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Fine-needle aspiration (FNA) is a safe, cost-effective diagnostic procedure used in the evaluation of thyroid nodules. The number of thyroid FNAs has dramatically increased over the past few years. In the absence of standardized procedures regarding the number of needle passes needed for diagnosis and the lack of clarity on the use of conventional smears (CS) versus liquid-based preparations (LBP), the demand of thyroid FNAs has led to increased workload on cytology laboratories, which can negatively affect patient safety. We implemented a standardized two needle passes for CS and collection of all needle rinses and additional pass material in CytoRich Red for ThinPrep LBP and compared the non-diagnostic and diagnostic rates before and after this intervention. There were 290 pre-intervention cases and 348 post-intervention cases; of which, there were 17 (5.9%) non-diagnostic cases of the pre-intervention group and 27 (7.8) non-diagnostic cases of the post-intervention group. There was no statistically significant difference in non-diagnostic and diagnostic rates before and after the change (p = 0.347 by two-tailed Z test)., (© 2024 Wiley Periodicals LLC.)

Thyroid cytology is a rapidly evolving field that has seen significant advances in recent years. Its main goal is to accurately diagnose thyroid nodules, differentiate between benign and malignant lesions, and risk stratify nodules when a definitive diagnosis is not possible. The current landscape of thyroid cytology includes the use of fine-needle aspiration for the diagnosis of thyroid nodules with the use of uniform, tiered reporting systems such as the Bethesda System for Reporting Thyroid Cytopathology. In recent years, molecular testing has emerged as a reliable preoperative diagnostic tool that stratifies patients into different risk categories (low, intermediate, or high) with varying probabilities of malignancy and helps guide patient treatment., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fine needle aspiration cytology (FNAC) is the most useful tool in the diagnosis of thyroid nodules. Liquid-based cytology (LBC) is replacing the conventional smear (CS) for evaluation of thyroid FNAC. In our institution, thyroid FNAC preparation was changed from CS to LBC SurePath in July 2016. This study aimed to compare the diagnostic value of SurePath with that of CS in thyroid lesions., Methods: A total of 35,406 samples of thyroid FNAC (11,438 CS and 23,968 SurePath), collected from January 2010 to December 2022, were included in this study. We also examined the malignant rate using the surgical pathology diagnosis as the gold standard., Results: The distribution of TBSRTC cytological categories was equivalent between CS and SurePath. The rate of nondiagnostic/unsatisfactory category was higher in CS compared to SurePath (43.4% vs. 22.3%; p < .05). After routine use of SurePath, the surgical resection rate was reduced from 12.0% to 8.6% (p < .05) and the malignant rate increased from 32.2% to 41.5% (p < .05). The sensitivities of CS and SurePath were 71.0% and 82.0%, respectively, and the specificities were 99.0% and 97.3%, respectively, whereas the positive predictive values were 97.8% and 96.8%, respectively, and the negative predictive values were 85.0% and 84.6%, respectively. Diagnostic accuracy of CS and SurePath were 88.5% and 89.7% respectively., Conclusion: SurePath can increase the sample adequacy, increase the sensitivity and reduce the workload and avoid unnecessary surgeries with similar accuracy to CS., (© 2024 Wiley Periodicals LLC.)

Context: Fine-needle aspiration cytology (FNAC) is widely utilized for thyroid lesion diagnosis but faces challenges such as sample inadequacy and overlapping cytological features. This study examines how accurately these patterns correlate with histopathological diagnoses, shedding light on FNAC's limitations and diagnostic potential., Aims: To study the application of the architectural pattern of follicular cells in the interpretation of thyroid lesions and to demonstrate the diagnostic accuracy (DA) of FNAC., Settings and Design: Cross-sectional study carried over 1 year., Subjects and Methods: A total of 110 cases were reviewed by the cytopathologists. The prominent follicular cell architecture, namely macrofollicular, microfollicular, papillary, trabecular, three-dimensional clusters, and dispersed cells, was described in each case. In addition to these patterns, cellular morphology and background features were also noted, and a final cytological diagnosis was established. The cytology diagnosis was correlated with the histopathological diagnosis., Statistical Analysis Used: Sensitivity, specificity, positive predictive value, negative predictive value, DA of FNAC in diagnosing nonneoplastic and neoplastic lesions., Results: Macrofollicular pattern was seen in 80.26% of colloid goiter cases. Microfollicular pattern was observed in 72.2% of follicular neoplasm. About 62.5% of papillary thyroid carcinomas showed a papillary pattern. The trabecular pattern was seen in 42.86% of chronic lymphocytic thyroiditis and 16.67% of follicular neoplasms. The sensitivity and specificity of FNAC in diagnosing neoplastic lesions was 92.59% and 97.59%, respectively., Conclusions: FNAC is a simple, rapid, definite, and cost-effective primary diagnostic tool for thyroid evaluation. Cell architecture pattern is a simple and appropriate approach that complements cell morphology and background details in arriving at the final cytological diagnosis of thyroid lesions., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Thyroid nodule and cervical lymph node biopsy is the main clinical method for evaluating the condition and determining the follow-up treatment plan. The literature on thyroid nodule puncture predominantly focuses on thyroid fine needle puncture, and there are limited systematic articles on coarse needle aspiration for thyroid-related diseases and needle biopsy of thyroid-related cervical lymph node diseases. However, this shortage of articles does not reflect the diagnostic value of coarse needle aspiration in thyroid biopsy and cervical lymph node-related diseases. Currently, different departments of many hospitals in China are conducting or planning to perform needle biopsy of thyroid and cervical lymph node-related diseases to improve the standardization and safety of related operations. Standardization is needed for the indications, contraindications, perioperative period, postoperative complications management, puncture specimen processing, and related genetic analysis of thyroid and cervical lymph node puncture. For this purpose, Interventional Ultrasound Committee of Chinese College of Interventionalists organized a panel of domestic experts in the field of thyroid diseases to discuss and formulate a consensus. Based on the latest research progress, combined with the clinical realities in China, this Expert Consensus on Ultrasound Guided Thyroid and Neck Lymph Node Puncture (2023 edition) is released.

