatory Lesions: 

  • Abscess: A collection of pus, which may present as a painful, fluctuant mass. 
  • Cellulitis: Localized edema and erythema can result from cutaneous and subcutaneous tissue infections. 
  • Granuloma: A nodular inflammatory lesion that may occur in response to foreign material or infection. 

Other Malignant Tumors: 

  • Metastatic Tumors: Tumors that have spread to soft tissues from other primary sites, such as lung, breast, or kidney. 
  • Synovial Sarcoma: Another type of soft tissue sarcoma that often affects the extremities. 
  • Rhabdomyosarcoma: A malignant tumor arising from skeletal muscle, more commonly seen in children. 

Infectious Lesions: 

  • Soft Tissue Tuberculosis: Mycobacterial infection can mimic a soft tissue mass. 
  • Fungal Infections: Certain fungal infections can present as soft tissue masses. 

Pseudotumors: 

  • Pseudotumor or Pseudoaneurysm: False aneurysms or localized collections of blood may mimic soft tissue masses. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Surgery: 

  • Wide Local Excision: The mainstay of treatment for localized soft tissue sarcomas is surgical resection. To limit the chance of local recurrence, surgeons opt for a large area of excision with negative margins. 
  • Limb-Sparing Surgery: Whenever possible, limb-sparing surgery is preferred over amputation, preserving function and quality of life. Reconstruction techniques may be employed to maintain optimal function and appearance. 
  • Sentinel Lymph Node Biopsy: In select cases, particularly for high-grade tumors, sentinel lymph node biopsy may be performed to assess the risk of regional lymph node involvement. 

Radiation Therapy: 

  • Adjuvant Radiation: Adjuvant radiation treatment may be indicated after surgery to lower the chance of local recurrence, particularly if clear surgical margins are difficult to achieve or the tumor is large. 
  • Neoadjuvant Radiation: In some cases, radiation therapy may be administered before surgery (neoadjuvant) to shrink the tumor and facilitate a less extensive surgical resection. 

Systemic Therapy: 

  • Chemotherapy: Systemic chemotherapy may be considered for certain types of soft tissue sarcomas, particularly high-grade or metastatic tumors. It is often used in the adjuvant or neoadjuvant setting. 
  • Targeted Therapy: Some subtypes of soft tissue sarcoma may benefit from targeted therapies, which are designed to specifically target certain molecules involved in tumor growth. Examples include tyrosine kinase inhibitors. 
  • Immunotherapy: For some soft tissue sarcomas, immunotherapy may be studied in clinical trials with the goal of boosting the immune system’s capacity to identify and combat cancer cells. 

Follow-up and Surveillance: 

  • Frequent follow-up appointments are crucial to managing any side effects after therapy, keeping an eye out for recurrences, and attending to the patient’s general wellbeing. 
  • Periodically, imaging tests like CT or MRIs can be carried out to look for any indications of metastasis or recurrence. 

Clinical Trials: 

  • Clinical trial participation may be taken into consideration, particularly in patients that are advanced or refractory. Clinical trials aid in the assessment of novel therapeutics and treatment modalities. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of a non-pharmacological approach for treating Soft tissue Sarcoma

Surgery and Rehabilitation: 

  • Physical Therapy: Physical therapy is crucial to optimize function and mobility, especially after surgery. Strength, range of motion, and general physical health can all be enhanced by it. 
  • Occupational Therapy: Occupational therapists can assist in addressing challenges related to daily activities, providing adaptive strategies and devices as needed. 

Psychosocial Support: 

  • Counseling and Support Groups: Dealing with a soft tissue sarcoma diagnosis can be emotionally challenging. Psychotherapy, support groups, and counseling can help people deal with the psychological effects and offer emotional support. 
  • Mind-Body Techniques: Relaxation methods, mindfulness, and meditation are a few practices that can assist lower stress and enhance general wellbeing. 

Nutritional Support: 

  • Dietary Guidance: Proper nutrition is essential during and after treatment.  

