Carney complex is a rare type of multiple endocrine neoplasia syndromes (MENS) that is characterised by myxomas throughout the body, distinctive skin pigmentation and a predisposition to malignancy (cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs). Multiple endocrine neoplasia syndromes (MENS) are a rare group of neuroendocrine tumours characterised by tumours that develop in two or more endocrine glandsglands responsible for the production and secretion of hormones. Endocrine glands are responsible for the production and secretion of hormones, and help to control many vital bodily functions
Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cellsthe basic structural and functional unit of all living things, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
Familial cancer 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.
Carney complex is often confused with the conditions Carney-Stratakis syndrome (a rare condition that causes the development of paragangliomas and gastrointestinal stromal tumours (GISTs) only) and Carney triad (a very rare condition that causes the development of paragangliomas, GISTs, and pulmonary chondromas). While the three syndromes share a similar name, it is important to recognise they are different conditions. For more information on either Carney-Stratakis syndrome or Carney triad, please refer to their respective pages on the Rare Cancers Australia knowledgebase.
Carney complex tends to affect the sexes equally, and is generally diagnosed around the age of 20. However, anyone can develop this disease.
Carney Complex Related Tumours
Carney complex is most commonly associated with the development of myxomas, however it has also been linked to other types of tumours. Some examples include:
- Myxomas (benignnot cancerous, can grow but will not spread to other body parts, most commonly of the heart and skin).
- Pituitary adenomas.
- Benign peripheral nerve sheath tumours (BPNSTs).
- Malignant peripheral nerve sheath tumours (MPNSTs).
- Thyroid tumours (usually benign, can be malignantcancerous, may grow and spread to other areas of the body).
- Testicular cancer (most commonly Sertoli-Leydig cell tumours).
- Benign breast tumours.
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 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. However, each patient with Carney complex will present with a unique disease behaviour, with varying tumoura tissue mass that forms from groups of unhealthy cells 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 malignant (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 Carney complex 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 Carney complex 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 Carney complex may include:
- Annual echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow for cardiac myxomas in children and adults.
- Annual thyroid ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body for thyroid nodules in children and adults.
- Annual testicular ultrasound in males prior to puberty.
- Annual endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels beginning in adolescence, potentially including:
- Cortisol.
- Insulin-like growth factor-1 (IGF-1).
- Prolactin.
- Abdominal ultrasound at time of diagnosis in females.
Screening options for Carney complex 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
Carney complex is caused by a genetic mutation in the protein kinase A type-I alpha regulatory subunit (PRKAR1A) gene, which is responsible for promoting cell growth and division. It is an autosomal dominant disorder, which means you have a 50% chance of developing the condition if one of your parents carries the genetic mutation.
Symptoms
The symptoms of Carney complex often vary by the type(s) of tumours present. General symptoms of Carney complex may include:
- Skin pigmentation on the face, lips, eyes, trunk, or genital mucosa.
- Lentigines (small, raised spots that resemble freckles) on the skin.
- Blue nevi on the skin.
- Café-au-lait spots on the skin.
- Fever.
- 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.
- Unexplained weight loss/loss of appetite.
- Joint stiffness.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
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 Carney complex, 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.
- Genetic testing.
- Endocrine studies.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- Echocardiogram.
- Ultrasound.
- Electromyogram (EMG)a diagnostic procedure used to measure the response of nerves and skeletal muscles to electrical activity.
- Nerve conduction studiesa diagnostic procedure used to measure the speed of electrical impulses through a nerve.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
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 (removal of one testicle).
Once the testicle has been removed, it will be sent to a laboratory and analysed for cancer cells.