Abstract
Simple SummaryHistopathological diagnosis is prone to significant observer variation in the diagnosis of papillary thyroid carcinomas (PTCs) due to different thresholds of malignancy for RAS-like nuclear features (worrisome nuclear features of PTC). RAS-like PTCs in Western practice are differently classified by most Asian pathologists into follicular adenomas when they are not invasive, follicular carcinomas when they are invasive, and follicular variant PTCs when they have fully developed nuclear features. This commentary emphasizes that this observer variation in diagnosing RAS-like thyroid tumors among practices underlies several issues in thyroid nodule practice.Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50–90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35–50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category.
Highlights
There are several issues in thyroid nodule practice internationally
The author focuses on two debates and possible explanations in this commentary: (1) why the prevalence of BRAFV600E mutation was high (50–90%) in Asian papillary thyroid carcinoma (PTC) patient cohorts but low (35–50%) in most Western papillary thyroid carcinomas (PTCs) cohorts [2], and (2) why the BRAFV600E gene test identifies high-risk PTCs in Western patients [3,4,5,6], but the test results were not reproducible in most Asian patients [7,8,9,10,11,12,13]
Conflicts between different studies stem from a variety of reasons, including patient selection, different histological types included in the analysis, different methods applied for BRAFV600E testing, and epidemiological factors [2,6,14,15,16]
Summary
There are several issues in thyroid nodule practice internationally. The author hypothesizes significant misunderstandings and poor mutual incomprehension among thyroid researchers to be the major causes [1]. Conflicts between different studies stem from a variety of reasons, including patient selection, different histological types included in the analysis, different methods applied for BRAFV600E testing, and epidemiological factors [2,6,14,15,16]. The author believes it was due in significant part to an inconsistent diagnostic threshold of malignancy for Cancers 2022, 14, 812. Cancers 2022, 13, x Cancers 2022, 14, 812 including patient selection, different histological types included in the analysis, different methods applied for BRAFV600E testing, and epidemiological factors [2,6,14,15,16]. Th2eoafu11thor believes it was due in significant part to an inconsistent diagnostic threshold of malignancy for RAS-like follicular pattern neoplasms among pathologists, in addition to the RotAhSe-rlifkaectfoorlslimcuelnartiponatetderanbnoevoep. NNuuclcelaerarfefaetautruerseosfoefnecanpcasuplsautleadtefdollfioclulilcaur lpaartpteartntetrunmtourms.o(rAs).: n(Auc):lenaur cslceoarre s0coinrea 0foilnlicaufolallricaudlaernoadmean,o(mB)a: ,n(uBc)l:enaurcslceoarres2coinrea2NinIFaTNPI(FnTuPcl(enaurcelnealarregnelmaregnetm1e, nmte1m, mbreamnebriarrneegiurlraergiutyla1riatynd cahnrdomchartoinmcalteianricnlega0ri)n, g(C0)):,n(uCc)l:enaur cslceoarres3co(nreuc3le(narucelnelaarrgeenmlaerngtem1,emntem1,bmraenme birraengeuilrarreitgyu1la,rcihtyro1-, mchartoimn actlienarcilnegar1in)gin1)ainNaIFNTIPFTdPefdineefidnebdybNyiNkiifkoirfoorvoevteatla. l[.2[22]2.](.D(D):)f:ufulllylyddeevveeloloppeeddnnuucclleeaarrffeeaattuurreess ooff aa BBRRAAFF--lliikkee eennccaappssuullaatteedd ffoolllliiccuullaarr ssuubbttyyppee PPTTCC.. ((HHEE ssttaaiinn,, ××4400))
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
