Misrepresentations surround the occurrence, causes, and treatment of thyroid cancer in the pediatric patient population. It’s not as “rare” as once thought, and despite its treatability, there is still a ways to go in separating fact from fiction.
The mantra in recent years in the world of pediatric thyroid nodules has been that although nodules occur more rarely than in the adult population, they are more likely to be malignant. However, only half of that statement has proven true. Pediatric thyroid nodules do have a fivefold increased risk of malignancy, but, just as with adult nodules, the incidence of thyroid nodules and thyroid cancer is increasing. In “Cancer Incidence Rates and Trends among Children and Adolescents in the United States, 2001–2009,” published in Pediatrics, study authors analyzed data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results to confirm this increase. They suggest several possible causes, including environmental factors such as certain toxins or radiation exposure, but a definitive cause has not been identified.
Not So Rare
“Pediatricians and endocrinologists are seeing more cases of differentiated thyroid cancer, papillary in particular — more frequently than for what ‘rare’ would be a fair description, ” says Andrew J. Bauer, MD, FAAP, medical director of the Thyroid Center at the Children’s Hospital of Philadelphia (CHOP), and associate professor, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania. “Although some of this increase can likely be attributed to incidental findings on head and neck imaging, Bauer says much of it really is an increased incidence, and not just of subclinical lesions. “To compare it to a cancer that most people know about, papillary thyroid cancer has roughly the same incidence as non-Hodgkin lymphoma in the U.S. adolescent population, with an estimated incidence of 18 to 20 per million.”
Being very rare is not the only long-held belief about pediatric thyroid cancer that does not hold up under the microscope. Bauer co-chaired a task force that included 14 experts from seven countries and was sponsored by the American Thyroid Association (ATA) to author the first “Guidelines on the Evaluation and Management of Thyroid Nodules and Differentiated Thyroid Cancer in Children and Adolescents”, which was just published in April. Seeking treatment at a center experienced in pediatric thyroid cancer is a key recommendation. “It’s extremely treatable, but it is a cancer, so it still needs to be approached thoughtfully. Patients need to see physicians who understand how to stratify treatment,” Bauer says. He urges primary care physicians who find pediatric nodules to refer the patient to an endocrinologist. “Th e endocrinologist should be the gatekeeper and will look at the ultrasound to determine whether a fine needle aspiration biopsy is necessary. We’re trying to educate pediatricians and family physicians not to skip this important step in the evaluation process.”
Given the increased risk of malignancy in pediatric thyroid nodules, performing a biopsy might seem like a waste of time and money. “But that’s not the best approach,” Bauer says. “Not all nodules need biopsy, and not all nodules need surgery.” Fine needle aspiration (FNA) is a low-risk procedure, whereas thyroid surgery carries a significant risk of long-term complications. Forgoing FNA might save money in the short term, but doing what might have been an unnecessary surgery and causing hypoparathyroidism or damage to the recurrent laryngeal nerve is hardly cost-effective. Moreover, the patient’s quality of life may be significantly impaired. “A biopsy will provide the information you need to make the right decision as far as continuing to watch with ultrasound or moving to surgery, as well as optimizing and individualizing the extent of surgery,” Bauer says.
“Pediatricians and endocrinologists are seeing more cases of differentiated thyroid cancer, papillary in particular — more frequently than for what ‘rare’ would be a fair description.” — Andrew J. Bauer, MD, FAAP, medical director, Thyroid Center at The Children’s Hospital of Philadelphia, and associate professor, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
James D. Sidman, MD, director of ENT and Facial Plastic Surgery at the Children’s Hospitals and Clinics of Minnesota, and professor of Otolaryngology and Pediatrics at the University of Minnesota Medical School, agrees that a careful physical evaluation and management process is critical. “Don’t jump to a CAT scan,” he urges, “because the contrast can delay treatment. By far and away, the most frequent type of cancer we see is papillary carcinoma, which responds well to treatment and has a 95% – 100% remission rate when treated first by surgery and then by radioactive iodine therapy. Th e response should be, do an ultrasound.” He also agrees that much of the time FNA is in order. “But it can be controversial,” he says. “Some argue that putting a child through the sedation necessary for FNA is futile if the nodule is, say, a 2-cm solid nodule by ultrasound and would probably be removed anyway.”
Sidman also cautions physicians to have a high index of suspicion for the multiple endocrine neoplasia syndromes, which he sees about once a year. “If a child tests positive for the RET proto-oncogene, that patient might need to have a total thyroidectomy — you might not be able to do watchful waiting with that patient.” According to Bauer, the decision should be based on what the specific mutation is as well as the family history, referring to the recently updated ATA guidelines is the best place to start.
Sidman and Bauer agree saying that referral to the appropriate surgeon with plenty of material experience is key because a pediatric thyroidectomy is quite different from an adult thyroidectomy. “In the pediatric population, where almost all thyroid cancers are papillary, a pediatric ENT surgeon MAY BE required because it’s not a simple thyroidectomy,” Sidman says. “Papillary cancer patients MAY need to have a modified radical neck dissection to strip out all of the lymph nodes.” Bauer says the surgery should carry less than a 3% to 5% risk for serious complications, which requires a surgeon who performs 30 or more surgeries a year.
Opportunities to Improve Approach to Care
A hot topic gaining traction in pediatric thyroid cancer is molecular evaluation. “A biopsy is not always either benign or malignant, cancer or not cancer,” Bauer explains. “Th e reality is, about 25% of people fall into this gray zone in which you don’t have normal-looking cells but you don’t have cells that are clearly cancerous. In that case, we don’t know what the right surgery is, because if it’s benign, you didn’t need surgery, and if it’s malignant, you needed a total thyroidectomy and not a lobectomy.” Researchers have been finding adjunct ways of looking at the biopsy in adults, such as specific gene expression classifier panels or oncogene panels that test for RET/ PRC rearrangements and RAS or BRAF mutations, molecular alterations that predict whether that gray-zone biopsy is more likely to be benign or to be cancer and how the patient might respond to treatment. “We’re just starting to explore these tests in pediatrics, and we need more research to figure out how to use them with kids,” Bauer says, who presented an abstract on this topic at the ATA annual meeting in October 2014.
“In the pediatric population, where almost all thyroid cancers are papillary, a pediatric ENT surgeon is required because it’s not a simple thyroidectomy. Papillary cancer patients need to have a modified radical neck dissection to strip out all of the lymph nodes.” — James D. Sidman, MD, director, ENT and Facial Plastic Surgery, Children’s Hospitals and Clinics of Minnesota; professor of Otolaryngology and Pediatrics, University of Minnesota Medical School, Minneapolis
Another important new topic concern is quality of life for children and adolescents diagnosed with thyroid cancer. “People tend to say things like, ‘If you’re going to have cancer, thyroid cancer is the one to have because it’s so treatable,’ and patients hate that,” Bauer says. According to an abstract that he will co-present at the American Academy of Pediatrics in October 2015, kids shoulder the same posttraumatic stress burden with thyroid cancer as with, for example, Hodgkin lymphoma. “It’s good to say it’s very treatable, but don’t dismiss it. It’s not really true that anyone is lucky to have thyroid cancer,” he says. “Th at it’s treatable is a nice place to start, but that’s not the end of the story. Th e question is, what can we do to take better care of these patients, to individualize their treatment, and to maintain this excellent outcome? To dismiss thyroid cancer because it is very treatable isn’t fair to the patient.”
— Horvath is a freelance writer based in Baltimore, Md. She wrote about the link between obesity and breast cancer in the March issue.