Soft Tissue Sarcoma : Causes, Risk Factors

Soft tissue sarcoma can arise from any anatomical site and affect both young and elderly. Soft tissue sarcoma originates from the following types of tissues-

• Skeletal muscle
• Adipose cells
• Blood and lymphatic vessels
• Connective tissues
• Peripheral nerves
• Cells with common mesodermal origin

Soft tissue sarcoma arising from Adipose cells is called liposarcoma.

Soft tissue sarcoma arising from Blood and lymphatic vessels is called angiosarcoma. Chondro-osseous origin is seen in osteosarcoma. Myofibroblastic origin is seen in myxofibrosarcoma. Smooth muscle origin is seen in leiomyosarcoma. Extremity and trunk soft tissue sarcoma are more common than intraperitoneal and retroperitoneal soft tissue sarcoma. In extremities, the lower limb is more commonly affected than the upper limb, and the proximal part is more commonly involved than the distal part. The most commonly affected site in the extremities is the thighs. Rhabdomyosarcoma, hemangioma, neurofibroma, and alveolar sarcoma mainly affect children and young adults.

The most common type of pediatric soft tissue sarcoma is Rhabdomyosarcoma.

Causes of Soft Tissue Sarcoma

Most of the soft tissue sarcoma occurs sporadically. Other well-documented causes of soft-tissue sarcoma include:

• Germline mutations- Neurofibromatosis 1, Li Fraumeni syndrome, Familial adenomatous polyposis (FAP), Gardner’s syndrome.
• Radiation exposure
• Environmental exposure.

Risk Factors Of Soft Tissue Sarcoma:

Radiation: Increases the risk of soft tissue sarcoma. The effect of radiation is dose-dependent. Typically, radiation-induced soft tissue sarcoma occurs at the periphery of the radiation field. Types of soft tissue sarcoma associated with prior radiation exposure are

• Unclassified pleomorphic sarcoma
• Angiosarcoma
• Leiomyosarcoma
• Fibrosarcoma
• Malignant peripheral nerve sheath tumors

These radiation-induced soft tissue sarcomas have shorter disease-specific survival rates than the sporadic forms of these subtypes. Lower doses of radiation can increase the risk of soft tissue sarcoma in pediatric patients.

Other carcinogens that increase the risk are Thorotrast (Increases the risk of angiosarcoma, cholangiocarcinoma, and hepatic fibrosis), Arsenic, and Polyvinyl chloride. These three increase the risk of hepatic angiosarcomas.

To read more about the taxonomy of soft tissue sarcoma and some other important facts about soft tissue sarcoma, sign up for the SS Surgery course on PrepLadder. 

Pathology of Soft Tissue Sarcoma

Soft tissue sarcoma tends to grow along the fascial planes, compressing surrounding tissue and forming the pseudo capsule. The clinical behavior of soft tissue sarcoma is determined by its Anatomical location (depth), Grade, and Size. The most common route of spread is hematogenous. The most common site of metastasis is the lungs, but lymphatic metastasis is rare.

Clinical Features of Soft Tissue Sarcoma

The most common symptom is painless mass. Size at presentation is dependent on the location of the tumor. Smaller tumors are located in the distal extremities. Larger tumors are detected at the proximal extremity (especially in the thigh) and in the retroperitoneum. Retroperitoneal soft tissue sarcoma presents as a large asymptomatic mass.

Diagnosis of Soft Tissue Sarcoma

• Investigations done in soft tissue sarcoma are tru-cut biopsy or Core-cut biopsy. These are usually done USG or CT-guided and are diagnostic investigations.
• FNAC is done to confirm or to rule out a metastatic focus or local recurrence.
• MRI is an investigation of choice to assess the extent of extremity soft tissue sarcoma
• CECT is an investigation of choice to assess the extent of retroperitoneal soft tissue sarcoma.

Clinical Evaluation of Soft Tissue Sarcoma

The most common clinical presentation is a painless mass, which is the most common type of soft tissue sarcoma. The size of the mass at the time of presentation depends on the location of the tumor. So, small superficial and mobile masses are highly suggestive of soft tissue sarcoma (separate from the skeletal and neurovascular structure); such patients can be directly taken to the operation for resections with wide gross margins. If tumors are present close to the vital structures, these patients must be referred to centers with expertise in treating soft tissue sarcoma. In such patients, a pre-operative biopsy is not required. 

Additional oncology staging is needed if the lesions are larger and more complicated. 

Indications of Pre-operative Imaging and biopsy in Soft Tissue Sarcoma

Inability to determine the extent of mass on physical examination and to check for Suspected neurovascular involvement. Suspicion for regional or distant metastasis also requires imaging. Need for the operation that results in significant functional deficits

MRI is the most informative imaging modality for trunk and extremity soft tissue sarcoma. Chest CT scan is the most common site of metastasis in lung soft tissue sarcoma. CT ABD and Pelvis are done in patients having aggressive histological types such as myxoid or round cell sarcoma,  epithelioid sarcoma, angiosarcoma, or leiomyosarcoma. 

Brain Imaging is considered to exclude metastasis from the following: Alveolar soft part sarcoma, Clear cell sarcoma, and Angiosarcoma.  FNAC is mainly used in the diagnosis of local reference.

The investigation of choice for reliable diagnosis is core cut/true cut biopsy, which is an image-guided core needle biopsy. However, sometimes, the biopsy is not diagnostic when the patient has large cystic lesions or lesions with considerable myxoid trauma. Furthermore, the entire needle trajectory must be incorporated into the forthcoming surgery to decrease the risks of local recurrence. 

