Rhabdomyosarcoma

What is Rhabdomyosarcoma?

Some cancers develop from the connective tissues. This includes muscles, fats, bones, cartilage, blood vessels etc. the cancer that develops from skeletal muscles are called rhabdomyosarcoma.

There are three types of muscle tissues:

• Skeletal muscle: these are muscles that are controlled by our will. They are muscles of movement. They are also known as voluntary muscles.
• Smooth muscles: these are muscles that involve the internal organs. They are muscles which work on their own and are not controlled by our will. They are also known as involuntary muscles.
• Cardiac muscles: these are muscles which are a part of the heart.

When the foetus is in development, a group of cells called rhabdomyoblasts begin to develop and start forming skeletal muscle tissues.

Rhabdomyosarcoma (RMS) develops from this part of the cells. Since it is developmental cancer, it is more common in children.

Where does Rhabdomyosarcoma commonly occur?

Rhabdomyosarcoma not only develops at regions like arms and legs but also uncommon sites and sometimes even in regions which do not have skeletal muscles.

Some of the most common locations for Rhabdomyosarcoma are:

• Head and neck area:  near the eye, inside the nasal sinuses, base of the neck.
• Urinary and reproductive organs: urinary bladder, prostate, female reproductive organs
• Limbs (arms and legs)
• Abdomen and chest.

What are the risk factors associated with RMS?

• Age: it is more common in children, especially in the age group of 10 and below. It can occur in older individuals also.
• Gender: it is slightly more common in males than females.
• Genetic conditions: certain DNA changes can be inherited from the parents which leads to certain conditions. These are associated with specific cancers. Some of the associated syndromes are:
  1. Li-Fraumeni syndrome: have a tendency to develop breast cancer, leukaemia, and RMS
  2. Neurofibromatosis (von Recklinghausen disease): a syndrome that affects the nerve tissues and also increases the risk of RMS
  3. Beckwith-Wiedemann syndrome: high risk of developing Wilms tumour, RMS and kidney cancer.
  4. Costello syndrome: a rare childhood syndrome. The children are short, have high birth weights, and a large head. They are at a high risk of developing cancer.
  5. Noonan syndrome: a rare syndrome in which the children are short, have heart defects. Patients also have a defect in learning skills, and show higher risk of developing RMS.
• Exposures: when the mother is pregnant with the child, utmost care is to be taken to protect harmful agents from causing developmental disorders. Factors like X-ray radiations, use of drugs like marijuana have been linked to RMS.

What exactly causes rhabdomyosarcoma?

The exact mechanism of the occurrence of RMS is not known but researchers say that genetic changes that cause mutations in the DNA lead to abnormal division and growth of cancerous cells.

Human DNA is made up of various proteins, nitrogenous bases, sugars, and other organic components. They are arranged in a double helical form. Certain parts of a chromosome can shift from one chromosome to another. For example, in alveolar rhabdomyosarcoma, a part of chromosome 2 ends up attached to chromosome 13. This places two genes, one responsible for activation of other genes and the other responsible for muscle tissue cell growth, adjacent to each other. This probably activates the growth gene and leads to uncontrolled division.

Several genetic changes are required to make a healthy cell cancerous.

What are the different types of rhabdomyosarcoma?

The two basic types of RMS are the ones which affect children and the ones which affect adults.

RMS in children:

1. Embryonal rhabdomyosarcoma (ERMS):
   They are RMS which commonly affect the children below the age of 5. The cancer cells are spindle shaped, appearing similar to the normal developing muscle cells of 6-week-old foetus. The common locations for this type is head and neck area, vagina, bladder, prostate or testicles.
   There are two commonly found subtypes:
   1. Botryoid: they are commonly seen on the mucosal linings of the patient. It appears as a grape sized enlargement.
   2. Spindle: this subtype forms 3% of all the RMS. They are fascicular and spindle shaped. The cancer occurs in the para-testicular region. This subtype has an excellent chance of survival.
2. Alveolar rhabdomyosarcoma:
   This type of RMS makes for about 20-25% of the RMS. It is commonly seen in young adults and adolescents within the age group od 0 to 19. It is commonly seen in extremities, abdomen, trunk and peritoneum. It is more aggressive than ERMS.
   
   RMS in adults:
3. Anaplastic rhabdomyosarcoma:
   This type of RMS shows severe cellular changes which cannot even be recognised. They show a poor prognosis. They are more common in adults than in children. They may be localised to one region or widespread. The widespread version is also called diffuse version and has a poor prognosis. They are usually discovered in the extremities.
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What are the signs and symptoms?

The signs and symptoms are dependants on the location of the tumour.

