Mediastinal Seminoma

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Mediastinal seminoma is a malignant germ cell tumor in the mediastinum. The tumor usually occurs in the anterior-superior mediastinum in males aged 20-40 years old. The first-line treatment is with cisplatin based chemotherapy. To avoid the high morbidity and mortality associated with this condition, it must be promptly diagnosed and treated by a multidisciplinary team consisting of medical oncologists, radiation oncologists, and thoracic surgeons. When treatment is started early survival rates are > 90% 5 year survival.


  • Identify the etiology of mediastinal seminoma.
  • Outline the evaluation of mediastinal seminoma.
  • Summarize the management options available for mediastinal seminoma.


Mediastinal seminomas are a very rare germ cell tumor that occurs in the mediastinum. Germ cell tumors rarely occur outside of the gonads, with a rate of only 5% to 7%. If there is no primary testicular or ovarian mass, the tumor is considered extragonadal. The mediastinum and retroperitoneum are the most common locations for occurrence outside of the usual gonadal location, with the mediastinum being the most common extragonadal location. The seminomas can also occur in the sacrococcygeal region and central nervous system in the pineal gland. This occurs more commonly in children. Germ cell tumors comprise only 1% to 4% of all tumors found in the mediastinum and can be benign or malignant, with mediastinal seminomas being the latter.[1]

Mediastinal seminomas often have a very slow growth pattern, have limited potential to metastasize, symptoms are not very characteristic, and many patients often are asymptomatic with incidental findings. Mediastinal seminomas were first discovered in the late 1950s, and great progress has been made in curing patients of this disease and prolonging life. The 5-year survival rate has increased to 87% to 100%, similar to the results of testicular seminomas. Mediastinal seminomas are very sensitive to chemotherapy and radiation; therefore, these two modes are often the first line of treatment. Surgical intervention may also be used in the treatment of mediastinal seminomas.[2]

Mediastinal seminomas are usually found in the anterior-superior mediastinum. More specifically, they tend to develop where the innominate vein meets the superior vena cava. The mediastinum is defined by specific borders. The left and right pleura make up the lateral aspects of the mediastinum, while the thoracic inlet and the diaphragm make up the superior and inferior aspects, respectively. The anterior vertebral column is the posterior aspect of the mediastinum, while the anterior aspect is made up of the posterior sternum and costal cartilages. The mediastinum can then be subdivided into compartments, which aid in surgical planning.[3]

Mediastinal seminomas have the ability to become very large and can be difficult to differentiate from thymic fat and pericardial tissue. These tumors infiltrate surrounding organs early on in their growth process and, once they grow large enough, can cause the patient cardiac and respiratory problems, including difficulty breathing. If the tumor has spread outside of the thoracic cavity, it was probably found at a later stage. Metastasis occurs through the blood and mainly affects the lungs, liver, and bones. However, mediastinal seminomas usually remain contained in the chest.[2]


There are several thoughts on mediastinal tumor development and where the actual origin comes from. The first theory starts with the development of primitive germ cells that arise from the yolk sac or urogenital ridge. The germ cells usually move into the scrotum, but if this step fails, the germ cells may remain in the mediastinum or retroperitoneal space. Another theory discusses that the germ cells are totipotential cells that get lost in embryogenesis, which may lead to mediastinal or retroperitoneal tumors. The cause of the tumor is not known, but upon observation of men with Klinefelter syndrome, it has shown to have a higher prevalence.