Pain Management: 

  • Physical Modalities: Physical modalities such as heat, cold, massage, or acupuncture may contribute to pain management and enhance comfort. These approaches should be discussed with the healthcare team to ensure safety and appropriateness. 

Complementary Therapies: 

  • Acupuncture: Some individuals find relief from symptoms such as pain, nausea, or fatigue through acupuncture. 
  • Yoga and Exercise: Gentle forms of exercise, such as yoga, may help improve flexibility, reduce stress, and enhance overall well-being. Health care professionals should supervise exercise regimens and customize them to each person’s skills. 

Symptom Management: 

  • Lymphedema Management: For individuals at risk of or experiencing lymphedema after surgery, proper management and education on techniques to reduce swelling can be beneficial. 
  • Fatigue Management: Strategies to manage cancer-related fatigue may include energy conservation, sleep hygiene, and incorporating rest breaks into daily routines. 

Alternative Therapies: 

  • Art Therapy or Music Therapy: During treatment, creative arts treatments can offer a way for patients to express themselves and let go of their emotions. 

Use of chemotherapy in the treatment of soft tissue sarcoma

It plays a major role in the treatment of soft tissue sarcoma (STS), particularly in certain situations where systemic therapy is indicated. The decision to use chemotherapy is based on factors such as the histological subtype of the sarcoma, stage, grade, and whether the tumor has spread beyond the primary site.  

Adjuvant Chemotherapy: 

  • To lower the chance of recurrence, adjuvant chemotherapy is given following the main tumor’s surgical excision. 
  • It is typically considered for high-grade soft tissue sarcomas and cases where there is a higher risk of microscopic residual disease after surgery. 
  • The intention is to eradicate any cancer cells that may still be present and stop distant metastases from growing. 

Neoadjuvant Chemotherapy: 

  • Neoadjuvant chemotherapy is given before surgery and is aimed at shrinking the tumor to facilitate a more manageable surgical resection. 
  • It may be considered in cases where the tumor is large or the location makes surgery challenging. 

Atezolizumab: It is an immune checkpoint inhibitor. It makes it possible for the immune system to identify and combat the tumor by targeting the cancer cells’ programmed death-ligand 1 (PD-L1). It is used in certain cases of advanced or metastatic soft tissue sarcoma, particularly when the cancer has not responded to other treatment. 

Dactinomycin: It is an anthracycline antibiotic that interferes with the DNA synthesis of cancer cells, preventing their replication. It is used in the treatment of various cancers, including soft tissue sarcomas. It is often part of combination chemotherapy regimens. 

Doxorubicin Hydrochloride: It is also an anthracycline antibiotic with a mechanism similar to dactinomycin. It intercalates with DNA, inhibiting its synthesis and causing DNA damage. It is a commonly used chemotherapy drug for soft tissue sarcomas. It can be used alone or in combination with other agents. 

Eribulin Mesylate: It is a microtubule inhibitor that disrupts the microtubule dynamics, leading to cell cycle arrest and cell death. It is indicated for the treatment of advanced or metastatic liposarcoma, a subtype of soft tissue sarcoma. 

Imatinib Mesylate:It is a tyrosine kinase inhibitor that targets specific proteins involved in the growth and division of cancer cells, including those associated with certain types of sarcomas. 

Use of Targeted Therapy in the treatment of Soft tissue sarcoma

Targeted therapy has emerged as a valuable treatment approach for certain subtypes of soft tissue sarcoma (STS). In contrast to conventional chemotherapy, which affects cells that divide quickly, targeted therapies are made to specifically target the chemicals or pathways that are necessary for cancer cells to proliferate and survive. The use of targeted therapy in the treatment of soft tissue sarcoma aims to improve outcomes while minimizing damage to normal, healthy tissues. 

