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Representative examples of follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) in thyroid core needle biopsies and resection specimens. a–c FTA. a A low-power view of thyroid core needle biopsy (CNB) shows a microfollicular proliferative lesion lacking capsule or adjacent thyroid tissue, diagnosed as indeterminate follicular lesion with architectural atypia. b A high-magnification view reveals hyperchromatic round tumor cell nuclei lacking PTC-like nuclear features. c A surgical resection specimen revealed FTA. d–f FTC. d A low-magnification view of thyroid CNB shows an encapsulated microfollicular-patterned lesion with suspicious capsular invasion (arrow). e A high-power view reveals hyperchromatic round tumor cell nuclei, resulting in a diagnosis of follicular neoplasm without nuclear atypia. f A surgically resected specimen reveals FTC with minimal capsular invasion (arrows)
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This study was designed to evaluate the preoperative diagnostic categories of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) using thyroid core needle biopsy (CNB) and to analyze its impact on the risk of malignancy (ROM). A total of 2687 consecutive thyroid CNBs were reviewed retrospectively and classified int...
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Background:
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Objectives
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Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to cover a group of non-invasive encapsulated follicular-patterned thyroid lesions with very low malignant behavior. This nomination may have a great impact on the incidence of thyroid malignancy and the practice for endocrine pathologists. To demon...
Citations
... Additionally, it should be noted that diagnosing follicular pattern lesions in CNB specimens can be particularly challenging for pathologists, and the diagnostic rates within these CNB categories can fluctuate depending on the diagnostic thresholds used by pathologists. It has been reported that the diagnostic rates for categories II, III, and IV can vary significantly among different institutions [20,27,28]. For instance, if a microfollicular proliferative lesion is present and distinctly separated from the surrounding normal parenchyma by a fibrous capsule, it would be categorized as IV. ...
Background:
We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB).
Methods:
This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy.
Results:
Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system.
Conclusion:
Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.
... Categories III and IV are further divided into subcategories based on the status of nuclear atypia, architectural atypia, or oncocytic atypia. Subcategories that exhibit nuclear atypia (categories IIIa, IIIc, and IVb) raise concerns for conditions such as papillary thyroid carcinoma and NIFTP, which are typically associated with a higher ROM compared to subcategories that display architectural or oncocytic atypia [8,[12][13][14][15][16]. ...
... The method of estimating the cancer risk, which is based on histologic follow-up, overestimates the ROM, particularly for the categories I-III, where there is selection bias given the relatively small proportion of nodules that undergo excision. Although NIFTP is a surgical disease and cannot be preoperatively diag- nosed on CNB or FNA specimens, the morphologic features of NIFTP tend to lead to classification on CNB/FNA as either category III, IV, or V, thereby impacting the resultant ROM calculations [13,14,17,18]. The ROM for each category is shown when including and excluding NIFTP in malignancy, information that might help guide more conservative clinical management of some nodules. ...
... The presence of NIFTP lowers the ROM within the diagnostic category of the thyroid CNB reporting system. The corresponding modifications in the ROM within categories III and IV have been deduced from the observed shifts in malignancy risk from three retrospective studies [13,14,17]. ...
As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.
... At the same time, CNB was not shown to provide superior results compared to FNA in diagnosing papillary thyroid carcinomas [135]. Still, it appears superior to FNA in diagnosing follicular variant papillary thyroid carcinoma [136] and NIFTP [137]. Some authors claim CNB is not overall better than FNA in diagnosing thyroid nodules [138]. ...
Thyroid cancer is the most common endocrine malignancy, with increasing incidence over the past few decades. Fine needle aspiration (FNA) biopsy is the gold standard for preoperative diagnosis of thyroid malignancies. Nevertheless, this method renders indeterminate results in up to 30% of the cases. Therefore, these patients are often referred to unnecessary surgery to establish the diagnosis. To improve the accuracy of preoperative diagnosis, several other ways, such as ultrasonography, elastography, immunohistochemical analysis, genetic testing, and core needle biopsy, have been developed and can be used either in association with or as an alternative to FNA. This review aims to evaluate all these diagnostic tools to determine the most appropriate way of managing thyroid nodules and subsequently improve the selection of cases referred to surgery.
... In addition, there might be bias in the case selection because our institution is a tertiary referral hospital, and we only enrolled patients who underwent surgery with the category III/IV CNB results. The study samples were composed mainly of CNB category IV, and the proportion of category III was lower than in previous studies [2,32,33]. In cases with nuclear atypia suggesting PTC, we frequently perform VE1 IHC for detecting BRAF p.V600E (VE1) and convert morphologically indeterminate CNB results to a confirmative diagnosis of PTC. ...
