Rhabdomyosarcoma: Symptoms, Types, Causes and Treatment

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, but it can affect people of all ages. Despite decades of research, this aggressive cancer remains a challenging diagnosis, with significant differences in symptoms, causes, and outcomes depending on the subtype and patient age. In this article, we’ll break down the key aspects of RMS—its symptoms, types, causes, and available treatments—using the latest evidence from scientific research.

Symptoms of Rhabdomyosarcoma

Rhabdomyosarcoma can present with a wide range of symptoms, often depending on the tumor’s location in the body. For many families, the first sign is an unusual lump or swelling, but other symptoms can be subtle or mimic other less serious conditions. Understanding these signs is crucial for early detection and effective treatment.

Location	Common Signs	Possible Complications	Source(s)
Head & Neck	Swelling, pain	Nasal obstruction, eye problems	6
Genitourinary	Urinary retention, hematuria, scrotal swelling, vaginal mass	Infections, prolapsing mass	1
Limbs	Painless lump	Limited movement, pain	6
Abdomen/Pelvis	Abdominal mass, pain	Bowel or urinary issues	6

Table 1: Key Symptoms

How Symptoms Vary by Location

The diversity of symptoms in RMS is largely tied to where the tumor develops. Here are some of the most commonly affected areas and their typical presentations:

• Head and Neck: RMS in this region often causes painless swelling, but can also result in nasal congestion, bulging of the eye (proptosis), or even vision changes if the tumor presses on nerves or organs 6.
• Genitourinary Tract: In children, RMS may occur in the bladder, prostate, testes, or female genital tract. Symptoms include urinary or fecal retention, painful urination (dysuria), urinary tract infections, hematuria (blood in the urine), or painless scrotal swelling. Vaginal tumors may appear as a mass protruding at the vaginal opening 1.
• Limbs and Trunk: Often presents as a painless, enlarging lump. Pain or restricted movement may occur if the tumor grows large enough to press on nerves or muscles 6.
• Abdomen and Pelvis: Abdominal or pelvic RMS can cause a visible or palpable mass, pain, or symptoms related to pressure on internal organs such as constipation or difficulty urinating 6.

When to Seek Medical Attention

Because RMS can mimic common childhood complaints, it is sometimes overlooked until the tumor has grown. Early evaluation is key, especially if you notice:

• A lump that is growing or not going away
• Unexplained pain or swelling
• Blood in urine or stool
• Persistent infections without clear cause

Prompt diagnosis is essential for better outcomes.

Types of Rhabdomyosarcoma

RMS is not a single disease, but a family of tumors with distinct biological and clinical behaviors. Understanding the main types helps guide diagnosis, treatment, and prognosis.

Subtype	Typical Age Group	Main Features	Source(s)
Embryonal (ERMS)	Children <10 years	Most common, better prognosis	2 3 6
Alveolar (ARMS)	Adolescents/young adults	More aggressive, worse prognosis	2 3 4
Pleomorphic	Older adults	Rare in children, high grade	2 5
Spindle Cell/Sclerosing	Both children and adults	Rare, distinct molecular features	2 5

Table 2: Main Types of Rhabdomyosarcoma

Embryonal Rhabdomyosarcoma (ERMS)

• Prevalence: Most common subtype, especially in young children
• Sites: Frequently found in the head and neck region, genitourinary tract, and less commonly in the limbs
• Genetics: Often associated with loss at chromosome 11p15.5, affecting tumor suppressor genes 3 4
• Prognosis: Generally has a better outcome than other types 2 6

Alveolar Rhabdomyosarcoma (ARMS)

• Prevalence: More common in adolescents and young adults, but can occur in children
• Sites: Often affects limbs and trunk
• Genetics: Characterized by specific gene fusions, such as PAX3-FOXO1 or PAX7-FOXO1, resulting from chromosomal translocations 3 4
• Prognosis: More aggressive, with a higher tendency for metastasis and worse outcomes 2 4

Pleomorphic Rhabdomyosarcoma

• Prevalence: Rare in children; mainly affects older adults
• Features: High-grade tumors, larger in size, associated with a poorer prognosis 5
• Genetics: Accumulation of genetic alterations similar to other adult sarcomas 2

Rare Subtypes: Spindle Cell and Sclerosing

• Features: Newly recognized, can appear in both children and adults
• Molecular Traits: Show distinct genetic changes
• Importance: Ongoing research is clarifying their behavior and optimal management 2 5

The Importance of Subtyping

Correctly identifying the RMS subtype is critical for prognosis and treatment. Advances in genetic testing and immunohistochemistry have made subtyping more accurate, allowing for risk-adapted therapies and better patient outcomes 3 4 6.

Causes of Rhabdomyosarcoma

The reasons why rhabdomyosarcoma develops are complex and not fully understood. Both genetic predisposition and environmental factors play a role, but recent research highlights the importance of inherited genetic syndromes and tumor biology.

