Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors

Yuri E. Nikiforov, Raja R. Seethala, Giovanni Tallini, Zubair W. Baloch, Fulvio Basolo, Lester D. R. Thompson, Justine A. Barletta, Bruce M. Wenig, Abir Al Ghuzlan, Kennichi Kakudo, Thomas J. Giordano, Venancio A. Alves, Elham Khanafshar, Sylvia L. Asa, Adel K. El-Naggar, William E. Gooding, Steven P. Hodak, Ricardo V. Lloyd, Guy Maytal, Ozgur MeteMarina N. Nikiforova, Vania Nosé, Mauro Papotti, David Poller, Peter M. Sadow, Arthur S. Tischler, Michael Tuttle, Kathryn B. Wall, Virginia A. LiVolsi, Gregory W. Randolph, Ronald A. Ghossein

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Importance - Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.

Objective - To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.

Design, Setting, and Participants - International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.

Main Outcomes and Measures - Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.

Results - Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.

Conclusions and Relevance - Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

Original languageEnglish
Pages (from-to)1023-1029
Number of pages7
JournalJAMA Oncology
Issue number8
Early online date14 Apr 2016
Publication statusPublished - 1 Aug 2016


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