Also known as:
Scientists want to classify different forms of cancer because it helps them to predict how a particular cancer will progress and often determines what the best treatment is. Rhabdomyosarcoma has been difficult to diagnose and classify and various attempts have been made over the years to improve this. The World Health Organisation now lists four main types:
Alveolar rhabdomyosarcoma – ARMS
Embryonal rhabdomyosarcoma – ERMS
Pleomorphic rhabdomyosarcoma – PRMS
Spindle cell/sclerosing rhabdomyosarcoma – SCRMS
In addition there is:
Botryoid rhabdomyosarcoma (a subtype of embryonal rhabdomyosarcoma)
How rare is rhabdomyosarcoma?
In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers. In England there are an average of 112 cases of rhabdomyosarcoma each year, an incidence of 0.2 cases per 100,000, with most of the cases being the alveolar or embryonal type. It is most common in young people, where the incidence is closer to 0.5 cases per 100,000, making it the most common soft tissue sarcoma in children.
The numbers of people affected seem to vary round the world, but this might reflect different approaches to diagnosis.
What is rhabdomyosarcoma?
The word “rhabdomyosarcoma” describes what this cancer is.
“Rhabdo” means rod shaped – this describes the shape of the cells seen under the microscope.
“Myo” means to do with muscle. The cells that make up this cancer look like a type of young muscle cell called a myoblast although we are not sure whether the cancer starts in these cells or the process of becoming cancerous makes them behave a little like the cells that make up our skeletal muscles – the ones we use for conscious movement.
“Sarcoma” Rhabdomyosarcoma is a type of cancer called a sarcoma. Sarcomas start in cells that form the soft tissues and bones of the body. They can form in muscles, fat, nerves, tendons, cartilage and bones. All of these cells begin as a primitive type of cell called a mesenchymal cell that has the ability to develop into any type of soft tissue or bone.
For some excellent images of rhabdomyosarcoma cells, their behaviour and an explanation of how they are graded, follow this link.
We don’t know what causes rhabdomyosarcoma. There are probably many different chance events that could cause the particular damage that starts this cancer. We do know that some things increase the chance of getting rhabdomyosarcoma. There are a few rare inherited genetic conditions that often increase the chances of getting a range of cancers – Li-Fraumeni syndrome, neurofibromatosis, Noonan syndrome, Beckwith-Wiedemann, and Costello syndromes. Scientists collecting data about people with rhabdomyosarcoma have found a small increased risk for a number of factors such as exposure to radiation (X-rays) although these need to be repeated with more people across more countries to be more confident of a link.
The types of Rhabdomyosarcoma are all slightly different in their appearance, cause and behaviour:
Alveolar rhabdomyosarcoma (ARMS):
This type of rhabdomyosarcoma tends to affect slightly older children and teenagers. Tumours tend to form in the limbs and the trunk. It is called alveolar because the small, round tumour cells arrange themselves in groups that look like the tiny air sacs of the lungs, called alveoli.
Embryonal rhabdomyosarcoma (ERMS)
This type is found in very young children, usually under 4-5 years old. It often affects the head and neck or the genitals. Under a microscope the cells often look like immature muscle cells.
Pleomorphic Rhabdomyosarcoma (PRMS)
Pleomorphic means “having many different forms” and the cells of pleomorphic rhabdomyosarcoma are very mixed and many of them don’t look like any known type of normal cell (undifferentiated). This form progresses quickly and will need very intensive treatment
Spindle cell/sclerosing rhabdomyosarcoma (SCRMS)
Only recently described as a type of rhabdomyosarcoma, this cancer tends to form around the testicles. It looks like a mix of smooth muscle and skeletal muscle. This particular form is very treatable with 95% of patients alive at the key 5 year mark.
The initial symptoms of rhabdomyosarcoma depend very much on where it has developed. Around a third of tumours develop in the neck and head. They can cause headaches, interfere with cranial nerves making it difficult to control part of the face, or cause eyes to swell and be hard to control. A quarter of tumours start in the genito-urinary tract – the bladder, kidneys and reproductive organs. They can cause problems with weeing or there may be blood in the urine.
Tumours in the arms and legs are more common in adults and tend to be the pleomorphic type.
X-rays, CT and MRI scans will be used to confirm the size and shape of any tumour, and if they have spread (become metastatic). Rhabdomyosarcoma most often spreads to the lungs and bone marrow and scans will also check for this.
A small sample of the tumour called a biopsy will be taken and studied under a microscope by a histologist (person who studies cells). The shape and arrangement of the cells in the tumour gives them a clue as to what type of cancer it is. Histologists will also use immunohistochemistry to confirm whether particular proteins are in the cells. Immunohistochemistry uses antibodies – molecules that are normally found in your immune system to stick to and colour these proteins. Because rhabdomyosarcoma cells are muscle- like, the tests will be looking for proteins called myogenin, desmin, sarcomeric actin, myogenin, and myoglobin. They may also test for other proteins to rule out other conditions.
In the nucleus of our cells is the molecule of inheritance, DNA. It looks like a twisted ladder where the order of the rungs acts as a simple alphabet, spelling out the instructions for everything that our cells make and do. A gene is a short section of DNA that contains the instructions for making one protein – proteins make up much of our bodies and have many other functions.
