Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

BACKGROUND: Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. METHODS: CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. RESULTS: Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). CONCLUSIONS: This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

WHO 2022 updates on follicular cell and c-cell derived thyroid neoplasm.

The latest edition of the WHO Classification of thyroid tumors was released in 2022 and incorporates novel concepts vital to patient management. Thyroid follicular nodular disease is a term used to collectively represent a wide variety of benign and non-neoplastic lesions, including both clonal and non-clonal proliferations that manifest clinically as multinodular goiter. Thyroid neoplasms develop from follicular cells and can be either benign, low-risk, or malignant. To avoid classifying all lesions under 1 cm in diameter as low-risk illnesses, the new classification method highlights the need for subtyping papillary thyroid cancer based on histomorphologic indicators rather than tumor size. Formerly known as the cribriform-morular variety of papillary thyroid carcinoma, this tumor is now more commonly referred to by its more accurate name, cribriform-morular thyroid carcinoma. Its histogenesis is unknown. Similar to the traditional definition of 'poorly differentiated thyroid carcinoma' according to the Turin criteria, the newly defined 'differentiated high-grade thyroid carcinoma' encompasses papillary thyroid cancer, follicular thyroid carcinomas, and oncocytic carcinomas with high-grade characteristics linked to worse prognosis. The squamous cell subtype of anaplastic thyroid cancer has also recently been characterized as a distinct morphologic pattern. In this article, we will discuss the latest revision to the World Health Organization's classification system for thyroid cancer.

[Interpretation of the pathological diagnostic criteria and characteristics of high-grade thyroid follicular-derived carcinoma in the 5th edition WHO classification].

The 5th edition WHO classification of thyroid tumors proposed high-grade non-anaplastic thyroid carcinoma, which includes traditional poorly differentiated thyroid carcinoma (PDTC) and differentiated high-grade thyroid carcinoma (DHGTC), with a prognosis between highly differentiated thyroid carcinoma and anaplastic thyroid carcinoma (ATC), in which about 50% of patients do not take radioactive iodine. Therefore, this classification is of great clinical significance. This article interprets the diagnostic criteria and genetic features of high-grade non-anaplastic thyroid carcinoma in 5th edition WHO classification, comparing with ATC.

Follow-up and Outcomes of 186 Patients With Follicular Cell-Derived Thyroid Cancer Seen at a Referral Center by One Thyroidologist in 2015.

OBJECTIVE: To study the profile, management, and outcomes of follicular cell-derived thyroid cancer (FCDTC) before publication of the 2016 American Thyroid Association guidelines recommending less-aggressive thyroid cancer procedures. METHODS: Patients with FCDTC were seen by one thyroidologist at Mayo Clinic during the 2015 calendar year. Patients underwent surgical procedures for FCDTC in 2015 or earlier at Mayo Clinic or another institution. Follow-up data were collected from January 1, 2016, through July 20, 2022. Outcomes measured included tumor characteristics, treatment methods, adverse effects, diagnostic imaging methods, and primary tumor/metastasis status at the last follow-up. RESULTS: Of 186 included patients, 85 had total or near-total thyroidectomy. Bilateral disease was present in 35.5% of these patients, and contralateral involvement would have been missed by lobectomy for 9 (10%) patients with low-risk thyroid cancer. Additionally, 57% had positive neck lymph nodes identified during their surgical procedure, 25% (21% in central compartment) of which were undetected by preoperative ultrasonography. At the last follow-up, 65.6% of patients had no evidence of disease and 10.7% had distant metastases. CONCLUSION: This report outlines the profile and outcomes of patients with FCDTC who were treated at a referral center before the revised 2016 American Thyroid Association guidelines. Lobectomy for low-risk FCDTC may miss some cancer in the contralateral lobe. However, the clinical importance of these missed microcarcinomas is unclear. Preoperative ultrasonography effectively predicts lateral, but not central compartment, nodal metastases.

The value of a neural network based on multi-scale feature fusion to ultrasound images for the differentiation in thyroid follicular neoplasms.