Klinefelter patients have an extra X chromosome and have been shown to develop germ cell tumors of the mediastinum ten years earlier than those with normal genetic makeup. Further studies have shown that Klinefelter patients have low levels of testosterone and high levels of estradiol and luteinizing hormone. These hormone abnormalities point to a problem with the germ cell line, which can cause dysregulation of spermatogenesis and predispose the patient to extragonadal malignancies.[4][5]


The majority of germ cell tumors are benign, with only 20% being malignant. Of that 20%, seminomas make up the majority (about 50%) of malignant germ cell tumors. The mediastinum is the most common location for extragonadal germ cell tumors to reside. Mediastinal germ cell tumors represent a rare 3-10% of all mediastinal tumors and account for less than 5% of all germ cell neoplasms. Only 3% of mediastinal germ cell tumors arise in the posterior mediastinum, while the majority arise in the anterior mediastinum.[6]

 Mediastinal seminomas are just one type of mediastinal germ cell tumors affecting mostly male patients between the ages of 20 and 35. It is unknown as to why mediastinal tumors appear mostly in men. Mediastinal tumors are not typically discovered in patients from abroad until the fourth decade of life, most likely due to the fact that these countries are underdeveloped and have insufficient diagnostic methods. Though the rarity of this condition is not often questioned, it cannot be excluded that increased recognition of mediastinal seminomas would occur with more research and familiarity - not only by clinicians but also by pathologists.[2]


The pathology between mediastinal seminoma and gonadal seminoma are alike in many ways. The genetic components show very similar patterns of chromosomal changes. Sixty-nine percent demonstrate the same isochrome i (12p) malignant germ cell tumor. The majority of mediastinal seminomas are aneuploid, with very few having tetraploid DNA content. Metastases from the gonadal tissue are not responsible for mediastinal seminomas. When viewing the immunohistochemistry of the mediastinal seminoma tissue, 80% to 90% are reported to be positive for CAM 5.2, placental alkaline phosphatase (PLAP), and 70% of them show positivity for vimentin. CD 117 is also positive in the cell membrane, and there is often a paranuclear Golgi pattern present.


Mediastinal seminomas are indistinguishable from gonadal seminomas. They both are primitive germ cell tumors composed of somewhat uniform cells that have clear or eosinophilic, glycogen-rich cytoplasm. The cells have distinct cell borders with a round nucleus resembling primordial germ cells. The tumor cells grow in a way that represents a nesting pattern. Oftentimes, a fibrous septa is visualized between the aggregation of cells. A seminoma may be obscured by inflammatory cells, including lymphocytes and eosinophils, and scar tissue. And in other cases, seminomas may be misdiagnosed as thymic epithelial rumors as thymic tissue sometimes remains in the periphery of the seminoma.

History and Physical

Malignant tumors, such as mediastinal seminomas, usually cause a patient to experience symptoms, unlike benign tumors. A patient diagnosed with a mediastinal seminoma will most commonly present without any symptoms, but they can have symptoms secondary to compression of the surrounding organs, such as the heart and lungs, due to their bulkiness in nature.

Though many patients are asymptomatic, some patients present with dyspnea, cough, and chest pain. In the case of hormonally active tumors, patients may also present with tachycardia or hypertension. Some patients may present with superior vena cava syndrome due to the slow-growing nature of the tumor. Regardless of the presentation, the patient still needs a full physical exam.[6][2]


The first step in diagnosing a patient with a mediastinal tumor is performing a chest x-ray on the posteroanterior and lateral chest. A contrast-enhanced chest CT scan, an MRI, or a PET scan can then be used to further evaluate the mass depending on its origin and location. Because mediastinal seminomas are most commonly found in the anterior-superior mediastinum, a chest CT scan with contrast is the initially recommended imaging modality due to its ability to differentiate between masses that are solid versus cystic in nature. Magnetic resonance imaging can be used to demonstrate the precise location and pattern of mediastinal seminomas as well as invasion of adjacent structures such as the pleura. Seminomas typically present with homogenous internal attenuation as well as signal intensity on CT and MRI. They have clear cut boundaries except in the presence of hemorrhage and necrosis in which degenerative changes appear as small foci upon imaging. In the presence of seminomas, contrast shows minimal enhancement.[2][6][7]