Introduction: We successfully developed a broad spectrum of patient-derived endocrine organoids (PDO) from benign and malignant neoplasms of thyroid, parathyroid, and adrenal glands. In this study, we employed functionally intact parathyroid PDOs from benign parathyroid tissues to study primary hyperparathyroidism (PHPT), a common endocrine metabolic disease. As proof of concept, we examined the utility of parathyroid PDOs for bioenergetic and metabolic screening and assessed whether parathyroid PDO metabolism recapitulated matched PHPT tissues., Methods: Our study methods included a fine-needle aspiration (FNA)-based technique to establish parathyroid PDOs from human PHPT tissues (n=6) in semi-solid culture conditions for organoid formation, growth, and proliferation. Mass spectrometry metabolomic analysis of PHPT tissues and patient-matched PDOs, and live cell bioenergetic profiling of parathyroid PDOs with extracellular flux analyses, were performed. Functional analysis cryopreserved and re-cultured parathyroid PDOs for parathyroid hormone (PTH) secretion was performed using ELISA hormone assays., Results and Discussion: Our findings support both the feasibility of parathyroid PDOs for metabolic and bioenergetic profiling and reinforce metabolic recapitulation of PHPT tissues by patient-matched parathyroid PDOs. Cryopreserved parathyroid PDOs exhibited preserved, rapid, and sustained secretory function after thawing. In conclusion, successful utilization of parathyroid PDOs for metabolic profiling further affirms the feasibility of promising endocrine organoid platforms for future metabolic studies and broader multiplatform and translational applications for therapeutic advancements of parathyroid and other endocrine applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sekhar, Codreanu, Williams, Rathmell, Rathmell, McLean, Sherrod and Baregamian.)

Introduction: Thyroid fine-needle aspiration (FNA) is a well-established technique in the cytology literature. Through the introduction of rapid stains in cytology practice, the ever-increasing utility of rapid on-site evaluation (ROSE) has strengthened the place of FNA as a primary diagnostic method in patient management. There are few stain variants available in the market for ROSE, namely Diff-Quik (DQ), Toluidine blue, and ultrafast Papanicolaou stains. Recently, our group developed a new staining variant labeled as original "BlueStain®" technique that was not previously tested in this context., Methods: 40 FNA thyroid cases were studied. At least two slides were prepared from each patient: one stained by DQ and the other by BlueStain®. Simultaneously, a ROSE diagnosis was performed as the two staining methods were compared, evaluating the parameters of background, cellularity, details of colloid presence, cell morphology, nuclear details, cytoplasmic details, and overall staining, scored on a scale from 1 to 3, representing poor, average, and good, respectively., Results: The quality index was slightly better for BlueStain® (53% vs. 47%) but not significantly different between the two stains. BlueStain® provides better details in both the presence and type of colloid as well as nuclear details, which are regarded as very important for diagnosis in thyroid cytology. There were eight cases with discordant diagnosis when compared between two stains from the same patient. In five cases of indeterminate cases, BlueStain® allows to bring them to the benign category, probably because this staining method allows a clear observation of the colloid in the background of the smears. However, since we are observing two different slides, we cannot rule out that these differences are a question of sample collecting and/or smearing., Conclusions: Our data demonstrates that BlueStain® is suitable to provide good-quality slides for primary assessments of thyroid aspirates studied by ROSE. In fact, in some aspects, this new staining method shows better preservation of colloid and cell details, revealing itself as an alternative to the DQ stain variant, upholding performance level while being 10 times cheaper and simpler because it requires just one step of staining., (© 2022 S. Karger AG, Basel.)

Background: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination., Objective: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis., Design and Setting: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China)., Methods: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease., Results: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy., Conclusion: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Context.—: The use of whole slide images (WSIs) in diagnostic pathology presents special challenges for the cytopathologist. Informative areas on a direct smear from a thyroid fine-needle aspiration biopsy (FNAB) smear may be spread across a large area comprising blood and dead space. Manually navigating through these areas makes screening and evaluation of FNA smears on a digital platform time-consuming and laborious. We designed a machine learning algorithm that can identify regions of interest (ROIs) on thyroid fine-needle aspiration biopsy WSIs., Objective.—: To evaluate the ability of the machine learning algorithm and screening software to identify and screen for a subset of informative ROIs on a thyroid FNA WSI that can be used for final diagnosis., Design.—: A representative slide from each of 109 consecutive thyroid fine-needle aspiration biopsies was scanned. A cytopathologist reviewed each WSI and recorded a diagnosis. The machine learning algorithm screened and selected a subset of 100 ROIs from each WSI to present as an image gallery to the same cytopathologist after a washout period of 117 days., Results.—: Concordance between the diagnoses using WSIs and those using the machine learning algorithm-generated ROI image gallery was evaluated using pairwise weighted κ statistics. Almost perfect concordance was seen between the 2 methods with a κ score of 0.924., Conclusions.—: Our results show the potential of the screening software as an effective screening tool with the potential to reduce cytopathologist workloads.

Background: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA)., Objectives: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA., Methods: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics., Results: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient., Conclusions: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

Purpose: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet., Methods: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a "Surgical series" of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a "Cytological series" of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot., Results: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology., Conclusion: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer., (© 2021. The Author(s).)

Purpose: Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules., Methods: Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements., Results: At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03)., Conclusion: US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules., (© 2021. The Author(s).)

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems., Objectives: To compare the two systems for accuracy of cancer risk prediction., Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared., Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively., Conclusions: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems.

The use of reporting terminologies for thyroid FNA cytology enables standardisation and international alignment of the reporting of thyroid cytology results, which is essential. There are currently three major internationally recognised systems: Bethesda (TBS), UK RCPath (Thy), and Italian (TIR). A fourth terminology system used in Japan has identical categories to TBS but with different nomenclature. The aim of this review is to discuss the strengths and weaknesses of the TBS, UK RCPath, and TIR systems, and to make the case for international terminology harmonisation and standardisation., (© 2021 The Authors. Cytopathology published by John Wiley & Sons Ltd.)

Purpose: Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy., Methods: A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region., Results: Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013., Conclusions: The results of this population-based study describe recent variations over time and between surrounding areas of indicators of 'diagnostic pressure' on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas., (© 2021. The Author(s).)

Objectives: We aimed to provide the Asian experience with the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in pediatric thyroid nodules., Methods: Consecutive thyroid fine-needle aspirates (patient age, ≤18 years) were retrospectively collected from 7 tertiary centers in 5 Asian countries., Results: Of 194,364 thyroid aspirates, 0.6% were pediatric cases (mean age, 15.0 years). Among 827 nodules with accessible follow-up, the resection rate and risk of malignancy (ROM) were 36.3% and 59.0%, respectively. Malignant nodules (n = 179) accounted for 59.7% of resected nodules and 21.6% of all thyroid nodules with available follow-up. Compared with the published adult series, pediatric nodules had a higher resection rate and ROM, particularly in the indeterminate categories., Conclusions: Our study demonstrates that Asian pediatric thyroid nodules had higher ROM than those from adults. The prototypic outputs of TBSRTC may need to be adjusted in the pediatric population., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The clinical impact of the SIAPEC/SIE 2014 classification for thyroid cytology has been addressed in few studies that evaluated the malignancy rate and the relative prevalence of each category. No study analyzed its intra-observer and inter-observer reproducibility, so far., Methods: We retrospectively collected all "indeterminate" lesions diagnosed before (2011-2014) and after (2015-2018) the application of the SIAPEC/SIE 2014 classification at our Institution. Their relative malignancy risks were calculated based on available histological diagnoses. Cytological and clinical features of TIR3A were compared with the surgical outcome. Finally, a large set of samples was re-evaluated in blind of the original cytological and histological diagnoses by two pathologists, independently., Results: The prevalence of "indeterminate" diagnoses increased in years 2015-2018 (302/1482, 21% with 14% of TIR3A and 7% TIR3B categories) compared to years 2011-2014 (261/1680, 16%). Surgery was performed in 27% TIR3A and in 97% TIR3B cases. Malignancy rates were 40% for TIR3B and 17% for TIR3A, but were greatly influenced by the adoption of the WHO 2017 re-classification of encapsulated follicular-patterned lesions (decreasing to 28% and 6%, respectively). No criteria except for tumor size were associated to malignancy in TIR3A category. Intra-observer agreement of the experienced pathologist was 122/141 (86%), whereas inter-observer agreement between the expert and in-training pathologist was 95/141 (67%)., Conclusions: In this real-life experience, the sub-classification of TIR3A and TIR3B slightly increased the overall prevalence of "indeterminate" diagnoses. Malignancy rates were higher than estimated for both TIR3A and TIR3B categories. Agreement among observers highly depended on pathologist's training.

