Using advanced genetic testing and old-fash­ioned detective work, Brady pathologist Ezra Baraban, M.D., and colleagues have solved a mystery that involves an unusual, rare – and sneaky – form of bladder cancer.

Baraban had noticed a weird phenomenon in some urinary tract tumors that were sent to him for analysis: Some patients appeared to have what looked like “yolk sac tumors,” a rare type of cancer that typ­ically begins in germ cells (cells that make sperm or eggs), and is usually seen in the testes or ovaries of young patients.

But these weren’t young patients; the aver­age age was 78. “This raised a key question,” says Baraban: Why were older patients getting tumors known for striking young people? “Were these truly reproductive system tumors, or could they actually be an unusual form of bladder cancer?”

To investigate, he and colleagues studied a series of these tumors that showed yolk sac-like features. “Interestingly, many of these patients had a history of bladder cancer or pelvic radiation, and the tumors appeared to arise from the lining of the urinary tract — suggesting these were a deceptive form of bladder cancer.”

Baraban and colleagues then proved that in this case, looks can be deceiving: “Using advanced genetic testing, we found none of the typical markers of yolk sac tumors,” he continues. “Instead, the tumors carried genetic mutations that strongly resembled those seen in aggressive bladder can­cers,” including changes in the TERT and TP53 genes and deletions in other important regions of DNA commonly observed in bladder cancer.

“Clinically, these tumors were highly aggressive, with most patients experiencing recurrence or spread of the disease. The findings suggest that these rare tumors aren’t germ cell tumors after all, but rather a deceptive and highly aggressive variant of bladder cancer.” Recognizing this distinction, says Baraban, is critical for proper diagnosis and treatment, “opening the door to more effective care for patients facing these rare cancers.”

This work was published in Modern Pathology.