Seminomas account for 50% of testicular
germ-cell tumors, and more than 90% of these are classic
seminomas. When patients with a histologically pure testicular
seminoma show an elevated level of serum á-
fetoprotein (AFP), it is generally assumed that an undetected focus of
yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous
tumor. We studied 10 cases of histologically pure
seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary
tumors of the testis, and two presented with supraclavicular and ileal
tumors. The clinical stage at presentation varied: four
tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary
tumors and
metastases when present exhibited classic
seminoma histology without other germ-cell components. The
tumor cells expressed
keratin in seven cases. The pattern of
keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I
tumors underwent the conventional
therapy for pure
seminoma, i.e.,
orchiectomy and subsequent
radiation therapy. Five patients received treatment for non-seminomatous
tumors, i.e.,
chemotherapy after
orchiectomy. Extensive work-up failed to detect the primary
tumor in one patient, and he was treated for a non-seminomatous
tumor, undergoing
chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal
metastasis recently developed a second primary extragonadal mediastinal mixed
germ-cell tumor with YST and
embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (</= 16 ng/ml) of AFP in patients with an otherwise pure
seminoma may not indicate that there is a hidden focus of YST and that such patients should be treated with standard
therapy for
seminoma. Because this study includes very few patients, further studies are required to better understand the significance of borderline elevations of AFP in cases of histologically pure
seminoma.