Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the mediastinum--a clinicopathologic and immunohistochemical study of 64 cases

Abstract

Background: Yolk sac tumor (YST), embryonal carcinoma (EC), choriocarcinoma (CC), and combined germ cell tumors (CGCTs) of the mediastinum are uncommon neoplasms. Only sporadic cases have been documented in the literature; therefore, the clinical behavior of these tumors when located in the mediastinum remains relatively unknown.

Methods: The clinical and pathologic features of 64 cases of primary YST, EC, CC, and CGCTs without teratomatous components were reviewed. The immunohistochemical findings in 29 cases were also analyzed using a panel of monoclonal and polyclonal antibodies in formalin fixed, paraffin embedded tissues.

Results: The patients were all men between the ages of 14 and 63 years (mean, 38.5 years). Their clinical symptoms included chest pain, shortness of breath, chills, fever, and superior vena cava syndrome. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the lesions in 27 patients were described as large, soft, hemorrhagic, and in some cases necrotic, and varied in greatest dimension from 6 to 20 cm. Histologically, the tumors displayed morphologic features similar to those of their gonadal counterparts. Pure YSTs accounted for the majority of cases in this series (38 of 64, 60%), followed by pure CCs (8 of 64, 12%) and pure ECs (6 of 64, 9%). CGCTs accounted for only 18% of the total cases (12 of 64). YSTs showed a variety of growth patterns; however, the reticular pattern was the most commonly observed. ECs showed a more solid growth pattern with marked pleomorphism of the tumor cells and abundant areas of necrosis. CCs were characterized by the presence of cytotrophoblastic and syncytiotrophoblastic elements with frequent areas of necrosis and hemorrhage. The cases of nonteratomatous CGCT consisted of 5 cases of EC + YST, 2 cases of EC + seminoma, 4 cases of YST + seminoma, and 1 case of EC + CC. In clinical staging, 14 patients were Stage I, 6 were Stage II, and 19 were Stage III. Information on follow-up ranging from 1 month to 13 years was available for 40 patients. Seventeen patients with YST died of their tumors. Of these, 10 who presented with Stage III disease died within the first 2 years. Unfortunately, no clinical staging was obtained for the other 7 patients in this group, and they died within 6-36 months. It is noteworthy that 4 patients with YST have survived for more than 2 years; these patients presented in Stages I and II, and 2 of them received aggressive therapy with chemotherapeutic agents and radiation. Two patients with Stage III EC died within 2 years. The remaining 4 patients with EC were lost to follow-up. Eight patients with CC died within 6 months after initial diagnosis; 7 of them presented Stage III disease and only 1 presented with Stage I. In the nonteratomatous CGCT category, 2 patients with EC + YST died within 2 years after initial diagnosis, whereas 3 patients with YST + seminoma were alive after 4-9 years.

Conclusions: The results of this study confirm the aggressive nature of primary nonseminomatous germ cell tumor of the mediastinum; 72% of the patients with adequate follow-up died of their tumors within 6-36 months after diagnosis, despite aggressive therapy. Clinical and pathologic staging of mediastinal YST, EC, and CGCT are important parameters that may be helpful in predicting the clinical outcomes of patients with these tumors. The authors' findings suggest that the majority of tumors that are not limited to the mediastinum at the time of diagnosis have more aggressive behavior. On the other hand, mediastinal choriocarcinomas appeared to follow a very aggressive clinical course, regardless of treatment modality or clinical tumor stage.