- Author: Shabir Bhimji, MD, PhD; Chief Editor: Jeffrey C Milliken, MD more...
Germ cell tumors of the mediastinum are uncommon. Fewer than 5-7% of germ cell tumors occur outside the gonads, but of the extragonadal sites, the mediastinum is the most common location for these tumors. Other areas where germ cell tumors can occur are the retroperitoneum, the intra-abdominal cavity, and the chest. The exact mechanism whereby germ cell tumors originate in the mediastinum remains unknown.
Germ cell tumors in the mediastinum were first reported more than 50 years ago. Pathologic studies from autopsy data revealed that the tumors were usually large and frequently locally invasive.
The first theory on extragonadal malignant germ cell tumors postulated that the tumors developed from primitive germ cells in the endoderm of the yolk sac or from the urogenital ridge. These cells normally move into the scrotum during development, but when this migration fails, the cells may remain localized to either the mediastinum or the retroperitoneum. Other researchers hypothesized that these totipotential cells become detached during embryogenesis and result in primitive masses, which may develop into germ cell tumors. So far, however, no theory is proven.
No research documents that these cells metastasize from gonadal tissue. Mediastinal germ cells tumors are now postulated to be autonomous oncologic entities.
Seminomas usually develop in the anterosuperior mediastinum and can develop into fairly large tumors. The tumors usually grow at the juncture of the innominate vein and the superior vena cava. As a tumor grows, it can compress the above structures and invade the adjacent fatty tissues. When a seminoma is large, differentiating the mass from the thymic fat and surrounding pericardium is difficult.
The histology of mediastinal tumors is very similar to that of tumors in the gonadal tissues; however, most authorities believe that metastases from the gonadal area are not responsible for the growth of these tumors in the mediastinum. In adults, germ cell tumors are the third most common type of tumor in the anterior mediastinum; in children, they are the second most common anterior mediastinal mass.
Fortunately, most of these lesions are benign teratomas. Of the germ cell tumors, benign teratomas (ie, dermoid cysts) are the most commonly diagnosed mediastinal mass and are present in 50-70% of infants and children with germ cell tumors. Seminomas are the predominant malignant lesions, accounting for nearly 50% of mediastinal lesions.
Mediastinal seminomas are generally bulky tumors and tend to infiltrate into adjacent structures early in the growth process. The cells are large and contain variable amounts of glycogen. These tumors are composed of large cells with multiple nuclei, which closely resemble syncytiotrophoblasts.
Unlike other germ cell tumors, seminomas tend to remain localized in the chest, and only occasionally do they invade adjacent structures. However, these tumors are sometimes discovered late, and extrathoracic spread is sometimes observed. The usual route of metastases is hematogenous, and the major organs to which metastases occur are the lungs, liver, and bones.
Experimental evidence suggests that the cells responsible for mediastinal tumors are derived from germinal cells that transmigrate to the mediastinum from the urogenital ridge during embryonic life; however, not all authorities agree with this view of presupposed metastatic disease. Nevertheless, it is always important to make sure, through physical examination of the groin and scrotum, that no gonadal tumors are simultaneously present. (Click here to complete a Medscape CME activity on synchronous bilateral testicular seminoma.) Ultrasonography is sensitive for examination of the scrotal area, and computed tomography (CT) is essential for evaluation of the retroperitoneum.
Although the cause of these tumors is not known, men with Klinefelter syndrome have an increased prevalence of them. Individuals with this syndrome, consisting of an extra X chromosome, are known to develop mediastinal germ cell tumors at least 10 years earlier than persons without the syndrome. Further workup in these patients has shown abnormally low levels of testosterone and high levels of luteinizing hormone and estradiol. These discoveries suggest a primary germ cell defect, which may cause faulty spermatogenesis and a predisposition to extragonadal malignancies.
Malignant germ cell tumors of the mediastinum are rare, accounting for approximately 10% of all mediastinal tumors. These tumors occur almost exclusively in males, and the age at presentation is generally 20-35 years. More than one third of all malignant germ cell tumors are pure seminomas.
All types of malignant germ cell masses are more prevalent in males, and most of these males are symptomatic. Benign germ cell tumors, on the other hand, are distributed equally between the sexes, and most develop in the third decade of life. In children, mediastinal germ cell tumors can occur at any age and are equally divided between boys and girls.
Surgical results for mediastinal seminomas range from poor to borderline. All series in which a mediastinal mass has been completely resected have shown 5-year survival rates lower than 50%, with a greater than 40% chance of recurrence. However, most patients who present with seminomas have a large anterior mediastinal mass, and surgery is rarely the first choice of treatment.[2, 3]
In the past decades, the general trend has been to refer all patients with seminomas, regardless of size, for radiation therapy and chemotherapy. In current practice, seminomas are curable with aggressive treatment. The treatment of pure seminomas today is nonsurgical; only the small, resectable tumors in asymptomatic patients should be completely excised and managed with postoperative radiation therapy using doses of 40-50 Gy.
If distant metastases are detected at the time of diagnosis, the patient should be treated with intensive cisplatin-based combination chemotherapy. Even though these tumors are very sensitive to radiation, remissions are observed in only 50-70% of patients; therefore, combination chemotherapy is recommended for bulky disease, and radiation is recommended for localized disease.
For bulky tumors, induction chemotherapy is administered, and any residual disease revealed on CT is then resected to determine if a viable tumor remains. A finding positive for a tumor may dictate further therapy. If no lesion is observed on CT, no further therapy is warranted and the patient can be monitored with serial CT scans every 6-12 months. Current treatment regimens provide remission in more than 80% of individuals, and the 5-year survival rate is reported to be approximately 60-80%.
Joly et al retrospectively reviewed treatment outcomes for 19 patients with primary mediastinal germ cell tumors, three of whom had pure seminomas. Treatment consisted of cisplatin-based chemotherapy. At the conclusion of treatment, three patients had a complete response and negative marker, seven had a partial response and negative marker, five had a partial response and positive marker, three had progressive disease, and one had died. The 1-year overall survival rate was 78%; the 5-year overall survival rate, 36%; and the progression-free survival rate, 43%.
Liu et al reported their experience with 54 patients who had primary malignant mediastinal germ cell tumors (18 seminomas and 36 nonseminomatous germ cell tumors [NSGCTs]) with follow-up from 1990 to 2009. Two patients were treated with chemoradiotherapy alone, and the remaining 52 received surgical treatment (30 complete resections, 18 partial resections, and four biopsies). When last followed up, 17 patients remained alive (11 with seminomas and six with NSGCTs). The 5-year overall survival rate was 87.7% for patients with seminomas and 23.0% for patients with NSGCTs.
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