Cervical neuroendocrine tumours (NETs), also known as cervical carcinoid tumours, are a very rare form of neuroendocrine tumour 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, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, 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 cancer 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 grade 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, metastasis, and how the cancer cells look under the microscope. Staging 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 tissue 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 localised 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 bladder or rectum, 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 (node) 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:
- Surgery, 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-oophorectomy.
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- Bilateral salpingo-oophorectomy.
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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 risk factors of this disease. However, there may be a potential link to the development of this disease and infection 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 incontinence.
- Unexplained weight loss.
- Fatigue.
- 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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- Diarrhoea.
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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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- 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 diagnosis and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Pelvic examination.
- Cervical screening testa screening test that looks for signs of human papillomavirus (HPV) and abnormal cells in the cervix.
- Imaging tests, potentially including:
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- Pelvic ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
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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 surgerya 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.