FROM JAMA ONCOLOGY

The recent reclassification of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) – an action taken to better reflect the very low risk of adverse events associated with these tumors – has important clinical and psychological implications for patients.

“Even though physicians know that most thyroid cancers have an excellent prognosis, the impact on a patient of being given a diagnosis of cancer should not be underestimated,” Dr. Peter Angelos, professor of surgery and chief of endocrine surgery at the University of Chicago, said in an interview. “It is, however, critical for doctors and patients to understand that this change from ‘thyroid cancer’ to a ‘benign thyroid nodule,’ is not something that can be determined prior to surgery. Patients will still need thyroid operations to determine if their indeterminate nodules have cancer in them or not.”

The change in nomenclature followed an international, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC. Such patients are usually treated as having conventional thyroid cancer. The study included 109 patients with noninvasive EFVPTC who were followed for 10-26 years, and 101 with invasive EFVPTC who were followed for 1-18 years. At median follow-up of 13 years, all of the 109 patients with noninvasive EFVPTC were alive, and based on consensus diagnostic criteria developed by an Endocrine Pathology Society working group – a multinational panel of 24 thyroid pathologists – they had no evidence of disease, reported Dr. Yuri E. Nikiforov of the University of Pittsburgh and colleagues (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0386 ).

Most of those patients (67%) were treated only with lobectomy, and none received radioiodine (RAI) treatment.

Of the 101 with invasive EFVPTC, 12 experienced an adverse event, including 5 who developed distant (lung and/or bone) metastases. Two died from the disease, one had a lymph node recurrence, one had persistent disease, and five had detectable serum thyroglobulin and were considered to have indeterminate or biochemically incomplete response to therapy, the investigators said.

Based on the findings in the noninvasive EFVPTC patients, the recommended nomenclature change was adopted to reflect the main morphological features of, and lack of invasion of, the benign tumors as well as their very low risk of adverse outcome. To assist in the diagnosis of NIFTP in routine pathology practice, a simplified three-point diagnostic nuclear scoring scheme based on the six main consensus nuclear features of the tumors was developed and validated; the scoring scheme yielded sensitivity of 98.6%, specificity of 90.1%, and overall classification accuracy of 94.3% for NIFTP.

The study involved a review of digitized histologic slides collected at 13 sites in 5 countries. The pathologists who composed the working group conducted the review and consulted in a series of teleconferences and face-to-face meetings to establish the consensus criteria. They measured the frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence.

The findings suggest that “clinical management of patients with NIFTP can be deescalated because they are unlikely to benefit from immediate completion thyroidectomy and RAI therapy,” the investigators said.

“Staging would be unnecessary. In addition to eliminating the psychological impact of the diagnosis of cancer, this would reduce complications of total thyroidectomy, risk of secondary tumors following RAI therapy, and the overall cost of health care. Avoidance of RAI treatment alone would save between $5,000 and $8,500 per patient (based on U.S. cost),” they wrote, adding that an estimated 45,000 patients worldwide each year will be affected by this reclassification, resulting in significant reduction in “psychological burden, medical overtreatment and expense, and other clinical consequences associated with a cancer diagnosis.”

Dr. Martha A. Zeiger, professor of surgery at Johns Hopkins University, Baltimore, agreed that the change has important implications for patients.

“With the advent of new nomenclature for encapsulated follicular variant of papillary thyroid cancer, namely that it is now considered a benign tumor, thousands of patients who have carried this original diagnosis of cancer can breathe a sigh of relief. Our new understanding will also decrease the number of patients undergoing more extensive surgery and many can now be treated with a thyroid lobectomy only,” she said in an interview.

One thing the new nomenclature doesn’t do, however, is solve the problem of the suspicious or indeterminate thyroid fine needle aspiration diagnosis, she noted.

“Clouding the landscape even further is the fact that many of our commonly used molecular diagnostics were based on studies in which encapsulated follicular variant of papillary thyroid cancer was considered malignant, and were included in the analysis. Because of this, diagnostic molecular tools will likely now require a renewed scrutiny as to their true efficacy in differentiating benign from malignant tumors,” she said.

Dr. Nikiforov is a consultant for Quest Diagnostics. A coauthor, Dr. Sylvia Asa, is a member of the medical advisory board of Leica Aperio, and another coauthor, Dr. Virginia LiVolsi, is a consultant for Veracyte Inc. The project used a facility supported by the National Cancer Institute, and molecular analysis was supported in part by funds from the University of Pittsburgh Cancer Institute and the University of Pittsburgh Medical Center. The Endocrine Pathology Society working group conference was supported by a grant from CBLPath Inc. Dr. Angelos and Dr. Zeiger reported having no disclosures.

sworcester@frontlinemedcom.com

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