Appendiceal neuroendocrine tumours (NETs), also known as appendiceal carcinoid tumours, are a rare form of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that develop in the appendix, a small, finger-shaped pouch connected to the caecum of the large bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines/intestine. It sits on the lower right side of the abdomenstomach, stomach area, belly, and has an unknown function within the body.
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.
Appendiceal NETs generally affect the production of enterochromaffin cells, which can produce a variety of hormones – most commonly serotonin. Serotonin is a neurotransmitter that plays a crucial role in a variety of bodily functions, such as digestion and the regulation of mood, appetite and sleep.
Appendiceal NETs are slightly more common in females, and tend to be diagnosed before the age of 40. However, anyone can develop this disease.
Types of Appendiceal Neuroendocrine Tumours
Because of how rare appendiceal NETs are, there has been limited research done into the subtypes of this disease. However, one distinct variant has been identified.
Goblet Cell Carcinoma (GCC)
Goblet cell carcinomas (GCC) are rare neuroendocrine tumours that develop from goblet cells in the appendix, which are responsible for mucus secretion and production.
GCCs demonstrate a unique combination of both neuroendocrine cells and adenocarcinoma cells, which are cancerous cells that develop from mucus-producing cells. They tend to be more aggressive than classic neuroendocrine tumours, but are classified and staged as carcinomas of the appendix.
For more information on GCCs, please refer to the Rare Cancers Australia Goblet Cell Carcinoma (GCC) page.
Treatment
If an appendiceal 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. 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.
Cancers can be staged using the TNM staging system:
- T (tumoura tissue mass that forms from groups of unhealthy cells) 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 localisedaffecting only one area of body 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 localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade 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. This is often performed after a biopsyremoval of a section of tissue to analyse for cancer cells, and can help guide treatment options for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for appendiceal 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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- Appendectomycomplete removal of the appendix.
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- Right hemicolectomyremoval of a portion of the colon; can be the right side (right hemicolectomy) or the left side (left hemicolectomy) (for tumours larger than 2cm).
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- Liver resectionsurgical removal of tissue or part/all of an organ (for metastatic disease, very rare).
- Somatostatin analogues (SSAs)medication used to inhibit excessive hormone production (for metastatic disease, very rare).
- 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.
Risk factors
Because of how rare appendiceal NETs are, there has been limited research done into the risk factors of this disease.
Symptoms
Most patients with appendiceal NETs appear asymptomatic, and the tumours are often found incidentally. As the tumour progresses, some of the following symptoms may appear:
- Abdominal pain in the lower right quadrant (often caused by an appendicitisinflammation of the appendix).
- Gradual increase in waist size.
- Ascitesa buildup of fluid in the abdomen.
- Bloating.
- Changes in bowel habits, potentially including constipationa condition where a person has difficulty passing faeces/stools or diarrhea.
- Herniathe protrusion of organs or tissue through a weakened section of the abdomen.
- Ovarian massa growth of cells that come together to make a lump, may or may not be cancer/lump.
- Nauseato feel sick or likely to vomit and/or vomiting.
- Feeling full after eating little food.
- Carcinoid syndrome, 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 hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body 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.
- Bowel obstructiona complete or partial blockage of the bowel/intestines.
- Abdominal lumps.
- Gastrointestinal bleeding.
- Intussusceptiona serious condition that occurs when part of the intestine slides into another part of the intestine causing a bowel obstruction.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
Most appendiceal NETs are found incidentally when being treated for another condition, such as an appendicitis. If your doctor suspects you have an appendiceal NET, 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.
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- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- 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.
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- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
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- 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.
- Diagnostic laparoscopya minimally invasive surgical procedure that uses small incisions to access the body for procedures, often used for conditions that cannot be confirmed by scans and tests alone.
- Biopsy.