OBJECTIVE: The objective of this research was to create a deep learning network that utilizes multiscale images for the classification of follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) through preoperative US. METHODS: This retrospective study involved the collection of ultrasound images from 279 patients at two tertiary level hospitals. To address the issue of false positives caused by small nodules, we introduced a multi-rescale fusion network (MRF-Net). Four different deep learning models, namely MobileNet V3, ResNet50, DenseNet121 and MRF-Net, were studied based on the feature information extracted from ultrasound images. The performance of each model was evaluated using various metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, F1 value, receiver operating curve (ROC), area under the curve (AUC), decision curve analysis (DCA), and confusion matrix. RESULTS: Out of the total nodules examined, 193 were identified as FTA and 86 were confirmed as FTC. Among the deep learning models evaluated, MRF-Net exhibited the highest accuracy and area under the curve (AUC) with values of 85.3% and 84.8%, respectively. Additionally, MRF-Net demonstrated superior sensitivity and specificity compared to other models. Notably, MRF-Net achieved an impressive F1 value of 83.08%. The curve of DCA revealed that MRF-Net consistently outperformed the other models, yielding higher net benefits across various decision thresholds. CONCLUSION: The utilization of MRF-Net enables more precise discrimination between benign and malignant thyroid follicular tumors utilizing preoperative US.

A comparison of the WHO 2004 and WHO 2017 thyroid tumor classifications.

INTRODUCTION: The category of borderline malignancy or unknown malignant potential was added to the WHO's 2017 classification of thyroid tumours. A new histological variety of papillary tumours and Hurthle cell tumours was given as a separate entity. The classification has also adopted the Turin criteria for histological diagnosis of poorly differentiated cancer (PDC). SETTINGS AND DESIGN: Descriptive study. METHODS AND MATERIAL: From July 2018 to June 2022, 200 thyroid neoplasm patients at a tertiary care facility in western Maharashtra were participated in the prospective research over a period of 4 years. STATISTICAL ANALYSIS USED: The descriptive statistics were used to analyse the collected data. AIM: This study was undertaken to compare the old (2004) and new (2016) WHO classifications and their importance in the treatment of thyroid malignancies. RESULTS: Out of 200 cases, the age range of 31 to 40 years had the greatest number of cases. The ratio of females to males was 5:1. In our study, according to the WHO 2004 classification, malignant tumours comprised 57.5% of the cases, while benign tumours 42.5% of the cases. When tumours were subcategorized, the most frequent benign tumour was follicular adenoma (43.5%) and malignant tumour was papillary thyroid carcinoma (37%). Malignant tumours made up 47.5% of the cases when the tumours were reclassified using the revised WHO 2017 classification, followed by borderline tumours with 27.5% of the cases and benign tumours with 25% of the cases. The most frequent borderline tumour was NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) (17.5%), the most prevalent malignant tumour was papillary carcinoma (including its variant) (32%), and the most frequent benign tumour was follicular adenoma (27%). CONCLUSION: We concluded that the inclusion of the Boderline Category in the new WHO classification significantly improved thyroid cancer management. WHO 2017 classification prevents under diagnosis (in the case of benign tumors) and over diagnosis (in the case of malignant tumors).

Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study.

Differentiating BRAF V600E- and RAS-altered encapsulated follicular-patterned thyroid tumors based on morphology remains challenging. This study aimed to validate an 8-score scale nuclear scoring system and investigate the importance of nuclear pseudoinclusions (NPIs) in aiding this differentiation. A cohort of 44 encapsulated follicular-patterned tumors with varying degrees of nuclear atypia and confirmed BRAF V600E or RAS alterations was studied. Nuclear parameters (area, diameter, and optical density) were analyzed using a deep learning model. Twelve pathologists from eight Asian countries visually assessed 22 cases after excluding the cases with any papillae. Eight nuclear features were applied, yielding a semi-quantitative score from 0 to 24. A threshold score of 14 was used to distinguish between RAS- and BRAF V600E-altered tumors. BRAF V600E-altered tumors typically demonstrated higher nuclear scores and notable morphometric alterations. Specifically, the nuclear area and diameter were significantly larger, and nuclear optical density was much lower compared to RAS-altered tumors. Observer accuracy varied, with two pathologists correctly identifying genotype of all cases. Observers were categorized into proficiency groups, with the highest group maintaining consistent accuracy across both evaluation methods. The lower group showed a significant improvement in accuracy upon utilizing the 8-score scale nuclear scoring system, with notably increased sensitivity and negative predictive value in BRAF V600E tumor detection. BRAF V600E-altered tumors had higher median total nuclear scores. Detailed reevaluation revealed NPIs in all BRAF V600E-altered cases, but in only 2 of 14 RAS-altered cases. These results could significantly assist pathologists, particularly those not specializing in thyroid pathology, in making a more accurate diagnosis.

Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer.

PURPOSE: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting. METHODS: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports. RESULTS: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18-94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001). CONCLUSIONS: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More.

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS "nuclear" and AUS "other" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely "high-risk group" than the group including other subcategories, namely "low-risk group" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.

The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms.

Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

Diagnostic models for predicting malignancy in thyroid nodules classified as Bethesda Category III in an endemic region.

