Soft Tissue Sarcoma: Symptoms, Types, Causes and Treatment

Soft tissue sarcomas (STS) are an uncommon, complex group of cancers that develop from connective tissues such as fat, muscle, nerves, and blood vessels. Their rarity, combined with a broad diversity of subtypes and symptoms, can make them challenging to recognize and treat. In this article, we guide you through their symptoms, major types, underlying causes, and the current landscape of treatment options—empowering you to better understand this rare but significant disease.

Symptoms of Soft Tissue Sarcoma

Soft tissue sarcomas rarely cause symptoms in their early stages, which is why they often go unnoticed until they grow larger or spread. However, being aware of the possible warning signs can help with early detection and improve outcomes. Symptoms largely depend on the tumor’s location and size, but some hallmark signs have been identified by clinical guidelines and studies.

Symptom	Typical Presentation	Notable Details	References
Lump/Mass	Painless, enlarging bump	>5 cm, deep-seated, or rapidly growing	2 4 7
Pain	Aching or tenderness	More common if tumor compresses nerves/tissue	1 3 7
Swelling	Localized edema	Can be mistaken for benign conditions	2 4
Functional Issues	Difficulty moving, swallowing, breathing	Depends on anatomical site	3 7
Systemic Symptoms	Fatigue, weight loss	Usually in advanced disease	1 3

Table 1: Key Symptoms

Recognizing the Signs

The most common presenting symptom is a painless lump or swelling in the soft tissues—most often in the arms, legs, or trunk. These lumps are typically larger than 5 centimeters (about the size of a golf ball), deep within the tissue, and may grow rapidly over weeks or months 2 4 7. Pain is less common initially but can arise as the tumor enlarges and presses on surrounding nerves or muscles 1 3.

Alarm Symptoms and Clinical Clues

Certain features—termed "alarm symptoms"—should prompt immediate evaluation:

• Size >5 cm: Tumors greater than 5 centimeters are more likely to be malignant.
• Deep-seated location: Tumors under the muscle, rather than just beneath the skin.
• Rapid growth: A quickly enlarging mass is more concerning.
• Functional symptoms: Difficulty with movement, swallowing, breathing, or unexplained persistent pain, especially if deep and not linked to injury 2 3 7.

It’s important to note that up to one-third of sarcomas are discovered incidentally, without these classic warning signs, often during imaging for unrelated issues 2. When sarcomas occur in the head and neck, symptoms such as nasal obstruction, hoarseness, or swallowing difficulties may be the first clue 3.

Symptom Burden in Advanced Disease

Patients with advanced STS often report a high burden of physical and psychological symptoms. These include:

• Pain (77%)
• Lack of energy/fatigue (73%)
• Difficulty sleeping (56%)
• Feeling bloated or abdominal discomfort (49%)
• Shortness of breath (49%)

Psychological distress is also significant in advanced cases, underscoring the need for supportive and palliative care 1.

Types of Soft Tissue Sarcoma

Soft tissue sarcomas are strikingly diverse, with over 80 recognized histological subtypes, each with unique features and clinical behaviors. Understanding the major types helps guide diagnosis, treatment, and prognosis.

Type	Typical Location	Common Subtypes/Features	References
Liposarcoma	Thigh, retroperitoneum	Myxoid, well-differentiated, dedifferentiated	7 9 13
Leiomyosarcoma	Uterus, abdomen, limbs	Smooth muscle origin; aggressive	7 9 13
Synovial Sarcoma	Extremities (near joints)	Young adults, can mimic benign lesions	7 13 15
Undifferentiated Pleomorphic Sarcoma	Limbs, trunk	Previously MFH; pleomorphic cells	7 13 15
Malignant Peripheral Nerve Sheath Tumor	Nerves (arms/legs)	Linked to neurofibromatosis in some cases	7 15
Rhabdomyosarcoma	Head, neck, genitourinary	More common in children	3 7 9 15

