Spindle Cell Sarcoma: Symptoms, Types, Causes and Treatment

Spindle cell sarcoma is a rare and complex group of cancers that can affect various tissues and organs. Often challenging to diagnose and treat, these tumors are characterized by the presence of spindle-shaped cells seen under the microscope. In this article, we break down the key symptoms, types, causes, and treatment options for spindle cell sarcoma, offering clear explanations and insights from recent research.

Symptoms of Spindle Cell Sarcoma

Spindle cell sarcomas can be elusive, often presenting with subtle or nonspecific symptoms. Because these tumors can develop in different parts of the body—such as soft tissue, bone, or organs—their symptoms can vary widely. Early detection is difficult, as many patients notice symptoms only when the tumor has grown large or caused complications.

Symptom	Description	Common Sites	Source(s)
Mass	Painless, enlarging lump or swelling	Soft tissue, skin	2 4 8
Pain	Discomfort or tenderness in affected area	Paraspinal, chest	2 4
Obstruction	Blockage of normal organ function	Heart (atrial)	1
Shortness of Breath	Difficulty breathing, often due to metastasis	Lungs	2
Dermatologic Findings	Skin changes, may mimic other conditions	Neck, skin	3 8
Recurrence	Tumor returns after treatment	Various	2 4

Table 1: Key Symptoms

Masses and Swelling

The most common symptom is the appearance of a mass or lump, which may be painless and grow slowly over time. Many patients discover the tumor incidentally, or it becomes noticeable after it reaches a significant size. For example, in the paraspinal musculature or extremities, a gradually enlarging lump may be the only sign 2 4. In skin or subcutaneous tissues, a mass may be mistaken for a benign lesion 8.

Pain and Discomfort

Pain is not always present, but when the tumor presses against nerves, muscles, or bones, it can cause tenderness or discomfort. In some cases, such as paraspinal tumors, pain may be the first noticeable symptom 2.

Organ-Specific Symptoms

When spindle cell sarcoma develops in organs, it can cause specific symptoms:

• Heart: Tumors in the heart (e.g., left atrial spindle cell sarcoma) can cause obstruction of blood flow, local invasion of tissues, or even sudden cardiac death 1.
• Lungs: Metastases to the lungs may present as shortness of breath or pleural effusion 2.

Dermatologic and Atypical Presentations

In rare cases, spindle cell sarcomas may present with dermatologic findings, such as a mass on the neck mimicking lymph node metastasis, especially in patients with a history of cancer 3. In the skin, spindle cell sarcoma may appear as a localized mass, often painless 8.

Recurrence and Metastasis

A key feature of spindle cell sarcoma is the risk of local recurrence after treatment and the potential for distant metastasis, particularly to the lungs 2 4. This underscores the importance of long-term follow-up.

Types of Spindle Cell Sarcoma

Spindle cell sarcomas are not a single disease but a family of tumors sharing a common spindle-shaped cell morphology. They can arise in various tissues and have different biological behaviors, grades, and prognoses.

Type	Key Features	Typical Age Group	Source(s)
Undifferentiated/Unclassified	Lacks clear tissue origin, aggressive	Adults, rare in children	2 7 12
Low-grade Fibromyxoid Sarcoma	Slow-growing, may have giant rosettes	Young adults	4
Spindle Cell Sarcoma with NTRK1 Fusion	Myopericytic/haemangiopericytic pattern, targetable	Children & adults	5
Histiocytic Sarcoma (Spindle type)	Mainly skin, less aggressive than round cell	Various	8
Cardiac Spindle Cell Sarcoma	Highly aggressive, rapid progression	Young to middle-aged	1
Kaposi’s Sarcoma (Spindle cells)	Associated with HHV8, vascular, spindle proliferation	All ages	6 9

Table 2: Main Types of Spindle Cell Sarcoma

Undifferentiated/Unclassified Spindle Cell Sarcoma

These tumors are diagnosed when no specific line of differentiation can be identified under the microscope. They are aggressive, prone to local recurrence and metastasis, and commonly occur in adults but can appear at any age. Treatment is challenging due to their unpredictable behavior 2 7 12.

Low-grade Fibromyxoid Sarcoma and Hyalinizing Tumors

A distinctive low-grade subtype, sometimes featuring "giant rosettes," tends to grow slowly and may have a better prognosis if excised widely. However, limited follow-up makes long-term outcomes uncertain 4.

Spindle Cell Sarcoma with NTRK1 Gene Fusion

Some spindle cell sarcomas, especially those with a myopericytic or haemangiopericytic pattern, possess specific genetic fusions (e.g., NTRK1). These can occur in both children and adults and are notable because they may respond to targeted therapies 5.

Histiocytic Sarcoma (Spindle Type)

Histiocytic sarcomas can be classified by cell type; the spindle cell variant primarily affects the skin and tends to be localized and less aggressive than the round-cell type 8.

Cardiac Spindle Cell Sarcoma

Spindle cell sarcoma of the heart is extremely rare but highly aggressive, often presenting late with symptoms of obstruction or sudden cardiac events 1.