Introduction: Thyroid fine-needle aspiration (tFNA) is a powerful screening tool for assessing solitary thyroid nodules. Generally, morphologic evaluation of smears yields an accurate diagnosis; but, in some cases it is useful to have a cell block (CB) to conduct ancillary studies such as immunohistochemistry (IHC). Cytologic diagnoses guide clinical decisions, so it is important that accurate and efficient diagnoses be rendered. Our study evaluates the diagnostic utility of the CB in the evaluation of tFNAs., Materials and Methods: We performed a retrospective chart review of all tFNA specimens from January 2014 to July 2019. Data collected included TAT (in days), diagnosis, if a CB was prepared, and if it was diagnostically contributory. Descriptive statistics were calculated. Data were analyzed using the χ 2 test and the Mann-Whitney U-test., Results: Of the 2321 specimens, 40.2% (933) had CB and only 0.3% (7) were diagnostically contributory. IHC was used for 2 cases. For cases with CB, the median TAT was one day [0-18 days] and the median TAT without CB was 0 [0-9 days]. There was a significant difference in TAT between cases with a CB and those without. Most cases without a CB had same-day TAT (66.4%), whereas only 1.1% of those with a CB had same day TAT. Cases with CB were more likely to have a TAT >1 day (65% versus 12.1%) or >3 days (25.4% versus 10%) than those without a CB (P < 0.0001)., Conclusions: We found the diagnostic utility of CB for tFNAs to be very low. The addition of a CB added at least 1 day to the TAT in all diagnostic strata. The additional time causes patients to wait for results, even for nondiagnostic studies. The increased TAT, resources, and manpower use may be reduced if CB were produced only as needed-if the results of the smear were ambiguous or if ancillary tests were needed to confirm the diagnosis., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the incidence, risk of malignancy, and management of "suspicious for malignancy" (SFM) for non-papillary carcinoma diagnoses according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)., Materials and Methods: A retrospective search was performed for all thyroid fine-needle aspirations (FNAs) with an SFM diagnosis in the electronic Pathology database at The Johns Hopkins Hospital from 2000 to 2019. During this period, a total of 644 cases were diagnosed as SFM. Of these, 55 cases of "suspicious for non-papillary thyroid carcinoma" (SNPTC) were identified. These 55 cases were then compared with 65 random cases of "suspicious for papillary thyroid carcinomas" (SPTC) diagnoses as a control group., Results: The SNPTC subgroup consisted of 28 cases of "suspicious for medullary thyroid carcinoma" (SMTC) (50.91%), 4 cases of "suspicious for metastasis" (SMET) (7.27%), 3 cases of "suspicious for malignant lymphoma" (SML) (5.45%), 2 cases of "suspicious for poorly-differentiated thyroid carcinoma" (SPDC) (3.64%), and 18 cases of "suspicious for malignancy, not otherwise specified" (SNOS) (32.73%). When compared to SPTC, SNPTC patients' average age was older (P = 0.004). Ancillary studies assisted in diagnosing SNPTC more so than SPTC (P < 0.001). Immunohistochemical studies were performed for 11 cases, molecular studies for 6 cases, and needle rinse calcitonin level for 1 case. When correlated with surgical follow-ups, the risk of malignancy (ROM) was 91.18% for SNPTC compared to 93.75 for SPTC%., Conclusions: SNPTC was rarely diagnosed when compared with SPTC. SMTC was the most commonly diagnosed SNPTC subgroup, followed by SNOS. The ROM of SNPTC was slightly lower than that of SPTC. Ancillary studies and previous clinical history, in addition to cytomorphology, was helpful when rendering the diagnosis of SNPTC., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Fine needle aspiration (FNA) is the reference standard for the diagnosis of thyroid nodules. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been successfully used to discriminate the proteomic profiles of benign and malignant thyroid FNAs within the scope of providing support to pathologists for the classification of morphologically borderline cases. However, real FNAs provide a limited amount of material due to sample collection restrictions. Ex vivo FNAs could represent a valuable alternative, increasing sample size and the power of statistical conclusions. In this study, we compared the real and ex vivo MALDI-MSI proteomic profiles, extracted from thyrocyte containing regions of interest, of 13 patients in order to verify their similarity. Statistical analysis demonstrated the mass spectra similarity of the proteomic profiles by performing intra-patient comparison, using statistical similarity systems. In conclusion, these results show that post-surgical FNAs represent a possible alternative source of material for MALDI-MSI proteomic investigations in instances where pre-surgical samples are unavailable or the number of cells is scarce.

Introduction: There are few studies on the role of puncture feeling in thyroid nodules during ultrasound-guided fine-needle aspiration cytology (US-FNAC), although it is expected to become a new predictive technique. We aimed to analyze the importance of puncture feeling in combination with US-FNAC and investigate whether it can be used as an indicator to predict the nature of thyroid nodules., Materials and Methods: From January 1, 2018, to October 31, 2020, a total of 623 thyroid nodules were included. Puncture feeling was classified as "soft," "hard," or "hard with grittiness." The correlation between puncture feeling and postoperative pathology and the diagnostic value of FNAC combined with puncture feeling were analyzed, and the influence of thyroid nodule size on puncture feeling, FNAC, and FNAC combined with puncture feeling was studied. We further explored the correlation between puncture feeling and histopathology in Bethesda III and IV thyroid nodules., Results: There was a significant correlation between puncture feeling and postoperative pathology (p < 0.001). The sensitivity, negative predictive value, and total coincidence rate of US-FNAC combined with puncture feeling for the diagnosis of thyroid nodules were higher than those of US-FNAC alone (96.1, 83.6, and 94.7% vs. 89.0, 65.5, and 89.7%, respectively). Thyroid nodule size was the influencing factor for puncture feeling, FNAC, and FNAC combined with puncture feeling (p < 0.05 for all). The area under the curve for puncture feeling, FNAC, and FNAC combined with puncture feeling for thyroid nodules of size ≤1 cm was greater than for modules of size >1 cm. Puncture feeling was of great value in diagnosing Bethesda III thyroid nodules (p < 0.001), and all Bethesda IV thyroid nodules had puncture feeling of soft., Conclusion: Puncture feeling is of great value during US-FNAC. "Hard" and "hard with grittiness" were indicators for malignancy, while "soft" indicated that the thyroid nodule was likely to be benign. The diagnostic value of US-FNAC combined with puncture feeling for thyroid nodules is higher than US-FNAC alone, especially when nodule size is ≤1 cm. Puncture feeling is of great value in predicting the nature of Bethesda III thyroid nodules., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction: The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hürthle cell type (HLUS)" category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance., Methods: 93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hürthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP., Results: The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hürthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively., Conclusion: RON for AUS predominantly Hürthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance., (© 2020 Wiley Periodicals LLC.)

