| The Testicular Cancer Resource Center |
Most germ cell tumors arise in the gonads: the testicles in males and the ovaries in females. Occasionally, however, a germ cell tumor develops somewhere else in the body without evidence of a primary tumor in either gonad. These are called extragonadal germ cell tumors (EGCTs), meaning germ cell tumors arising outside the gonads.
Extragonadal germ cell tumors are rare, accounting for only a small percentage of all germ cell tumors. They occur much more often in males than females, particularly when we are talking about malignant tumors in adolescents and adults. They can occur in females, however, and some types of extragonadal germ cell tumors are seen primarily in infants and children.
During very early embryonic development, primordial germ cells first appear near the yolk sac, outside the embryo itself. They then migrate into the developing embryo and eventually reach the testes or ovaries. Primary extragonadal germ cell tumors are believed to arise when some of these germ cells fail to reach the gonads and remain at other sites, usually along the body's midline, where they can later give rise to a germ cell tumor.
Not every germ cell tumor found outside the testicle is truly primary to that location. Sometimes the tumor is actually metastatic testicular cancer arising from a very small, hidden, or spontaneously regressed "burnt-out" testicular tumor. This is particularly important when a germ cell tumor is found in the retroperitoneum. For that reason, the testicles need to be examined carefully, and a testicular ultrasound is usually part of the evaluation even when no lump can be felt.
Extragonadal germ cell tumors can arise in several locations, most often along the midline of the body. Important sites include:
Germ cell tumors can occasionally arise at other sites as well. Age, sex and tumor location strongly influence which types of tumor are most likely and how they are treated.
Extragonadal germ cell tumors can be either benign or malignant. In infants and young children, many are benign mature teratomas, especially tumors arising in the sacrococcygeal region. These tumors may still need major surgery because of their size or location, but benign still means benign.
Malignant extragonadal germ cell tumors can contain the same basic germ cell tumor types seen in the testicle, including seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed germ cell tumors.
A couple of terminology points are worth knowing. Germ cell tumors arising in the brain are usually called germinomas rather than seminomas, and the ovarian counterpart of seminoma is called dysgerminoma.
The evaluation depends on where the tumor is located, but usually includes imaging and the germ cell tumor markers AFP, beta-hCG and LDH. A biopsy may be needed to determine exactly what kind of tumor is present.
In males, determining whether the tumor is truly extragonadal is an important part of the diagnosis. A careful testicular examination and ultrasound can sometimes identify a small or burnt-out primary tumor that was not otherwise apparent. This distinction matters because the site where the tumor actually began can substantially affect both treatment decisions and prognosis.
Treatment depends on the tumor type, location, age of the patient, and how far the tumor has spread. Seminoma and germinoma generally respond very well to treatment. Nonseminomatous tumors can be more complicated, particularly when they arise in the mediastinum.
Malignant mediastinal and retroperitoneal germ cell tumors are usually treated with cisplatin-based combination chemotherapy, much like metastatic testicular germ cell cancer. For nonseminoma, surgery to remove tumor remaining after chemotherapy can be a very important part of treatment. This is especially true for primary mediastinal nonseminoma, where successful treatment may require both chemotherapy and major thoracic surgery.
Germ cell tumors arising in the brain are treated differently from mediastinal and retroperitoneal tumors, often using chemotherapy and radiation according to the exact tumor type and location. Pediatric extragonadal tumors also have their own treatment approaches and should be managed by teams experienced with childhood germ cell tumors.
The outlook depends greatly on the type and location of the tumor. Seminoma and germinoma generally have a more favorable prognosis than nonseminomatous tumors.
For adult malignant germ cell tumors outside the brain, doctors often use the same International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system used for metastatic testicular cancer. Extragonadal seminoma is classified as either good prognosis or intermediate prognosis, depending mainly on whether the cancer has spread to organs other than the lungs. There is no poor-prognosis seminoma category.
For nonseminoma arising in the retroperitoneum, the prognosis group can be good, intermediate, or poor depending on the tumor-marker levels and where the cancer has spread. A primary mediastinal nonseminoma is different: it is classified as poor prognosis by definition, regardless of the tumor-marker levels. These tumors have unusual biological features and are more difficult to cure than most other germ cell tumors. Even so, modern treatment cures roughly 40-50% of patients with primary mediastinal nonseminoma.
Patients with extragonadal germ cell tumors are very likely to benefit from the experience of a center that treats a lot of germ cell cancer. This is especially true for primary mediastinal nonseminoma, where treatment often requires close coordination between medical oncologists and experienced thoracic surgeons. We strongly recommend that you or your doctor contact a germ cell tumor expert for treatment advice.
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