Kaposi’s Sarcoma and Spindle Cells

While not a classic spindle cell sarcoma, Kaposi’s sarcoma features spindle-shaped tumor cells of endothelial origin, driven by human herpesvirus 8 (HHV8) infection 6 9.

Causes of Spindle Cell Sarcoma

The exact causes of spindle cell sarcoma are not fully understood. Like many cancers, the development of spindle cell sarcoma is likely due to a combination of genetic, environmental, and possibly viral factors.

Cause	Mechanism or Risk Factor	Notes	Source(s)
Genetic Mutations	Chromosomal abnormalities, gene fusions (e.g., NTRK1)	May be targetable	5
Prior Radiation	Secondary sarcoma after radiotherapy	Latency period common	3
Viral Infection	Human herpesvirus 8 (Kaposi’s sarcoma)	Endothelial transformation	6 9
Unknown / Sporadic	No clear risk factor	Most cases	2 7
Tumor Size & Grade	Larger, higher-grade tumors more likely to metastasize	Disease progression	2

Table 3: Causes and Risk Factors

Genetic Factors

Some spindle cell sarcomas are associated with specific genetic alterations, such as gene fusions involving NTRK1. These mutations can drive tumor growth and may serve as targets for new therapies 5.

Prior Radiation

A subset of spindle cell sarcomas develops as a secondary malignancy after radiotherapy, particularly in patients previously treated for other cancers (e.g., breast cancer). These typically appear years after exposure 3.

Viral Oncogenesis

Kaposi's sarcoma, featuring spindle-shaped cells, is directly linked to infection with human herpesvirus 8 (KSHV/HHV8). The virus induces changes in mesenchymal stem cells, leading to the proliferation of malignant spindle cells 6 9.

Tumor Grade, Size, and Sporadic Cases

Most spindle cell sarcomas arise without a clear cause. The risk of metastasis and aggressive behavior is greater for larger and higher-grade tumors 2 7.

Treatment of Spindle Cell Sarcoma

Treatment strategies for spindle cell sarcoma are guided by tumor location, grade, stage, and patient factors. Surgery remains the cornerstone, but advances in chemotherapy, targeted therapy, and experimental approaches are expanding options.

Treatment	Description / Indication	Effectiveness / Notes	Source(s)
Surgery	Wide excision with clear margins	Reduces recurrence risk	2 4 7
Radiation	Adjuvant or neoadjuvant use	For local control	2 7
Chemotherapy	Doxorubicin, cisplatin, gemcitabine/docetaxel	Variable efficacy; limited in high-grade/metastatic	11 12 13
Targeted Therapy	Pazopanib, NTRK inhibitors	Promising in selected cases	5 12
Metabolic Therapy	Recombinant methioninase (rMETase)	Overcomes chemo resistance	10 13
Metastasectomy	Surgical removal of lung metastases	For isolated metastases	2

Table 4: Treatment Approaches

Surgery

Complete surgical excision with adequate margins (≥1 cm or to a fascial barrier) is the primary treatment. Wide excision reduces the risk of local recurrence. For some subtypes, such as hyalinizing spindle cell tumors, wide excision appears to offer excellent local control 2 4 7.

Radiation Therapy

Radiation is often used before (neoadjuvant) or after (adjuvant) surgery, especially for tumors in locations where achieving clear margins is difficult. It helps control local disease but does not address distant metastasis 2 7.

Chemotherapy

Chemotherapy regimens, including doxorubicin, cisplatin, gemcitabine, and docetaxel, have variable effectiveness. For high-grade or metastatic disease, response rates are modest, and outcomes remain poor in many cases 11 12 13. Some tumors are resistant to standard chemotherapy.

Targeted and Novel Therapies

• Tyrosine Kinase Inhibitors: Pazopanib, a multi-targeting tyrosine kinase inhibitor, has shown improved efficacy in resistant undifferentiated spindle cell sarcoma compared to standard chemotherapy 12.
• NTRK Inhibitors: Tumors with NTRK1 gene fusions may be sensitive to specific inhibitors, highlighting the importance of genetic testing 5.
• Metabolic Therapy: Recombinant methioninase (rMETase) is a novel agent that targets tumor metabolism and has demonstrated the ability to overcome chemotherapy resistance in preclinical models 10 13.

Management of Metastases

For patients with isolated lung metastases, surgical removal (metastasectomy) can be considered. Long-term surveillance is critical, as late metastases are not uncommon 2.

Conclusion

Spindle cell sarcoma represents a diverse and challenging group of cancers, with symptoms and outcomes that vary by tumor type and location. Here’s what to remember:

• Symptoms are often subtle and may include painless masses, pain, or organ-specific signs.
• Types range from undifferentiated, aggressive tumors to low-grade variants; some are associated with specific genetic mutations or viral infections.
• Causes are mostly unknown, but prior radiation and genetic or viral factors play a role in some cases.
• Treatment centers on surgery, with radiation, chemotherapy, targeted, and metabolic therapies tailored to the individual and tumor characteristics.
• Long-term follow-up is crucial due to the risks of recurrence and late metastasis.

Understanding spindle cell sarcoma requires a nuanced approach, with careful diagnosis, multidisciplinary management, and ongoing research into new therapies offering hope for improved outcomes.