Background: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts., Methods: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient., Results: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%)., Conclusion: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Thy3a (AUS/FLUS) is an indeterminate and heterogeneous category in thyroid cytology. Thy3a reporting rates vary widely, with many laboratories documenting overuse. Subclassification of Thy3a helps with risk stratification. We aimed to investigate whether subclassification can also help address Thy3a overuse. We compare the UK reporting system with other terminologies., Methods: An audit of thyroid fine needle aspirations (FNAs) reported at our institution between 2012 and 2017 was performed. Thy3a FNAs followed by histology were reviewed and subcategorised into four subgroups: Scanty Atypia (SA), Scanty Microfollicular (SMF), Favour Benign (FB) and Thyroiditis versus Neoplasm (TVN). Review and subclassification were blinded to histology outcomes. FNAs were correlated with histology and statistical analysis was performed., Results: Our Thy3a rate was high (24% of all thyroid FNAs). For 336 Thy3a FNAs with histology, the malignancy rates of the four subgroups were: SA 68%, SMF 20%, FB 4%, TVN 31%. There were significant associations between subgroup and malignancy risk, and between subgroup and tumour risk. On histology, SA had more malignancies than expected and FB had fewer. SA and SMF had more tumours than expected and FB had fewer. SMF and Thy3f FNAs were similar in terms of tumour and malignancy outcomes., Conclusions: Subclassification of Thy3a FNAs into these four subgroups is recommended. This can improve risk stratification and help address overuse of Thy3a. We propose that some FB and SMF cases could be safely diverted to Thy2 and Thy3f respectively. We compare various reporting terminologies and question how indeterminate FNAs should be classified., (© 2020 John Wiley & Sons Ltd.)

Objective: To compare the frequency of fine needle aspiration (FNA) cytological results between nodules 1 cm or less and nodules greater than 1 cm., Methods: All FNAs performed between January 2016 and December 2019 at an institute in Brazil were analysed. For each nodule, at least two conventional slides were produced (one stained by Giemsa and the other by hematoxylin and eosin). All cases were reviewed by two cytopathologists and were reported following the Bethesda System. Clinical information (gender and age) and ultrasound data (nodule size and location) were collected. The magnitude of association was measured using the prevalence ratio (PR) with 95% confidence intervals (CIs) considering two groups of nodules: 1.0 cm or less, and greater than 1 cm., Results: A total of 3703 nodules were analysed from 3265 patients (2906 women [88.48%], 359 men [11.51%], with a combined mean age of 52 years). Considering the prevalence ratio of Bethesda categories between these two groups of nodules, the nondiagnostic or unsatisfactory category (PR: 3.0, 95% CI: 2.2-4.2) and the suspicious for malignancy category (PR: 1.6, 95% CI: 1.1-2.4) were significantly associated with nodules measuring 1 cm or less., Conclusion: Our results demonstrated that nodules 1 cm or less are significantly associated with the nondiagnostic and suspicious for malignancy categories of the Bethesda System when compared to nodules greater than 1 cm., (© 2020 John Wiley & Sons Ltd.)

Background: Rapid on-site evaluation (ROSE) is a valuable tool for specimen adequacy assessment in thyroid ultrasound (US)-guided fine-needle aspiration (US-guided FNA). To reduce the risk of nondiagnostic samples, additional needle passes may be needed at ROSE to ensure adequate sampling. Recommendations regarding the number of aspirates to ensure specimen adequacy are not well defined. Furthermore, there are limited data regarding nodule characteristics that may require increased sampling. In this study, we investigate conditions associated with requiring more than three needle passes during ROSE., Methods: A retrospective quality review of all patients who underwent US-guided thyroid FNA by a single board-certified radiologist over a 1-year period was performed. A total of 122 patients were identified: 70 with three passes performed and 52 with more than three passes to achieve adequacy., Result: Our data demonstrate that large nodules (≥3 cm) were more likely than small nodules (≤1.1 cm) to require more than three passes to achieve adequacy. If a nodule was predominantly cystic or mixed cystic and solid, the sample was often adequate with only three passes. In cases of thyroiditis or nodules suspicious or diagnostic of neoplasia, there is a trend to require only three passes for adequacy., Conclusion: On the basis of the data presented in this study, cytopathologists should be prepared for the potential need to obtain additional needle passes in larger (≥3 cm) nodules and provide reassurance to patients that this is an anticipated finding for these larger nodules., (© 2020 Wiley Periodicals LLC.)

Background: The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) altered the practice of thyroid pathology and reduced the risk of malignancy (ROM) associated with the indeterminate categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC). It has been proposed that the evaluation of the risk of neoplasm (RON) is important in cytologic-histologic correlation studies., Methods: A total of 5224 thyroid aspirates were performed at our institution during an 8-year period. Of the 1475 cases (28%) with surgical follow-up, the histologic diagnoses comprised benign non-neoplastic (BNN, n = 669), follicular adenoma (FA, n = 188), NIFTP (n = 42), papillary microcarcinoma (PMC) (n = 223), and malignant neoplasm excluding PMC (n = 353). The RON was calculated to include neoplasia with low risk biologic behavior (FA, NIFTP, PMC) and malignant neoplasms. In contrast, the ROM was reserved for malignant neoplasms excluding PMC., Results: The RON for each TBSRTC category was: nondiagnostic (ND) 38.3%, benign 20.9%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) 63.2%, follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) 83.9%, suspicious for malignancy (SFM) 94%, and malignant 100%. The ROM excluding PMC was: ND 14%, benign 1.6%, AUS/FLUS 17.8%, FN/SFN 28.4%, SFM 84.4%, and malignant 99.5%., Conclusions: The RON and ROM support the recommended management guidelines from TBSRTC for all categories, except for FN/SFN. Histopathologic follow-up of FN/SFN aspirates in our study contain a very high rate of neoplasm (83.9%), which might support the management preference of conservative surgery., (© 2020 Wiley Periodicals LLC.)

