Familial GIST syndrome, also known as primary familial GIST syndrome, is a rare genetic disorder that causes the development of gastrointestinal stromal tumours (GISTs), a rare type of sarcomacancer arising from bones and/or soft tissue that forms in the lining of the gastrointestinal tract. It is caused by the genetic mutation of two tyrosine kinase genes, which are important for intracellular signals.
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
Familial GIST syndrome tends to affect the sexes equally, and tend to be diagnosed earlier than sporadic GISTS (often between the ages of 25-45). However, anyone can develop this disease.
Familial GIST Related Tumours
Familial GIST syndrome is associated with the development of GISTs only.
A gastrointestinal stromal tumoura tissue mass that forms from groups of unhealthy cells (GIST) is a rare type of sarcoma (cancer arising from bones or soft tissues) that forms in lining of the gastrointestinal tract. More specifically, they develop in interstitial cellsthe basic structural and functional unit of all living things of Cajal (ICC), which play a critical role in the intestinal contractions required for digestion. The gastrointestinal tract is primarily responsible for food digestion and nutrient uptake, and is made up of organs such as the stomach, small intestinea section of the gastrointestinal tract that recieves food from the stomach and absorbs the nutrients from food, also called small bowel, and large intestine (colonthe longest portion of the large bowel that absorbs water and salts from ingested food). GISTs are most commonly found in either the stomach, or the small intestine.
Unlike sporadic GIST, people with this condition tend to be diagnosed at a younger age, affects both sexes equally, and often have more than one tumour.
For more information on sporadic GISTs, please refer to the Rare Cancers Australia Gastrointestinal Stromal Tumours (GIST) page.
Treatment
As GIST is the only malignancy thus far that is associated with this disease, familial GISTs are staged and graded in the same way.
If GIST is detected, it will be staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissuea group of cells that work together to perform a function.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localisedaffecting only one area of body cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment of Childhood GIST
Due to the rarity of GIST in childhood, there are fewer treatment options than adults with GIST. Treatment options for childhood GIST may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
- Gastrectomycomplete or partial removal of the stomach.
- Complete or partial resectionsurgical removal of tissue or part/all of an organ of the intestine.
- Abdominoperineal resectionsurgical removal of the anus, rectum and a portion of the sigmoid colon through an incision in the abdomen.
- Pancreaticoduodenectomyremoval of part of the pancreas (generally the head), the first part of the small intestine (duodenum), part of the stomach, the gallbladder, and part of the common bile duct; also known as a Whipple procedure, also known as a Whipple procedureremoval of part of the pancreas (generally the head), the first part of the small intestine (duodenum), part of the stomach, the gallbladder, and part of the common bile duct; also known as a pancreaticoduodenectomy.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Treatment of GIST in adults
Adults with GIST have more treatment options that children with this disease. However, like childhood GIST, chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells and radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells are not often used to treat this type of cancer.
Treatment options for GISTs in adults may include:
- Surgery, potentially including:
- Gastrectomy.
- Complete or partial resection of the intestine.
- Abdominoperineal resection.
- Pancreaticoduodenectomy, also known as a Whipple procedure.
- Targeted therapy.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Clinical trials.
- Palliative care.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Familial GIST has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them.
Screening options for Familial GIST may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
Familial GIST syndrome is caused by genetic mutations in two particular genes:
- KIT (c-KIT, involved in intracellular signalling).
- PDGFRA receptors (platelet derived growth factor receptor alpha receptors, involved in intracellular signalling).
Familial GIST syndrome is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
GIST may appear asymptomatic in the early stages. Adults and children with GIST may experience some of the following symptoms:
- Bloodthe red bodily fluid that transports oxygen and other nutrients around the body in stoolwaste product from the bowel sent to the anus for removal; also known as faeces or poo and/or vomit.
- Abdominal pain and/or massa growth of cells that come together to make a lump, may or may not be cancer.
- Bloating.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Difficulties/pain when swallowing.
- Unexplainable weight loss/loss of appetite.
- Nauseato feel sick or likely to vomit and/or vomiting.
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection (low levels of red blood cells).
- Blocked intestinesportion of the digestive system that digests food (small intestine) and absorbs salts and water (large intestine), also called bowel, which carry its own set of symptoms:
- Abdominal cramping and/or swelling
- Nausea and/or vomiting.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Constipationa condition where a person has difficulty passing faeces/stools.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with Familial GIST, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Endoscopic ultrasoundan ultrasound taken during an endoscopy.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs, most commonly a gastroscopyexamination of the stomach and part of the small bowel with a small, flexible instrument known as a gastroscope.
- Biopsyremoval of a section of tissue to analyse for cancer cells.