Cause Type	Key Examples	Risk/Association	Source(s)
Genetic Syndromes	Li-Fraumeni (TP53), NF1, Costello, Beckwith-Wiedemann, DICER1	Strong increased risk	7 8 9
Genetic Mutations	PAX3/7-FOXO1 fusion, 11p15.5 loss	Subtype-defining	3 4
Environmental	Parental exposures, birth factors	Less clear, under study	8
Age/Sex/Location	Young age, male sex, certain geographies	Higher incidence	6 8

Table 3: Key Causes and Risk Factors

Genetic Predisposition Syndromes

A significant proportion of RMS cases, especially in children, are linked to underlying genetic syndromes. These include:

• Li-Fraumeni Syndrome (TP53 mutations): Strongly increases risk for RMS and other cancers 7 9
• Neurofibromatosis Type 1 (NF1): Associated with various tumors, including RMS 7 9
• Costello and Noonan Syndromes: RAS pathway mutations increase RMS risk 7 9
• Beckwith-Wiedemann Syndrome: Overgrowth disorder with increased risk for RMS 9
• DICER1 Syndrome: Rare, but important in some genitourinary RMS cases 9

Studies show that about 7–10% of children with RMS carry a germline cancer-predisposition variant, often in syndromes already known to increase RMS risk 7. Embryonal RMS (ERMS) shows a higher rate of such variants than alveolar RMS (ARMS) 7.

Tumor-Defining Genetic Changes

• ARMS: Characterized by gene fusions (PAX3/7-FOXO1), which drive tumor growth and are directly involved in cancer development 3 4
• ERMS: Typically shows chromosomal loss at 11p15.5, affecting key tumor suppressor genes 3 4

Environmental and Perinatal Factors

While the vast majority of cases have no clear environmental trigger, some studies have explored links between RMS and perinatal or parental exposures (such as parental smoking, birth weight, or other birth factors), but the evidence remains inconclusive 8.

Demographic Risk Factors

• Age: Most common in children under 10; risk decreases with age 6 8
• Sex: Slightly more common in males 8
• Geography: Incidence rates vary, but RMS is primarily a pediatric cancer worldwide 6 8

Takeaway

Although many cases arise sporadically, genetic counseling and testing should be considered for all children with RMS, especially when there’s a family history or features suggestive of a cancer predisposition syndrome 7 9.

Treatment of Rhabdomyosarcoma

Treatment of RMS has advanced significantly, but it remains a complex, multidisciplinary challenge. The approach is highly individualized, depending on the tumor’s subtype, location, genetic features, and whether it has spread.

Treatment	Main Approach	Patient Group/Goal	Source(s)
Chemotherapy	Multi-agent regimens (IVA, etc.)	All, risk-adapted	6 10 11 12
Surgery	Tumor removal when feasible	Local control	6
Radiotherapy	Site-specific, for local control	Inoperable or high-risk	6 10 13
Maintenance Therapy	Vinorelbine + low-dose cyclophosphamide	High-risk, relapse prevention	11
Immunotherapy/Experimental	NK cell therapy, cytokines	Refractory/relapsed cases	13

Table 4: Main Treatment Strategies

Standard-of-Care: Multimodal Therapy

1. Chemotherapy

• First-line treatment: Nearly all patients receive chemotherapy, usually a combination of drugs such as vincristine, actinomycin D, ifosfamide, and cyclophosphamide (IVA or VAC regimens) 6 12.
• High-risk patients: More intensive regimens, sometimes including newer agents like irinotecan or etoposide, are used for metastatic or relapsed disease 10.
• Doxorubicin: While effective, trials show that adding doxorubicin to standard IVA regimens does not significantly improve outcomes but increases side effects 12.

2. Surgery

• If feasible, surgical removal of the tumor is performed. The approach depends on site and size. Complete resection is associated with better outcomes, but sometimes only a biopsy or partial removal is possible due to tumor location 6.

3. Radiotherapy

• Used when surgery cannot completely remove the tumor or when the tumor is in a sensitive location.
• Also critical in high-risk or metastatic disease, sometimes combined with chemotherapy or immunotherapy 6 10 13.

Risk-Adapted and Maintenance Therapy

• Stratification: Treatment intensity is tailored based on risk factors—tumor size, site, spread, and genetic features (such as fusion status) 6.
• Maintenance chemotherapy: Prolonged, lower-intensity regimens with drugs like vinorelbine and low-dose cyclophosphamide have been shown to improve survival in high-risk patients, reducing relapse rates 11.
• Outcome: Five-year survival rates for localized disease have improved, but metastatic RMS remains challenging, with survival less than 20% for high-risk patients 10.

New and Emerging Therapies

• Immunotherapy: Adoptive transfer of natural killer (NK) cells, sometimes expanded with interleukin-15 and interleukin-21, is a promising new approach for refractory or radiation-resistant RMS. Early studies show enhanced anti-tumor activity and potential for combining with standard treatments 13.
• Molecular targeted therapy: Advances in genetic testing may soon allow more personalized treatments based on tumor subtype and mutations 6 13.

Long-Term Care and Survivorship

• RMS survivors require monitoring for late effects of therapy, including growth disturbances, organ toxicity, and secondary cancers. Ongoing research aims to balance cure with quality of life 6.

Conclusion

Rhabdomyosarcoma is a complex disease with diverse presentations, driven by both genetic and environmental factors. Over the past decades, improved understanding of its types, causes, and treatment has led to better outcomes for many patients. However, challenges remain—especially for those with high-risk or metastatic disease.

Key Takeaways:

• Symptoms depend on tumor location and can range from painless lumps to urinary or visual issues; early detection is vital 1 6.
• Types include embryonal, alveolar, pleomorphic, and rare subtypes, each with distinct age groups, genetics, and prognosis 2 3 4 5 6.
• Causes are often genetic, with several syndromes and mutations increasing risk; environmental links are less clear 7 8 9.
• Treatment is multimodal: chemotherapy, surgery, and radiotherapy, with risk-adapted and maintenance strategies improving survival. New immunotherapies offer hope for the future 6 10 11 12 13.

Continued research and personalized care are essential to further improve outcomes and quality of life for patients with rhabdomyosarcoma.