Background: Multinucleated giant cell (MGC) present in a variety of non-neoplastic and neoplastic lesions of the thyroid on cytology samples. We aimed to investigate whether certain MGC features that can help us in routine cytopathology practice., Method: One hundred and thirty seven cases thyroid fine-needle aspiration material, which was diagnosed as indeterminate or malignant according to the Bethesda categorization, were reviewed. All cytomorphological features of the MGCs were documented. These features correlated with Bethesda categories and the final diagnosis of the subsequent surgical specimen., Results: The presence of the MGCs was identified in 42% of the samples (58 cases-total 236 MGCs). Eighty eight of them (37%) had dense cytoplasm, 148 of them had foamy cytoplasm. The mean number of dense and foamy MGC per case was higher in the malignant category (3.2 for dense MGC and 6 for foamy MGC per case). All dense MGCs were found to be in patients with papillary thyroid carcinoma (PTC). Remarkably, follicular patterned lesions had less often dense MGC compared to papillary patterned lesions (16.6% and 46.8% respectively). We detected a nuclear irregularity in 49 dense MGC (55%), groove-like features in 24 dense MGC (27.2%), and presence of some material/cell in 8 dense MGC (9%)., Conclusion: The presence of dense MGC is an important finding for guiding accurate Bethesda categorization, especially in indeterminate and malignant categories. Besides, the presence of some material or cell in MGCs cytoplasm can be an important indicator for the prognosis of the PTC cases., (© 2020 Wiley Periodicals LLC.)

Adamantinoma-like Ewing sarcoma (ALES) is a rare variant of Ewing sarcoma family of tumors (ESFTs). ALES is characterized by translocations of the EWSR1 (Ewing sarcoma breakpoint region 1) gene on chromosome 22, morphologic features of small round blue cell tumors with focal squamous differentiation, and a unique immunoprofile. Herein, we report a 21-year-old patient who presented with severe, acute onset back pain. Imaging revealed a large, exophytic, heterogeneously enhancing mass in the left thyroid and numerous lytic bone lesions. Fine-needle aspiration of the thyroid, revealed a cellular smear with "small round blue cell" morphology. The unique immunoprofile of positive ESFT markers (NKX2.2 and CD99), along with positive markers of squamous epithelial differentiation (AE1/AE3 and p40), led to a diagnosis of ALES. This was confirmed by fluorescence in situ hybridization, which demonstrated EWSR1 rearrangement in 74% of nuclei., (© 2020 Wiley Periodicals LLC.)

Thyroid ultrasound with gray-scale and color Doppler is the most helpful imaging modality to differentiate normal thyroid parenchyma from diffuse or nodular thyroid disease by evaluating glandular size, echogenicity, echotexture, margins, and vascularity. The various causes of diffuse thyroid disease often have overlapping sonographic imaging features. Thyroid nodules may be hyperplastic or neoplastic, with most due to benign hyperplastic changes in architecture and benign follicular adenomas; only a small percentage are malignant. A systematic approach to nodule morphology that includes evaluation of composition, echogenicity, margin, shape, and any echogenic foci can guide decision to biopsy or follow nodules., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Primary thyroid lymphoma (PTL) is a rare malignant disease. Its prognosis depends on early diagnosis. The role of fine-needle aspiration (FNA), including smear cytology, cell block (CB) techniques, and immunohistochemistry (IHC) sections in the diagnosis of PTL is still unclear. Here we reported 19 cases of PTL and literature review to evaluate the diagnostic accuracy for lymphoma by cytology., Methods: Our study retrospectively reviewed 19 patients diagnosed with PTL at the affiliated hospital of Southwest Medical University in China from June 2011 to May 2019. According to the Bethesda system for reporting thyroid cytopathology, the CB sections were evaluated for the presence of single tumor cells. IHC was performed on CB., Results: The diagnostic accuracy for PTL of FNA, CB with smears, and the joint application of the three methods (FNA + CB + IHC) of our study with 19 cases was 68.4% (13/19), 83.3% (15/18), and 100% (17/17), respectively., Conclusion: The present study demonstrates that FNA has low sensitivity in diagnosing PTL, but the joint application of FNA, CB, and IHC might provide high diagnostic accuracy for lymphoma and should be applied in all cases where the clinical suspicion is high regardless of the FNA findings., (© 2020 Wiley Periodicals LLC.)

Adamantinoma-like Ewing Sarcoma (ALES) is a rare subtype of Ewing sarcoma family of tumors (EFTs) which are defined by their EWSR1 gene rearrangements. We present a case of a 15-year old female with a swelling in her anterior neck of 4 months duration which had recently begun to rapidly grow in size. Fine needle aspiration showed a small blue round cell tumor with immunoreactivity for cytokeratin, CD99 and FLI1. Material for molecular testing was available on the resection specimen. Demonstration of t(11;22) (EWS-FLI1) was helpful in establishing the diagnosis., (© 2020 Wiley Periodicals LLC.)

Background: Cystic thyroid lesions represent one of the most common causes of unsatisfactory fine-needle aspiration sampling. Thus, it is important to access the maximum number of follicular cells from cystic fluid in order to reduce unsatisfactory rates. We compared the traditional method of smearing with an alternative one., Methods: For each thyroid nodule, two smears were collected. Each smear was prepared using a distinct approach: either using the traditional technique or the alternative. Clinical data were taken from cytopathological request forms. The cytological aspects of the smears (eg, adequacy and number of cells) were observed during microscopy analysis. No cases were found to be suspicious for malignancy during ultrasound analysis (categories TR1 or TR2 according to ACR TI-RADS)., Results: Thirty-five cases were analyzed. For smears prepared using both the traditional and the alternative techniques, 20 and 4 cases, respectively, were unsatisfactory. In the 20 unsatisfactory traditional smear cases, 9 (45%) showed enough cells for diagnosis in cytospin and/or cell block samples; the four unsatisfactory alternative method cases showed the same. There was a statistical difference between the two methods of collecting a smear concerning sample adequacy (P < .001), but there was no statistical difference regarding the cellularity (P = .842)., Conclusion: In our data, the alternative method of using only one slide and the needle tip had higher rates of adequate sampling. Since it is cost effective and does not change the cytological analysis, this proposed alternative method can be useful in cases of cystic thyroid lesions., (© 2020 Wiley Periodicals LLC.)

Classification schemes for reporting thyroid cytology of fine needle aspiration (FNA) of thyroid nodules are largely used in clinical practice, but the level of inter-observer agreement among cytopathologists is poorly acknowledged. The present study aimed to explore the inter-observer agreement among the experienced authors of the 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC). A stratified randomization was performed in order to obtain a sample homogeneously distributed and representative of all ICCRTC classes. Four high-experience raters were randomly selected among the extensors of the Italian consensus. They independently reviewed 60 FNA samples blindly of the initial cytological report and clinical features. Their overall agreement was evaluated according to Fleiss' kappa. The overall inter-observer agreement was moderate (κ 0.46). Specifically, a good agreement was found when the samples were consistent for malignancy (TIR5) or were not adequate for diagnosis (TIR1) (κ 0.67 and κ 0.73, respectively). A moderate agreement was present for suspicious-for-malignant category (TIR4), and a fair agreement was recorded in the two intermediate ones (TIR3A and TIR3B) (κ 0.36 and κ 0.35, respectively). For clinical purposes, the agreement was good (κ 0.74) in differentiating cases with surgical indication (TIR4/TIR5) from those in which surgery is not essential or requires limited extension (TIR3B/TIR3A/TIR2). In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons.

