The College of American Pathologists (CAP) should require more detailed reporting of specific characteristics of lymph node metastases, especially micrometastases, similar to that used in breast cancer, in order to help clinicians make more informed treatment decisions for thyroid cancer patients. That was the recommendation of Mark L. Urken, MD, Chief of the Division of Head and Neck Surgical Oncology at Beth Israel Medical Center and Co-director of the Institute for Head and Neck and Thyroid Cancer, both in New York City, writing in an article now online ahead of print in Endocrine Pathology (DOI 10.1007/s12022-013-9282-7).
More specific reporting of the histologic features of involved lymph nodes in papillary thyroid cancer could help doctors better determine which patients might be spared radioiodine treatment for smaller metastases, which research indicates may not need additional therapy, he said.
CAP does not currently require that pathologists include detailed findings above and beyond lymph node positivity, as part of their standard reporting protocol for thyroid cancer, he noted. Similarly, the American Joint Committee on Cancer (AJCC) does not utilize the size, number, or presence of extranodal extension as part of the standard staging for well-differentiated thyroid cancer.
However, clinicians have come to recognize that these specific features have prognostic implications, Urken noted. Large clinical trials have not been conducted to verify the growing number of published papers that suggest that larger-volume nodes, clinically evident nodes (detected by physical exam or imaging studies), increased number of positive nodes, and lymph nodes with extranodal extension have greater prognostic significance.
It is imperative that these features be reported by all pathologists in order to set the stage for those large-scale studies to be conducted, he said.
Elaborating in an interview, Urken said that with the rapid rise in thyroid cancer in the United States and questions about the best treatment options for small lymph node metastases in differentiated cancer, it is time for the College to adopt a strategy for more detailed reporting similar to the protocol currently utilized in breast cancer pathologic reporting.
“The increased number of patients with thyroid cancer is staggering, and the percentage of patients with positive nodes in well-differentiated thyroid cancer has been reported to be as high as 80 percent,” he said. “However, many of those patients have microscopic nodal deposits that are probably not clinically significant and should not influence a patient's disease stage the way a macroscopic deposit does. What we need is better guidance on treatment options based on these characteristics of lymph node metastases.”
The AJCC, the most commonly used staging system, upstages a patient who is over the age of 45 with a single positive node in the central compartment to stage 3. Similarly, a single positive node in the lateral compartment leads to upstaging to stage 4.
“This is true regardless of the size of the involved node,” he explained. “Clinicians understand that there are differences in outcomes depending on the size and other characteristics of lymph node metastases, and that these histologic features should have an impact on treatment and prognosis, but the CAP has lagged behind in reporting this information. I was trying in the article to emphasize that pathologists need to be reporting this information so that clinicians can conduct the appropriate clinical studies to more effectively manage these patients.”
MARK L. URKEN, MD
It is becoming increasingly evident that macroscopic and microscopic nodes represent differences in disease biology, Urken continued. The differences in disease that allow lymph nodes in one patient to reach the level of being clinically evident by either physical exam or routine imaging studies, as well as the ability for the cancer to extend outside the lymph node capsule, known as extranodal extension, have led a growing number of clinicians, and even clinical practice guidelines, to stratify nodal metastases on the basis of these features, he said.
However, all lymph node metastases in differentiated thyroid cancer do not have the same clinical significance with respect to the risk of recurrence and the risk of death, and CAP has not mandated that pathologists include these findings as part of their standard reporting protocol in thyroid cancer.
“There is significant data in the medical literature that indicates that whereas in the past, positive nodes led to a recommendation to administer radioactive iodine, different nodal characteristics may not require adjuvant therapy at all,” he said.
“This is not a rogue paper—it is based on good research showing that the current one-size-fits-all treatment approach may not apply to many patients, especially when smaller-sized cancers are considered. Currently nodal size is not being reported as part of the CAP protocol even though there is a significant body of evidence of these differences. CAP would prefer that changes in their reporting protocol be based on controlled trials, but we cannot get there until CAP requires pathologists to report these additional data points.
“Right now we do not have enough information on affected individuals,” he continued. “What we have at any given time is simply a snapshot of what the disease is doing at the particular time of diagnosis, but we do not know where it will go because we are lacking data. What we currently receive from pathologists does not provide enough insight on how a disease will evolve in a given patient that will allow individualized cancer management decisions to be made.”
GREGORY RANDOLPH, MD
Asked for his opinion, Gregory Randolph, MD, Director of the General Otolaryngology and Thyroid Surgical Services at Massachusetts Eye and Ear Infirmary and Associate Professor of Otolaryngology/Head and Neck Surgery at Harvard Medical School, said that about one-third of patients with thyroid cancer have nodal metastases clinically recognizable at presentation, and yet their overall prognosis is favorable.
“Patients with such nodes are associated with higher rates of subsequent recurrence. This occurs in about 20 percent of such patients compared with only three to five percent of patients without them,” he said.
“The problem is that as many as 80 percent of patients with papillary cancer of the thyroid, the most common form of thyroid cancer, nodal metastases can't be felt manually or observed on ultrasound or radiographic studies in that they are microscopic. These microscopic nodes do not increase the rate of subsequent nodal recurrence in distinction to the clinically recognizable nodal metastases. This has led to confusion on how to best manage patients.”
Often any pathologically positive findings, including microscopic nodal metastases, are treated the same as more overt clinical nodal disease, he noted. “There is a trend toward taking a more conservative, wait-and-see approach with such microscopic patients. Our work within the ATA [American Thyroid Association] has shown that the risk of recurrence is far less in microscopic patients compared with those with larger clinically recognizable nodal metastases.”
Treating lymph node “positivity” needs to be stratified, based on the size of these metastases, he continued. “Right now it is not and as a result, there is a ‘microscopic upstaging,’ which can result in excess treatment with radioiodine in patients and result in unwanted side effects. This is simply not a rational approach to treatment.
“I believe Dr. Urken's paper will help motivate pathologists to gather important node-size information to help us better stratify the node-positive neck in patients with thyroid cancer. We agree with his approach and these important recommendations.”