Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas - A clinicopathologic and immunohistochemical study of 120 cases

BACKGROUND. Primary seminomas of the mediastinum are unusual neoplasms that are morphologically indistinguishable from their gonadal counterparts but may have different biologic behavior because they arise at this particular location. METHODS. The clinical and pathologic features in 120 cases of primary mediastinal seminoma were reviewed, and the immunohistochemical staining patterns in 50 of these tumors were also analyzed. RESULTS. The patients were all men between the ages of 14 and 79 years (mean age, 46.5 years). Their clinical symptoms included cough, chest pain, and dyspnea. In some patients, the lesions were asymptomatic and discovered incidentally on routine chest radiographs. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the tumors were described as soft and tan, with a slightly lobulated cut surface, and measured up to 16 cm in greatest dimension. Histologically, the morphologic features were similar to those of tumors occurring in the gonads, namely, a neoplastic proliferation of round-to- polygonal cells with indistinct cell borders, clear-to-lightly-eosinophilic cytoplasm with round-to-oval nuclei and prominent nucleoli, associated with a prominent inflammatory background composed mainly of mature lymphocytes. Necrosis, hemorrhage, multi-nucleated giant cells, granulomatous reaction, and remnants of thymic tissue were observed in a variable number of cases; mitoses were rare. Immunohistochemical studies in 50 cases showed cytoplasmic staining with placental alkaline phosphatase in 80% of the tumors, focal dotlike positivity for CAM 5.2 low-molecular-weight keratins in 75%, focal cytoplasmic staining for wide-spectrum keratin in 70%, focal positive reaction with vimentin in 70%, and focal positivity with HCG in singly scattered cells in 5%. Immunostains for carcinoembryonic antigen, epithelial membrane antigen, and α-fetoprotein were negative in all the cases studied. Fifty patients were Stage I, 3 patients were Stage II, and 12 patients were Stage III. Clinical follow-up information was obtained for 65 cases (54%). Forty-nine patients were alive and disease free after a period ranging from 1 to 19 years (mean follow-up, 10 years). Sixteen patients died within the same period and were found to have metastases to distant organs. Of the 16 patients who died, 6 showed extension of the tumor outside of the mediastinal compartment at the time of initial diagnosis (Stage III lesions). Aside from clinical staging, the authors' findings also suggest that patients >37 years have worse outcomes than younger individuals. The authors were unable to find any correlation between histopathologic features and clinical behavior in any of these cases. CONCLUSIONS. Clinical and pathologic staging of mediastinal seminomas are important parameters that can be useful in determining the clinical outcomes of patients with these tumors. Tumor invasion into adjacent organs represents a marker of increased morbidity and mortality. The authors' findings suggest that patients with mediastinal seminomas may have a very good prognosis when the diagnosis is made early; patients with more advanced lesions may require more aggressive therapy for improved local control and prevention of distant metastases.