Objective : Thyroid nodules are highly prevalent and a common clinical problem worldwide. How to identify the nature of a nodule is a major concern of clinicians. Fine needle aspiration cytology (FNAC) has an established role and is well-utilized in nodule management. However, the unsatisfactory nondiagnostic and indeterminate rates limit its usage and lead to some unnecessary surgery. Hashimoto thyroiditis (HT) is prevalently found concurrent with thyroid nodules. Whether HT can influence the accuracy of cytopathological diagnosis of nodules is still controversial. Methods : We collected medical records of 1,063 patients with thyroid nodules who had done FNAC in our hospital from 2015 to 2016. Thyroid function, anti-thyroid autoantibody levels, thyroid ultrasound records, and cytological and histopathological results of nodules were reviewed to analyze the impact of HT on FNAC outcome. Results : A total of 1,063 patients with an average age of 44 ± 13 years old were retrospectively reviewed for pathological and clinical data. Patients with different cytological diagnoses had comparable positive rates of anti-thyroid autoantibodies. One hundred patients were confirmed to have concurrent HT by histopathology after surgery. The overall nondiagnostic and indeterminate cytology rates were 11.9% and 25% respectively. No statistical difference was found either in the rate of a nondiagnostic cytology results or in the rate of indeterminate cytology results between patients with positive anti-thyroid autoantibodies and patients with negative test for anti-thyroid autoantibodies ( P > 0.05). The same was true between patients with histopathologically confirmed HT and HT-negative ones ( P > 0.05). Conclusions : The presence of concurrent HT, whether clinically implied with positive anti-thyroid autoantibodies or pathologically confirmed, is unlikely to predispose an FNAC diagnosis of thyroid nodules to be non-diagnostic or indeterminate.

Objective: Fine-needle aspiration cytology is the risk stratification tool for thyroid nodules, and ultrasound elastography is not routinely used for the differential diagnosis of thyroid cancer. The current study aimed to compare the diagnostic parameters of ultrasound elastography and fine-needle aspiration cytology, using surgical pathology as the reference standard., Methods: In total, 205 patients with abnormal thyroid function test results underwent ultrasound-guided fine-needle aspiration cytology on the basis of the American College of Radiology Thyroid Imaging-Reporting and Data System classification and strain ultrasound elastography according to the ASTERIA criteria. Histopathological examination of the surgical specimens was performed according to the 2017 World Health Organization classification system. Moreover, a beneficial score analysis for each modality was conducted., Results: Of 265 nodules, 212 measured ≥1 cm. The strain index value increased from benign to malignant nodules, and the presence of autoimmune thyroid diseases did not affect the results (p>0.05 for all categories). The sensitivities of histopathological examination, ultrasound elastography, and fine-needle aspiration cytology for detection of nodules measuring ≥1 cm were 1, 1, and 0.97, respectively. The working area for detecting nodule(s) in a single image was similar between strain ultrasound elastography and fine-needle aspiration cytology for highly and moderately suspicious nodules. However, for mildly suspicious, unsuspicious, and benign nodules, the working area for detecting nodule(s) in a single image was higher in strain ultrasound elastography than in fine-needle aspiration cytology., Conclusion: Strain ultrasound elastography for highly and moderately suspicious nodules facilitated the detection of mildly suspicious, unsuspicious, and benign nodules.

Background: Thyroid fine needle aspiration (FNA) is the mainstay for diagnosis of malignancy, and is an integral part of current thyroid nodule assessment. The present study analyzes the diagnostic accuracy of palpation-directed versus ultrasound guided fine-needle aspiration in patients who underwent surgery for thyroid nodules., Methods: A retrospective chart review of all consecutive patients who had FNA biopsy (palpation or ultrasound guided) of thyroid nodules and underwent thyroid gland surgery between 1998 and 2014 was conducted. The FNA findings of the palpation-guided and ultrasound-guided groups were compared for baseline characteristics. Moreover, the diagnostic accuracy of FNA findings and surgical histopathology results were analyzed., Results: A total of 1174 patients were included in the study with a mean age of 46.3 ± 11.7 years and the majority were females (75.5%). Among the study population, 392 (33.4%) patients underwent US-guided FNA; 570 (48.6%) had palpation-guided FNA in clinic and no FNA was done in 212 (18%) cases. Patients underwent US-guided FNA were more likely to have suspicion of malignancy ( p = 0.001), and had indeterminate findings ( p = 0.001). On the other hand, palpation-guided FNA group had significantly higher frequency of benign cytology ( p = 0.001). With respect to the suspicion for malignancy as well as malignancy, the US-guided group had a similar diagnostic accuracy in comparison to the palpation group. The proportion of malignancy finding on US-guided FNA (8.9%) was higher than the palpation-guided FNA (6.4%) that had been confirmed on postoperative histopathological examination ( p = 0.95)., Conclusion: The present study demonstrates higher sensitivity of US-guided thyroid FNA biopsies over palpation-guided FNA for the suspicion of malignancy; however, the accuracy is comparable. Moreover, both groups showed more postoperative malignancy in the benign and unsatisfactory categories than predicted in the Bethesda system. Further prospective studies are needed to underpin a realistic correlation between FNA and final histopathology reports.

There is increasing evidence showing that clinicians employ different management strategies in their use of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this meta-analysis, we investigated the differences in diagnosis frequency, resection rate (RR), and risk of malignancy (ROM) between Western (ie, American and European) and Asian cytopathology practices. We searched PubMed and Web of Science from January 2010 to January 2019. Proportion and 95% CIs were calculated using a random-effect model. We used independent sample t tests to compare frequencies, RR, and ROM between Western and Asian practices. We analyzed a total of 38 studies with 145,066 fine-needle aspirations. Compared with Asian practice, Western series had a significantly lower ROM in most of TBSRTC categories, whereas the RR was not statistically different. Focusing on indeterminate nodules, the RR in Western series was significantly higher (51.3% vs 37.6%; P = .048), whereas the ROM was significantly lower (25.4% vs 41.9%; P = .002) compared with those in Asian series. The addition of Asian cohorts increased ROM for most of diagnostic categories compared with the original TBSRTC. In conclusion, this study demonstrates a difference in Western and Asian thyroid cytology practice, especially regarding the indeterminate categories. Lower RR and higher ROM suggest that Asian clinicians adopt a more conservative approach, whereas immediate diagnostic surgery is favored in Western practice for indeterminate nodules. The addition of Asian series into a meta-analysis of TBSRTC altered ROM for several categories, which should be considered in future revisions of TBSRTC., (© 2019 American Cancer Society.)

Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) comprises 6 categories used for the diagnosis of thyroid fine-needle aspiration biopsy (FNAB). Each category has an associated risk of malignancy, which is important in the management of a thyroid nodule. More accurate predictions of malignancy may help to reduce unnecessary surgery. A machine learning algorithm (MLA) was developed to evaluate thyroid FNAB via whole slide images (WSIs) to predict malignancy., Methods: Files were searched for all thyroidectomy specimens with preceding FNAB over 8 years. All cytologic and surgical pathology diagnoses were recorded and correlated for each nodule. One representative slide from each case was scanned to create a WSI. An MLA was designed to identify follicular cells and predict the malignancy of the final pathology. The test set comprised cases blindly reviewed by a cytopathologist who assigned a TBSRTC category. The area under the receiver operating characteristic curve was used to assess the MLA performance., Results: Nine hundred eight FNABs met the criteria. The MLA predicted malignancy with a sensitivity and specificity of 92.0% and 90.5%, respectively. The areas under the curve for the prediction of malignancy by the cytopathologist and the MLA were 0.931 and 0.932, respectively., Conclusions: The performance of the MLA in predicting thyroid malignancy from FNAB WSIs is comparable to the performance of an expert cytopathologist. When the MLA and electronic medical record diagnoses are combined, the performance is superior to the performance of either alone. An MLA may be used as an adjunct to FNAB to assist in refining the indeterminate categories., (© 2020 American Cancer Society.)

Background: Ultrasound (US) risk stratification systems (RSSs) have been developed to reduce the number of unnecessary fine needle aspirations (FNAs) of thyroid nodules. These systems were designed primarily to identify papillary thyroid carcinomas, thus their performance on follicular thyroid carcinoma (FTC) is debatable. The present study was undertaken to investigate the accuracy of RSSs in selecting FTCs for FNA., Methods: Patients with FTC who underwent US examinations between 2012 and 2018 in 2 institutions were selected. US images were reviewed retrospectively, and FTCs were reclassified according to the American Association of Clinical Endocrinologist/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), American College of Radiology (ACR-TIRADS), 2015 American Thyroid Association, British Thyroid Association, European Thyroid Association, Korean Society of Thyroid Radiology and Korean Society of Radiology, and Thyroid Imaging Reporting and Data System (TIRADS). Risk class and indication for FNA were assessed., Results: Forty-five FTCs from 45 consecutive patients were included in the study. The median tumor diameter was 32 mm (range, 11-100), and ovoid isoechoic nodule with or without lobulated margins was the most frequent presentation. When FTCs were classified according to RSSs, the most common categories were intermediate and high risk, though 1 case in 3 was not classifiable. FTCs were classified as high risk/high suspicion/malignant in 11% to 74% of cases, with a statistically significant difference among the systems. FNA was indicated in 69% to 100% of cases, with good agreement among AACE/ACE/AME, ACR-TIRADS, and TIRADS., Conclusion: Current RSSs show high performance in selecting FTCs for FNA. This result is mainly due to the dimensional RSSs cutoffs indicating FNA. On the contrary, given the reported unsuspicious echo-structural presentation of FTC and the recognized limitation of cytological assessment to detect it, caution is advised when using US to manage cytologically indeterminate nodules., (© 2020 American Cancer Society.)

Thyroid nodules are initially handled by fine needle aspiration (FNA). However, the stance of thyroid core needle biopsy (CNB) still is a challenge. This study aimed to compare the diagnostic performances and conclusive rates of FNA and CNB for the diagnosis of thyroid nodules and to define effective indications of CNB. This retrospective study enrolled 1,060 consecutive thyroid nodules in 1,037 patients who underwent FNA from January 2008 to May 2008, and 462 consecutive nodules in 453 patients who underwent CNB from January 2014 to December 2015 at our institution. Ultrasound (US) features were classified according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and Korean TIRADS (K-TIRADS). We compared diagnostic performances and conclusive rates between FNA and CNB groups. Propensity score matching was conducted to match FNA patients with CNB patients. After matching, the diagnostic performances for selecting surgical candidates and predicting malignancy were comparable between the two biopsy groups. Based on US findings, conclusive results were obtained significantly more in CNB than in FNA when thyroid nodules were classified as ACR TI-RADS or K-TIRADS category 4 and measured larger than 2 cm. Diagnostic performances between FNA and CNB were comparable. Superiority of CNB to FNA was found for thyroid nodules larger than 2 cm and classified as ACR TI-RADS or K-TIRADS category 4.

Background: Distinctive rounded structures termed spherules have been observed in thyroid fine-needle aspiration (FNA) samples. Although they are often small and interpreted as microfollicles, spherules are notable for the even spacing of the follicular cells along the perimeter of the structure. Because they have an orderly architectural arrangement, it has been hypothesized that spherules are benign and do not carry the same risk of malignancy that traditional microfollicles do. The aim of this study was to identify the clinical significance and histopathologic correlate of spherules., Methods: Thyroid FNAs (n = 637) with an interpretation of atypia of undetermined significance (AUS) were reviewed for the presence of spherules, which were defined as small follicles with a rounded, smooth, sharply defined outer contour, evenly spaced nuclei, and a 3-dimensional appearance. Cases were included if spherules accounted for >50% of follicular cell arrangements. Clinical, histopathologic, molecular, and sonographic follow-up data were obtained., Results: Twenty-five spherule cases were identified, and they represented 3.9% of all AUS cases reviewed. All 24 cases with follow-up had a benign outcome. Eleven were tested with the Afirma gene expression classifier; 8 were benign according to the gene expression classifier, and 3 were suspicious but histologically benign after surgical resection. Four additional cases were histologically benign after surgery. Five patients had repeat benign cytology. Four patients had repeat stable ultrasound findings., Conclusions: Thyroid nodules diagnosed as AUS, if composed predominantly of spherules, are associated with a benign outcome. Recognizing this distinctive cytomorphologic finding may help to reduce the number of FNAs interpreted as AUS and save patients from unnecessary additional testing and surgery., (© 2019 American Cancer Society.)

