Diagnosis And Treatment Of Mediastinal Germ Cell Tumours

  • Drew Gallagher B.Sc. Biomedical Science, University of Manchester, UK

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The mediastinum is the chest compartment of your body that is limited on either side by your lungs and communicates with the neck and the abdominal cavity.1 This is where the heart is located and further divides it into anterior and posterior parts. The anterior mediastinum is a space where certain tumours are known to occur more commonly, in addition to their primary location. Germ cell tumours are one such entity. Germ cell tumours in the posterior mediastinum are extremely rare.

Overview of mediastinal germ cell tumours

You may have heard of germ cells. As suggested by their name, these are the cells that are located in the ‘germ line centres’ or reproductive organs of a person and help to produce eggs and/or sperm cells for reproduction. In people assigned female at birth, these are the ovaries and in people assigned male at birth, these are the testes (can be called gonads). 

However, some of these germ cells can be left in another location during organ formation before birth, and then later in life, tumours can arise there instead of in the reproductive organ. These are also known as extragonadal germ cell tumours. They are commonly known to occur in midline structures and the anterior mediastinum is a well known site.

The term germ cell tumours is used generally to include both growths (tumours) that are benign or non-cancerous, as well as those which are malignant and known as cancerous. There are many different subtypes of both benign and malignant tumours and the subtypes in turn can predict, to a large extent, how the tumour will behave and the outcome for the patient.

Majority of the mediastinal germ cell tumours are benign. Of these, the commonest occurring subtype is teratomas. The mediastinal germ cell tumours that are malignant can be divided into two types: seminomatous cancers and non-seminomatous cancers in AMABs or dysgerminomas and non-dysgerminomas in AFABs. Of the AMAB cancers, seminomatous cancers or in other words seminomas are the most common. The non-seminomatous tumours include embryonal carcinoma, chorio carcinoma and yolk sac tumours. This subtyping occurs when tumour samples are taken and looked at under the microscope. While benign tumours occur equally in both genders, malignant tumours are more common in AMABs.

Importance of early diagnosis and treatment

Just like any other tumour, mediastinal germ cell tumours need early diagnosis so that appropriate treatment can be initiated. However, specifically for germ cell tumours in the mediastinum, it is very important to know the subtype of the tumour since their behaviour varies greatly. Also, some of the germ cell tumours are known to be associated with certain syndromes, or a collection of symptoms occurring in a specific disease so it’s useful to identify that too. One such syndrome is Klinefelter syndrome.

It is important to identify that early due to other implications of that disease.2 Additionally, some mediastinal germ cell tumours are reported to be associated with hematological malignancies (blood cancers), therefore early diagnosisis vital.2


Clinical presentation and symptoms

The symptoms of mediastinal germ cell tumours mostly occur due to their growth in the chest cavity. Patients can complain of chest pain and a cough. In addition, the tumour can compress the major veins which drain the body and direct that blood flow to the heart. The compression of some of these veins causes back congestion in organs, resulting in swelling of the face, headaches and rapid breathing. Some of these symptoms are collectively known as SVC obstruction syndrome. Less specific symptoms that can occur with any tumour, such as weight loss and night sweats may be experienced.

Imaging studies

A tumour in the mediastinum, if not symptomatic, is often found incidentally during a chest x-ray done for another cause. A CT scan or MRI is often needed to identify the extent of the mass plus extension and invasion into nearby structures. This will show a mediastinal shadow or mass, sometimes with calcifications as is usually the case of teratomas. The seminomas usually do not show calcifications.

presence of fat is suggestive of a mediastinal germ cell tumour while a fat fluid level or bone is suggestive of a teratoma. Some other non-seminomatous tumours which are aggressive may show invasion into local structures such as the coverings of the heart or lungs known as the pericardium and pleura respectively. 