Follicular-patterned lesions often have indeterminate results (diagnostic category III or IV) by core needle biopsy (CNB) and fine needle aspiration (FNA). However, CNB diagnoses follicular neoplasm (category IV) more frequently than FNA. Therefore, we aimed to develop a risk stratification system for CNB samples with category III/IV using immunohistochemistry (IHC). The specificity of the RAS Q61R antibody was validated on 58 thyroid nodules with six different types of RAS genetic variants and 40 cases of RAS wild-type. We then applied IHC analysis of RAS Q61R to 207 CNB samples with category III/IV in which all patients underwent surgical resection. RAS Q61R IHC had 98% sensitivity and 98% specificity for detecting the RAS p.Q16R variant. In an independent dataset, the positive rate of RAS Q61R was significantly higher in NIFTP (48%) and malignancies (45%) than in benign tumors (19%). The risk of NIFTP/malignancy was highest in the group with nuclear atypia and RAS Q61R expression (86%) and lowest in the group without both parameters (32%). The high-risk group with either nuclear atypia or RAS Q61R had 67.3% sensitivity, 73.4% specificity, 75.2% positive predictive value, and 65.1% negative predictive value for identifying NIFTP/malignancy. We conclude that RAS Q61R IHC can be a rule-in diagnostic test for NIFTP/malignancy in CNB category III/IV results. Combining of the histologic parameter (nuclear atypia) with RAS Q61R IHC results can further stratify CNB category III/IV into a high-risk group, which is sufficient for a surgical referral, and a low-risk group sufficient for observation.
... Previous studies have reported that the rates of CNB categories vary significantly among different institutions. Supplemental Table S1 shows the preoperative and postoperative results of the CNB performed in three Korean institutions [28,29]. The rate of inconclusive results (category I and III) was lower in our institution than in the other two institutions. ...
Background:
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods:
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results:
Compared to FNA, CNB showed lower rates of inconclusive results categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%-62% vs. 23%-36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion:
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.
... The follicular variant of papillary thyroid carcinoma (FVPTC), the second most common type of PTC found in [9][10][11][12][13][14][15][16][17][18][19][20][21][22].5% of all PTCs [1,2], is a diagnostically problematic These authors contributed equally: Ji-Ye Kim, Sunhee Chang entity. FVPTCs are often misdiagnosed on fine needle aspiration (FNA), due to its focal papillary nuclear features [3]; in addition, FVPTCs represent a mixed group of tumors with two biologically distinct subtypes [1,[4][5][6]-the encapsulated FVPTC (eFVPTC) and infiltrative FVPTC (iFVPTC). ...
... Existing preoperative assays for thyroid nodules are FNA, core needle biopsy (CNB), and ultrasonography (US), each with its own diagnostic advantages [2,[10][11][12][13][14][15][16][17][18][19][20][21]. FNA is the standard diagnostic tool for thyroid nodules due to its cost-effectiveness, low complication rate, and rapid results [2,10,16]. ...
... However, FVPTC has been a major limitation of FNA diagnosis as many studies have shown high false negative rates of FNA due to focal papillary nuclear features of FVPTCs, which overlap with the cytology of benign lesions [3,12,13]. CNB has been suggested as an alternative diagnostic technique for thyroid nodules of nondiagnostic or indeterminate cytology because it acquires larger amounts of tissue, facilitating in improved diagnosis based on histology [14][15][16]20]. High-resolution US examination of thyroid nodules has also been thoroughly studied with regard to its ability to discriminate between benign and malignant lesions [10-13, 18, 21]. ...