 In addition to size, location, and CT attenuation of mediastinal tumors, it is equally important to assess for the shape, for the abnormal shape of any structure, as well as the displacement of any structure within the mediastinum, may be indicative of an underlying mass. When it is unknown whether a mediastinal tumor is malignant or benign, a PET CT scan is advised. Additional PET CT scans can be done to evaluate the patient’s response to treatment, specifically chemotherapy.  Treatment can be started based on tumor markers alone, but it is best to have a tissue diagnosis. A core needle biopsy is the recommended technique for tissue sampling. If a core needle biopsy does not provide the sample that is needed, a surgical biopsy can be performed through an anterior mediastinotomy, also known as the Chamberlain procedure. A fine-needle aspiration sample can be performed, but this technique can have a discrepancy in tissue diagnosis and may miss a poorly differentiated cancer from a mediastinal seminoma.[7]

Germ cell tumors that are malignant, such as mediastinal seminomas, may secrete alpha-fetoprotein, embryonal carcinoma components, and human chorionic gonadotropin (beta hCG). These three labs are tumor markers, which, in conjunction with imaging, can be utilized in the diagnosis of mediastinal seminomas and in evaluating a patient’s response to therapy.  Pure mediastinal seminomas do not secrete AFP. Mediastinal seminomas usually have elevated beta hCG levels in one-third of all patients. If the beta hCG is greater than 1,000, a non-seminomatous component may be present and should be evaluated.[6]

Lastly, mediastinal gonadal tumors should be excluded in the diagnosis of a patient with a primary mediastinal germ cell tumor, such as mediastinal seminoma. Gonadal germ cell tumors usually involve metastasis to retroperitoneal lymph nodes; whereas, primary mediastinal germ cell tumors can metastasize to cervical and abdominal lymph nodes.[6]

Treatment / Management

The first-line treatment in the case of pure seminomas has always been chemotherapy and radiation, no matter the size of the tumor. In most cases, surgical intervention is reserved for those tumors unsuccessful with radiation, chemotherapy, or both. Nowadays, surgical excision has become the first-line treatment for small, resectable tumors with postoperative radiation for the asymptomatic patient. Cisplatin-based combination chemotherapy with etoposide and bleomycin is recommended as first-line treatment, regardless of distant tumor metastasis for 3 to 4 cycles. If the patient has pulmonary disease at baseline, Bleomycin should be avoided. Ifosfamide can then be added to the regimen of cisplatin and etoposide for 3 to 4 cycles. Chemotherapy treatment should be monitored with the trending of tumor markers to monitor the response rate of the chemotherapy. If metastatic disease is diagnosed in the beginning, the patient should undergo cisplatin-based chemotherapy for distant disease, and radiation should be administered from the local mediastinal disease. Radiation has been extremely successful in mediastinal seminomas; however, recent studies have shown chemotherapy as first-line treatment as radiation to the chest has shown many side effects, including increased cardiac/pulmonary events, secondary malignancies, and other associated toxicities due to radiation to the mediastinum.[8]

In the case of a large tumor, chemotherapy is administered initially, and surgical excision is then performed on any remaining disease if deemed resectable on imaging. The patient may then be monitored every 6 to 12 months with serial CT scans. Good risk patients that have no sign of pulmonary metastasis and are treated with chemotherapy first line have a survival rate of >90%. If a patient has a contraindication to chemotherapy, radiation is given at a level of 35 to 50 Gy to the mediastinum and the supraclavicular fossa bilaterally.[9]

If a residual mass is found, it should be evaluated with histologic confirmation prior to treatment because it may be a necrotic mass instead of cancer. The treatment of residual mass is a topic of debate. Masses < 3 cm can be closely monitored. When the mass is > 3cm, it has a chance of possibly harboring residual malignant disease. Multiple modalities can be used for monitoring the mass. Close monitoring with serial CT scans of the chest, PET scans of the chest with FDG, or possibly an open biopsy can be performed for actual tissue diagnosis. These approaches to monitoring residual masses can be performed eight weeks of status post-chemotherapy. If the patient does have biopsy proving residual disease or evidence of a growing mass, they can be treated with salvage chemotherapy, radiation, or even surgical resection.[10][11][12][13]

After the chemotherapy is completed and a CT scan is performed showing a residual mass but normalized tumor markers, these patients can be evaluated for surgical excision. Surgical intervention depends on the location of the tumor. As the majority of mediastinal seminomas occur in the anterior mediastinum, a median sternotomy is often utilized. A sternotomy, thoracotomy, VATS, or robotic surgical technique can also be used in the removal of either an anterior or posterior seminoma.

