Germ Cell Tumors: Overview, Treatments & Prognosis

What Are Germ Cell Tumors?

Germ cell Tumors (GCTs) arise from primordial germ cells — the early embryonic cells that give rise to sperm in males and ova in females. Most GCTs develop in the gonads (testes or ovaries), but extragonadal GCTs can occur in midline locations such as the mediastinum, retroperitoneum, or central nervous system due to aberrant migration of primordial germ cells during embryogenesis. Due to the migration patterns of germ cells during foetal development. GCTs can be benign (noncancerous) or malignant (cancerous) and, while rare overall, are a notable cause of cancer in children and adolescents. Fortunately, most GCTs are highly treatable, especially when detected early.

Types of Germ Cell Tumors

Germ cell Tumors are classified into several types based on their cell composition and characteristics:

• Teratomas: These Tumors may be benign or malignant and often contain a mix of different tissue types, such as hair, teeth, or bone.
• Seminomas: Malignant Tumors that develop in the testes and generally have a slow growth rate.
• Nonseminomatous Germ Cell Tumors (NSGCTs): More aggressive malignant Tumors that include yolk sac Tumors, choriocarcinomas, and embryonal carcinomas.
• Dysgerminomas: The ovarian equivalent of seminomas, these Tumors are usually malignant.
• Germinomas: Most often arise in the central nervous system, particularly the pineal or suprasellar regions; gonadal germinomas are rare.
• Yolk sac Tumors (endodermal sinus Tumors): Malignant neoplasms that mimic yolk sac structures; they are the most common malignant testicular and ovarian germ cell Tumors in children.
• Choriocarcinomas: Highly malignant trophoblastic germ cell Tumors that produce β-hCG and can occur in the testes, ovaries, or extragonadal midline sites.
• Embryonal carcinomas: Aggressive, pluripotent malignant GCTs that often occur as part of mixed germ cell Tumors.
• Mixed germ cell Tumors: Contain more than one histologic type and are common in both the testes and ovaries.

Common Sites of Germ Cell Tumors

• Testes (testicular Tumors)
• Ovaries (ovarian Tumors)
• Mediastinum (anterior mediastinum, especially in young men)
• Retroperitoneum (abdomen/back of the abdomen)
• Sacrococcygeal region (base of the spine)
• Brain (especially pineal and pituitary regions)

Causes and Risk Factors for Germ Cell Tumors

The exact cause of germ cell Tumors is not well understood, but several factors may increase an individual's risk of developing these Tumors:

1. Genetic predisposition: Chromosomal abnormalities such as Klinefelter syndrome (47,XXY) are strongly associated with mediastinal nonseminomatous GCTs.
2. Undescended testicle (cryptorchidism): In males, failure of the testicle to descend into the scrotum during foetal development increases the risk of testicular germ cell Tumors.
3. Family history: A family history of testicular germ cell tumour slightly increases risk, but the overall heritability remains low.
4. Disorders of sex development: Conditions affecting sexual development can predispose individuals to germ cell Tumors.
5. Previous history of germ cell tumour: A prior occurrence of a germ cell tumour increases the risk of developing future Tumors.
6. Age and sex: Germ cell Tumors are most common in adolescents and young adults and are more frequent in males.
7. Environmental factors: While no specific environmental causes have been definitively identified, ongoing research is investigating potential links.
8. Abnormal migration of germ cells: During foetal development, germ cells that migrate to incorrect locations may give rise to extragonadal Tumors.

Symptoms of Germ Cell Tumors

The symptoms of GCTs can vary depending on the tumour's location and type. Some common signs and symptoms include:

• A lump or swelling in the affected area (testes, ovaries, abdomen, etc.)
• Pain or discomfort in the region of the tumour
• Abdominal distension or bloating
• Back pain (especially with pelvic or abdominal Tumors)
• Unexplained weight loss
• Early puberty (in rare cases, due to hormone production by the tumour)
• Difficulty breathing or chest pain (if the tumour is located in the chest)
• Neurological symptoms (if the tumour is in the brain)
• Constipation or urinary symptoms (if a pelvic or abdominal mass presses on nearby organs)

If you experience any of these symptoms persistently, it's essential to consult a doctor for prompt evaluation.