Tyrosine Kinase Inhibitors (TKIs): 

  • Imatinib (Gleevec): Imatinib is a tyrosine kinase inhibitor that targets the activity of specific proteins involved in the abnormal growth of cancer cells. It is used primarily in the treatment of gastrointestinal stromal tumors (GISTs), which are a type of soft tissue sarcoma. 
  • Sunitinib (Sutent): Sunitinib is another TKI that may be used for the treatment of advanced GISTs. 

mTOR Inhibitors: 

  • Sirolimus (Rapamune) and Everolimus (Afinitor): These drugs belong to the class of mTOR inhibitors. They interfere with the mammalian target of rapamycin (mTOR) pathway, inhibiting cell growth and proliferation. Sirolimus, in the form of sirolimus protein-bound particles (Fyarro), is specifically used for advanced or metastatic soft tissue sarcoma. 

PD-1/PD-L1 Inhibitors: 

  • Atezolizumab (Tecentriq): Atezolizumab is an immune checkpoint inhibitor that targets the programmed death-ligand 1 (PD-L1) on cancer cells. It is used in certain cases of advanced or metastatic soft tissue sarcoma, particularly when the cancer has not responded to other treatments. 

Histone Deacetylase (HDAC) Inhibitors: 

  • Romidepsin (Istodax): Romidepsin is an HDAC inhibitor that may be considered for the treatment of certain subtypes of soft tissue sarcoma. 

Angiogenesis Inhibitors: 

  • Pazopanib (Votrient) and Axitinib (Inlyta): These are tyrosine kinase inhibitors that also have anti-angiogenic properties. They can be used in the treatment of advanced soft tissue sarcomas. 

Use of Immunotherapy in the treatment of Soft tissue sarcoma

For soft-tissue (STS) subtypes, immunotherapy has shown promise as a treatment option, especially when other options may not be as successful. Immunotherapy works by harnessing the body’s immune system to recognize and attack cancer cells. Immunotherapy represents a groundbreaking cancer treatment method that leverages the body’s immune system to combat the disease. Substances either produced by the body or synthesized in a laboratory are employed to enhance, guide, or restore the body’s innate defenses against cancer. 

One specific form of immunotherapy is immune checkpoint inhibitor therapy. Within the immune system, certain cells, such as T cells, and some cancer cells possess proteins known as checkpoint proteins on their surface. These proteins play a major role in regulating immune responses, preventing them from becoming excessively strong and sometimes impeding T cells from effectively eliminating cancer cells.  

There are distinct types of immune checkpoint inhibitor therapy: 

CTLA-4 Inhibitor Therapy: 

  • It is a protein located on the T cells surface that helps regulate the body’s immune responses. When the CTLA-4 binds to another protein B7 on a cancer cell, it hinders the T cell’s ability to eliminate the cancer cell. 

Ipilimumab:It is a CTLA-4 inhibitor, is under study for its potential application in treating soft tissue sarcoma. 

PD-1 and PD-L1 Inhibitor Therapy: 

  • PD-1 is a protein present on the surface of T cells, contributing to the moderation of immune responses. PD-L1, found on certain cancer cells, interacts with PD-1 and impedes the T cell’s capacity to eradicate the cancer cell. 
  • PD-1 and PD-L1 inhibitors prevent the binding of PD-1 and PD-L1 proteins, allowing T cells to target and eliminate cancer cells more effectively. 

Pembrolizumab and nivolumab: Both PD-1 inhibitors, are utilized in the treatment of progressive and recurrent soft tissue sarcoma. 

Use of Intervention with a procedure in treating Soft tissue sarcoma

Biopsy: 

  • It is a crucial diagnostic procedure aimed at confirming the presence of soft tissue sarcoma, determining its specific histological subtype, and assessing its grade. 
  • Tissue samples are obtained from the tumor site using either percutaneous needle biopsy or surgical biopsy, providing essential material for laboratory analysis. 
  • Biopsy results serve as the foundation for treatment planning, guiding clinicians in determining the most appropriate therapeutic approach based on the tumor’s characteristics and behavior. 