Surgical Technique

Complete surgical evaluation should be performed before and after completion of their chemotherapy regimen. Attention should be placed on their lung function, especially if they received bleomycin. Patients may need to undergo DLCO and pulmonary function to make sure bleomycin-induced pulmonary fibrosis did not occur. 

The surgical procedure should begin with the placement of a double-lumen endotracheal tube in case one of the lungs needs an area of resection. Access should be gained in the femoral vessels in case the superior vena cava has any involvement, and resection should be performed. The patient is placed in the supine position, and a median sternotomy is then performed as this is the surgical incision of choice for tumors located in the anterior mediastinum. Multiple approaches can be performed depending on the preoperative CT images of the tumor. If the tumor is large and extends into one of the pleural spaces, a clamshell thoracotomy can be performed. This technique allows for anatomical lung resection if needed. A hemiclamshell can also be performed with a neck incision if the tumor is extending into the neck region. A trap door incision can be performed if there is evidence of involvement of the subclavian vessels or if the proximal clavicle needs to be resected. A posterolateral thoracotomy can be performed to resect a posterior mass, but the mediastinal structures can not be accessed from this technique; therefore, the patient would need to undergo an anterior approach if any structures are needed to be resected. 

 Once the chest is open, and the mediastinal structures are identified along with the mass, the decision can be made if anything needs to be resected in addition to the mediastinal mass. If the mass is distorted with local structures, a frozen section can be sent to look for mass involvement in the structures. The surgeon must make a decision to resect certain structures in the chest versus leaving a possible tumor burden behind. Some of the tumor burden may be able to be peeled off important structures. If the peeled portion is sent for the frozen section and only reveals fibrotic tissue, then peeling will suffice for the treatment of removing the tissue.

If the frozen section shows a tumor, then en bloc resection should be performed. The frozen section is not always determinate of the entire mass, so any suspicion of remaining cancer should be resected when feasible. Recent studies have shown that up to 66% of the remaining tissue contains cancerous cells. There should be a very low threshold to resect any tissue that is near or looks concerning. When the tumor markers are still positive, it is likely that there are still cancerous cells present in the remaining mass. When the markers have returned to normal levels, there is likely only fibrosis remaining in the tissue mass. 

Depending on the location of the remaining mass and if there is a high concern or tissue biopsy proving that cancer remains, you must decide if the nearby structures can be resected. If present in thymus tissue, it is best to excise all thymus tissue en bloc. If the pericardium is involved posteriorly, it can be fully resected en bloc as well. If the lung is involved, a non-anatomical resection or wedge resection is usually performed as long as negative margins can be achieved. Rarely do lobectomies, or entire pneumonectomies need to be performed, but occasionally need to be due to tumor size or location in the hilum of the lung. When dissecting the mass from the lung, the lung can be compressed. Positive pressure ventilation can help show the surgeon the planes of dissection between the mass and lung.

If the phrenic nerve is involved with a tumor, all attempts should be made to save the phrenic nerve. If only one of the nerves is involved and all of the mass can be cleanly resected, then the phrenic nerve should be removed with the specimen. When the phrenic nerve is resected, the surgeon must think about the plication of the diaphragm to avoid lower lobe atelectasis. Do not resect both phrenic nerves. If the right or left innominate vein is involved, they can also be resected en bloc. If both are resected, a graft will need to be placed. If the superior vena cava is involved, usually sharp dissection can remove the tumor; however, if there is a clear invasion into the vessel, it can also be resected en bloc. Once the surgical resection is complete and the chest is closed, the final pathology should be reviewed. If cancerous cells remain present in the chest, chemotherapy can be initiated again.

