Fibrosarcoma: Symptoms, Types, Causes and Treatment

Fibrosarcoma is a rare but aggressive form of cancer that arises from fibrous connective tissue. It can occur in both children and adults, affecting various body parts including soft tissue, bone, and even skin. Despite medical progress, diagnosing and treating fibrosarcoma remains challenging due to its rarity, diverse presentation, and resemblance to other tumors. This article explores the key aspects of fibrosarcoma—including its symptoms, types, causes, and current treatments—based on the latest scientific findings.

Symptoms of Fibrosarcoma

Fibrosarcoma symptoms often develop gradually and can vary depending on the tumor's location and size. Early signs are usually subtle, which can cause delays in diagnosis. Recognizing these symptoms can lead to earlier detection and improved outcomes.

Symptom	Description	Common Sites	Source(s)
Pain	Persistent, localized pain	Abdomen, limbs, jaw	1 2 8
Swelling	Noticeable lump or mass	Soft tissue, bone, jaw	1 2 8
Obstruction	Blockage of nearby organs	Gastrointestinal tract	1
Systemic Signs	Anemia, fever, fatigue	Abdomen (esp. children)	1
Functional Loss	Limited motion, trismus, fracture	Jaw, limbs	2 8

Table 1: Key Symptoms

Common Presentations

Fibrosarcoma can manifest differently depending on its location:

• Soft Tissue and Retroperitoneum: Inflammatory fibrosarcoma in the abdomen may cause pain, anemia, fever, and sometimes a palpable mass. Gastrointestinal obstruction can occur if the tumor compresses the intestines 1.
• Head, Neck, and Jaw: When fibrosarcoma occurs in the mandible or oral cavity, patients often experience pain, swelling, loosening of teeth, difficulty opening the mouth (trismus), or even pathological fractures 2.
• Bone: Primary bone fibrosarcoma typically presents as a painful, enlarging mass. Swelling and sometimes pathological fractures can occur. Well-differentiated tumors may have a better prognosis than more aggressive ones 8.
• Skin and Subcutaneous Tissue: Tumors such as dermatofibrosarcoma protuberans (DFSP) may initially appear as small, firm bumps, and can recur locally if not completely removed 4.

Systemic and Advanced Symptoms

• General Symptoms: Some patients, especially children with abdominal tumors, may have systemic signs like anemia and fever 1.
• Complications: As tumors grow, they can invade adjacent structures, leading to gastrointestinal obstruction, nerve compression, or loss of function in the affected area 1 2.

Diagnostic Challenges

Fibrosarcoma’s symptoms overlap with those of other soft tissue and bone tumors, complicating early diagnosis. For example, jaw fibrosarcoma can mimic dental infections, while abdominal cases may resemble benign inflammatory conditions 1 2. Persistent or unexplained pain and swelling should prompt further medical investigation.

Types of Fibrosarcoma

Fibrosarcoma is not a single disease but a spectrum of tumors with varying behaviors, histological features, and preferred locations. Understanding these types helps guide both prognosis and treatment.

Type	Age Group	Typical Site	Source(s)
Adult-type Fibrosarcoma	Adults (rare)	Limbs, trunk, head/neck	3
Infantile/Juvenile	Children	Mesentery, retroperitoneum	1 6
Inflammatory Fibrosarcoma	Children, YA	Abdomen, mediastinum	1 5 6
Bone Fibrosarcoma	Adults/children	Long bones, jaw, spine	8
Fibrosarcomatous DFSP	All ages	Skin, subcutaneous	4

Table 2: Major Types of Fibrosarcoma

Adult-Type Fibrosarcoma

• Overview: Once thought to be a common soft tissue sarcoma in adults, it is now recognized as exceedingly rare (<1% of soft tissue sarcomas) 3.
• Sites: Most often found in the lower extremities, trunk, head and neck, but can occur elsewhere.
• Behavior: Can be locally aggressive and metastasize, particularly to lungs. Half of patients may die from the disease within a few years if not effectively treated 3.

Infantile/Juvenile and Inflammatory Fibrosarcoma

• Infantile Fibrosarcoma: Primarily affects infants and young children, often presenting as rapidly growing masses in the extremities or abdomen.
• Inflammatory Fibrosarcoma: Shares features with inflammatory myofibroblastic tumor, but displays more aggressive behavior, especially in the mesentery and retroperitoneum of children and young adults 1 5 6.
  • Symptoms: Abdominal pain, anemia, fever, and gastrointestinal obstruction.
  • Behavior: Can recur locally and, rarely, metastasize 1.

Bone Fibrosarcoma

• Location: Arises from the medullary cavity of bones, commonly affecting long bones, jaw, and spine 8.
• Clinical Course: Pain and swelling are typical. Well-differentiated tumors have a better prognosis than high-grade ones. Up to 30% of cases may be secondary to other tumors or prior radiation 8.

Fibrosarcomatous Dermatofibrosarcoma Protuberans (FS-DFSP)

• Nature: Represents a high-grade transformation of a usually low-grade skin tumor (DFSP).
• Sites: Most often on the trunk and limbs 4.
• Course: More aggressive than ordinary DFSP, with higher rates of local recurrence and risk of metastasis (especially to lungs and bone) 4.

Other Variants and Diagnostic Challenges

• Overlap with Other Tumors: Many tumors formerly classified as fibrosarcoma are now reclassified as myxofibrosarcoma, solitary fibrous tumor, synovial sarcoma, or other spindle cell neoplasms due to improved diagnostic criteria 3.
• Histological Spectrum: The boundaries between fibrosarcoma, myofibroblastic tumors, and other spindle cell sarcomas can be subtle, complicating diagnosis and management 5 6.

Causes of Fibrosarcoma

The underlying causes of fibrosarcoma are complex and can vary by age group, tumor type, and individual risk factors. While many cases are spontaneous, certain genetic, environmental, and iatrogenic factors have been identified.

Cause	Example/Detail	Risk Group	Source(s)
Genetic Factors	Susceptibility genes	All	7
Prior Radiation	Secondary sarcoma post-therapy	Adults, bone tumors	3 8
Chronic Inflammation	Ongoing tissue injury	All (esp. animals)	7 5
Chemical Exposure	Industrial chemicals, toxins	All	7
Childhood Origin	Developmental or unknown	Children	1 6
Trauma	Physical injury	Rare, disputed	7

Table 3: Major Causes and Risk Factors

Genetic and Cellular Factors

• Inherited Susceptibility: Some individuals may have genetic predispositions that increase their risk of developing fibrosarcoma, although specific mutations are not yet well characterized in humans 7.
• Cell of Origin: Fibrosarcoma arises from fibroblasts or myofibroblasts, the cells responsible for forming connective tissue and healing wounds 5 6.

Environmental and Iatrogenic Triggers

• Radiation Exposure: Both adult-type and bone fibrosarcomas can develop after prior radiotherapy for other cancers. These secondary sarcomas may appear years after the initial treatment 3 8.
• Chronic Inflammation and Trauma: Persistent tissue injury, inflammation, or even trauma has been implicated, particularly in animals, though the link in humans is less clear 7 5.

Chemical Carcinogens

• Chemical Exposure: Certain chemicals have been linked to fibrosarcoma development, especially in occupational settings 7.

Pediatric and Developmental Origins

• Childhood Tumors: Many fibrosarcomas in children, especially the inflammatory and infantile forms, have no clear causative factors and may be related to developmental processes or as-yet-unidentified genetic events 1 6.

Unresolved and Complex Etiology

• Overlap with Other Tumors: The distinction between reactive, inflammatory, and neoplastic processes is not always clear. Some tumors previously thought to be post-inflammatory pseudotumors are now recognized as part of a spectrum that includes inflammatory fibrosarcoma 5 6.
• Viruses: Studies have not found a role for viruses such as Epstein-Barr or cytomegalovirus in the pathogenesis of inflammatory fibrosarcoma 6.

