Diagnosing a germ cell tumor (GCT) – the most common form of testicular cancer in young men – is a mostly straightforward business, says urologic pathologist Ezra Baraban, M.D. “These tumors are usually easy to identify when they form a noticeable mass in the testicle.” However, in about 12 percent of cases, GCTs are much harder to figure out – because they spread to other parts of the body without creating a telltale lump or mass. “This makes diagnosis especially challenging, and can delay life-saving treatment.” 

Recently, Baraban and colleagues reviewed 55 perplexing cases of elusive GCTs, “which first appeared as metastases, with spread to such distant sites as the abdomen or neck. Surprisingly, only a small minority of patients had a testicular mass at the time of diagnosis.” In most cases, the tumor was first identified through a needle biopsy, “a very small sample that can be hard to interpret. We found that these needle biopsies were prone to diagnostic errors.” 

Not only was there not a lot of tissue to work with, says Baraban, but “more than half of the tumors also showed markers commonly seen in other cancers, which added to the confusion. As a result, only about a third of cases were correctly identified as GCTs from the start.” 

How can diagnosis of these tricky tumors be improved? 

With tenacity, as Baraban and colleagues showed, and by using increasingly specific tests. “We found that using tests for protein markers like OCT3/4 and CD30 greatly improved the chances of making the right diagnosis,” Baraban explains, “but these can only be applied if one already suspects the diagnosis.” In especially unusual cases, a genetic test (FISH for isochromosome 12p) also helped confirm the diagnosis. This study, published in the American Journal of Surgical Pathology, “emphasizes the importance of combining clinical insight, advanced testing, and a high level of suspicion when establishing the diagnosis of these metastatic germ cell tumors,” Baraban says, “especially since they respond remarkably well to chemotherapy when diagnosed and treated in time.”