Table 2: Major STS Types

Histological Diversity

STS is not a single disease but a collection of distinct tumors arising from different connective tissues. The most common adult types include:

• Liposarcoma: Develops from fat cells; can be slow-growing or aggressive 7 9 13.
• Leiomyosarcoma: Arises from smooth muscle, often in the uterus, abdominal cavity, or limbs 7 9 13.
• Synovial Sarcoma: Often found near joints in young adults; may be mistaken for benign conditions 7 13 15.
• Undifferentiated Pleomorphic Sarcoma (UPS): Previously called malignant fibrous histiocytoma, it exhibits highly variable cell shapes 7 13 15.

Other notable subtypes include malignant peripheral nerve sheath tumors (often associated with neurofibromatosis) and rhabdomyosarcoma (predominantly in children but possible in adults) 3 7 9 15.

Site-Specific Considerations

• Extremities (arms/legs): Most common location; includes many subtypes.
• Retroperitoneum (abdomen): Liposarcoma and leiomyosarcoma are most frequent here.
• Head and neck: Rare, but includes rhabdomyosarcoma and neurogenic sarcomas 3 7 9.
• Visceral sites: Organs such as the uterus or gastrointestinal tract may harbor specific sarcoma types 7.

Molecular and Pathological Features

Advances in genomics have revealed that some STS subtypes are driven by specific gene mutations, translocations, or alterations, which can influence behavior and response to therapy 6 13. This molecular heterogeneity is increasingly important for personalized treatment approaches 6 9 13.

Causes of Soft Tissue Sarcoma

The exact causes of most soft tissue sarcomas remain elusive, but several environmental, genetic, and biological factors have been identified that increase risk.

Cause	Description	Example/Risk Factor	References
Sporadic	No known cause	Most cases	10 12
Genetic Syndromes	Inherited mutations	Li-Fraumeni, Neurofibromatosis type 1	10 12
Radiation Exposure	Previous radiotherapy	For other cancers	10
Environmental	Chemical exposure (rare)	Vinyl chloride, arsenic	10
Molecular Alterations	Gene mutations, amplifications	TP53, RB1, chromosomal translocations	6 12 13

Table 3: Causes and Risk Factors

Sporadic Cases

The vast majority of STS cases are sporadic, meaning they arise in individuals without any identifiable risk factor or inherited predisposition 10 12. The rarity and diversity of these cancers make it difficult to pinpoint specific causes for most patients.

Genetic Predisposition

A small but important subset of patients develop sarcoma as part of inherited cancer syndromes. Conditions linked to higher risk include:

• Li-Fraumeni syndrome (TP53 mutations)
• Neurofibromatosis type 1 (NF1 mutations)
• Familial retinoblastoma (RB1 mutations) 10 12

These syndromes often present with multiple cancer types, including STS, at younger ages.

Environmental and Treatment-Related Factors

Radiation therapy is the most clearly established environmental risk factor for developing STS, sometimes appearing years after treatment for another cancer 10. There is weak evidence linking certain chemicals (e.g., vinyl chloride, dioxins, arsenic) to sarcoma risk, but these are rare causes 10.

Molecular Pathogenesis

At the cellular level, STS are driven by a variety of genetic changes:

• Gene mutations: In TP53, RB1, and ATRX—tumor suppressors involved in cell cycle regulation 6 12 13.
• Chromosomal translocations: Create fusion genes in some subtypes (e.g., synovial sarcoma).
• Copy number changes: Gains and losses of chromosomal material are common in sarcomas, leading to abnormal gene expression 6.

Emerging research also highlights the role of cancer stem cells, which may contribute to tumor initiation, progression, resistance to therapy, and recurrence 12.

Treatment of Soft Tissue Sarcoma

Treatment of soft tissue sarcoma is highly individualized, guided by tumor size, location, subtype, stage, and patient factors. Effective management typically involves a multidisciplinary team in specialized centers. The mainstays of therapy are surgery, radiation, and (when appropriate) chemotherapy, with targeted and immunotherapies becoming increasingly important.