Differential Diagnosis

In the diagnosis of mediastinal seminomas, it must be determined through imaging whether or not the mass is solid or cystic in nature. The majority of mediastinal masses consist of benign teratomas or dermoid cysts. This is extremely important, especially if the mass is mistaken for a benign tumor as the treatment would be significantly insufficient, and the tumor would continue to grow. Secondly, mediastinal seminomas may be mistaken for a gonadal germ cell tumor, for gonadal germ cell tumors often have metastases to the retroperitoneal lymph nodes. As mediastinal seminoma is a primary mediastinal germ cell tumor, metastasis is likely to be found not in retroperitoneal lymph nodes, but rather the lungs, liver, or bones. Lastly, the larger a mediastinal seminoma is, the more difficult it is to determine it from thymic fat and surrounding pericardium. Other differential diagnoses for mediastinal seminoma include thymoma, thymic carcinoma, mediastinal melanoma, lymphoma,  and clear cell carcinoma (primary or metastatic).[6]


Mediastinal Germ Cell Tumor Staging

  • Stage 1: A well-circumscribed tumor with or without adhesions to the pericardium or pleura, but no, there is no evidence of any microscopic invasion into adjacent structures. 
  • Stage 2: Tumor is confined to the mediastinum with evidence of macroscopic and/or microscopic infiltration into adjacent structures, including the pleura, pericardium, or great vessels. 
  • Stage 3: Tumor present with metastases
    • Stage 3A: Metastatic disease present in intrathoracic organs
    • Stage 3B: Extrathoracic metastases


When aggressive radiation and chemotherapy treatments are utilized, seminomas are curable no matter the size. The recommended initial treatment had transitioned from only radiation to cisplatin-based combination chemotherapy. The prognosis of patients who undergo surgical treatment for mediastinal seminoma is poor. Almost half of the tumors recur post-op and less than 50% of patients live past five years with complete tumor resection and greater than 40% show recurrence when undergoing complete resection. Over the years, newer treatment regimens have increased remission rates to over 80% as well as increased the 5-year survival rate. Recent studies have shown survival rates > 90% when cisplatin-based chemotherapy is started early.[8]


Complications of mediastinal seminomas involve invasion and compression of nearby structures such as the heart and lungs. It can also include local metastasis to these main organs or even distant metastasis to the liver and bones. Complications of the surgical intervention on mediastinal seminoma include the risk of causing damage to the phrenic nerve, bleeding, or development of a pyothorax. The larger the seminoma, the more dangerous these complications can be. It becomes very difficult to differentiate seminoma tissue from lung parenchyma when the tumor becomes large enough to invade nearby organs. Extreme caution must be taken by the surgeon when surgical intervention is the chosen treatment modality.


Consulting Teams

  • Medical oncology
  • Radiation oncology
  • Thoracic surgery 
  • Internal medicine 

Deterrence and Patient Education

Patients experiencing or having experienced a mediastinal seminoma should be encouraged to resume physical activity, eat a healthy diet, and refrain from any sort of anabolic steroid. In addition, patients should pay special attention to any symptoms that may symbolize the recurrence of the disease, such as dyspnea, cough, pressure in the chest, or weight loss. They should also attend follow-up appointments with their physician.

Enhancing Healthcare Team Outcomes

Mediastinal seminomas are a relatively rare malignant disorder that is best treated by an interprofessional team. These tumors are usually curable with aggressive chemotherapy and radiation. Surgical intervention is used in some cases when the tumor is small and localized. However, in either case, recurrence may take place, and repetition of these treatment modalities or a combination of them may need to be utilized. In order for any of these steps to occur, a team of various medical personnel is required including physicians, surgeons, pharmacists, nurses, lab, and surgical technicians. All of these people must maintain effective and efficient communication with each other to give the patient the best outcome possible. Overall, the younger the patient, the better prognosis they can have based on their ability to handle more aggressive treatment.

Article Details

Article Author

Michael A. Bishop

Article Editor:

Chris Kyriakopoulos


10/8/2022 4:47:47 PM

PubMed Link:

Mediastinal Seminoma



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