What are the other Names for this Condition? (Also known as/Synonyms)

• Extragenital Germ Cell Tumor

What is Extragonadal Germ Cell Tumor? (Definition/Background Information)

• Extragonadal Germ Cell Tumors are formed when germ cells, which are the precursors of sperm cells or ovum, travel to other parts of the body and grow into tumors. These tumors are also referred to as germ cell neoplasm
• They usually occur along the midline, especially in the mediastinal cavity between the lungs. They may occur in the back wall of the abdomen (retroperitoneum), the pineal gland of the brain, or in other regions of the body
• Extragonadal Germ Cell Tumors may benign, borderline, or low malignant potential (LMP), or malignant tumors
  • Benign tumors are not cancers and do not spread or metastasize
  • Borderline or low malignant potential (LMP) tumors are usually benign, but some behave like cancers    
  • Malignant tumors are cancers that spread and metastasize
• Extragonadal Germ Cell Tumors are classified into:
  • Benign teratoma, which is the most common type of such tumor
  • Malignant seminoma
  • Malignant non-seminomatous germ cell tumors that include embryonal carcinomas, malignant teratomas, endodermal sinus tumors, choriocarcinomas, and mixed cell tumors
• Extragonadal Germ Cell Tumors most commonly occur in young males, and are usually associated with Klinefelter syndrome
• The symptoms depend on the site and size of the tumor. The tumors most commonly occur in the cavity between the lungs (mediastinum), and cause chest pain
• The prognosis depends upon many factors that include the type and stage of the tumor. The most common, which is benign teratoma, has the best prognosis and may be completely cured with surgery alone

Who gets Extragonadal Germ Cell Tumor? (Age and Sex Distribution)

• Extragonadal Germ Cell Tumors are rare and account for only a small percentage of the germ cell tumors. It is far less common than gonadal germ cell cancers, which occurs in ovaries and testis
• They commonly tend occur in younger individuals, especially males; though the condition can occur in both males and females

What are the Risk Factors for Extragonadal Germ Cell Tumor? (Predisposing Factors)

The most important risk factor for Extragonadal Germ Cell Tumor is Klinefelter syndrome. In this syndrome, males inherit an extra X chromosome and are at an increased risk of Extragonadal Germ Cell Tumors.

Additionally, as with other gonadal tumors, the risk factors for Extragonadal Germ Cell Tumors may include:

• Genetic mutations
• Male sex
• Presence of a condition called gonadal dysgenesis (which causes the abnormal development of a testicle) increases the risk
• Individuals with low birth weight may have an increased risk of developing the tumors
• Family or personal history: Individuals with a family history of testicular or ovarian cancers
• Infertility
• Smoking: Some studies have shown that longstanding smoking can increase the risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Extragonadal Germ Cell Tumor? (Etiology)

The cause of Extragonadal Germ Cell Tumors is not completely understood. It is believed to occur due to the abnormal migration of precursors of sperm and ovum during development. Some factors that may be responsible for its development include:

• Genetic defects in the number of X chromosomes such as Klinefelter syndrome, Turner syndrome, etc.
• Genetic mutations: Researchers have documented certain genetic changes within the tumor. However, cases where these specific genetic mutations have been observed are rare. Thus, studies regarding genetic changes are limited
• Family history of Extra Gonadal Germ Cell Tumors

What are the Signs and Symptoms of Extragonadal Germ Cell Tumor?

The signs and symptoms of Extra Gonadal Germ Cell Tumors depend on a number of factors such as:

• Size of the tumor
• Histological type of tumor
• If the tumor is a cyst or a solid mass
• Whether tumor produces hormones
• Spread of tumor locally
• Rupture of the cystic mass
• Extent of bleeding within the tumor
• Whether the tumor is present as part of a syndrome (underlying condition). In such a case, the signs and symptoms associated with the accompanying syndrome may exist

Sometimes the tumor that is usually well-defined shows no signs and symptoms. Usually, a benign growth develops over months to years. About 50-70% of the time, the tumor occurs in the mediastinum (space between the lungs) and most commonly presents as a pain in the chest. The condition may also lead to:

• Difficulty in breathing, swallowing
• Cough
• Weight loss
• Facial swelling
• Hoarseness of voice

When Extra Gonadal Germ Cell Tumors occur in the retroperitoneum it may cause:

• Abdominal pain (the pain is usually a pelvic pain)
• Abdominal swelling due to the mass or due to fluid accumulation in the belly (called ascites)
• Increased abdominal girth due fluid accumulation (ascites)
• Persistent feeling of abdominal bloating with nausea or vomiting
• Changes in bowel movements, such as constipation
• Feeling full sooner after a meal (easily having a feeling of satiety)
• Loss of appetite with weight loss
• Fatigue (feeling tired easily)
• Frequent urination (polyuria) and difficulty while urinating

In rare cases, when tumors occur in the brain, the symptoms may include:

• Headache, nausea, and vomiting due to increased intracranial pressure
• Deterioration of intellectual function, seizures, movement disorders, or visual difficulties, depending on the region of brain compressed by the tumor
• Trouble with eye movement
• Precocious pseudo-puberty, where the individual attains puberty too soon
• Diabetes insipidus, due to which the individual urinates frequently and passes abnormally high amounts of urine
• Growth hormone and thyroid hormone deficiencies

In general, the Extragonadal Germ Cell Tumor is a combination of cystic and solid mass; it is usually slow-growing, but sometimes grows rapidly.

