Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma

Abstract

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.

AHNS Series: Do you know your guidelines? AHNS Endocrine Section Consensus Statement: State‐of‐the‐art thyroid surgical recommendations in the era of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features

“…The reclassification of the noninvasive encapsulated FVPTC as NIFTP7 has significant implications for the practice of thyroid cytopathology 8. The most significant change will involve a decrease in the implied risk of malignancy, particularly for cases classified into 3 so‐called “indeterminate” diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology: (1) Bethesda class III= atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); (2) Bethesda class IV= follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN); and (3) Bethesda class V= suspicious for malignancy (SFM) 9, 10, 11.…”

“…The majority of these point mutations lead to codon 61 glutamine substitutions. Other driver mutations identified in NIFTP include PAX8‐PARG (4%‐22%),1, 3 THADA fusions (22%), and occasionally BRAF K601E mutations 7. A distinctive aspect of NIFTP lesions is the absence of BRAF V600E , TERT , RET , and NTRK fusions and other mutations associated with classical and tall cell variant PTCs.…”

“…Based on the significant lack of tumor recurrence in several retrospectively analyzed NIFTP cohorts,7, 24, 25 patients with resected solitary NIFTP tumors should require less active follow‐up than that recommended for patients with “low‐risk recurrence of differentiated thyroid cancer” in the 2015 American Thyroid Association guidelines 26. Measurement of yearly quantitative thyroglobulin in patients with NIFTP is also appropriate, with expected values 6 weeks after surgery <5 ng/mL for total thyroidectomy patients and levels <30 ng/mL for lobectomy patients, in the absence of thyroglobulin antibodies 27.…”

Pathology Image-Sharing on Social Media: Recommendations for Protecting Privacy While Motivating Education

“…For example, Twitter has been used to disseminate and discuss findings from society meetings, as strikingly demonstrated by the 2016 United States and Canadian Academy for Pathology (USCAP) meeting in Seattle, which generated over 19,000 tweets and over 28 million impressions [5,6]. Pathology discussions on social media also concern updates on diagnostic criteria, such as the recent changes in thyroid cancer classification [7,8]; World Health Organization (WHO) monographs [9]; regulatory frustrations; and research findings. There are numerous subspecialty interest groups, including a nephrology journal club with over 3,000 followers on Twitter [10] and a variety of pathology discussion groups on Facebook (e.g., dermatopathology and bone and soft tissue pathology, which had over 21,000 and 18,000 members, respectively, in April 2016 [11]).…”

NIFTP: A Critical Pathologist View

“…The study of Nikiforov et al, 1 laid the foundations of this new discovery, which are: a. The morphological features, i.e., the follicular growth pattern and nuclear features of papillary thyroid carcinoma (PTC);…”