Germ Cell Cancer Explained

Cancer is a collective term for conditions in which cells divide abnormally and uncontrollably, causing disruption to body tissues and organs. The origin of cancer ranges from hereditary to environmental factors. One of the lesser known origins of cancer is germ cells. 

What are germ cell tumours?

Germ cell tumours (GCTs) are tumours that originate from reproductive cells in the body. These reproductive cells are found in reproductive organs, such as ovaries for the development of eggs in women or testicles for the development of sperm in men. 

Germ cell tumours arise from cells called pluripotent stem cells which have the potential of becoming any type of cell in the body (blood cells or kidney cells). Due to the nature of the cell, different types of cancerous and non-cancerous tumours can be formed when abnormalities are found within it.¹

Doctors often find these germ cells in other parts of the body such as the spine or abdomen, causing tumours called extragonadal germ cell tumours (EGGCTs). There is still debate on how these rare tumours are developed as there are some EGGCTs seen in patients without the presence of spreading (metastatic) primary tumours in their reproductive organs.² 

Since these tumours arise from abnormal reproductive cells, there is a chance that the underlying genetic defects in these cells can be passed down to the next generation.¹ 

Germ cell tumours are very rare in children accounting for about 3% of childhood cancers as it is primarily caused if inherited from a parent.¹ Due to the complexity of these tumours, doctors recommend extensive testing to accurately determine the type of tumour before administering any treatment.  

Types of germ cell tumours

Germ cell tumours are described based on the organ it originated from, such as ovarian or testicular cancer, along with terms explaining its subtype based on how the cells look under a microscope. 

These tumours are mainly divided into benign (non-cancerous) and malignant (cancerous) types. Benign germ cell tumours contain teratomas, a type of tumour containing different types of tissues, such as muscle, bone, and even hair.

Malignant germ cell tumours are divided into:

• Seminoma germ cell tumours (dysgerminomas in women): These are tumours which only contain one type of cell
• non-seminoma germ cell tumours (non-dysgerminomas in women): these tumours tend to develop from a mixture of cells, such as embryonal cancerous cells and teratoma cells. Some of the non-seminoma germ cell tumours are yolk sac tumours, choriocarcinoma, and embryonal carcinomas 

Seminoma cells and non-seminoma cells are both present in some germ cell tumours. These are typically classified and treated by doctors as non-seminoma tumours.³ The germ cell tumours are found in reproductive organs and other regions in the body. The germ cell tumours are commonly found in:⁴

• Ovaries: non-cancerous cysts (dysgerminoma) and rare ovarian cancer
• Testicles: Seen as testicular cancer in men and slow growing tumours called seminomas are seen in adolescents
• Extragonadal germ cell tumours (EGGCTs): These tumours appear outside of the reproductive organs around the midline region of organs such as mediastinum in the chest (mediastinal germ cell tumours), tailbone or coccyx (sacrococcygeal germ cell tumours), the area behind the stomach (retroperitoneal germ cell tumours) and the brainstem/pineal gland region in the brain

Understanding the types of germ cell tumours and the region they are found is helpful for doctors to see their progression and decide on a better treatment strategy. 

What causes them?

The causes of germ cell cancers are not very well known. After extensive study of these tumours, doctors and scientists narrowed down some of the possible causes such as:^1,5

• Hereditary: other family members who had germ cell tumours
• Birth defects such as spina bifida in the spine or other pelvic defects 
• Androgen insensitivity syndrome: It is a condition where the individual is genetically male but is resistant to a male hormone called androgen. They are at risk of developing benign tumours which can become malignant.  
• Turner syndrome/gonadal dysgenesis: a genetic condition affecting only women, where one of their sex chromosomes (X chromosome) is partially or fully missing causing their body not to initiate puberty. They are at risk of developing benign cysts which could turn malignant in their ovaries. 
• Klinefelter’s syndrome: a genetic condition affecting only men, where they have an extra sex chromosome (normal male: XY, Klinefelter’s: XXY). They are at risk for developing testicular cancer and mediastinal germ cell tumours.
• Cryptorchidism: if a child has an undescended testicle, they have a risk of developing testicular cancer.

What are the symptoms?

Germ cell cancer symptoms depend on the type, stage and region of the tumour. Some of the commonly seen symptoms are:⁶

• Abdominal pain
• Constipation and weak bladder if the tumour is in the pelvic region
• Weakness in the legs in case of spinal tumours pressing on leg nerves
• Chest pain and shortness of breath if the tumour is near the lungs
• Visible mass near tailbone or anus in infants and children
• Unusual testicular shape and associated pain
• Early development of breasts, pubic hair, and vaginal bleeding in pre-pubescent girls

These symptoms may be associated with other diseases. If you or anyone you know experiences these symptoms it is advised to see a doctor for further diagnosis. 

What are the risk factors?

Germ cell cancers are caused by genetic disorders. The known risk factors are:^1,5

• Familial history: parents with faulty genes in their reproductive cells can pass it down to their children 
• Younger age groups (<3 years and infants)
• Race
• Cryptorchidism: risk of testicular cancer especially in children   
• Androgen insensitivity syndrome  
• Turner syndrome
• Klinefelter’s syndrome

If you have familial history or any of these genetic disorders, talk with your doctor about early detection using genetic testing and other methods for disease prevention. 

Diagnostics

Based on your history and physical examination, the doctor may prescribe tests such as:⁶

• Imaging tests: Computed tomography (CT) scans are used to scan the pelvis, abdomen, and chest, and ultrasounds to visualise ovaries and testes to check for the presence of tumours. To clearly visualise the presence of any tumours, ingestible contrast dye is administered. Magnetic resonance imaging (MRI) is used as a further test to measure the size of the tumour

• Blood tests: Blood count, liver, and kidney functions are assessed. Blood tests check the elevated levels of alpha 1-fetoprotein (AFP) and beta-human chorionic gonadotropin (bHCG). AFP is known as a tumour marker for testicular cancer

• Biopsy: A small piece of tissue from a tumour present in the pelvis or surrounding lymph node is removed by the doctor to check the presence of germ cells. A pathologist then studies the tissue under a microscope to learn more about the cells to find out if it is benign or malignant

The doctor usually combines these tests to confirm the presence of germ cell cancer. If they suspect your tumours are more advanced, they might do more diagnostic testing such as lung function, a lymph node biopsy, and extensive imaging to find out if the cancer has already spread. 

How are they treated?

The treatment is planned after a thorough diagnostic evaluation is completed. The doctor considers factors such as age, medical history, presence of other disorders, and the size, stage, location, and spread of the tumour. Germ cell cancers are usually treated with a combination of these treatment strategies:^3,6

• Surgery: Doctors recommend surgery if the tumours are confined to one organ. To effectively remove all the germ cell tumours, the ovary and testicles are removed in the process. Surgery is only suggested based on age and overall physical health

• Chemotherapy: Chemotherapy is used after surgery to kill any remaining germ cell tumour cells. Chemotherapeutic drugs are effective in treating and even completely curing certain germ cell cancers even if it has spread

• Radiotherapy: Radiotherapy is not usually used to treat germ cell tumours. In certain cases, doctors aim to use radiation to shrink the tumours to manage symptoms or for surgical removal

There is a chance of cancer coming back (relapsing) even after treatment. It is therefore very important to have regular check-ups with your doctor. Talk with your doctor or oncologist about your symptoms and priorities (such as fertility and having children later in life) to get the best treatment strategy for you.  

Summary

Germ cell cancer is a type of rare cancer starting in the reproductive cells. Even though it is a rare cancer, treatment is very promising. That being said, any cancer diagnosis is extremely difficult. Remember that you are not alone and there is support available from cancer support groups and your doctors to maintain your mental health and cope with it better. 

If you are aware of germ cell cancers running in your family, it is best to have a discussion with them and opt for early preventive genetic testing.