• Neck, chest, back, limbs, groin: the first symptoms are of swelling which may or may not have pain. They may have reddish induration around.
• Eyes: bulging of the eyeball, pain, blurred vision, patient may appear squint.
• Sinuses: ear ache, headache, nasal stuffiness, sinus congestion
• Bladder and prostate: blood in the urine with painful urination.
• Vagina: vaginal bleeding
• Abdomen: nausea, vomiting, pain and constipation
• Bile ducts (rare): yellowing of eyes, jaundice
• Advanced stages: painful lumps, weakness, bone pain, and weight loss.

How are rhabdomyosarcomas discovered?

Certain diagnostic aids are used to identify RMS, their type, and stage.

After taking a thorough history and medical examination, the doctor may perform diagnostic tests to confirm the cause for the swelling or lump.

• Imaging:
  X-rays: tumours can be seen but they cannot visualize deep structures, can only be used for bony regions.
  C T scan: a more detailed image is obtained of the deeper structures like the muscles. They help to visualize the size, spread, dimensions and extent of the tumour accurately. The patient is asked to drink a solution which helps in producing a contrast dye. This solution may sometimes cause allergic reactions, so the patient must inform the physician about previous allergies.
  MRI: they also show a very detailed image which include the muscles, fat, connective tissues, and the tumour in great detail. This can be useful especially for planning the surgery. this is a longer procedure and the patient may feel claustrophobic.
  Bone scan: a small amount of radioactive material is injected into the tumour site and it settles down in abnormal parts of the tumour. It is then captured as hotspots on the scan.
  Ultrasound: waves and their echoes are made use to produce an image on the screen. The abnormalities are detected. It is useful for pelvic and abdominal scans.
• Biopsy:
  A small portion o the tissues are taken and sent for imaging under microscope. This test is usually confirmatory for RMS. There are various types of biopsy depending on the region of taking the tissues and the size of tissues taken. Example, core needle biopsy, fine needle aspiration cytology, bone marrow aspiration, and lumbar tap.

What is the RMS staging that is followed?

There are many staging systems. One of the most popular staging system is the TNM system.

Another clinical grouping system is used for the diagnostic and treatment purposes. It goes as follows:

CLINICAL STAGING:

GROUP 1:

Localised RMS that can be completely removed by surgery. this includes about 10 to 15 %RMS patients.

GROUP 2:

This includes children who have had almost all the visible parts of the cancer removed by surgery but the cancer cells are seen in the edges, which would mean that the cancer has spread to the nearby lymph nodes or may be left behind or both. About 20% of the RMS patients belong to this group.

GROUP 3:

These patients have parts of the tumour left behind as they could not be completely removed. They can be seen with naked eye. They may have spread to the nearby lymph nodes but no sign of spread to the distant parts. About 50% of the patients are belonging to this type.

GROUP 4:

At the time of diagnosis, these patients have RMS spread to distant locations like the lungs, liver, bones, bone marrow, muscles or distant lymph nodes.

Risk groups:

LOW RISK GROUP:

• TNM stage 1 ERMS who fall into clinical stages 1, 2, 3
• TNM stage 2 or 3 ERMS who fall into clinical stages 1 and 2

INTERMEDIATE RISK GROUP:

• TNM stage 2 or 3 ERMS who are in clinical group 3
• ARMS with clinical group 1,2,3

HIGH RISK GROUP:

• ERMS or ARMS with clinical staging 4

What are the treatments available for RMS?

There are many different specialists who’s help is required for the successful treatment of RMS.

• Orthopaedic surgeon – for treatments in relation to muscles and bones
• Paediatric oncologist – specializes in treating kids with cancer
• Radiation oncologist – specializes in radiation therapy
• Pathologist – specializes in identifying and staging of the cancer
• Physiatrist – specializes in physical rehabilitation of the patient

SURGERY:

It is usually the first step in RMS treatment. The entire tumour is excised if possible, if not, maximum excision without morbid loss of structure and function is carried out. It is usually accompanied by chemotherapy and radiation therapy.

CHEMOTHERAPY:

There are two main treatments in chemotherapy for RMS.

The VAC regimen: Vincristin, Actinomyosin D, Cyclophosphamide

The IVA regimen: Ifosfamide, Vincristin, Actinomyosin D

Other drugs that can be used supplementally are: Cisplatin and Doxorubicin

RADIATION THERAPY:

It is generally used when the tumour cannot be surgically removed. It can also be used along with surgical techniques. Radioactive seeds may also be placed to provide radiation in specific locations.

IMMUNOTHERAPY:

This type of treatment focusses on building the patient’s immune system to fight against cancer cells. It is still under development. One of the examples are dendritic cells which are directed against foreign cells with a certain fusion protein to focus the immune system to the malignant cells.