Cervical neuroendocrine tumours (NETs), also known as cervical carcinoid tumours, are a very rare form of neuroendocrine tumoura tissue mass that forms from groups of unhealthy cells that develops from the cervix, a part of the female reproductive system that connects the uterus to the vagina. It has many important functions, including fluid production for vaginal health, mucus production to assist sperm in the fertilisation process, and it acts as a barrier to hold the baby in the uterus until birth.
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.
Cervical NETs are most commonly diagnosed around the age of 40, however it can affect anyone with a cervix – including pre-menopausal women, teenagers, transgender men, non-binary individuals, and intersex people – at any age.
Types of Cervical Neuroendocrine Tumours
Because of how rare cervical NETs are, there has been limited research done into the types of this disease. However, some variants of this disease have been identiftied.
Neuroendocrine Carcinomas of the Cervix
Neuroendocrine carcinomas of the cervixare a rare type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that are characterised by abnormal looking cancer cells under the microscope. There are two primary subtypes of this disease.
Small Cell Carcinoma of the Cervix
Small cell neuroendocrine carcinomacancer arising from tissues that line organs of the cervix (SCNECC), also known as oat cell neuroendocrine carcinoma of the cervix, is the most common variant of cervical NETs; however, they represent a very small proportion of cervical cancers. This type of tumour is often classified as a type of extrapulmonary small cell lung cancer, as the cells present are identical under a microscope. Unfortunately, SCNECC is often aggressive and may not have as good of a prognosisto predict how a disease/condition may progress and what the outcome might be as other types of cervical cancers.
Large Cell Carcinoma of the Cervix
Large cell carcinomas of the cervix are a very rare form of cancer that is often associated with large cell undifferentiated carcinoma of the lungs. Unfortunately, large cell carcinomas of the cervix are often aggressive, and may not have as good of a prognosis as other types of cervical cancers.
Typical Carcinoid Tumour of the Cervix
Typical carcinoid tumours of the cervix are a less common type of cervical NET that are generally classified as gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells one (slow growing) neuroendocrine tumours. These tumours are less common than atypical carcinoid tumours of the cervix, and can have a good prognosis when caught early.
Atypical Carcinoid Tumour of the Cervix
Atypical carcinoid tumours of the cervix are a more common type of cervical NET that are generally more aggressive than typical carcinoid tumours of the cervix. This subtype is more likely to metastasise, and may not have as good of a prognosis as other types of cervical cancers.
Treatment
If a cervical 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.
FIGO Staging System
Gynaecological cancers, such as cervical NETs, can be staged using the Federation of Gynaecology and Obstetrics (FIGO) system from stage I to IV:
- Stage I: cancer cells are confined to cervix tissuea group of cells that work together to perform a function only. This stage is also known as early-stage cancer.
- Stage II: cancer cells have spread to the upper two-thirds of the vagina and/or other nearby tissue. This is also known as localisedaffecting only one area of body cancer.
- Stage III: the cancer has become larger and has spread to lower third of the vagina and/or the side of the pelvic wall. Lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid and kidneys may be affected. This is also known as advancedat a late stage, far along or metastatic cancer.
- Stage IV: the cancer has spread to the bladdera hollow, muscular sac in the pelvis that stores urine or rectumthe last section of the large intestine/bowel that holds waste until it is ready to be removed from the body, or to more distant organs, such as the lungs or the liver. This is also known as advanced or metastatic cancer.
TNM Staging System
The TNM system can also be used to classify a cervical NET. The TNM system is comprised of:
- 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 nodes.
- 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 tissue.
- 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 localised 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.
- 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. They will then discuss the most appropriate treatment option for you.
Treatment Options
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for cervical 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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- Cone biopsythe surgical removal of a cone-shaped piece of tissue from the cervix to test for cancer cells.
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- Trachelectomycomplete or partial removal of the cervix.
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- Hysterectomycomplete or partial removal of the uterus.
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- Unilateral salpingo-oophorectomyremoval of one ovary and fallopian tube.
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- Bilateral salpingo-oophorectomyremoval of both ovaries and fallopian tubes.
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- Anterior pelvic exenterationremoval of reproductive organs (uterus, cervix, ovaries, fallopian tubes), part or all of the vagina, pelvic lymph nodes, urethra, lower portion of the ureters and the bladder.
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- Posterior pelvic exenterationremoval of reproductive organs (uterus, cervix, ovaries, fallopian tubes), part or all of the vagina, pelvic lymph nodes, lower portion of the bowel and the rectum.
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- Total pelvic exenterationremoval of reproductive organs (uterus, cervix, ovaries, fallopian tubes), part or all of the vagina, pelvic lymph nodes, lower portion of the bowel, rectum, urethra, lower portion of ureters and the bladder.
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- Lymphadenectomysurgical removal of lymph node(s).
- Somatostatin analogues (SSAs)medication used to inhibit excessive hormone production .
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, potentially including brachytherapya type of internal radiation therapy where radioactive material is placed inside or near a tumor to deliver targeted radiation.
- 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.
Cervical Neuroendocrine Tumour Treatment and Fertility
Treatment for cervical NETs may make it difficult to become pregnant. If fertility is important to you, discuss your options with your doctor prior to the commencement of treatment.
Risk factors
Because of how rare cervical NETs are, there has been little research done into the riskthe possibility that something bad will happen factors of this disease. However, there may be a potential link to the development of this disease and infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body with the human papillomavirus (HPV), which is a sexually transmitted disease (STD).
Symptoms
Some patients with cervical NETs will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:
- Changes in menstrual periods, such as irregular periods, unusual vaginal bleeding, or vaginal bleeding post menopause.
- Abnormal vaginal discharge.
- Pelvic pain and/or pressure.
- Pain during intercourse.
- Bleeding after intercourse.
- Urinary changes, such as changes in frequency, urgency and/or incontinenceloss of control over release of urine or faeces.
- Unexplained weight loss.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Abdominal pain/discomfort/pressure.
- 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 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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- Fatigue.
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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 cervical 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.
- Pelvic examinationa physical exam of the external and internal female pelvic organs.
- Cervical screening testa screening test that looks for signs of human papillomavirus (HPV) and abnormal cells in the cervix.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- Pelvic ultrasounda type of medical imaging that uses sound waves to create detailed images of the organs and structures within the pelvis, including the uterus, ovaries, and surrounding tissues.
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- 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.
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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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- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers 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.
- Biopsyremoval of a section of tissue to analyse for cancer cells.