Yolk sac tumours (YSTs), also known as endodermal sinus tumours or primitive endodermal tumours, are rare and often aggressive tumours that develop from cellsthe basic structural and functional unit of all living things similar to those found in the yolk sac, allantois (an embryonic/fetal membrane that contributes to the formation of the umbilical cord) and mesenchyme (a type of embryonic connective tissuea group of cells that work together to perform a function that acts as a precursor to many of the body’s connective tissues, including bone, cartilage, bloodthe red bodily fluid that transports oxygen and other nutrients around the body and muscle) of an embryo.
Germ cell tumours are a rare group of neoplasms that arise from primordial germ cellsa cell that develops into reproductive cells (eggs in females, sperm in males) – the cells responsible for developing into reproductive cells (gametes) such as ovum and sperm. These tumours typically originate in the gonads, which are the organs that produce gametes (ovaries in females and the testicles in males). These tumours are referred to as gonadal germ cell tumours. In some cases, germ cells can migrate to other parts of the body during early embryonic development, leading to tumoura tissue mass that forms from groups of unhealthy cells formation outside of the gonads later in life. These are known as extragonadal germ cell tumours, and are most commonly found in the brain, mediastinumthe space between the lungs that holds many important structures, including the heart, trachea and oesophagus, retroperitoneuma space located behind the abdomen that contains many important bodily structures, such as the kidneys, or sacrococcygeal region.
In many cases, YSTs can increase the levels of alpha-fetoprotein (AFP), which is a hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body produced by the liver that is responsible for transporting heavy metal ions in fetal blood during the early stages of pregnancy.
YSTs are more common in females, and tend to be diagnosed in infancy, childhood or adolescence. However, anyone can develop this disease.
Types of Yolk Sac Tumours
YSTs can be classified by their location within the body.
Gonadal Yolk Sac Tumours
Gonadal YSTs are more common, and develop in either the ovaries or testicles.
Ovarian Yolk Sac Tumours
Ovarian YSTs are the second most common type of ovarian germ-cell tumour, and are the most common type of malignantcancerous, may grow and spread to other areas of the body ovarian germ-cell tumour in children. Unlike most YST’s, ovarian YST’s typically present in females in their 20’s. While ovarian YSTs can be aggressive, they can have a good prognosisto predict how a disease/condition may progress and what the outcome might be when found early.
Testicular Yolk Sac Tumours
Testicular YSTs are the most common form of testicular cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs in childhood, and can be broadly classified into two subtypes: post pubertal and prepubertal YSTs.
- Post pubertal testicular YSTs: are often components of mixed germ-cell tumours (a cancer containing cells from different germ-cell tumours) and tend to be diagnosed in males between the ages of 15-40 years old.
- Pre pubertal testicular YSTs: are often ‘pure’ germ-cell tumours (a cancer containing only one type of germ cell) and tend to be diagnosed in males under two years of age.
Post pubertal testicular YSTs are generally more aggressive, and may not have as good of a prognosis. Comparatively, pre-pubertal YSTs are generally less aggressive, and can have a good prognosis when found early.
Extragonadal Yolk Sac Tumours
Extragonadal YSTs are much less common than gonadal embryonal carcinomas, and develop in areas other than the gonads.
Intracranial Yolk Sac Tumours
Intracranial YSTs are a rare type of germ-cell tumour that develops in the brain, most commonly in the pineal, suprasellar, and posterior third ventricular regions. It is most commonly found in childhood and adolescence, however patients presenting outside of this age range have been reported. Intracranial YSTs are often aggressive, and may not have as good of a prognosis as other types of YSTs.
Mediastinal Yolk Sac Tumours
Mediastinal YSTs are a rare type of germ-cell tumour that develops in the mediastinum, most commonly the anterior mediastinum. It is most commonly found in males between the ages of 20-30 or in females around one year old. Mediastinal YSTs are often aggressive, and adolescents and adults over 15 years old may not have as good of a prognosis as other types of YSTs. Children and adolescents under 15 years old generally have a better prognosis when compared to adults.
Sacrococcygeal Yolk Sac Tumours
Sacrococcygeal YSTs are a rare type of germ-cell tumour that develops in the sacrococcygeal region, which is the area where the sacrum and coccyx regions of the spine are connected. These tumours are most common in children under the age of three, including neonates (newborns under one month old) and fetuses. Sacrococcygeal YSTs are often aggressive, and may not have as good of a prognosis as other types of YSTs.
Rare Extragonadal Yolk Sac Tumours
These types of YSTs are considered to be very rare:
- Retroperitoneal YST.
- Extracranial head and neck YST.
- Endometrial YST.
Treatment
If a YST 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 help your doctors determine the best treatment for you.
FIGO Staging System – Ovarian Yolk Sac Tumours
Ovarian cancers can be staged using the Federation of Gynaecologythe study of the female reproductive system and related diseases and Obstetrics (FIGO) system from stage I to IV:
- Stage I: cancer cells are confined to one or both ovaries only. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby organs in the pelvis, such as the uterus, fallopian tubes, bladder and/or bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines. This is also known as localised cancer.
- Stage III: the cancer has become larger and has spread beyond the pelvis into the lining of the abdomen (peritoneumthe membrane that lines the abdominal cavity). Lymph nodes are also often affected. This is also known as advanced or metastatic cancer.
- Stage IV: the cancer has spread to more distant organs, such as the lungs or the liver. This is also known as advancedat a late stage, far along or metastatic cancer.
TMN Staging System
All other YSTs can be staged using the TNM staging 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 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 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 advanced 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. They will then discuss the most appropriate treatment option for you.
Treatment Options
Treatment is dependent on several factors, including location, age, stage of disease and overall health.
Treatment options for YSTs 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 as possible – will vary based on tumour location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy 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.
Gonadal Yolk Sac Tumour Treatment and Fertility
Treatment for ovarian and testicular YSTs 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 YSTs are, there has been limited research done into the riskthe possibility that something bad will happen factors of this disease. However, a link has been found between the development of mediastinal germ cell tumours and males with the genetic disorder Klinefelter syndrome.
Symptoms
The symptoms of YSTs will vary based on location.
Symptoms of Ovarian Yolk Sac Tumours
Symptoms of ovarian YSTs may include:
- Abdominal distention.
- Abdominal pain.
- Lower abdominal or pelvic massa growth of cells that come together to make a lump, may or may not be cancer.
- Unusual vaginal bleeding not associated with menstruation.
Symptoms of Testicular Yolk Sac Tumours
Symptoms of testicular YSTs may include:
- A painless mass in the testicle(s).
- Changes in testicular size and/or shape.
- A feeling of heaviness and/or unevenness in the scrotum.
Symptoms of Intracranial Yolk Sac Tumours
Symptoms of intracranial YSTs vary based on location.
Pinel Gland Region
- Hydrocephalusa build up of cerebrospinal fluid (CSF) in the brain, causing pressure and potentially damaging brain tissue, which carries its own set of symptoms:
- Headaches.
- Nauseato feel sick or likely to vomit and/or vomiting.
- Difficulties with eye movement.
- Difficulties with balance.
- Difficulties with walking.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Memory problems.
- Seizures.
- Behavioural and/or cognitive changes.
- Vision changes, such as double vision and difficulty looking up.
Suprasellar and Third Ventricular Regions
- Irregular sleep.
- Early puberty in children.
- Delayed puberty in children.
- Stunted growth in children.
- Changes in eyesight, such as loss of peripheral vision or loss of vision.
- Diabetes insipidus (disorder causing fluid imbalance in the body), which carries its own set of symptoms:
- Polyuriafrequent urination.
- Intense thirst.
- Isolated growth hormone deficiency, which carries its own set of symptoms:
- Poor growth.
- Impaired hair and/or nail growth.
- Delayed development of teeth.
- Delayed puberty.
- Hypoglycaemialow blood sugar in infants and toddlers.
- Decreased energy levels.
- Increased fat around the face and/or abdomenstomach, stomach area, belly.
Symptoms of Mediastinal Yolk Sac Tumours
Symptoms of mediastinal YSTs may include:
- Dyspneadifficulty breathing, shortness of breath.
- Chest pain.
- Persistent cough.
- Weight loss.
- Fevers.
- Haemoptysiscoughing up blood.
- Superior vena cava syndrome, which has its own set of symptoms:
- Coughing.
- Dyspnea.
- Swelling of the face, neck, and/or upper arms.
Symptoms of Sacrococcygeal Yolk Sac Tumours
Symptoms of sacrococcygeal YSTs may include:
- Palpable mass in sacrococcygeal area.
- Pain in sacrococcygeal area.
- Changes in bowel habits, such as constipationa condition where a person has difficulty passing faeces/stools.
- Changes in urinary habits, such as urinary retention.
- Difficulties with bowel movements.
- Abdominal distention.
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 YST, 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.
- Endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
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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.
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- Chest X-raya type of medical imaging that uses x-ray beams to create detailed images of the body (mediastinal YSTs).
- 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 (where possible).
Exploratory Surgery
After conducting the previously mentioned diagnostic tests, your doctor may strongly suspect that you have testicular or ovarian cancer. In most cases, a diagnosis can be confirmed after a biopsy, where a section of tissue is removed and analysed for cancer cells. However, doctors avoid conducting a biopsy in patients who have suspected testicular and ovarian cancer as there is a small risk that making an incision in the scrotum or ovary could cause cancer cells to spread. As such, the only way to confirm the diagnosis safely is to remove the affected gonad.
Once the gonad has been removed, it will be sent to a laboratory and analysed for cancer cells.