BACKGROUND: This study aims to develop a diagnostic model to help physicians determine whether thyroid nodules categorized as atypia of undetermined significance (AUS) in category III of the Bethesda system are benign or malignant preoperatively. To create a diagnostic model for predicting thyroid nodules' benign or malignant with AUS cytology based on clinical, ultrasonographic, and cytopathological findings. METHODS: This is a retrospective cohort study involving patients (>19) at risk of thyroid cancer who had thyroidectomy after an AUS cytology. The dataset consists of 53 variables 204 nodules from 183 patients. Binary logistic regression and factor analysis methods were used to identify risk factors for malignancy. Finally, four prediction models were developed using different approaches, based on clinical, pathological clinical + pathological, and the factors. RESULTS: A total of 88 (48.1%) of 183 patients diagnosed with AUS were benign and 95 (51.9%) the malignant. After determining risk factors, four prediction models were developed based on different approaches to assist physicians in deciding to detect AUS nodules early. It was seen that bilaterality was found to be a risk factor for malignancy in the clinical model (pbilaterality = .03) and it was also seen that the pathological variables pale chromatin and irregular contours in the oncocyte variables were risk factors for malignancy (ppalechromatin = .02, pirregularcontoursintheoncocyte = .04). The best model obtained sensitivity and specificity values are 73% and 87% based on clinical and pathological variables. CONCLUSION: This comprehensive study may provide a more in-depth understanding of AUS and make a notable contribution to healthcare professionals before surgery.

[Bethesda 2023: A new terminology for thyroid cytopathology]. / Bethesda 2023: nouvelle terminologie en cytopathologie thyroïdienne.

A third update of The Bethesda System for Reporting Thyroid Cytopathology has been published in 2023 following the first (2010) and second (2017) versions. The main modifications are the following 1) a new co-Editor, 2) 4 associate editors, 3 of them from Europe, 3) the inclusion of 65 co-authors, 19 of them from Europe, 4) 2 new chapters: one dealing with pediatrics thyroid cytopathology and the other one describing molecular cytopathology profiling, 5) updated risks of malignancy (ROM), 6) a terminology in line with the 2022 WHO classification of thyroid tumors, 7) diagnostic categories now defined by a unique name, 8) 2 subtypes in the "Atypia of Undetermined Significance" category with corresponding ROM.

Differentiated high grade thyroid carcinomas: Diagnostic consideration and clinical features.

BACKGROUND: Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing. MATERIALS AND METHODS: Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase. RESULTS: Case cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17-84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm2 (range 0-7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease. CONCLUSIONS: Our institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.

NIFTPs may be reclassified not only from FVPTCs but also from follicular adenomas.

Few studies have focused on reclassifying follicular adenomas (FAs) as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), but none have been conducted in America or Europe. The aims of this study were to analyze the prevalence of NIFTP reclassified from follicular variant of papillary thyroid carcinomas (FVPTCs) and FAs before NIFTP was defined in the literature, the rate of NIFTP among PTC (papillary thyroid carcinomas) established in real time between 2017 and 2022, and demographic, ultrasonographic, and cytologic characteristics of NIFTPs compared with FVPTCs and FAs. This was a retrospective cohort study of tumors diagnosed as PTCs (n = 247) and FAs (n = 144) at a Brazilian hospital. Overall, 13.4% of PTCs and 7% of FAs were reclassified as NIFTPs. The rate of real-time diagnosed NIFTPs among PTC was 12.3%. The median tumor size was larger among NIFTPs (3.0 cm) than FVPTCs (1.1 cm; P < 0.01). A high-risk ultrasonographic pattern was rare in NIFTPs (5.6%). The cytologic classifications differed between FVPTCs and NIFTPs (P < 0.01), and the most frequent category among NIFTPs was 'follicular neoplasm' (52.6%). The category 'suspicious for malignancy' was frequent in FVPTCs and rare (5.3%) in NIFTPs. In conclusion, FVPTCs and FAs may be reclassified as NIFTPs. The prevalence of NIFTPs reclassified from FAs was lower in our cohort than in Asian studies. The rate of NIFTPs reclassified from PTC was similar to that of NIFTPs diagnosed in real time and was aligned with rates reported in studies from America and Europe. Preoperative features could not differentiate NIFTPs from FVPTCs or FAs.

Two-tier subclassification of the Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) in thyroid cytology.

