A 16-year-old boy visited multiple doctors over the course of a year after developing pain that started in his knee, and each scan suggested he had cancer, yet no blood test could prove it. Finally, a pathologist had an idea, Lisa Sanders reports for New York Times Magazine.

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Searching for a diagnosis

The boy first complained about pain in his right knee while his family was on vacation in Florida for spring break. By the end of the school year, his knee was still causing discomfort, so his mother took him to see an orthopedic surgeon, who ordered an X-ray. The X-ray found a thickening of the thigh bone's outer layer, Sanders reports.

Doctors ordered an MRI, which showed a number of small bright spots in the knee. To the surgeon, these appeared to be a sign of cancer.

The boy was then referred to a doctor specializing in bone cancer. By the time the boy had a bone scan, pain had developed in his left hip and thigh. The bone scan revealed lesions there, as well, and on his arm, foot, and ankle, all three of which began to hurt, Sanders reports.

But despite the MRI findings, the doctors had a problem proving that the boy had cancer: It didn't show up in any of his blood tests, Sanders reports. He had a biopsy of a lesion in his knee and in his arm, but both showed no signs of cancerous cells, Sanders reports. A biopsy of his bone marrow showed abnormal clumps of lymphocyte, a kind of white blood cell, but no sign that the cells were cancerous.

Every specialist the boy saw had the same problem—each was concerned the boy had cancer, but no blood test could prove it. The boy had no other symptoms aside from pain.

By the next school year, the boy was referred to the Mayo Clinic, where specialists ordered another biopsy of a bony lesion and another bone marrow sample, Sanders reports. The findings were abnormal, but they still didn't provide evidence of cancer.

Finally, a definitive diagnosis

As the medical mystery continued, a family friend reached out to William Gahl, who ran the Undiagnosed Diseases Program at NIH.

The boy's mother emailed the program and gathered the information from the boys' previous tests and got a letter of referral from his doctor.

Danica Novacic was assigned the boy's case, and as she looked over the boy's medical records, she worried the boy had cancer and that he didn't have much time, Sanders reports.

Novacic shared the boy's case with Julie Fanburg-Smith, a pathologist at NIH also assigned to the case. Fanburg-Smith was an expert in rare diseases, and she had her own theory about what might be ailing the boy.

While lymphoma is commonly diagnosed by using a standard set of stains on biopsied samples to reveal tell-tale signs of disease, Fanburg-Smith knew of a rare and aggressive form of lymphoma that wouldn't be revealed by the usual stains.

To test her theory, she requested unstained bone and bone marrow tissue from the labs where the boy previously had biopsies. She then used different stains to create her own slides—and sure enough, she discovered signs of lymphoma.

The boy was diagnosed around Christmas. "You think, no one wants to hear that," he said of being diagnosed with cancer, "but for me it was a huge relief."

The boy went through four rounds of chemotherapy, and afterward, a PET scan found that he was cancer free.

As of May 2019, two years after the PET scan cleared him, he was still in remission, and Sanders reports that his doctors believe he'll stay that way (Sanders, New York Times Magazine, 5/15).