The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification

Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice

“…The diagnostic threshold of PTC-type malignancy in Western pathology practice has been significantly modified since the 1980s, and cases with delicate nuclear changes in RAS-like tumors were accepted as evidence of malignancy [19,35]. This diagnostic tendency (low threshold of diagnostic nuclear features of PTC) made non-invasive encapsulated follicular variant PTC the most frequent histological subtype in Western patient cohorts [4,19,22,39,40], but not in Asian patients where only fully developed nuclear features indicated follicular variant PTCs [24][25][26][41][42][43][44]. This different threshold for malignancy in follicular pattern tumors was confirmed as the cause of the significant observer variation among pathologists when evaluating the same specimens [17,18,[45][46][47][48], particularly between Asian and Western pathologists [17,18,45].…”

“…Renshaw and Gould explained their motivation to over-diagnose uncertain cases rather than under-diagnose them in North American practice [51]. The gap between North America and the rest of the world became wider, and non-invasive encapsulated follicular variant PTC accounted for nearly 30% of PTC in North American practice [22,39,40,52,53], whereas it was low (1-5%) in most Asian thyroid practices [24,25,[41][42][43][44]48], some European institutes [14,[54][55][56], and a few US centers [25,57]. Hodak et al discussed this overdiagnosis in their excellent commentary, suggesting that for many patients with thyroid cancer, we may often be violating the important dictum primum non nocere (first, do no harm patients) [58].…”

“…However, Western pathologists often diagnose follicular pattern tumors with delicate nuclear features as malignant tumors (follicular variant PTC) regardless of invasive growth [4,[19][20][21][22] (Figure 1). The benign/malignant observer variation in delicate nuclear features (worrisome for PTC) of non-invasive encapsulated RAS-like neoplasms is significant among pathologists, particularly between Asian and Western pathologists [1,17,18,[23][24][25]. The guest editor of this Special Issue of molecular advances and targeted therapy in Asian thyroid practice believes this caused significant differences between Asian and Western thyroid nodule practices, which are evident from the above two debates and other studies in this Special Issue.…”

Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile

“…The original rate of 18.6%, among 3400 PTC cases, published in a seminal paper [ 5 ] has been shown to be higher than average in recent analyses. The recent meta-analysis showed the worldwide NIFTP incidence to be 6%, with an Asian vs. Western discrepancy [ 18 ]. The Asian continent was represented by 28 institutions from 9 countries and the incidence varied from 0.4% in China to 14.4% in India with 2.1% NIFTP Asian rate on average [ 18 ].…”

“…The recent meta-analysis showed the worldwide NIFTP incidence to be 6%, with an Asian vs. Western discrepancy [ 18 ]. The Asian continent was represented by 28 institutions from 9 countries and the incidence varied from 0.4% in China to 14.4% in India with 2.1% NIFTP Asian rate on average [ 18 ]. The reasons for discrepancy are multifactorial, and may be as follows: racial and ethnical background and mutation profile represent biological factors [ 18 ], but the threshold for diagnosing PTC nuclear features was shown to differ in American vs. Japanese and Korean series [ 18 , 19 , 20 , 21 , 22 ].…”