BACKGROUND: The Bethesda category III, AUS/FLUS, comprises a heterogeneous group of thyroid lesions with variable risk of malignancy (ROM). This study evaluates ROM in two subgroups of this category based on nuclear atypia and architectural atypia. METHODS: Cases in Bethesda category III were reported based on nuclear atypia (AUS) and architectural atypia (FLUS). ROM was calculated by comparing the cytologic diagnosis to the follow-up histologic diagnosis. RESULTS: Among the 610 Bethesda category III cases in this study, 306 (50.2%) and 304 (49.8%) cases were reported as AUS and FLUS, respectively. One hundred and eighty six of 306 AUS (60.8%) and 193 of 304 FLUS (63.5%) cases underwent surgical intervention. ROM of the cases in Bethesda category III was 12.8% if all cases were counted and 20.6% if only surgical cases were counted. When analyzing separately, ROM of AUS cases was 17.0% and 28.0% with all cases and surgical cases only, respectively. For FLUS cases, ROM was 8.6% and 13.5% with all cases and surgical cases only, respectively. CONCLUSION: In Bethesda category III, ROM in the cases with nuclear atypia was significantly higher than the cases with architectural atypia. Sub-classifying the Bethesda Category III cases with nuclear atypia and architectural atypia, respectively may better stratify the ROM.

Molecular-derived risk of malignancy and the related positive call rate of indeterminate thyroid cytology diagnoses as quality metrics for individual cytopathologists.

BACKGROUND: Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow-up studies. However, traditional cytologic-histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular-derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics. METHODS: This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2-year period with at least 3 years of follow-up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic-type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic-histologic correlation outcomes. RESULTS: The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%-20.8%), 28.1% (range, 22.1%-36.7%), and 27.0% (range, 19.5%-41.5%), respectively, and most individual cytopathologists' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p = .06), the AUS PCRs were quite different (p = .002). By cytologic-histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false-positive cases. CONCLUSIONS: MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement.

Utility of Six Ultrasound-Based Risk Stratification Systems in the Diagnosis of AUS/FLUS Thyroid Nodules.

RATIONALE AND OBJECTIVES: To estimate the diagnostic performance of the currently used ultrasound (US)-based risk stratification systems (RSSs) (American Thyroid Association, American Association of Clinical Endocrinologists, American College of Endocrinology, and Association Medici Endocrinology Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules, European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults [EU-TIRADS], American College of Radiology Thyroid Imaging Reporting and Data System [ACR-TIRADS], Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules [C-TIRADS], and Thyroid Imaging Reporting and Data System Developed by Kwak et al [Kwak-TIRADS]) for atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. MATERIALS AND METHODS: This retrospective study included 514 consecutive AUS/FLUS nodules in 481 patients with final diagnosis. The US characteristics were reviewed and classified using the categories defined by each RSS. The diagnostic performance was evaluated and compared using a generalized estimating equation method. RESULTS: Of the 514 AUS/FLUS nodules, 148 (28.8%) were malignant and 366 (71.2%) were benign. The calculated malignancy rate increased from the low-risk to high-risk categories for all RSSs (all P < .001). Interobserver correlation for both US features and RSSs showed substantial to almost perfect agreement. The diagnostic efficacy of Kwak-TIRADS (AUC=0.808) and C-TIRADS (AUC=0.804) were similar (P = .721) and higher than those of other RSSs (all P < .05). The EU-TIRADS and Kwak-TIRADS exhibited similar sensitivity (86.5% vs 85.1%, P = .739) and were only higher than that of the C-TIRADS (all P < .05). The specificity of C-TIRADS and ACR-TIRADS were similar (78.1% vs 72.1%, P = .06) and were higher than those of other RSSs (all P < .05). CONCLUSION: Currently used RSSs can provide risk stratification for AUS/FLUS nodules. Kwak-TIRADS and C-TIRADS have the highest diagnostic efficacy in identifying malignant AUS/FLUS nodules. A detailed knowledge of the benefits and shortcomings of the various RSSs is essential.

[Molecular and other ancillary tests proposed by The Bethesda system for reporting thyroid cytopathology 2023]. / Les tests moléculaires et autres techniques ancillaires en cytologie thyroïdienne selon Bethesda 2023.

For the first time the 2023 version of The Bethesda System for Reporting Thyroid Cytology dedicates a whole chapter (chapter 14) to ancillary studies almost exclusively represented by molecular testing. The latest data reported bring some evidence that molecular testing could help to optimize the diagnostic performance of « indeterminate ¼ categories (AUS and NF). Other studies suggest a promising role to guide the management of suspicious of malignancy and malignant categories. Indeed, the recognition of prognostic and predictive biomarkers analyzed on cytological samples, regardless of how it is collected, has progressed thanks to advances in our knowledge of molecular abnormalities of thyroid tumors. The chapter 14 is presented here highlighting the current and emerging roles of « in-house ¼ and commercialized molecular testing as presented by TSBRTC.