Primary mediastinal nonseminomatous germ cell tumor

Germ cells are the cells that normally become sperm or eggs. Germ cell tumors usually start in the testicles or ovaries. Sometimes they start in other parts of the body, most often along the middle: the chest, the back wall of the abdomen or the pineal gland in the brain. These are called extragonadal germ cell tumors. This page is about those that start in the mediastinum, the space in the chest between the lungs.

Germ cell cancers are split into seminomas and nonseminomas. Nonseminomas include embryonal carcinoma, endodermal sinus tumor, choriocarcinoma, malignant teratoma and mixed germ cell tumors. A seminoma in the chest is usually very curable. A nonseminoma in the chest is harder to treat. The international system used to group germ cell cancers places every mediastinal nonseminoma in the poor-prognosis group, whatever else is found.

Doctors first make sure the cancer did not start in a testicle and spread to the chest, because that is a different diagnosis. A benign (noncancerous) teratoma is also a separate diagnosis and is treated with surgery alone.

The exact cause is not known. The NCI explains that these tumors form from developing sperm or egg cells that end up outside the testicles or ovaries. One proposed idea is that some germ cells stop on their way to the testicles before birth and stay in the chest.

The NCI lists being male and being age 20 or older as risk factors. These tumors are also more common in men with Klinefelter syndrome, in which a male has an extra X chromosome. MedlinePlus Genetics explains that Klinefelter syndrome is not inherited; it comes from a random error when egg or sperm cells form. A review of these tumors advises checking patients for Klinefelter syndrome.

Mediastinal nonseminomas often carry gene changes that are less common in testicular germ cell tumors, especially in the TP53 gene. Researchers think this may help explain why these tumors have a poorer outlook.

These tumors are usually large by the time they are found, and most people have symptoms. Common ones are shortness of breath, cough, chest pain and weight loss. Others include coughing up blood, fever, night sweats and swelling of the breast tissue in men (gynecomastia). A large tumor can also press on a large vein in the chest (superior vena cava syndrome).

The cancer can spread to lymph nodes in the chest and to the lungs, liver, bones, brain and heart. Spread to organs other than the lungs is linked with a worse outlook.

This tumor also has a rare link to blood cancers. In a large international study, about 1 in 17 people with mediastinal nonseminoma developed a blood disorder, often within months of diagnosis. The most common is a type of acute myeloid leukemia called acute megakaryoblastic leukemia. The NCI says this risk is not caused by treatment. A review notes that these blood cancers have been very hard to treat.

Treatment usually takes several months: cycles of chemotherapy, then major chest surgery for many people. Before chemotherapy, men are offered semen testing and sperm banking, because treatment can affect sperm count and quality.

Some side effects can last. Cisplatin can affect the kidneys, cause numbness or tingling, and harm hearing, so at least one hearing test is advised after treatment. Bleomycin can scar the lungs. Low testosterone is common and is linked with sexual problems, metabolic problems and distress. Heart and blood vessel disease is more common later in life after this treatment, so a review advises regular heart checks.

After treatment, blood tumor markers such as AFP are checked, and scans are repeated, to watch for the cancer coming back. Many people live with fear that it will return, and some have trouble thinking clearly (brain fog). A review recommends checking mental health and offering counseling.

No donor is involved in treating this tumor. When a transplant is used, it is autologous: the person’s own blood-forming stem cells are collected from the blood and frozen. After very high-dose chemotherapy, the cells are given back to rebuild the bone marrow. It is often done two or three times in a row (a tandem transplant). EBMT’s recommendations do not list a donor transplant as an option for germ cell tumors themselves.

The role of this own-cell transplant is debated. EBMT’s 2025 recommendations call it a standard of care for germ cell tumors that resist platinum chemotherapy or come back a second time, and a clinical option as first treatment for mediastinal nonseminoma. The NCI summary is more cautious. It says people with nonseminoma germ cell tumors outside the testes who relapse respond poorly to salvage treatment, including transplant, and that a randomized trial of germ cell tumors found more side effects but no survival gain with high-dose treatment. Newer reports are more hopeful: at Indiana University, 9 of 32 people (28%) treated this way after relapse had no sign of cancer at last follow-up. A large international trial called TIGER, open to germ cell tumors from any site, has finished enrolling and has not yet posted results.

Rarely, a person with this tumor develops a related leukemia. A 2023 review says these patients should be considered promptly for a donor (allogeneic) stem cell transplant, although outcomes for these leukemias have been poor. Outside that rare situation, the sources describe no role for a donor. Registry volunteers help people with leukemia and other blood diseases that need donated cells.