Another important part of the investigation work up for a mediastinal tumour is that the patient should always be checked for a primary tumour at the gonads, meaning testes or ovaries. This should include an ultrasound scan. This is because the tumour in the mediastinum could have occurred in two ways. One way is arising from germ cells left behind at organ formation before birth. The second way is due to a spread from a tumour in the testes or ovaries. This process is called metastasis, meaning a tumour spreading from its organ of origin to others.

As a percentage of incidence, tumours arising from left over germ cells in the mediastinum are rare compared to those occurring as a metastasis from the testes or ovaries. Therefore if there are concurrent germ cell tumours in the testis/ovary as well as in the mediastinum, the testis/ovary tumour is always considered as primary. The one in the mediastinum is considered the metastasis or the secondary.

Tumour markers

An important feature of these germ cell tumours is that they secrete certain hormones and substances that are somewhat correlated to their cell type.

The secretions of these into the blood stream cause their usual levels to be elevated and this can show up in blood tests. These hormones are also called tumour markers.7

For example, seminoma can cause an increase in a substance called LDH (Lactate Dehydrogenase) and a hormone called Beta HCG without an increase in another substance called AFP (Alpha Fetoprotein). Embryonal carcinomas can cause an elevation in LDH and AFP. A yolk sac tumour can increase AFP but not the others mentioned. A choriocarcinoma can increase Beta HCG but not the others. Therefore, although not to be relied on solely by their increase, the tumour markers can suggest the tumour type to a certain extent. 

It is also worth noting that these tumour subtypes can occur as a combination and at tumour resection and sampling, it is important to discover all the components as the outcomes vary according to subtype.

Biopsy and histopathological examination

The diagnosis of germ cell tumours require sampling of the tumour tissue and looking at it under the microscope. The procedure is called a biopsy and looking through the microscope is the histopathological examination.

Tumour samples are obtained through a process called mediastinoscopy where there is direct visualisation of the mediastinum through a camera.

The first step in microscopy is to confirm that this is a germ cell tumour. This is because there can be other tumours that can cause a mediastinal mass or growth, such as lymphoma, thymoma and even thyroid tumours.

The next step is to see whether it's a benign tumour, a seminomatous tumour or a non-seminimatous tumour if in an AMAB and whether a dysgerminoma or non-dysgerminoma if in an AFAB.

While usual microscopic assessment is enough to assess a benign tumour like teratoma, most other tumours need confirmation by using additional staining of cells via a method called immunohistochemistry. The use of immunohistochemistry helps to confirm and differentiate seminomas as well as non-seminomas, such as embryonal carcinomas, yolk sac tumours or choriocarcinomas.

This is important since the prognosis in different subtypes vary considerably. For example, choriocarcinoma and embryonal carcinoma are two of the subtypes with the worst outcomes.7 This means these cancers are capable of spread and growth that is much worse than others and therefore does not predict a good overall outcome for the patient. 

Staging and prognostic factors

Staging systems

Most tumours are categorised into stages depending on factors like their size, location, extent of invasion to nearby structures etc. This also applies for mediastinal germ cell tumours when they are thought to be primarily from the mediastinum and not spread as a secondary tumour from gonadal tissue such as the testes.

One such staging system is known as Moran and Suster2 and it considers factors like invasion to lung or heart covering tissue, invasion to other organs within the chest cavity and beyond the chest cavity.

According to most staging systems

  • Stage 1 is when the tumour is within the mediastinum and does not invade the pleura or pericardium
  • Stage 2 is when the tumour does show invasion to these structures, either by naked eye vision (macro) or from viewing through a microscope (micro)
  • Stage 3 means the tumour has spread to other organs, in other words metastasised
  • Stage 3a means the tumour has spread or metastasised to organs within the chest cavity
  • Stage 3b means the tumour has spread to outside of chest cavity

Factors influencing prognosis

The prognosis or outcome is mainly determined by the type of the tumour.

The best outcome is for the benign tumour category called teratomas and if it is a type called mature teratomas, without any other malignant components, the prognosis is excellent.

Increased age, tumour spread to organs other than lungs and high levels of tumour markers are some of the more general poor prognosis factors.2

Treatment options

The treatment options vary depending on the histological subtypes of the tumour. The options include surgical removal, chemotherapy or radiation.

For benign tumours like teratomas, without high-risk features, the best treatment is surgical removal. This includes a procedure called median sternotomy or posterolateral thoracotomy which are the different surgical approaches taken to access the mediastinum.

Seminomatous tumours on the other hand, are well known to be sensitive for chemotherapy. Therefore there are specific chemotherapy regimes that are used such as Bleomycin, Etopside and Cisplatin (BPE) for example, which are given in combination as several cycles.

For non-seminomatous tumours, such as embryonal carcinomas, yolk sac tumours etc, the treatment includes chemotherapy as a first line treatment, followed by surgical resection for any remaining cancer. There is also a place for radiotherapy.

Another treatment entity called high dose chemotherapy followed by stem cell transplant is also a treatment option used for high risk subtypes.

Surgical management

This is the treatment of choice for benign tumours such as Teratomas especially the type called mature teratomas. This is reported to be curative. They are not responsive to chemotherapy.

However, increased age as well as a malignant component in the teratoma shows poor outcome compared to those without it.


There are several chemotherapy regimes that are used mainly for seminomatous and non-seminomatous tumours except teratomas. Seminomas especially are known to be very chemosensitive and has good prognosis. Any worse outcome is due to the local spread of the disease at diagnosis or in other words stage at diagnosis. 


This is reported to be useful and effective as a local therapy with studies showing it to be an independent prognostic marker.12 

High-dose chemotherapy and stem cell transplantation

This too is another regime of treatment that is reported to be useful to high risk tumour subtypes.12

Follow-up and surveillance

Monitoring tumour markers

Monitoring of tumour markers are done for follow up of disease. This is said to be best done a few weeks after chemotherapy. Negative or declining tumour markers are reported to be an independent prognostic factor.

Imaging studies

Serial chest x-rays as well as CT scans are recommended as follow up after treatment for mediastinal germ cell tumours.

Long-term follow-up care

After treatment regimes and if deemed to be cured, it is essential that the patient is followed up for recurrence of tumour. These usually include series of visits to the doctors with serial tumour markers as well as serial chest x-rays and CT scans. Due to concerns of radiation with CT scans, they are done at lesser intervals. The patients are usually categorised into different risk categories and the frequency of these investigations are based on that category.

Prognosis and survival rates

Factors influencing prognosis 

This includes tumour type, spread to other organs and also tumour markers.

Survival rates based on stage and treatment response

Out of the malignant or cancerous tumours, seminomas have the best outcome with treatment such as chemotherapy. The predicted survival at 10 years is 75%.2 A reason for worse prognosis would be if it were diagnosed at an advanced stage such as with spread to organs like the liver or two other organs.

With regard to non-seminomatous tumours arising primarily in the mediastinum, prognosis is worse than if they occurred in the reproductive organs.3 The usual 5 year survival for these tumours are around 45%.3 These tumours also have worse prognosis if they are spread to other organs and if the tumour marker levels were high before treatment.

Radiotherapy is reported to be an independent prognostic factor for overall survival. 


The mediastinum is the chest cavity that is lined by lungs on either side. A type of cell called germ cells which usually occur in reproductive organs can be left over in the mediastinum during organ formation before birth and later cause tumours. These tumours are called extragonadal germ cell tumours and commonly occur in midline structures such as the mediastinum, especially the anterior mediastinum. Conversely, tumours in the reproductive organs can also spread here. Consequently, these tumours need a detailed investigation including checking of the reproductive organs as well spreading to other organs.