Treatment	Main Use	Key Features/Comments	References
Surgery	Primary/localized disease	Wide excision with negative margins	7 8 9 11
Radiation	Adjunct to surgery	Pre- or post-operative; improves control	7 8 9 15
Chemotherapy	Advanced/high-risk	Doxorubicin, ifosfamide; subtype-based	7 13 14 15
Targeted Therapy	Metastatic/refractory	Pazopanib, trabectedin, eribulin	13 14 16
Immunotherapy	Select subtypes	Checkpoint inhibitors in trials	5 16
Palliative Care	Symptom control	Advanced/relapsed cases	1 7

Table 4: Main Treatment Approaches

Surgery: The Cornerstone

Surgical removal with wide, negative margins is the primary treatment for localized STS and offers the best chance for cure 7 8 9 11. Surgery should be performed by experienced teams in specialized centers. Limb-sparing techniques are prioritized to maintain function, sometimes combined with reconstructive procedures 7.

Radiation Therapy

Radiotherapy is often used alongside surgery—either before (neoadjuvant) or after (adjuvant)—especially for high-grade, deep, or large tumors (>5 cm), or when achieving clear margins is challenging 7 8 9 15. Preoperative radiation may reduce long-term complications, while postoperative radiation is chosen if wound healing is a concern 7.

Chemotherapy

Chemotherapy may be employed in several settings:

• Neoadjuvant (before surgery): To shrink tumors and increase resectability, particularly in high-risk patients 15.
• Adjuvant (after surgery): Still debated, but may be offered to select high-risk patients 7 13 14 15.
• Advanced/metastatic disease: Doxorubicin and ifosfamide are standard first-line agents; later lines may include gemcitabine/docetaxel, trabectedin, eribulin, or pazopanib, with choices increasingly tailored to tumor subtype 13 14 16.

Targeted and Immunotherapies

Recent years have seen promising developments:

• Targeted agents: Such as pazopanib (for non-adipocytic sarcomas), trabectedin (for leiomyosarcoma and liposarcoma), and eribulin (for adipocytic sarcoma) provide more options for refractory disease 13 14 16.
• Immunotherapy: Checkpoint inhibitors (e.g., pembrolizumab) show response in select immune-rich subtypes. B-cell-rich tumors may respond better to immunotherapy, highlighting the potential of immune profiling to guide treatment 5 16.

Supportive and Palliative Care

For advanced or symptomatic patients, supportive care—including pain management, psychological support, and symptom control—is critically important to maintain quality of life 1 7. Early referral to palliative care can help manage the significant symptom burden in advanced disease.

Personalized and Multidisciplinary Approach

Given the complexity and rarity of STS, treatment planning should involve a multidisciplinary team—including surgical, medical, and radiation oncologists, radiologists, pathologists, and allied health professionals—ideally at a sarcoma reference center 7 8 9. Increasingly, therapy is tailored to histological and molecular subtype, and clinical trials are vital for continued progress 13 15 16.

Conclusion

Soft tissue sarcoma is a rare, multifaceted disease that demands awareness, expertise, and individualized care. Here are the main takeaways:

• Symptoms are often subtle—a painless, growing lump is the most common sign, but advanced disease can cause significant pain, fatigue, and functional problems.
• STS encompasses over 80 subtypes, each with distinct behaviors and treatment needs.
• Most cases arise sporadically, but some are linked to genetic syndromes or prior radiation.
• Treatment is multidisciplinary and should be centralized in specialized centers, with surgery as the mainstay, complemented by radiation, chemotherapy, and, increasingly, targeted and immunotherapies.
• Personalized approaches and clinical trials are shaping the future of STS care, promising better outcomes for patients facing this rare cancer.

If you or someone you know has concerns about a persistent lump or unexplained symptoms, especially if it’s enlarging or deep, consult a healthcare professional—early evaluation can make a critical difference.