Imaging-guided Biopsy: 

  • Imaging-guided biopsy is employed when tumors are deep-seated or challenging to access directly. Techniques such as computed tomography (CT) or ultrasound-guided biopsy help obtain samples for diagnosis and molecular testing. 
  • Imaging technologies guide the biopsy needle precisely to the tumor site, ensuring accurate and targeted sample collection. 
  • This minimally invasive method facilitates the acquisition of tissue samples in a precise manner, contributing to an accurate diagnosis and molecular characterization of the tumor. 

Preoperative Embolization: 

  • Preoperative embolization is performed to decrease tumor vascularity and reduce intraoperative bleeding, particularly in large or highly vascular soft tissue sarcomas. 
  • Embolic agents are injected into the blood vessels supplying the tumor, blocking blood flow and preparing the tumor for safer surgical removal. 
  • By minimizing intraoperative bleeding, preoperative embolization enhances the safety and efficacy of surgical resection, while also improving the visualization of tumor margins. 

Radiofrequency Ablation (RFA) and Microwave Ablation: 

  • RFA and microwave ablation are local ablative techniques employed to destroy tumor tissue, especially in cases where small, localized soft tissue sarcomas are present, or surgery is not a viable option. 
  • A probe is inserted into the tumor, delivering heat energy to eliminate cancer cells and achieve local tumor control. 
  • Providing a minimally invasive alternative, these techniques are often used in conjunction with other treatments to target and eliminate cancer cells effectively. 

Cryotherapy: 

  •  Cryotherapy involves freezing cancer cells, inducing cell death and tissue destruction, particularly applicable to small and accessible soft tissue sarcomas. 
  • Cryoprobes are inserted into the tumor, and substances like liquid nitrogen or argon gas are circulated to freeze and destroy the tumor tissue. 
  • Offering a minimally invasive approach, cryotherapy provides effective local tumor control while preserving surrounding healthy tissues. 

Percutaneous Ablation: 

  • Percutaneous ablation techniques, including RFA, microwave ablation, and cryotherapy, are utilized to treat metastatic soft tissue sarcomas or recurrent tumors. 
  • Similar to primary tumor ablation, these techniques are performed percutaneously under image guidance for precise targeting. 
  • This minimally invasive option contributes to local tumor control, particularly in cases where surgery is not a feasible option. 

Palliative Procedures: 

  • Palliative procedures, such as tumor debulking or drainage of symptomatic fluid collections, are performed to reduce the symptoms and enhance the quality of life in individuals with advanced or metastatic soft tissue sarcomas. 
  • These procedures aim to reduce tumor burden or manage symptoms such as pain or fluid accumulation, focusing on improving the patient’s comfort. 
  • Providing symptomatic relief and supportive care, palliative procedures play an important role in addressing the needs of patients with advanced disease. 

Use of phases in managing Soft tissue sarcoma

Diagnosis and Staging: 

  • Diagnosis: Accurate diagnosis is crucial and often involves a biopsy to identify the type of soft tissue sarcoma. 
  • Staging: Determining the extent of the disease helps in planning the appropriate treatment. Staging may involve imaging studies such as MRI, CT scans, and sometimes PET scans. 

Multidisciplinary Team Consultation: 

  • Specialists including medical oncologists, radiation oncologists,surgeons, and pathologists, collaborates to discuss the best treatment options for the patient. 

Surgery: 

  • Resection: Surgery is often the primary treatment, aiming to remove the tumor with clear margins. In some cases, this might involve limb-sparing surgery or amputation, depending on the tumor location and size. 

Radiation Therapy: 

  • Adjuvant Radiation: Administered in order to eliminate the possibility of a local recurrence and to target any cancer cells that may still be present after surgery. 
  • Neoadjuvant Radiation: Administered before surgery to shrink tumors and facilitate surgical removal. 

Chemotherapy: 

  • Neoadjuvant or Adjuvant Chemotherapy: Used to shrink tumors before surgery or target any potential metastases after surgery. 

Targeted Therapy: