What Is Rhabdomyosarcoma

Overview 

Rhabdomyosarcoma (RMS) is a complex and highly aggressive type of childhood cancer.¹ The name itself categorises the cancer as a sarcoma, meaning it originates from a primitive type of cells that are meant to develop into muscle cells. It is known to be the most common soft tissue sarcoma in children. Soft tissue sarcomas themselves make up nearly 7% of childhood cancers, with half being RMS.² However, the condition is also seen in adults.

With many years of clinical and scientific research, the condition is better understood. In this article, we shall discuss the causes, risk factors, signs and symptoms, and treatment of Rhabdomyosarcoma.

Types of rhabdomyosarcoma

Before exploring the types of RMS, it is essential to understand the mechanism of cancers in general. Cancer, also called neoplasm, refers to a condition caused by abnormal, unnecessary, excessive, and uncontrolled cell growth with the potential to invade nearby structures or spread to other parts of the body. RMS is a form of cancer that involves tissue called mesenchymal tissue, which is capable of being converted into myogenic cells.

Two major forms of Rhabdomyosarcoma exist. These are: 

• Alveolar RMS (ARMS), often found in the trunk or extremities and
• Embryonal RMS (ERMS), which usually occurs in the head, neck, and other areas. 

Both of these are caused by different mechanisms. This classification is based on the appearance of the respective cells under light microscopy. Furthermore, ARMS has often been noted to be associated with chromosomal translocations involving chromosomes 2 or 1 and chromosome 13. Chromosomal translocation is when a chromosome breaks and completely or partially attaches to a different chromosome. The World Health Organisation (WHO) recognises two additional subtypes: Pleomorphic RMS and spindle cell RMS. The spindle cell variety is seen in children and has a poorer outcome. 

Causes and risk factors 

Identifying a cause for Rhabdomyosarcoma is challenging. However, risk factors have been studied that may contribute to a higher chance of encountering the condition in some people.

The chance of having RMS is influenced by several factors pertaining to the tumour and the individual. For example, a recent analysis has shown that the diagnosis of ERMS has been up to 2.5 times more frequent than ARMS.³ 

Age

Age is another determining factor for RMS incidence. ERMS is the most common form of the condition in early childhood, with a probable second peak in early adolescence. This is called a bimodal peak. Bimodal peaks are not observed in children with ARMS, whose incidence remains constant throughout childhood and adolescence.⁴ 

In contrast to these two more conventional forms, the WHO-classified pleomorphic RMS primarily occurs in adults assigned male at birth (AMAB) in their 6th decade of life.⁵ “Pleomorphic” RMS in children is typically classified as ERMS with diffuse anaplasia.

Sex

RMS incidence also varies by sex, as children assigned male at birth have been noted to have a higher incidence of ERMS compared to those assigned female at birth (AFAB).

Genetic factors

Children with certain genetic disorders tend to develop Rhabdomyosarcoma more frequently than unaffected children. Syndromes that are most commonly associated with ERMS include:

• Li-Fraumeni syndrome (mutation of the TP53 gene, which is a tumour suppressor)
• Neurofibromatosis type I (caused by deletions in the NF1 gene) 
• Costello syndrome (mutation of the HRAS gene, an oncogene) 
• Noonan syndrome  
• Beckwith-Wiedemann syndrome
• DICER1 syndrome (germline DICER1 mutations)

Environmental risk factors

Exposure to several environmental agents and other factors has been implicated in RMS risk in children. Many published reports have identified the following factors which contribute to the condition:

• Prenatal X-ray exposure 
• Parental recreational drug use
• Birth defects
• Allergies during childhood
• Vaginal bleeding during pregnancy
• First-degree relative with RMS
• Use of fertility medications (for example, metformin)

Signs and symptoms of Rhabdomyosarcoma

Swelling or lump

Rhabdomyosarcomas can arise as a lump in almost any part of the body. However, the most common sites depend on the subtype of RMS: 

• ERMS most commonly arises in the head and neck, the eye socket, or in the genital area. These appear as painless lumps or as a protruding eye.
• ARMS, on the other hand, arises at the extremities and limbs, and in some cases in the head, neck or torso.⁴ 
• A tumour in the head or neck area can block the nasal passage and produce nose or throat discharge.

Pain and changes in bowel or bladder habits 

• A tumour in the abdomen can cause pain or discomfort in the abdomen. 
• Another manifestation may be difficulty in passing stools (constipation).
• A tumour in the urinary bladder may present with blood in the urine and difficulty passing urine.

Spread

This cancer can spread to distant parts of the body through the bloodstream (haematogenous route) or the lymphatic system. Sites of spread include the lungs, bone, and bone marrow.

This can present as body aches and bone pain, as well as difficult or painful breathing.

Diagnosis of rhabdomyosarcoma

To diagnose Rhabdomyosarcoma, your doctor may ask you for a detailed history of clinical signs you may have noticed in your child or any problems the child complains of. A clinical examination may also be performed.

Based on this, various diagnostic tests may be prescribed to identify RMS. Common ones include:

• Your child may need a small operation to remove a sample from the tumour (a biopsy) so that it can be examined under a microscope. This is usually done under a general anaesthetic.
• Various tests may be done to check the exact size of the tumour and to find out if it has spread to any other part of the body. These may include imaging scans, blood tests and biopsy.

 Imaging scans

• Chest X-ray to check the lungs
• Ultrasound scan
• Computerized Tomography (CT) scan
• Magnetic Resonance Imaging (MRI)

Blood tests

Routine blood tests, as well as a Bone marrow biopsy, may be advised.

Biopsy

This involves extracting a small piece of tissue from the lump that is suspected to be a tumour. The tissue is sent into a laboratory for analysis under a microscope, which identifies the presence of RMS. It can also classify the subtype present. The biopsy may be:

• An incisional biopsy (removal of a portion of the lesion by making a small cut)
• An excisional biopsy (removal of the entire lesion)
• A core needle biopsy.

Treatment of rhabdomyosarcoma 

Chemotherapy 

Chemotherapy is a modality of treatment that involves the use of drugs to destroy cancer cells, called cytotoxic drugs. These can be given at two separate times depending on the individual circumstance:

• To shrink the tumour before surgery, making the procedure itself easier
• After a surgical excision to reduce the chances of cancer coming back

The anti-cancer drugs prescribed and the length of treatment depend on the type and stage of the rhabdomyosarcoma. This will be decided by a clinician after careful consideration and diagnostic testing.

The standard chemotherapy regimen for rhabdomyosarcoma is a combination of drugs, including the following: 

• Vincristine
• Actinomycin
• Cyclophosphamide/Ifosfamide. 

In recent clinical trials, modifications to this standard chemotherapy protocol have been made, and improvements in patient conditions have been reported.⁶

Surgery 

If it is possible, the doctors may suggest your child have a surgical procedure to remove all of the tumour or as much as possible of the tumour. This can be challenging to perform without damaging surrounding tissue or organs. The operation will depend on the size of the tumour and the site in your body. The surgeon or your healthcare provider will explain the procedure, its benefits, aims and any possible complications. Chemotherapy may be given before the operation, as mentioned above, to shrink the tumour and make it easier to remove with surgery. 

Radiation therapy

Radiotherapy is a procedure involving the exposure of cancer cells to high-energy radiation. This can damage and kill them, thus controlling their division. This may be done following surgery to manage the residual cancer cells. If surgery isn’t possible or feasible, a combination of chemotherapy and radiotherapy may be prescribed.

Prognosis 

Many children are offered a treatment regime as part of a clinical research trial. These trials aim to improve our understanding of RMS and its manifestations and identify the best way to treat it. This is usually done by comparing the standard treatment with a new or modified version. Specialist doctors and other healthcare and research staff carry out trials for children’s cancer. If appropriate, your child’s medical team may talk to you about taking part in a clinical trial. This is a completely voluntary participation, and any questions you have will be answered by those involved. Written information is provided to help explain things clearly and elaborately. 

It is best to discuss these options with your healthcare provider.

Summary

Rhabdomyosarcoma is a type of soft tissue tumour commonly seen in children. It has two distinct forms commonly diagnosed and two additional ones recognised by the WHO. Most children with rhabdomyosarcoma are diagnosed before they are 10 years old. It’s more common in children with AMAB than those in AFAB.

The condition presents with a painless swelling in different parts of the body (depending on the subtype of RMS), and in some cases with bone pains, tiredness, abdominal pain, constipation, and trouble breathing.

RMS is diagnosed by blood tests and radiological imaging (CT scans, MRI). Treatment may be surgical, chemotherapy, radiotherapy or a combination of these. 

If you suspect your child may have RMS, it is essential to contact your healthcare provider immediately.