How is Extragonadal Germ Cell Tumor Diagnosed?

Extragonadal Germ Cell Tumors are diagnosed by a detailed medical history and physical examination. Additionally, the following examination and tests may be performed:

• Blood tests to measure tumor markers such as
  • Serum alpha fetoprotein (AFP)
  • Beta subunit of human chorionic gonadotropin (beta-hCG)       
  • Lactate dehydrogenase (LDH)
  • Placental alkaline phosphatase
  • Estrogen levels
  • Testosterone levels
  • Vasopressin levels
• Liver function tests
• Chest x-ray
• Testicular and pelvic ultrasound to rule out primary tumor in the testis or in the ovaries
• CT, MRI, and PET scan of the chest, abdomen, or pelvis to identify and stage the tumors
• Cytogenetic analysis to rule out Klinefelter syndrome
• Tissue biopsy of the tumor: A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing and very rarely electron microscopic studies. Examination of the biopsy under a microscope by a pathologist is considered to be the gold-standard in arriving at a conclusive diagnosis 

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Extragonadal Germ Cell Tumor?

The complications of Extragonadal Germ Cell Tumors may occur due to the tumor, distant metastasis, or secondary to treatment. The complications may include:

• Pneumonia
• Superior vena cava syndrome, due to obstruction of the superior vena cava (large vein carrying blood to heart) which may cause:
  • Breathing and swallowing difficulties
  • Facial swelling        
  • Cough
  • Swelling in the arm
  • Chest pain
  • Hoarseness of voice, nasal stuffiness
  • Headache
  • Pleural effusions
  • Light-headedness, nausea
• Backaches, either due to the primary tumor or due to metastatic tumors
• Visual complications
• Bleeding, anemia
• Inadvertent damage of vital nerves, blood vessels, and surrounding structures during surgery may occur depending on the location of the tumor in the body
  • Some tumors which are away from the vital organs can be removed, usually with no significant damage
  • However, some tumors may grow close to the vital organs and structures that makes their surgical removal difficult and challenging
• Retrograde ejaculation, if nerves are damaged during the surgery
• Side effects from chemotherapy (toxicity) and radiation therapy can occur in case of malignant tumors
• Infertility, depending on the type of treatment given
• Paralysis

Extragonadal Germ Cell Tumors is a fatal condition that can result in death, if early diagnosis and treatment is not provided. 

How is Extragonadal Germ Cell Tumor Treated?

The treatment of the Extragonadal Germ cell Tumor is based on the stage, type, and location of the tumor. It may include:

• Surgical removal of the tumor (if it is benign teratoma)
• For malignant type, the treatment may consist of:
  • Surgery to remove the tumor and the lymph nodes draining the tumor region
  • Debulking surgery to reduce tumor mass (especially in choriocarcinoma), followed by a combination of chemotherapy and radiation therapy. The debulking procedure helps the chemotherapy treatment to be more effective, because there is less tumor mass for the medication to act on
  • Chemotherapy to kill cancer cells using cytotoxic drugs
  • Radiation therapy to destroy cancer cells using high-energy radiation
• Occasionally, based upon the location of the tumor, a complete removal of the tumor may be difficult. In such cases, the tumor may recur
• Sometimes the tumor is at an inaccessible location, or is unsafe for a surgical intervention. In such cases, non-invasive procedures, such as chemotherapy and radiation therapy, are generally adopted
• Palliative therapy, in case the cancer is inoperable
• Follow-up care with regular screening and check-ups are important
• The healthcare provider will determine the best course of treatment depending on each individual’s specific circumstances. 

How can Extragonadal Germ Cell Tumor be Prevented?

Currently, there are no known ways to prevent Extragonadal Germ Cell Tumors from developing.

• Prenatal testing for Klinefelter syndrome may help reduce risks and avoid the condition from developing in the offspring
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child

What is the Prognosis of Extragonadal Germ Cell Tumor? (Outcomes/Resolutions)

The prognosis of the Extragonadal Germ Cell Tumors depends on the type, stage, and location of the tumor. Non-malignant teratomas have excellent prognosis and can be cured with a complete resection.

• Among the malignant types, the prognosis depends on:
  • The stage of the tumor
  • Type of the tumor: Seminomatous tumors having better prognosis than non-seminomatous tumors
  • Location of the tumor
  • Presence of metastasis and organs involved with the metastasis      
  • Ki-67 value: It is a protein found in cells that is a good indicator of how fast the tumor cells are growing. The ki-67 value is determined by a pathologist and is usually mentioned in the pathology report
  • Age of the Individual
  • Overall health of individual
• Early diagnosis with close monitoring and treatment of the tumor is important. A prompt treatment and early tumor recognition will help in having an optimal outcome

Additional and Relevant Useful Information for Extragonadal Germ Cell Tumor:

• The gene chip assays can identify multiple mutations in the tumor and help physicians to decide on the best course of treatment.
• There are many online groups available for individuals diagnosed with Extragonadal Germ Cell Tumors that provide supportive care, encouragement, and bring a measure of relief to the affected individuals and their families