Background: Programmed death-ligand 1 (PD-L1) expression is emerging as an important predictive biomarker in anti-PD-L1 cancer immunotherapy. Its role has been clearly defined in various human cancers and is linked to a poor prognosis and resistance to anticancer therapies. The role of PD-L1 in thyroid cancers has not been well defined in fine-needle aspiration cytology (FNAC). The authors examined the performance of PD-L1 immunostaining in liquid-based cytology (LBC) to determine whether it could be a biomarker of malignancy or aggressive disease., Methods: From January 2018 to March 2019, 236 thyroid lesions, which had been diagnosed by FNAC as indeterminate lesions, suspicious for malignancy (SFM), and malignant, were enrolled. PD-L1 immunostaining was performed on both LBC and corresponding histology samples., Results: The FNAC cohort included 50 benign negative controls, 42 samples of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33 samples of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 53 samples that were suspicious for malignancy (SFM), and 58 malignant samples. AUS/FLUS samples included 3 goiters, 32 follicular adenomas (FAs), 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 5 invasive follicular variants of papillary thyroid carcinoma (I-FVPTCs), and 1 follicular carcinoma; whereas FN/SFN samples included 24 FAs and 9 malignancies (4 I-FVPTCs, 1 NIFTP, 3 papillary thyroid carcinomas [PTCs], and 1 oncocytic follicular carcinoma). The 53 SFM samples were diagnosed on histopathology as 2 FAs, 5 NIFTPs, 15 I-FVPTCs, and 31 PTCs; whereas the 58 malignant specimens included 5 NIFTPs, 5 I-FVPTCs, and 48 PTCs. Increased plasma membrane and cytoplasmic PD-L1 expression was found in 79 cases (38.5%), including 61 PTCs (conventional and variants). Negative PD-L1 expression was found in NIFTPs and FAs. A BRAF V600E mutation was identified in 15% of PD-L1-positive malignancies., Conclusions: The current data suggest that PD-L1 expression in the thyroid gland might represent a marker of malignancy that correlates with PTC, but not with NIFTP. Thyroid neoplasms with PD-L1 expression also ae enriched with BRAF V600E mutations, suggesting that they are associated with more aggressive behavior., (© 2019 American Cancer Society.)

Ancillary molecular testing has emerged as a promising way to refine the preoperative risk stratification of thyroid nodules with indeterminate fine needle aspiration (FNA) biopsy results. Commercially available molecular tests for thyroid FNAs include those that analyze samples for mutations and gene fusions, gene expression alterations, microRNA expression alterations, chromosomal copy number alterations, or a combination thereof. This review summarizes the performance characteristics of the most current iterations of three tests currently marketed for cytologically indeterminate thyroid nodules: ThyroSeq v3, ThyGeNEXT/ThyraMIR, and Afirma Gene Sequencing Classifier., (© 2019 S. Karger AG, Basel.)

Introduction: The Acibadem Health Group (AHG) has been using telepathology/digital pathology stations since 2006. In 2013, the system was changed from videoconferencing to digital pathology (whole-slide imaging) utilizing 3DHISTECH scanners and software. In 2017, digital cytology started to be used for routine cytopathologic diagnosis for thyroid fine-needle aspiration (FNA) cases., Material and Methods: Two hundred and twenty-seven thyroid cases were received for analysis using telecytology (TC) during the period from November 2017 to May 2018. Rapid on-site evaluation was performed at the Atakent Hospital of the AHG by a cytotechnologist and scanned on the same day. For every case, there were Diff-Quik- and Papanicolaou-stained FNA smears. Each glass slide was digitized with a 3DHISTECH whole-slide scanner in 1 focal Z-plane at ×40 magnification., Results: Two hundred and twenty-seven thyroid FNA specimens were retrieved, of which 25 had histologic follow-up. Samples were classified as nondiagnostic in 3%, benign in 74%, atypia of undetermined significance/follicular lesion of undetermined significance in 13%, suspicious for follicular neoplasia/follicular neoplasia in 3%, suspicious for malignancy in 4%, and malignant in 3%. When only the "suspicious for malignancy" and "malignancy" categories were considered positive tests, cytology sensitivity and specificity using TC for diagnosis was 100%., Conclusions: Our data demonstrate that TC is suitable to provide a primary diagnosis in daily routine cytology practice. Despite the promising results, there were some challenges stemming from the novelty of using TC for the primary diagnosis. The study also addresses both advantages and disadvantages of TC in daily practice to increase the efficiency of the technique in primary diagnosis., (© 2019 S. Karger AG, Basel.)

Objective: We aimed to investigate the value of the combined use of high-resolution ultrasound thyroid imaging reporting and data system (TI-RADS) classification and thyroid fine needle aspiration cytology (Bethesda classification) for the qualitative diagnosis of benign and malignant thyroid nodules., Methods: We enrolled 295 patients with 327 thyroid nodules who were scheduled to undergo thyroid nodule surgery. Before surgery, all the patients underwent ultrasound and scoring with the TI-RADS classification, along with thyroid fine needle biopsy cytology under ultrasound guidance (US-FNAC) and scoring with the Bethesda classification. After surgery, the TI-RADS and Bethesda classification scores, separately and in combination, were compared with the postoperative pathological results in terms of the differential diagnosis of thyroid nodules., Results: TI-RADS classification score 4 exhibited the highest diagnostic value for thyroid cancer; the sensitivity, specificity, and accuracy were 92.7%, 70.7%, and 87.1%, respectively, whereas the Kappa and receiver-operating characteristics (ROC) values were 0.651 and 0.817, respectively. Moreover, Bethesda classification score 3 exhibited the highest diagnostic value for thyroid cancer; the sensitivity, specificity, and accuracy were 90.0%, 94.3%, and 91.1%, respectively, whereas the Kappa and ROC values were 0.78 and 0.914, respectively. With regard to the combined diagnostic method, a score of 7 exhibited the highest diagnostic value for thyroid cancer; the sensitivity, specificity, and accuracy were 97.3%, 92.0%, and 95.9%, respectively, whereas the Kappa and ROC values were 0.893 and 0.946, respectively., Conclusion: The combination of high-resolution ultrasonography TI-RADS classification and US-FNAC (Bethesda classification) can improve the accuracy of malignant thyroid nodules diagnosis.

Purpose: The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular categories of cytological diagnosis., Methods: 25,220 FNA performed in a single center in years 2005-2017 were analyzed. Almost all the examined patients were exposed to moderate iodine deficiency for most of their lives. The distribution of FNA outcome categories was compared between two groups: with or without HC (HC and non-HC). The RoM was evaluated on the basis of postoperative histopathological examination (3082 patients)., Results: HC were found in 7.5% of diagnostic FNA. HC nodules were classified into categories II (78.2% vs. 91.9%, p < 0.0000) and VI (0.4% vs. 1.2%, p = 0.0017) less often than non-HC nodules, but more frequently to categories III (14.4% vs. 5.8%, p < 0.0000), IV (11.2% vs. 0.9%, p < 0.0000) and V (1.5% vs. 0.8%, p = 0.0013). There were no significant differences in RoM between HC and non-HC nodules. The RoM in HC and non-HC nodules of particular categories of the Bethesda system was as follows: II: 1.8% vs. 0.8%, III: 9.7% vs. 3.8% when only the last FNA was considered and 10.8% vs. 6.4% when the category III in any performed FNA was considered; IV: 12.7% vs. 10.9%; V: 41.7% vs. 58.2%; and VI: 100% vs. 96.9%., Conclusions: HC nodules are classified into categories of equivocal cytological outcomes more often than nodules without HC. Nevertheless, the presence of HC in a smear does not significantly affect the RoM of FNA categories.