The mother was in a grocery store on the North Side of Chicago when she got the news. “I talked to a doctor who might be able to help figure out what’s wrong with your son,” her friend said. The words were a relief; she had been searching for months.
The woman, her husband and their 16-year-old son were in Florida for spring break several months earlier when the boy first mentioned the pain in his right knee. That school year, he had thrown himself into sports with enthusiasm — first softball, then basketball, playing almost every day — so his mother wasn’t surprised that he was having pain, only that he complained about it.
When the knee was still bothering him at the end of the school year, she took him to an orthopedic surgeon. The pain was there most days and always much worse at night, the boy explained. The doctor ordered an X-ray, which showed a thickening of the thigh bone’s outermost layer. Next the boy had an M.R.I. That’s when their nightmare really began. The M.R.I. showed several small bright spots in the normal gray tones of the knee. To the surgeon, this looked like cancer, and he referred the boy to a doctor specializing in cancer of the bone.
Elusive Cancer
Soon after the M.R.I. of his right knee, the boy’s left hip and thigh started to hurt. A bone scan ordered a few days later showed lesions there, too, as well as on his arm, foot and ankle. Those sites soon joined in the cacophony of his pain.
But his blood tests were unremarkable. They gave no sign of a cancer’s presence. He had a biopsy of the lesion in his knee. Another of the one in his arm. Neither showed any cancerous cells. A biopsy of his bone marrow did show abnormal clumps of a kind of white blood cell called a lymphocyte, but there was no sign that these cells were cancerous.
The boy would go on to see many specialists. Each was concerned, but despite all the testing the cause of the bright white spots remained elusive. And his case was even more confusing because, though the scans looked ominous, the boy appeared well. Other than the pain, he had no symptoms.
All cancers begin with a cell that goes wild, reproducing endlessly and creating masses of identical cells. This super-proliferation, often caused by a single identifiable mutation, is what usually indicates cancer. But if this was cancer, why couldn’t the doctors find those identical cells?
CreditPhoto illustration by Ina Jang
Hitting the Road for an Answer
When there was no explanation by the end of the summer, the family spent the last week of September at the Mayo Clinic in Rochester, Minn. Specialists there reviewed all the studies that had been done and added a few of their own. They ordered yet another biopsy of a bony lesion and another sample of the bone marrow. While neither was completely normal, no one could find evidence of cancer. When the doctor from Mayo called with what should have been good news, the mother broke into tears. What else can it be? she pleaded. He’s in so much pain. Every new scan showed more lesions. The disease was clearly progressing. Where else could they go? He should follow up in a couple of months, she was told. There was clearly something going on, but it wasn’t clear what.
After watching the mother receive the news from Mayo, one of her closest friends made up her mind to try to find her some help. An internet search provided a name she thought was promising: Dr. William Gahl. He ran the Undiagnosed Diseases Program at the National Institutes of Health. She found a number listed for Gahl’s office and called. It was Saturday, so she was shocked when someone answered the phone. “Who’s this?” she asked. This is Bill Gahl, the voice answered. Who’s this?
She got over her surprise and told him she had a friend whose son was in need of a diagnosis. She had two minutes, the voice told her, a little brusque but clearly interested. She quickly outlined the boy’s puzzling case. It sounded like something they might be able to help with, Gahl told her. He gave her instructions on what her friend should do next.
Trying to Diagnose the Undiagnosable
She immediately called the mother. She explained the lucky phone encounter and passed on the email address Gahl had sent her. The mother looked up the Undiagnosed Diseases Program. It was, she saw, a part of the N.I.H. devoted to improving the diagnosis of rare disorders. It was started by Gahl in Bethesda, Md., in 2008, but over the past decade 11 other clinical sites have joined the program to create a network across the country; it has helped with hundreds of cases that baffled other doctors.
The mother followed the instructions on the website. She collected the records of all the tests her son had and asked his doctor to send a letter of referral, as requested. And then she waited. She knew it could be weeks before she heard from the doctors there — if her son’s case was accepted — and possibly months before he could be seen.
At the program, the case was assigned to Danica Novacic, an internist who reviewed most of the cases that came to their Bethesda clinic. As she pored over the boy’s medical record, Novacic became alarmed. Like many of the doctors who had already seen the boy, she was worried that this was a cancer. Those accepted into the program usually have to wait months for an appointment. She was concerned that he didn’t have that kind of time.
A Pathologist Has an Idea
Novacic shared the case with N.I.H. pathologists. Pathologists identify cancers and other tissue abnormalities in large part by staining tiny fragments of biopsied tissue cut in slices thinner than a human hair. Each stain highlights specific elements of the cell that would otherwise be invisible. Then the pathologist tries to identify the nature of the abnormality based on what they see in the stained tissue, along with the clinical information about the patient — age, exam and previous test results.
Julie C. Fanburg-Smith, the N.I.H. pathologist assigned to this case, was an expert in rare cancers. She painstakingly reviewed each of the stained slides sent by the boy’s doctors. Like those previous doctors, however, she was unable to identify any cancerous cells. Under normal circumstances, she might have waited for the child to come to Bethesda and repeat the study. But she agreed with Novacic that time was short, so she reached out to the labs where the biopsies were performed. Could they send her bone and bone marrow tissue that hadn’t been stained? She had a diagnosis in mind, and there were other stains that would help her confirm her hunch.
When she received the tissue, she made new slides, which confirmed her hypothesis: The teenager had a rare and aggressive lymphoma of the bone. Lymphomas are cancers of lymphocytes and normally originate in the lymph nodes. Not this one. The clumps of lymphocytes seen in the bone marrow were cancerous — but it took some unusual stains to reveal that.
Bad News, Good News
The boy and his parents got the diagnosis from the program two weeks before Christmas. It was news he had been waiting for. “You think, no one wants to hear that,” he told me, “but for me it was a huge relief.” Knowing what it was meant he would have a chance to treat it.
Chemotherapy was tough. Each cycle consisted of a weeklong infusion of selective poisons. He barely had time to recover from the nausea and fatigue when it was time for the next cycle. The first three cycles were bad but manageable. The fourth was hellish. After that, he was scheduled to have a PET scan to see if more treatment was needed.
The boy remembers saying a prayer as he entered the scanner — he wasn’t sure he could handle more chemo. It was a couple of terrible days waiting for the answer to come back. The news was good: He was cancer free.
That was two years ago, and he has just completed his first year of college. He is still in remission. And because this cancer has a remarkable response to chemotherapy, his doctors think he’ll stay that way.