PTEN hamartoma tumoura tissue mass that forms from groups of unhealthy cells syndrome (PHTS) is a group of genetic conditions that causes the development of multiple benignnot cancerous, can grow but will not spread to other body parts (non-cancerous) and malignantcancerous, may grow and spread to other areas of the body (cancerous) tumours throughout the body. It is caused by a mutation of the phosphatase and tensin homolog (PTEN) gene, which is a tumour suppressor gene located on chromosome 10.
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.
PHTS tends to affect the sexes equally, and is generally diagnosed between the ages of 30-50. However, anyone can develop this disease.
Types of PTEN Hamartoma Syndrome
There are four types of PHTS, which are characterised by tumour locations and disease characteristics.
Cowden Syndrome
Cowden syndrome, also known as multiple hamartoma syndrome, is the most common subtype of PHTS, and is associated with the development of malignancies – most commonly breast, thyroid and kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body cancers – as well as other benign growths. For more information on Cowden syndrome, please refer to the Rare Cancers Australia Cowden Syndrome page.
Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
Bannayan-Riley-Rubalcaba syndrome (BRRS), also known as Bannayan-Zonana syndrome, Ruvalcaba-Myhre syndrome and Riley-Smith syndrome, is a less common variant on PHTS that is often diagnosed in early childhood. It is characterised by a large head size (macrocephaly), dark freckle-like spots on the penis in males and multiple benign growths. While the likelihood of people with BRRS developing cancer is not well understood, it is recommended that people with the disease have regular check-ups to monitorto check on, keep track of for any signs of malignancy.
Proteus Syndrome
Proteus syndrome (PS), also known as elattoproteus syndrome and elephant man disease, is a rare subtype of PHTS that is often diagnosed in childhood. It is characterised by abnormal bone and bloodthe red bodily fluid that transports oxygen and other nutrients around the body vessela tube that carries bodily fluid, such as blood or lymph fluid, around the body growth, multiple skin lesions, multiple benign growths, and overgrowth of different body parts over time. While the likelihood of people with PS developing cancer is not well understood, it is recommended that people with the disease have regular check-ups to monitor for any signs of malignancy.
Proteus-like Syndrome
Proteus-like syndrome is a rare subtype of PHTS that describes patients who do not meet the diagnostic criteria for PS, but have many of the characteristics of the disease associated with the condition. Similarly to PS, it is generally diagnosed in childhood and may exhibit some of the same symptoms – including abnormal bone and blood vessel growth, multiple skin lesions and multiple benign growths. While the likelihood of people with Proteus-like syndrome developing cancer is not well understood, it is recommended that people with the disease have regular check-ups to monitor for any signs of malignancy.
Types of Tumours Associated with PTEN Hamartoma Syndrome
PHTS may result in the development of some of the following:
- Benign 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.
- Lipomas
- Café au lait macules.
- Intramuscularinto or within a muscle lesions.
- Fibromas.
- Breast cancer (most common malignancy).
- Breast cancer (Male).
- Endometrial cancer.
- Thyroid cancer.
- Colorectal cancer.
- Kidney cancer (Renal Cell Carcinoma (RCC)).
- Dysplastic gangliocytoma (also known as Lhermitte-Duclos disease).
- Cutaneous Melanoma.
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 (whether the cancer has spread to other parts of the body) 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 PHTS will present with a unique disease behaviour, with varying cancer 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 cancer present.
- Cancer location.
- Whether or not the cancer has 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 PHTS 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.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
- 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 PHTS 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 PHTS may include:
- Annual physical exam starting at 18 years, or five years before the age of the first relevant cancer diagnosis in the family (whichever comes first).
- Clinical breast exam every 6-12 months in females starting at age 25.
- Annual mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue in females starting at 30-35 – breast MRI should also be considered.
- Annual thyroid ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body from time of diagnosis.
- Annual ultrasound every 1-2 years starting at age 40 – MRI or CT scan can also be considered.
- Transvaginal ultrasounda type of pelvic ultrasound that involves inserting a device (known as a transducer) into the vagina to produce sound waves and create images of internal female reproductive organs in greater detail in post-menopausal females as needed.
- Colonoscopyan examination of the large intestine/bowel with a small, flexible instrument known as a colonoscope every five years starting at age 35, or more frequently if symptomatic or if polyps have been found.
- Annual skin examinations.
Screening options for PHTS 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
PHTS is caused by a genetic mutation of the phosphatase and tensin homolog (PTEN) gene, which is a type of tumour suppressor gene. For patients with Cowden syndrome, two other genes, KLLN and WPP1, may also cause the disease in some families. PHTS are autosomal dominant diseases, which means you have a 50% chance of inheriting the condition if one of your parents carries the mutation.
Symptoms
The symptoms of PHTS often vary by the type(s) of tumours present. General symptoms of PHTS 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.
- Intellectual disability.
- Thyroid abnormalities, such as benign tumours and goitres.
- Testicular lipomatosis.
- Lipomas.
- Polyps in the gastrointestinal tract.
- Fibromas.
- Dark freckle-like spots on the penis in males.
- Vascular anomalies (abnormalities with blood vessels).
- Intramuscular lesions.
- Muscle weakness.
- High-arched palate of the mouth.
- Abnormal range of motion of joints, also known as joint hypermobility.
- Haemangiomas.
- Overgrowths of cells on the face.
- Low muscle tone (hypotonia).
- Seizures (less common).
- Autism spectrum disorder (ASD).
- Funnel chest.
- Abnormalities of the spine, potentially including scoliosis, kyphosis, or kyphoscoliosis.
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 PHTS, 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.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- 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.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers 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.