Mediastinal Nonseminoma

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Continuing Education Activity

Germ cell tumors are cancers that arise from the reproductive cells of the testis or ovaries. Germ cell tumors can arise along the track of the migration of primordial germ cells. Mediastinal non-seminomatous cancers encompass a group of germ cell cancers that affect men. Their presentation can be vague, and diagnosis requires a high index of suspicion. Management involves meticulous coordination of care with different specialties. This activity reviews the evaluation and management of mediastinal nonseminomas and highlights the role of the interprofessional team in the care of affected patients.


  • Identify the etiology of mediastinal non-seminomas.
  • Explain the diagnostic workup for a mediastinal nonseminoma.
  • Review the treatment and management options available for mediastinal nonseminomas.
  • Outline interprofessional team strategies for improving outcomes in patients with mediastinal nonseminomas.


Germ cell tumors are cancers that arise from the reproductive cells of the testis or ovaries. Sometimes, the germ cells may arise in the mediastinum, chiefly in young males. Of these, nearly 70% are non-seminomas and the rest are seminomas. Non-seminomas include the following:

  • Embryonal carcinomas
  • Yolk sac tumors
  • Teratomas
  • Choriocarcinomas

The only well-known risk factor for extragonadal germ cell tumors is Klinefelter syndrome. In the majority of patients with extragonadal tumors, there is no evidence of a primary malignancy in the scrotum. In most patients, the mediastinal non-seminomas do not produce symptoms until they get large and occupy space.


A vast majority of germ cell tumors are gonadal in location. However, germ cell cancers can arise outside the gonads, from the remnants of primordial germ cells along their path of migration, and are called extragonadal germ cell tumors. Extragonadal germ cell tumors are rare tumors accounting for 1 to 5 % of all germ cell tumors[1]. The common locations of extragonadal germ cell tumors are mediastinum, retroperitoneal area, pineal gland, and the suprasellar area. Tumors arising in the mediastinum are called mediastinal germ cell tumors, and they are the most common type of extragonadal germ cell tumors.


Mediastinal germ cell tumors are very rare and represent 3% to 10% of all mediastinal tumors and are more common in men. Similar to gonadal germ cell tumors, mediastinal germ cell tumors are broadly divided into seminomatous and non-seminomatous germ cell tumors based on tumor histology. Yolk sac tumor, teratoma, choriocarcinoma, embryonal carcinoma are the common sub-types of mediastinal non-seminomatous germ cell tumors. When the tumor contains more than one cell line, it is referred to as a mixed germ cell tumor, and it is considered as a non-seminomatous germ cell tumor even if there is a component of seminoma. Mature teratomas are benign in nature. Among the various subtypes, the mediastinal yolk sac tumor is the commonest histological subtype (about 60%)[2]. Mediastinal non-seminomatous germ cell tumors most commonly affect children and young adults. However, a few cases have been reported in older adults as well[3]. Mediastinal non-seminomatous germ cell tumors can be associated with genetic disorders such as Klinefelter syndrome and other hematological malignancies such as acute myeloid leukemia, mastocytosis, and myelodysplastic syndromes[4].


Besides the mediastinum, extragonadal tumors can also be found in the sacral area, retroperitoneum, pineal gland, thyroid, stomach, liver, and prostate. The general belief is that the germ cell tumors in extragonadal sites are derived from misplaced primordial germ cells during embryogenesis.

History and Physical

Presenting manifestations depend on the histological subtype, the size of the tumor, and the rapidity of growth. Mature teratomas, which are slow growing, can often be diagnosed incidentally. The common clinical symptoms of mediastinal non-seminomatous germ cell tumors are cough, dyspnea, chest pain, fever, night sweats, and weight loss. Rarely the tumor can compress critical structures such as the superior vena cava in the mediastinum resulting in manifestations of superior vena cava syndrome such as facial plethora and prominent neck veins. Compression of the bronchus can result in post-obstructive pneumonia, and hemoptysis can be seen when erosion into the bronchus occurs. 


A complete physical exam including a genital exam is crucial. Alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (b-HCG), and lactate dehydrogenase (LDH) are the tumor markers that can be elevated in these patients[5]. Patients with benign teratomas do not have elevated b-HCG or AFP. Levels of AFP and HCG are elevated in the majority of patients with mediastinal non-seminomas. Cytogenticstudents are often done to rule out Klinefelter syndrome

Mediastinal germ cell tumors are noted as an anterior mediastinal mass in an x-ray. Teratomas can manifest with derivatives of more than one germ layer that can be seen in an x-ray including in bones, calcification, and teeth. Although chest x-rays can identify a larger mediastinal mass, a computed tomography (CT) or magnetic resonance imaging (MRI) of the chest is required to define the size, borders, and location of the mass accurately. Patients with an extragonadal germ cell tumor have a higher risk of harboring a metachronous testicular tumor. A testicular ultrasound is mandatory to rule out a co-existing testicular tumor.

The differential diagnoses of mediastinal non-seminomatous germ cell tumors include retrosternal thyroid tumors, lymphomas, and thymic tumors. A workup for the anterior mediastinal tumors noted above is recommended, including obtaining serum levels of lactate dehydrogenase (LDH) and thyroid-stimulating hormone (TSH). A tissue diagnosis is needed for a definitive histologic diagnosis and to plan subsequent management. However, seeding is an issue and in the appropriate clinical setting with elevated markers, a biopsy is not required.

Treatment / Management

Mediastinal non-seminomatous germ cell tumors are considered poor-risk tumors[6]. No standardized staging system exists for mediastinal germ cell tumors. Treatment strategies for mediastinal non-seminomatous germ cell tumors are largely determined by the histology of the tumor. The rare occurrence of these tumors leads to the paucity of large randomized controlled studies to guide treatment. Treatment strategies are based on small case series, retrospective data, single-center studies, and the literature from gonadal germ cell tumors. Chemotherapy and surgery are two main modalities that have been evaluated for the treatment of mediastinal germ cell tumors.

Teratomas are refractory to chemotherapy, thus surgical resection is the treatment of choice for benign teratomas[7]. The mainstay of treatment for mediastinal non-seminomatous germ cell tumors other than mature teratoma is multi-agent chemotherapy followed by salvage surgery to resect any residual tumors. The chemotherapy regimen includes a combination of cisplatin with bleomycin and etoposide (BEP) or with ifosfamide and etoposide (VIP) for four cycles. In a trial that compared bleomycin and etoposide to ifosfamide and etoposide in 304 patients with advanced or disseminated germ cell tumors, the response rates, complete remission rates, and two-year overall survival were similar between the two groups[8]. Ifosfamide and etoposide are sometimes preferred over the bleomycin-containing regimen in patients with mediastinal non-seminomatous germ cell tumors because of potential pulmonary toxicity with bleomycin and the potential need for salvage surgery after chemotherapy. Sequential treatment with chemotherapy followed by autologous stem cell transplantation has been shown to improve survival and might be a good strategy in certain patients[9]. Tumor markers such as AFP and b-HCG need to be followed to assess response to chemotherapy and early fall in tumor markers would be helpful to plan subsequent treatment. 

Surgical resection of any residual mass is recommended to improve overall outcome[10][11] and is recommended even if serum tumor markers remain elevated after chemotherapy for patients who are good surgical candidates. In a salvage surgery study that included 32 patients with residual mediastinal non-seminomatous tumor after chemotherapy, 66% of resected tumors were noted to be viable, 22% of tumors were teratoma, and 12% were necrosis. Additional systemic chemotherapy is recommended in patients who had a viable residual tumor.  Unlike mediastinal seminomas, there is no role for radiation therapy in the treatment of mediastinal non-seminomatous germ cell tumors. Today it is recommended that surgery be undertaken if the residual mass is more than 3 cm. if the mass is a necrotic lesion or mature teratoma, no further chemotherapy is necessary.

Differential Diagnosis

  • Thymoma
  • Lymphoma
  • Tuberculosis
  • Sarcoma
  • Neurogenic tumors
  • Myasthenia gravis


Stage 1: Well circumscribed lesion with or without local extension to the pericardium or pleura, but without any microscopic evidence of local invasion into the adjacent tissues

Stage ll: Lesion confined to the mediastinum with microscopic and/or macroscopic evidence of infiltration into the adjacent tissues

Stage lll: Lesion with metastatic lesions. Stage llla is metastases limited to the thorax and stage lllb is extrathoracic spread.


The prognosis depends on the following factors:

Histology: in general seminomas have a better prognosis than non-seminomas

Localization of lesions. Those localized to the scrotum or retroperitoneum tend to have a better prognosis than the intracranial or mediastinal lesions

The higher the initial levels of B HCG and AFP the worse the prognosis.

Following chemotherapy, the survival of mediastinal seminomas is far better than non-seminomas. Overall, germ cell tumors of the mediastinum tend to be resistant to chemotherapy, can compromise respiratory function and a few patients may develop a hematological malignancy. Patients with mediastinal seminomas and metastatic disease have the worst survival.


  • Development of hematological malignancy
  • Respiratory compromise
  • Chemotherapy associated complications
  • Radiation associated complications like accelerated coronary disease

Postoperative and Rehabilitation Care

Long-term follow-up is necessary as late recurrences are not uncommon. Children administered radiation may develop intellectual deterioration and hearing problems.

Pearls and Other Issues

Mediastinal germ cell tumors have worse outcomes compared to testicular germ cell tumors[12]. The overall prognosis of mediastinal non-seminomatous germ cell tumors is inferior to mediastinal seminomas, teratomas, and gonadal non-seminomatous germ cell tumors. The five-year overall survival ranges between 35% to 45%[13]. Considering most patients with mediastinal non-seminomatous tumors are younger, close surveillance with labs, a physical exam, and imaging are needed for identifying recurrence early. Furthermore, these patients would need to be monitored for long-term, chemotherapy-related complications including metabolic syndrome, pulmonary toxicity, neuropathy, cardiovascular events, infertility, and secondary hematological malignancies. Preserving fertility is a major consideration in these young patients and efforts should be made to bank sperm before chemotherapy.

Enhancing Healthcare Team Outcomes

Management of mediastinal nonseminoma comprises a team of providers with surgical oncologists, medical oncologists, and radiologists[14]. Surgical oncologist plays a role in resection of cancer or for biopsies. After this, a medical oncologist typically carries forward management with chemotherapy. Radiologists play a key role in reading scans pre and post-treatment so that the effectiveness of treatment can be measured. Nursing staff and pharmacists also play a very important role in proper verification of chemotherapy drug doses, administration, and side effects management. Close communication between the team members is vital for improving outcomes. [Level 5]

Article Details

Article Author

Srinath Sundararajan

Article Editor:

Yvonne M. Carter


8/9/2021 4:54:22 PM



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