Treatment of Fibrosarcoma

Treatment strategies for fibrosarcoma depend on tumor type, location, grade, and stage. Surgery remains the cornerstone, but advances in chemotherapy, radiotherapy, and experimental therapies are expanding options for patients.

Treatment	Description/Use	Indications	Source(s)
Surgery	Wide excision, amputation	Most cases	1 3 4 8
Radiation	Adjuvant/primary for inoperable	Some soft tissue/bone cases	8 4
Chemotherapy	Doxorubicin, others; variable role	Advanced/metastatic cases	9 10 12
Targeted/Novel	Hydrogels, gene therapy, MSCs	Experimental/clinical trial	9 10 11

Table 4: Main Treatment Modalities

Surgical Management

• Primary Approach: Surgery is the mainstay for most fibrosarcomas. Wide local excision with negative margins is preferred to prevent recurrence 1 3 4 8.
• Amputation: In bone fibrosarcoma, especially of the limbs, amputation may be necessary if complete resection is not feasible 8.
• Skin/DFSP Variants: For fibrosarcomatous DFSP, wider excision or Mohs micrographic surgery may be warranted due to the higher risk of recurrence and metastasis 4.

Radiotherapy

• Role: Fibrosarcoma is often considered radioresistant, but radiotherapy may be used as an adjunct to surgery or for unresectable tumors. Radiation can also help control local recurrences 8 4.

Chemotherapy

• Agents: Doxorubicin is the most frequently used agent, especially for advanced or metastatic disease 9 12.
• Resistance: Chemoresistance, particularly to doxorubicin, poses a significant challenge. New research suggests that molecules like piR-39980 may help overcome resistance by modulating drug accumulation and DNA repair pathways 12.
• Local Delivery: Innovative approaches, such as injectable pH-responsive hydrogels loaded with chemotherapy drugs, are being explored to enhance local tumor control and minimize systemic toxicity 9.

Emerging and Experimental Treatments

• Combination Therapies: Combining arsenic trioxide with irradiation has shown enhanced cell-killing effects in laboratory and animal models, suggesting potential for improved outcomes 10.
• Gene and Cell Therapy: Mesenchymal stem cells (MSCs) are being investigated as delivery vehicles for targeted gene therapy. For example, MSCs engineered to express inducible nitric oxide synthase have demonstrated significant anti-tumor effects in animal models 11.
• Immunotherapy and Molecular Targeting: As understanding of the molecular underpinnings of fibrosarcoma evolves, therapies targeting specific pathways may become available.

Prognosis and Follow-up

• Recurrence: Local recurrence is common, especially if margins are inadequate 1 4.
• Metastasis: Lung is the most frequent site of metastasis, particularly for high-grade or fibrosarcomatous variants 1 3 4.
• Survival: Prognosis is better for well-differentiated, low-grade tumors and when complete excision is achieved. High-grade, aggressive, or recurrent tumors have a poorer outlook 3 4 8.

Conclusion

Fibrosarcoma is a rare and heterogeneous group of tumors that demand early recognition, accurate diagnosis, and a multidisciplinary approach to treatment. Ongoing research is paving the way for more effective and targeted therapies.

Key Takeaways:

• Fibrosarcoma symptoms are often subtle and depend on tumor location, with pain and swelling being typical.
• Several types exist, including adult, infantile, inflammatory, bone, and fibrosarcomatous variants.
• Causes range from genetic predisposition to radiation, chronic inflammation, and possibly chemical exposures.
• Surgery is the primary treatment, but advances in chemotherapy, targeted drug delivery, and cell/gene therapy offer hope for improved outcomes.
• Early diagnosis and complete surgical excision are critical for the best chance of cure or long-term control.

By understanding the complexities of fibrosarcoma, patients and healthcare providers can work together towards timely diagnosis, optimal treatment, and, hopefully, better futures for those affected by this challenging disease.