Peutz-Jeghers syndrome (PJS) is a rare genetic condition that increases the riskthe possibility that something bad will happen of developing certain types of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs, most notably colonthe longest portion of the large bowel that absorbs water and salts from ingested food cancer. It is caused by an alteration in the serine/threonine kinase 11 (STK11) gene, which is a tumoura tissue mass that forms from groups of unhealthy cells suppressor. People with PJS often develop multiple benignnot cancerous, can grow but will not spread to other body parts polyps (which develop as hamartomas), as well as dark skin macules in and around the mouth, eyes, nostrils and fingers.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk 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.
PJS is generally diagnosed equally among the sexes, and is often diagnosed between the ages of 10-30. However, anyone can develop this disease.
PJS Related Tumours
PJS is most commonly associated with the development of colorectalrelating to the colon or rectum in the large bowel/intestine cancer, however it has also been linked to other types of tumours. Some examples include:
- Colorectal (bowel) cancer.
- Stomach (gastric) cancer.
- Small bowel cancer.
- Pancreatic cancer.
- Breast cancer.
- Ovarian cancer.
- Cervical cancer.
- Testicular cancer, most commonly Sertoli-Leydig cell testicular cancer.
- Cholangiocarcinoma.
- Lung cancer.
- Gallbladder cancer.
- Oesophageal cancer.
Treatment
When cancers are detected, they are 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 cellsthe basic structural and functional unit of all living things 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. However, each patient with PJS will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignantcancerous, may grow and spread to other areas of the body (cancerous) or benign (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also 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 options for tumours associated PJS may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – this will vary based on tumour location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill 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.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of PJS 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. For patients with PJS, the screening guidelines differ between children and adults.
Childhood PJS Screening Guidelines
For children with PJS, screening guidelines may include:
- Gastroscopyexamination of the stomach and part of the small bowel with a small, flexible instrument known as a gastroscope at 8-10 years old. If polyps are detected, this may need to be repeated every 2-3 years.
- Colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope at 8-10 years old. If polyps are detected, this may need to be repeated every 2-3 years.
- Video-capsule endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs at 8-10 years old. If polyps are detected, this may need to be repeated every 2-3 years.
- CT and/or MRI of the small bowel at 8-10 years old. If polyps are detected, this may need to be repeated every 2-3 years.
- Annual physical exams in girls starting at eight years old to check for signs of early puberty.
- Annual testicular exams in boys starting at age 10.
Adulthood PJS Screening Guidelines
For adults with PJS, screening guidelines may include:
- Gastroscopy every 2-3 years starting at 18 (if not already).
- Colonoscopy every 2-3 years starting at 18 (if not already).
- Video-capsule endoscopy every 2-3 years starting at 18 (if not already).
- CT and/or MRI of the small bowel every 2-3 years starting at 18 (if not already).
- MRI or endoscopic ultrasoundan ultrasound taken during an endoscopy of the pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation every 1-2 years starting at 30-35 years old.
- Annual testicular examinations in males (continued from childhood).
- Annual pelvic examinations and pap smears in females starting at 18-20 years old.
- Clinical breast examination every 6-12 months in females starting at age 30.
- Annual mammograms in females starting at age 30.
Screening options for PJS 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
PJS is caused by a genetic mutation in the STK11 tumour suppressor gene, which acts to inhibit cell growth to prevent overproduction of cells and the development of tumours. It 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
The symptoms of PJS often vary by the type(s) of tumours present. General symptoms of PJS may include:
- Dark brown skin macules in and around the mouth, eyes, nostrils and fingers.
- Hamartomatous polyps in the gastrointestinal tract.
- Abdominal pain and/or discomfort.
- Changes in bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines movements, potentially including:
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Constipationa condition where a person has difficulty passing faeces/stools.
- Feeling of incomplete bowel movement.
- Thin bowel stools.
- Bloodthe red bodily fluid that transports oxygen and other nutrients around the body in stools.
- Constipation.
- Unexplained weight loss/loss of appetite.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Nauseato feel sick or likely to vomit and/or vomiting.
Symptoms related to specific tumours can be found on our knowledgebase.
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 PJS, 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.
- Pelvic examinationa physical exam of the external and internal female pelvic organs.
- Blood teststesting done to measure the levels of certain substances in the blood.
- 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.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue.
- Exploratory procedures, potentially including:
- Colonoscopy.
- Gastroscopy.
- Video-capsule endoscopy.
- Biopsyremoval of a section of tissue to analyse for cancer cells (where applicable).
Biopsy and Testicular Cancer
After conducting the previously mentioned diagnostic tests, your doctor may strongly suspect that you have a testicular cancer. In most cases, a diagnosis can be confirmed after a biopsy, where a section of tissuea group of cells that work together to perform a function is removed and analysed for cancer cells. However, doctors avoid conducting a biopsy in patients who have suspected testicular cancer as there is a small risk that making an incision in the scrotum could cause cancer cells to spread. As such, the only way to confirm the diagnosis safely is to perform a unilateral orchidectomyremoval of one testicle.
Once the testicle has been removed, it will be sent to a laboratory and analysed for cancer cells.