When the core needle biopsy is non-diagnostic, opt for an incisional biopsy. In up to 74% of patients who have undergone trunk or unplanned sarcoma resection, there is a residual disease at the time of reresection. 

Postoperative surveillance is important for soft tissue sarcoma as there is a considerable risk of recurrence.

Physical examination is needed every 3-6 months for 2-3 years, every 6 months for the next 2 years, and then annually. Radiographic surveillance of the chest, abdomen, and pelvis should be done at regular intervals. CT and MRI should be individualized based on tumor characteristics and patient. Patients with closed surgical margins and ominous histological types require shorter imaging frequencies. 

For soft tissue sarcoma patients, history and physical examination are first considered. CT and MRI are performed at the primary site. This is followed by a core needle biopsy. If the biopsy is non-diagnostic, an incisional biopsy is performed. The biopsy is based on histological type, size, grade, and patient age.  There are two types: low-grade soft tissue sarcoma and high-grade soft tissue sarcoma. 

• In low grade, the functional sparing complete excision is done. Suppose there are negative margins, and no adjuvant therapy is needed. Suppose there is a microscopic positive margin; postoperative IMRT (intensity-modulated radiotherapy) is done if the recurrence results in significant functional loss. 
• In high-grade soft tissue sarcoma like Ewing or Rhabdo, pre-operative chemotherapy is considered. Furthermore, if the tumor size is up to 5 cm, function-sparing complete excision is done. If the size is more than 5 cm and less than 10 cm, pre-operative chemotherapy is considered in patients with synovial sarcoma or Round cell sarcoma/ pleomorphic liposarcoma. If the size is more than 10 cm, pre-operative chemotherapy is done in all patients. 

Functional sparing complete excision is done only if the margin is more than or equal to 1 cm. If the size of the tumor is less than or equal to 5 cm, adjuvant therapy is recommended.  If the size of the tumor is between  5 cm and 10 cm, perioperative BRT or perioperative IMRT is considered.  If the size of the tumor is greater than or equal to 10 cm, IMRT is considered.  If the margin is less than or equal to 1 cm or microscopically positive -

• If the size of the tumor is less than or equal to 5 cm, perioperative BRT or perioperative  IMRT. 
• If the size of the tumor is between  5 cm and 10 cm, perioperative BRT or perioperative IMRT is considered. 
• If the size of the tumor is greater than or equal to 10  cm, postoperative IMRT is considered. 

Treatment of Soft Tissue Sarcoma

• Adequate excision + adjuvant radiotherapy +/- adjuvant chemotherapy, depending upon the type, is the treatment option for soft tissue sarcoma.
• The two most active chemotherapy agents are doxorubicin and ifosfamide.

Sarcomas with lymph node metastasis are Malignant fibrous osteosarcoma, Angiosarcoma, Rhabdomyosarcoma, Clear cell sarcoma, Epithelioid sarcoma, and Synovial sarcoma.

Advantages of Delivery of neoadjuvant radiation for STS

• Before surgical resection, target tissue oxygenation is superior, and the radiation field includes a smaller volume of adjacent non-tumor tissue than the radiation field after surgical resection.
• If radiation is delivered pre-operatively, patients would be predicted to complete all therapy components more promptly.
• The neoadjuvant radiotherapy rarely results in measurable tumor shrinkage, but it may cause histological tumor necrosis.
• Complete pathologic response after neoadjuvant therapy is an important prognostic factor for breast cancer, esophageal cancer, and rectal cancer.
• For example, if a patient has a positive margin after preoperative radiotherapy, then there is no significant reduction in local recurrence after the administration of a postoperative radiation boost.

Regional Chemotherapy For Locally Advanced Extremity Soft Tissue Tumor (limb Perfusion)

• It is commonly used in the treatment of locally advanced melanoma.
• It involves the placement of intravenous and intraarterial catheters.
• It is positioned within the affected limb proximal to the tumor.
• A combination of limb vasculature and intravascular catheters completes a circuit, and hyperthermic chemotherapy is circulated via this circuit.
• A tourniquet is applied proximal to the tip of the catheters. It separates the limb circulation from the systemic circulation to minimize systemic chemo-toxicity.
• The most commonly used perfusion agents are melphalan, TNF-alpha, and IFN-gamma.

Important predictors of metastases in Soft Tissue Sarcoma

• The most important predictor is tumor grade.
• Other predictors include tumor size, bone or neurovascular involvement, and tumor depth.
• The most common site of metastases is Lungs.
• For example, If a patient has isolated pulmonary metastasis, it should be resected if feasible.
• In the absence of effective systemic therapy, repeated pulmonary metastasectomy is recommended.
• Most STS are chemo-resistant. Exceptions are angiosarcoma and synovial sarcoma.

Prognosis  of Soft Tissue Sarcoma

The best prognostic factor for soft tissue sarcoma is tumor grade. The best prognosis is seen in extremity soft tissue sarcoma. Most common cause of death is metastasis. The 5-year survival rate for soft tissue sarcoma is 50-60%.

Also Read: What Are Tumor Markers And Their Role

Frequently Asked Questions:

Q: What is the Soft tissue sarcoma arising from Adipose cells known as?

Answer: Liposarcoma.

Q: What is the Soft tissue sarcoma arising from Blood and lymphatic vessels called?

Answer: Angiosarcoma. 

Q: What is the most important predictor of metastasis in soft tissue Sarcoma?

Answer: Tumor grade.

Q: What is the Best prognostic factor od soft tissue sarcoma?

Answer: Tumor Grade 

Hope you found this blog helpful for your NEET SS Surgery Oncology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.