Diagnostic Evaluation for Germ Cell Tumors

Diagnosing germ cell Tumors involves a combination of clinical evaluation, laboratory tests, and imaging studies to determine the type, location, and extent of the tumour. The process usually begins with a thorough medical history and physical examination, followed by specialised blood tests for tumour markers and various imaging tests to locate and characterise the tumour. In some cases, a tissue biopsy may be necessary to confirm the diagnosis and guide treatment decisions.

Blood Tests and Imaging to Diagnose Germ Cell Tumors

Several blood tests can help detect and monitor GCTs by measuring specific tumour markers:

• Alpha-Fetoprotein (AFP) Test, Serum
• Beta-hCG (Human Chorionic Gonadotropin) Test
• LDH (Lactate Dehydrogenase) Serum Test

Imaging tests play a crucial role in locating and staging GCTs:

• Ultrasound (testicular, pelvic, or abdominal) is typically the first-line imaging technique used to localise a suspected mass, particularly in the testicles or abdominal region.
• CT scan (computed tomography) is commonly used for staging the disease and assessing whether the germ cell tumour has spread to other areas of the body.
• MRI (magnetic resonance imaging) provides detailed images that help evaluate the extent of soft tissue involvement by the tumour.
• Chest X-ray is performed to check for the presence of metastases in the lungs, which are a common site for germ cell tumour spread.
• FDG-PET scan is mainly useful in assessing residual masses after chemotherapy in seminoma, but has limited value for nonseminomatous GCTs and to detect both local and distant spread.
• Biopsy, which involves taking a tissue sample, is necessary for confirming the diagnosis through histological analysis.

Your healthcare team will determine the most appropriate diagnostic tests based on your individual case.

Treatment Modalities for Germ Cell Tumors

Treatment for germ cell Tumors depends on the histologic subtype, stage, primary site (gonadal or extragonadal), and the patient’s overall condition..

The main treatment modalities include:

1. Surgery: The mainstay of treatment for localised Tumors; may involve removal of the tumour and affected organ (such as orchiectomy for testicular germ cell Tumors or oophorectomy for ovarian germ cell Tumors).
2. Chemotherapy: Chemotherapy is commonly used for malignant or advanced-stage germ cell Tumors. It is also used in certain tumour types at earlier stages due to their high sensitivity to chemotherapy.
3. Radiation therapy: Radiation therapy is used in selected cases, particularly for seminomas and some intracranial germinomas, which are more responsive to radiation.
4. High-dose chemotherapy with stem cell transplant: High-dose chemotherapy with autologous stem cell rescue may be considered for relapsed or refractory germ cell Tumors after standard cisplatin-based regimens.
5. Targeted therapy/immunotherapy: Targeted therapy and immunotherapy remain investigational; no targeted agents have yet demonstrated proven survival benefit in GCTs and may offer potential benefits for patients with refractory or relapsed germ cell Tumors, though they are not yet standard treatment.

Surgical Options and Approaches

Surgical removal is often the first and most crucial step in treating germ cell Tumors, particularly when the tumour is localised and accessible. Procedures may include orchiectomy (removal of testicle), oophorectomy (removal of ovary), resection of extragonadal Tumors, or removal of metastatic lymph nodes. The goal of surgery is to achieve complete excision with minimal damage to surrounding tissues. In some cases, fertility-sparing surgery may be possible, especially in children and young adults.

Chemotherapy Regimens

• BEP (Bleomycin, Etoposide, Cisplatin): This is the standard first-line chemotherapy regimen for many malignant germ cell Tumors, particularly testicular cancer. It is highly effective and widely used in both early and advanced stages.
• EP (Etoposide, Cisplatin): This regimen is used when bleomycin is contraindicated, such as in patients with pre-existing lung disease or those at high risk of pulmonary toxicity.
• VIP (Etoposide, Ifosfamide, Cisplatin): VIP is typically reserved for patients with relapsed or refractory germ cell Tumors.
• Carboplatin-based regimens: May be used in selected paediatric or low-risk adult patients, particularly to minimize toxicity in place of cisplatin or in individuals who are unable to tolerate standard cisplatin-based therapies.

