Although testicular cancer is the most common malignancy in men between the ages of 15 and 34 years, the incidence is still quite low, being estimated at 5 in 100,000 (National Cancer Institute's cancer results, 1995-1999). Screening with serum markers would not be practical, given the poor specificity of the existing markers, as false-positive values would far outnumber true positives for screening. Nonetheless, tumor markers retain an important role in diagnosis. Nowhere is this more evident than in extragonadal GCTs, which can often present as poorly differentiated cancer of unknown origin. In the setting where normal histologic criteria are absent, positive immunohistochemical staining for AFP or hCG (or even elevated serum levels) can confirm the diagnosis and allow appropriate therapy. Finally, i(12p), which is expressed in more than 80% of GCTs and is rarely expressed in other malignancies, may be an additional aid.

In testicular primaries, markers sometimes have an important diagnostic role as well. Patients with NSGCTs present with elevated AFP or hCG in 85%

of cases (AFP alone in 40% of cases, hCG alone in 50 to 60%).58 Seminoma patients, on the other hand, never present with elevated AFP, but 10 to 25% present with detectable hCG, which implies syncytiotro-phoblastic elements, even if not visible by routine microscopy. In the common presentation of a painless testicular mass, elevated markers are practically pathognomonic of GCT and can predict histology to a degree. AFP suggests the presence of embryonal or yolk sac elements, and hCG, especially at high levels, suggests elements of choriocarcinoma. Elevated AFP levels in the face of a histologic diagnosis of seminoma mean that NSGCT elements exist somewhere in the primary tumor and/or metastasis. In these cases, management should be conducted as though the diagnosis were NSGCT.

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