We can find the order of these letters by sequencing the DNA. Changes to the sequence are called mutations. Some mutations have little effect on us, but others can lead to cancer by changing the amount or activity of the proteins that are made.
Some cancers have a very characteristic mutation that can be used to both confirm the diagnosis and as a potential target for developing drugs to treat the disease. Scientists have analysed the DNA sequence of many tumours from people with different types of rhabdomyosarcoma.
Most people with ARMS have a particular genetic change that distinguishes it from ERMS and these changes are used to help diagnose the type of rhabdomyosarcoma. These genes are called PAX3-FOXO1 or a PAX7-FOXO1 fusions (genes are named for scientists to understand, which can make them confusing if you’re not used to them – they are included here as they might be mentioned by doctors). In this case large chunks of DNA have been swapped between two separate genes that leads to a protein being made that combines some of the features of both. Unfortunately this new protein switches on many genes that are thought to be what leads to the cancer developing.
If there is a suspicion that a tumour is rhabdomyosarcoma, genetic testing can be used to try and confirm whether it is the alveolar (ARMS) or embryonal (ERMS) type. This is important because ARMS is a more progressive form of cancer and will need to be treated more aggressively than ERMS
The genetic changes in the pleomorphic and spindle cell forms are not understood well enough for it to be used in diagnosis.
The NHS will also do tests for other genes called NTRK1/2/3. These are genes for part of a chain of messengers that can be mutated to a form that tells cells to divide uncontrollably. Although very few chondrosarcomas will have this mutation, drugs that stop NTRK acting (larotrectinib) can help slow the disease if a patient has tested positive for it.
What are the current treatment options for rhabdomyosarcoma?
The treatment plan for each person’s rhabdomyosarcoma will depend on the “risk” that is assessed for that tumour. The risk is a combination of the type, location, size, spread and genetics, and will be either low, standard, high or very high.
As with most tumours, surgery is the main treatment if it is possible without causing too much damage to important organs. There may be some chemotherapy given first to reduce the size of the tumour and increase the chance of the surgery being able to remove all of the tumour. Alternatively removing as much of the tumour as possible reduces the intensity of other treatments needed afterwards.
In the past radiotherapy was avoided in order to reduce the chances of radiation causing problems later in life, but studies have shown that RT has a big impact on the survival of patients and is now used for all but the least risky cases. The dose and type of radiotherapy is carefully controlled to get the best result for as little radiation exposure as possible. There are now more patients being given a type of radiotherapy called brachytherapy where tiny radioactive beads or strips are put directly into the tumour so the radiation can reach the cancer cells without having to pass through as much healthy tissue.
The main chemotherapy treatment for rhabdomyosarcoma is called IVA for short and uses three drugs called ifosfamide, vincristine, and actinomycin D. Ifosfamide damages the DNA of cells that are dividing, vincristine blocks cells from physically dividing. Actinomycin D sticks to DNA in a way that stops it unwinding so it can be copied before being shared equally into new cells.
The dose and number of cycles (periods of regular treatment with breaks between) will depend on the risk level. In the USA there is a slightly different drug combination used called VAC, but trials have found no difference in their effectiveness.
What current clinical trials are there for rhabdomyosarcoma?
Information current as of: 22nd June 2023
There are very many trials being run in the USA, which may bring better treatments for patients in the UK.
For patients in the UK there are two trials, one looking at using a fluorescent dye to improve the ability of surgeons to find and remove as much of a tumour as possible, the second is called FaR-ARMS and is a very large and inclusive study aiming to improve treatments with both current and new treatments for any patient with RMS.
The study summary is below: (copied from clinicaltrials.gov)
FaR-RMS is an overarching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS). It is a multi-arm, multi-stage format, involving several different trial questions. FaR-RMS is intended to be a rolling programme of research with new treatment arms being introduced dependent on emerging data and innovation. This study has multiple aims. It aims to evaluate the impact of new agent regimens in both newly diagnosed and relapsed RMS; whether changing the duration of maintenance therapy affects outcome; and whether changes to dose, extent (in metastatic disease) and timing of radiotherapy improve outcome and quality of life. In addition the study will evaluate risk stratification through the use of PAX-FOXO1 fusion gene status instead of histological subtyping and explore the use of FDG PET-CT response assessment as a prognostic biomarker for outcome following induction chemotherapy.
Newly diagnosed patients should, where possible, be entered into the FaR-RMS study at the time of first diagnosis prior to receiving any chemotherapy. However, patients can enter at the point of radiotherapy or maintenance, and those with relapsed disease can enter the study even if not previously entered at initial diagnosis. Patients may be entered into more than one randomisation/registration, depending on patient risk group and disease status.
Where can I find CLL support groups?
The main UK sarcoma support site
Sarcoma support groups
A list of local and online groups for general sarcoma or more specific conditions
The bone cancer research trust
A charity focussing on bone cancers with excellent information and patient stories
Awareness and symbols
All sarcomas have July as their awareness month. The ribbon for sarcomas is yellow