PurposeFollicular variant papillary thyroid carcinoma (FVPTC) is a problematic entity. FVPTCs are often misdiagnosed by the standard fine needle aspiration (FNA); in addition, FVPTCs represent a mixed group of tumors with two biologically distinct subtypes: The indolent encapsulated FVPTC and the aggressive infiltrative FVPTC. Recent changes in guidelines suggests that FVPTC management may be improved if subtypes can be determined preoperatively. Preoperative assays, FNA, core needle biopsy (CNB), and ultrasonography (US) were compared for their ability to identify and subtype FVPTCs to determine the most appropriate test to manage FVPTCs.Methods
The preoperative assays and clinicopathologic variables of 255 resected FVPTCs cases at Samsung Medical Center between 2012 and 2016 were retrospectively evaluated.ResultsCNB had the overall best ability to manage FVPTCs with the highest rate of diagnosis indicating surgery, lowest rate of inconclusive results, high sensitivity (88.9%), specificity (87.7%), negative predictive value (97.0%), diagnostic odds ratio (DOR; 56.9), and excellent predictive ability (AUC 0.906) for differentiating FVPTC subtypes. US had a moderate DOR (12.8), good predictive ability (AUC 0.802), high sensitivity (75.0%) and specificity (81.0%). CNB and US both had significantly higher accuracy for discriminating FVPTC subtypes than FNA (AUC 0.908 and 0.877 > 0.671; p < 0.05). The excellent performance of CNB could be attributed to distinct histologic differences between FVPTC subtypes.ConclusionCNB and US had superior performance to FNA in the identification and subtyping of FVPTC. In institutions with skilled and experienced operators, CNB is the preferred method for evaluating possible FVPTC lesions.
... The results of preoperative US and FNAC are similar to those reported in other series [10,[22][23][24]. However, CB displayed higher malignant results in NIFTP than previously published [25,26]. Again, the individual criteria of the pathologists from the two institutions providing these results when interpreting nuclear changes might explain this discrepancy. ...
PurposeTo determine the rate of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in a multi-institutional series from the Iberian Peninsula and describing this NIFTP cohort.Methods
Retrospective study of papillary thyroid carcinoma (PTC) or well-differentiated tumours of uncertain malignant potential (WDT-UMP) diagnosed between 2005 and 2015 and measuring ≥5 mm in adult patients from 17 hospitals. Pathological reports were reviewed to determine the cases that fulfil the original criteria of NIFTP and histology was reassessed. Rates were correlated with the number of PTC and its follicular variant (FVPTC) of each institution. Demographic data, histology, management, and follow-up of the reclassified NIFTP cohort were recorded.ResultsA total of 182 cases with NIFTP criteria were identified: 174/3372 PTC (rate: 5.2%; range: 0–12.1%) and 8/19 WDT-UMP (42.1%). NIFTP rate showed linear correlation with total PTC (p: 0.03) and FVPTC (p: 0.007) identified at each centre. Ultrasound findings were non-suspicious in 60.1%. Fine-needle cytology or core biopsy diagnoses were undetermined in 49.7%. Most patients were treated with total thyroidectomy. No case had nodal disease. Among patients with total thyroidectomy, 89.7% had an excellent response evaluated 1 year after surgery. There were no structural persistence or relapses. Five patients showed residual thyroglobulin after 90 months of mean follow-up.ConclusionsNIFTP rate is low but highly variable in neighbouring institutions of the Iberian Peninsula. This study suggests pathologist’s interpretation of nuclear alterations as the main cause of these differences. Patients disclosed an excellent outcome, even without using the strictest criteria.
... It is recommended that the category IV should be subclassified into four subgroups according to nuclear atypia, histologic growth patterns, and cell type. The subclassification reflects differences in histology and the risk of malignancy in the thyroid nodules [88]. ...
... Focal nuclear atypia in follicular neoplasm raises the possibility of NIFTP and follicular variants of papillary carcinoma (Fig. 6C, D) [57,[88][89][90]. Before the NIFPT era, this subcategory frequently turned out to be a follicular variant of papillary carcinoma after surgery [89,90]. ...
Ultrasound-guided core needle biopsy (CNB) has been increasingly used for the pre-operative diagnosis of thyroid nodules. Since the Korean Society of the Thyroid Radiology published the ‘Consensus Statement and Recommendations for Thyroid CNB’ in 2017 and the Korean Endocrine Pathology Thyroid CNB Study Group published ‘Pathology Reporting of Thyroid Core Needle Biopsy’ in 2015, advances have occurred rapidly not only in the management guidelines for thyroid nodules but also in the diagnostic terminology and classification schemes. The Clinical Practice Guidelines Development Committee of the Korean Thyroid Association (KTA) reviewed publications on thyroid CNB from 1995 to September 2019 and updated the recommendations and statements for the diagnosis and management of thyroid nodules using CNB. Recommendations for the resolution of clinical controversies regarding the use of CNB were based on expert opinion. These practical guidelines include recommendations and statements regarding indications for CNB, patient preparation, CNB technique, biopsy-related complications, biopsy specimen preparation and processing, and pathology interpretation and reporting of thyroid CNB.
