Cowden syndrome, also known as multiple hamartoma syndrome, is a rare genetic condition that increases the riskthe possibility that something bad will happen of certain types of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. It is caused by a mutation of the phosphatase and tensin homolog (PTEN) gene, which is a tumoura tissue mass that forms from groups of unhealthy cells suppressor gene. Cowden syndrome is the most common type of PTEN hamartoma syndrome.
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.
Cowden syndrome tends to affect the sexes equally, and is generally diagnosed between the ages of 30-40. However, anyone can develop this disease.
Cowden Syndrome Related Tumours
Cowden syndrome is most commonly associated with the development of hamartomas, however it has also been linked to other types of tumours. Some examples include:
- Benignnot cancerous, can grow but will not spread to other body parts growths, including:
- Hamartomas (most common benign growth).
- Trichilemmomas (benign, wart-like growths that start in the hair follicles).
- Oral papules or fibromas.
- Keratoses on the surfaces of the hands and feet.
- Breast cancer (most common malignancy).
- Endometrial cancer.
- Thyroid cancer.
- Colorectal (bowel) cancer.
- Kidney cancer (Renal Cell Carcinoma (RCC)).
- Dysplastic gangliocytoma (also known as Lhermitte-Duclos disease).
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 Cowden syndrome 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 with Cowden syndrome 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 – these will vary based on tumour type and 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 Cowden syndrome 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. Some recommendations for Cowden syndrome may include:
- Annual physical exam starting at age 18 or five years before the earliest known cancer in the family was diagnosed (whichever comes first).
- Annual breast mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue and/or breast MRI starting at age 30 or 10 years before the earliest known breast cancer in the family was diagnosed (whichever comes first).
- Colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope every five years starting at age 35 or 5-10 years before the earliest known colonthe longest portion of the large bowel that absorbs water and salts from ingested food cancer in the family was diagnosed (whichever comes first).
- Annual skin examinations.
- Annual thyroid ultrasounds starting at age seven.
- Consideration of endometrial screening at age 35 in females.
- Consideration of renal ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body at age 40, then every 1-2 years.
Screening options for Cowden syndrome 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
Cowden syndrome is caused by a genetic mutation of the phosphatase and tensin homolog (PTEN) gene, which is a type of tumour suppressor gene. Two other genes, KLLN and WWP1, may also cause Cowden syndrome in some families. Cowden syndrome is an autosomal dominant disorder, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
The symptoms of Cowden syndrome often vary by the type(s) of tumours present. General symptoms of Cowden syndrome may include:
- Hamartomas.
- Trichilemmomas (benign, wart-like growths that start in the hair follicles).
- Oral papules or fibromas.
- Keratoses on the surfaces of the hands and feet.
- Macrocephaly (abnormally large head).
- Intellectual disability.
- Autism spectrum disorder.
- Thyroid abnormalities, such as benign tumours and goitres.
- Testicular lipomatosis.
- Lipomas.
- Polyps in the gastrointestinal tract.
- Fibromas.
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 Cowden syndrome, 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.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- 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:
- Mammogram.
- 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.
- Ultrasound.
- Exploratory procedures, such as an endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs.
- Biopsyremoval of a section of tissue to analyse for cancer cells.