The tumours can be incidentally found as a mass in the chest on x-rays or they can cause symptoms like chest pain, cough, congestion of face or nonspecific symptoms. Mediastinal germ cell tumours can also cause an elevation in certain substances/ hormones presence in the blood making it possible to detect by blood tests. X-rays and CT scans are the other investigative tools that are needed. Usually an ultrasound scan of the testes or ovaries is also needed to check for a primary tumour occurring in these organs.

Once a tumour is detected on imaging, it needs sampling and testing with microscopy where it will be subtyped. A process called mediastinoscopy enables one to view the mediastinum and obtain tumour samples for this purpose. According to the subtype and stage of tumour, meaning how much it has spread, the treatment regime will be decided. It can usually be a multi-modal approach.

The treatments available include surgical resection for benign or non-cancerous growths like mature teratomas; chemotherapy for seminomas; or a combination of them and/or radiotherapy for other non-seminomatous tumours.

The survival or prognostic factors include, type of tumour, spread to organs, stage at diagnosis and sometimes the type of treatment given such as radiotherapy and also levels of tumour markers.

Cured patients need to be followed up and checked for recurrence of tumour with serial x-rays or CT scans and tumour markers.


  1. What is the Mediastinum? [Internet]. Cleveland Clinic. Available from: https://my.clevelandclinic.org/health/body/24113-mediastinum
  2. Kang J, Mashaal H, Anjum F. Mediastinal Germ Cell Tumors [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563232
  3. Mediastinal Germ Cell Tumor - an overview | ScienceDirect Topics [Internet]. www.sciencedirect.com. [cited 2023 Jul 17]. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/mediastinal-germ-cell-tumor
  4. Mediastinal Germ Cell Tumor Imaging and Diagnosis: Practice Essentials, Radiography, Computed Tomography. eMedicine [Internet]. 2023 Jun 13 [cited 2023 Jul 17]; Available from: https://emedicine.medscape.com/article/359110-overview
  5. O’Brien T, Power DG. Mediastinal germ cell tumour during the COVID-19 pandemic. BMJ Case Reports. 2020 Jul;13(7):e237003.
  6. Shinagare AB, Jagannathan JP, Ramaiya NH, Hall MN, Van den Abbeele AD. Adult Extragonadal Germ Cell Tumors. American Journal of Roentgenology. 2010 Oct;195(4):W274–80.
  7. Germ cell tumors [Internet]. www.pathologyoutlines.com. [cited 2023 Jul 17]. Available from: https://www.pathologyoutlines.com/topic/mediastinumgermcell.html
  8. Hasle H, Jacobsen BB, Asschenfeldt P, Andersen K. Mediastinal germ cell tumour associated with Klinefelter syndrome. European Journal of Pediatrics. 1992 Oct;151(10):735–9.
  9. Mediastinal germ cell tumours [Internet]. www.cancerresearchuk.org. Available from: https://www.cancerresearchuk.org/about-cancer/mediastinal-germ-cell-tumours
  10. Childs W, Goldstraw P, Nicholls J, Dearnaley D, Horwich A. Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery. British Journal of Cancer. 1993 May;67(5):1098–101.
  11. Kalhor N, Moran CA. Primary germ cell tumors of the mediastinum: a review. Mediastinum. 2018 Jan 9;2:4–4. https://med.amegroups.org/article/view/3961/4719
  12. 1.Kumar N, Madan R, Dracham CB, Chandran V, Elangovan A, Khosla D, et al. Primary mediastinal germ cell tumors: Survival outcomes and prognostic factors – 10 years experience from a tertiary care institute. Rare Tumors. 2020 Jan;12:203636132097222. https://journals.sagepub.com/doi/full/10.1177/2036361320972220
  13. https://www.annalsofoncology.org/article/S0923-7534(19)34133-X/fulltext#secst0325

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Curent role as Specialty Doctor in Histopathology and previously as Associate Specialist in GI pathology. STEM ambassador and former freelance copywriter for advertising agencies and healthcare institutes.

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