Testicular neuroendocrine tumours (TNETs), also known as testicular carcinoid tumours, are a very rare form of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that develops in the testicles. The testicles (or testes) are two egg-shaped glands of the male reproductive system that sit outside of the body in a skin sac called the scrotum.
The testicles are responsible for the production and storage of sperm, the male gamete (reproductive cell) that swims to fertilise the female gamete, called ova or eggs. They are also responsible for producing and secreting testosterone, the primary male hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body. Testosterone is responsible for the regulation of sexual development (including development of male reproductive organs, and secondary sex characteristics such as facial hair and voice deepening), bone and muscle massthe total amount of skeletal muscle tissue in the body, fat distribution, sex drive (or libido), sperm production and red bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell production.
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, blood 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.
TNETs are often diagnosed in men between the ages of 30-40, however, they can affect anyone with testicles – including men, teenagers, transgender women, non-binary individuals, and intersex people – at any age.
Types of Testicular Neuroendocrine Tumours
There are three primary types of TNETs, which are classified by their location of origin and if they develop alongside another condition:
- Primary TNET (cancer originates in the testicles).
- Secondary TNET (cancer originated in another location and metastasised/spread to testicles).
- TNET associated with teratoma (TNET developed after or alongside a teratoma, which is a type of germ-cell tumoura tissue mass that forms from groups of unhealthy cells often found in the gonads).
Treatment
If a testicular NET 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. Staging and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 localised 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 localisedaffecting only one area of body cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 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 options for testicular NETs may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
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- Unilateral orchidectomyremoval of one testicle/orchiectomy.
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- Bilateral orchidectomyremoval of both testicles/orchiectomy.
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- Lymphadenectomysurgical removal of lymph node(s).
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- Testicular prosthetic surgeryinsertion of a prosthetic testicle(s) after an orchidectomy.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells (limited).
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells (limited).
- Somatostatin analogues (SSAs)medication used to inhibit excessive hormone production .
- 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.
Testicular Neuroendocrine Tumour Treatment and Fertility
Treatment for TNETs may make it difficult to conceive a child. If fertility is important to you, discuss your options with your doctor and a fertility specialist prior to the commencement of treatment.
Risk factors
Because of how rare TNETs are, there has been little research done into the riskthe possibility that something bad will happen factors of this disease.
Symptoms
Some patients with TNETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:
- Testicular massa growth of cells that come together to make a lump, may or may not be cancer and/or swelling.
- Pain or discomfort in the testicle(s) and/or scrotum.
- Fluid build-up in the scrotum.
- Changes in testicular size and/or shape.
- A feeling of heaviness in the scrotum.
- A feeling of unevenness in the scrotum.
- Enlargement and/or tenderness of breast tissue caused by excess hormones.
- Cryptorchidism.
- Carcinoid syndrome (rare), which carries its own set of symptoms:
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- Facial flushing (usually red or purple in the face, neck, and/or upper chest).
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- Diarrhoeafrequent discharge of watery or loose stools from the body.
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- Wheezing.
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- Abdominal pain.
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- Carcinoid heart disease (plaques on the heart muscle caused by excess hormone production).
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- Faecal urgency.
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- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
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- Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
- Paraneoplastic syndromesa group of rare disorders that occur when the immune system has a reaction to a cancerous tumour within the body (rare).
- Hypercalcaemiaexcess levels of calcium in the blood (rare).
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 a TNET, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Imagingtests that create detailed images of areas inside the body tests, most commonly an ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Blood teststesting done to measure the levels of certain substances in the blood.
- Exploratory surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone.
Exploratory Surgery
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 biopsyremoval of a section of tissue to analyse for cancer cells, where a section of tissue 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 or both testicles, also known as orchiectomy.
Once the testicle has been removed, it will be sent to a laboratory and analysed for cancer cells.