Radiation Therapy in Germ Cell Tumors

Radiation therapy is primarily used for specific types of GCTs, such as seminomas and intracranial germinomas, due to their high sensitivity to radiation. It may be used after surgery to destroy residual tumour cells or for palliation in metastatic disease. The role of radiation has decreased for many germ cell Tumors due to the success of chemotherapy, but it remains important in particular subtypes like central nervous system germinomas and some seminomas.

Prognosis and Survival Rates

The prognosis for germ cell Tumors is generally very favourable, especially with early diagnosis and modern treatments. Germ cell Tumors are among the most curable solid malignancies, with overall 5-year survival exceeding 90% for testicular GCTs and 70–80% for extragonadal or advanced-stage disease as the 5-year survival rate exceeds 90%. Prognosis depends on factors such as tumour type, location, stage, response to treatment, and overall health. Even when diagnosed at a more advanced stage, many patients respond well to treatment. Long-term follow-up is essential due to the risks of recurrence or late effects of therapy.

Follow-Up and Surveillance Strategies

After completing treatment for a germ cell tumour, regular follow-up is essential to monitor for recurrence and manage any long-term side effects. Surveillance strategies may include:

• Regular physical examinations to monitor for recurrence
• Serial tumour marker blood tests (AFP, beta-hCG, LDH)
• Periodic imaging studies (ultrasound, CT, MRI as indicated)
• Long-term side effect monitoring, such as fertility assessments and cardiovascular health checks
• Psychosocial support and counselling as needed

Your healthcare team will develop a personalised follow-up plan based on your specific case and treatment history.

Prevention and Risk Reduction

• Regular self-examination of the testes for males, especially those with risk factors like undescended testicles or family history.
• Prompt medical attention for any testicular or abdominal masses, swelling, or pain.
• Genetic counselling is recommended for individuals with Klinefelter syndrome, disorders of sex development, or a family history of germ cell Tumors.
• Maintaining a healthy lifestyle, including a balanced diet, regular exercise, and avoiding smoking and excessive alcohol consumption.
• Attending regular check-ups and screenings as recommended by doctors, especially for those with increased risk factors.

Metropolis Healthcare is a leading chain of diagnostic labs across India, with a presence in over 750 towns, supported by a robust network of more than 220 laboratories, 4600+ service centres, and over 10,000 touchpoints. With a team of qualified blood collection technicians who make at-home visits for sample collection, Metropolis ensures a convenient and hassle-free experience for patients. The collected samples are processed at state-of-the-art diagnostic labs, and test reports are conveniently shared online via email and the user-friendly Metropolis Healthcare App.

FAQs

What causes germ cell Tumors?

The exact causes of germ cell Tumors are not fully understood, but factors like genetic predisposition, undescended testicles, disorders of sexual development, and abnormal germ cell migration during foetal development may increase the risk.

Are germ cell Tumors always cancerous?

No, germ cell Tumors can be benign (noncancerous) or malignant (cancerous). The type and behaviour of the tumour depend on the specific cell types involved and the tumour's location.

How are germ cell Tumors diagnosed?

Diagnosing germ cell Tumors typically involves a combination of physical examination, blood tests for tumour markers, imaging studies (such as ultrasound, CT, or MRI), and sometimes a tissue biopsy for histological confirmation.

What treatment options exist for germ cell Tumors?

Treatment for germ cell Tumors may include surgery to remove the tumour and affected organ, chemotherapy, radiation therapy (in selected cases), and sometimes high-dose chemotherapy with stem cell transplant for relapsed or refractory Tumors.

What is the prognosis for germ cell Tumors?

Germ cell Tumors are among the most curable cancers, with 5-year survival rates exceeding 90% for early-stage and many advanced cases. Prognosis depends on factors like tumour type, stage, location, and response to treatment.

Can germ cell Tumors be prevented?

While many risk factors for germ cell Tumors cannot be changed, steps like regular self-examination, maintaining a healthy lifestyle, attending recommended screenings, and promptly reporting any unusual symptoms to your doctor may help reduce your risk or detect Tumors early.

References

1. https://www.mayoclinic.org/diseases-conditions/germ-cell-tumors/symptoms-causes/syc-20352493
2. https://my.clevelandclinic.org/health/diseases/23505-germ-cell-tumor
3. https://www.cancerresearchuk.org/about-cancer/germ-cell-Tumors
4. https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-children/germ-cell-Tumors/
5. https://www.yalemedicine.org/conditions/germ-cell-tumors