Willard Standiford, M.D.

Infectious, oncologic and rheumatic conditions were all likely suspects for this puzzling disorder.

Catonsville, Md., pediatrician Willard Standiford wasn't quite sure what to make of his 9-year-old patient's symptoms. Over four days, she had experienced intermittent fever, fatigue, headache, nighttime chills, cough and throat pain, prompting her mom to take her to an ENT, who prescribed an antibiotic, and then-as symptoms persisted-to the nearest ED, where she was diagnosed with dehydration. As the symptoms still refused to go away, the family took her to Standiford, who suspected strep throat, which a throat culture and CBC quickly ruled out. "Her platelet count was completely normal, which was reassuring," says Standiford.

Perhaps a viral illness, Standiford thought. Had her family traveled recently? No. Recalling recent reports of parasitic meningoencephalitis, he asked if she had been swimming in a freshwater pond. No. An enteric summer virus? No, nothing to support that. Myocarditis, he wondered, but her heart sounded normal. Maybe Lyme disease or Rocky Mountain spotted fever, Standiford thought, noting the girl's fever and headache symptoms and the low sodium finding on her labs, which is associated with the illness. He prescribed the first line treatment, doxycycline.

But before sending his young patient home, he checked a tiny bump-a lymph node-the mother pointed to on the girl's groin. It felt "like a small lima bean," Standiford said. "I wasn't impressed, it wasn't particularly tender. We'll just follow it, I thought."

Five days later, however, his patient's mom called reporting an overnight temperature of 104 and a bump now "20 times bigger."

Indeed, during a follow-up exam, Standiford felt a hard nodule now the size of a walnut. "I suspect it had enlarged so rapidly that the capsule had tightened and made it very hard," Standiford says. He ordered an abdominal CT and a more comprehensive workup at St. Agnes Hospital in Baltimore.

There, pediatrician Michelle Gontasz agreed the case was puzzling. Building a differential, she and her team also considered the patient's family history of migraine, rheumatologic auto-immune disorders, hypothyroidism and Ehlers Danlos syndrome.

"We had this very broad differential, which made us ask 'Was this two different processes or one?'" Gontasz says. "But it seemed an infectious process was less likely because the abdominal mass, unlike a big abscess, was not tender and growing rapidly. That pushed an oncologic process to the top of our thinking."

Johns Hopkins pediatric resident Kimberly Dickinson, rotating through the pediatrics unit at St. Agnes at the time, agreed: "Despite a significant workup we didn't find the reason why she was febrile. A virus is always possible, and we were hopeful it was a viral syndrome, but in the back of our head we thought oncologic."

Gontasz repeated the labs and, noting the patient's lingering dry cough, ordered imaging of the chest, as well as the abdomen and pelvis. The results? CT showed markedly enlarged left retroperitoneal, pelvic, and right iliac lymph nodes concerning for lymphoma, as well as markedly enlarged left cervical lymph nodes. The patient needed an oncology consult and was transferred to the Johns Hopkins Children's Center.

There, pediatric oncology fellow David Young focused on the disseminated lymphadenopathy in the patient's neck, chest, abdomen and pelvis. Prompt treatment of lymphomas is critical, Young says, because of the possibility of tumor lysis syndrome, which develops when tumor cells burst and release their contents into the bloodstream causing system-wide toxicity. The thorough outpatient management by the patient's physician and comprehensive workup by pediatricians at St. Agnes, he adds, fully informed the oncology team and allowed them to move quickly.

"In kids this age you really should be thinking infectious, but it's good to have lymphoma, leukemia and solid tumors in the back of your mind, as well," says Young. "In this case you have two of the three oncologic emergencies, and the workup they did, the imaging and the blood work, took those off the table. The only thing left to do was get a piece of tissue for biopsy."

That lymph node biopsy uncovered an anaplastic large cell lymphoma (ACLC), a rare, fast growing blood cancer that generally responds well to chemotherapy. "I'm happy to say she is doing well," says Young.

The take home message for pediatricians, Dickinson asked Johns Hopkins pediatric residents at a recent noon conference?

"Be thorough and complete in your workup. It's easy to assume a viral syndrome, but we had a lot of discussion about ruling in or out different processes," says Dickinson. "This case also speaks to the training you get here, where we were able to do everything a subspecialist would want us to do."