Aspiration Of Thyroid Nodules Research Articles

Fine-Needle Aspiration of Subcentimeter Thyroid Nodules in the Real-World Management.

BackgroundThe Korea Thyroid Association published the revised guidelines for thyroid nodules in 2016. However, whether fine-needle aspiration is accurately performed based on indications and whether the results of this procedure are appropriately addressed according to clinical guidelines, particularly in subcentimeter nodules, are unclear.MethodsWe retrospectively analyzed the fine-needle aspiration data of 331 thyroid nodules of patients who were referred to a tertiary hospital clinic for fine-needle aspiration. Each nodule was categorized according to ultrasonography findings based on the recommendations of the Korea Thyroid Association for fine-needle aspiration. Only nodules with a final pathological diagnosis of benign or malignant made using the Bethesda system were included.ResultsUp to 32% of thyroid nodules that were not indicated for fine-needle aspiration were aspirated. Regarding subcentimeter nodules, only 28 of 123 (22.8%) aspirated nodules were indicated for fine-needle aspiration. Of the 49 malignant subcentimeter nodules, 33 (67.3%) underwent immediate surgery. Meanwhile, 14 (28.6%) nodules were lost to follow-up, and two (4.1%) were under active surveillance. Eighteen (36.7%) malignant subcentimeter nodules were not indicated for fine-needle aspiration but underwent surgical resection instead of active surveillance.ConclusionDespite the recommendations in the revised guidelines, several thyroid nodules that do not meet the indications for FNA are aspirated in real-world practice. To reduce overtreatment, a widespread knowledge of the correct indications for fine-needle aspiration is important in clinical practice, particularly for subcentimeter nodules.

Cytopathologic criteria and size should be considered in comparison of fine-needle aspiration vs. core-needle biopsy for thyroid nodules: results based on large surgical series.

To evaluate and compared the diagnostic performances of FNA and CNB using various cytopathologic criteria and size subgroups to see how the comparison results differ accordingly. From May 2012 to May 2019, 8187 thyroid nodules in 8139 patients who had undergone preoperative US-guided FNA or CNB at outside clinics were included in this retrospective study (mean size: 11.9 ± 9.5 mm). Preoperative US-FNA was performed in 7496 (91.6%) nodules and US-CNB was performed in 691 (8.4%) nodules. Propensity score matching was used to compare the sensitivities between FNA and CNB in diagnosis of malignancy and neoplasm according to different cytologic test criteria. Of the 8187 thyroid nodules, 7833 (95.7%) were malignant and 354 (4.3%) were benign. Mean size of the thyroid nodules in the CNB group was significantly larger than the FNA group, 15.7 ± 12.7 mm vs. 11.6 ± 9.0 mm, respectively (P < 0.001). After matching, sensitivity in the CNB group were significantly higher in the total population, and in subgroups <10 mm for criteria 1 and 2 (all P < 0.05, respectively). No significant differences were seen between the sensitivities of FNA and CNB for nodules ≥10 mm regardless of criteria in diagnosis of malignancy or neoplasm (all P > 0.05, respectively). Results comparing sensitivities between FNA and CNB differ according to the different cytopathologic criteria used for calculation. CNB has significantly higher sensitivity to FNA in subcentimeter nodules when using criteria 1 or 2. Diagnostic sensitivities did not show significant differences for nodules ≥10 mm regardless of the cytopathologic criteria used, that should be considered in selecting biopsy methods.

Diagnostic and prognostic value of a 7-panel mutation testing in thyroid nodules with indeterminate cytology: the SWEETMAC study

PurposeThe aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC).MethodsEligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III–V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription‐polymerase chain reaction (RT-PCR).ResultsAmong 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month’s follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%).ConclusionsBy increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancer patient subgroup.

Exploring the Inter-observer Agreement Among the Members of the Italian Consensus for the Classification and Reporting of Thyroid Cytology.

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.

Analytical validation of a novel targeted next-generation sequencing assay for mutation detection in thyroid nodule aspirates and tissue.

The identification of somatic mutations in cancer specimens enables detection of molecular markers for personalized treatment. We recently developed a novel molecular assay and evaluated its clinical performance as an ancillary molecular method for indeterminate thyroid nodule cytology. Herein we describe the analytical validation of the novel targeted next-generation sequencing (NGS) assay in thyroid samples from different sources. We present validation data of a novel NGS-based panel on 463 thyroid samples, including 310 fine-needle aspiration (FNA) specimens from different sources (FNA collected in preservative solution, liquid-based, and stained smears), 10 fresh frozen, and 143 formalin-fixed paraffin-embedded (FFPE) thyroid tissue specimens. Sequencing performance in the different samples was evaluated along with reproducibility, repeatability, minimum nucleic acid input to detect variants, and analytical sensitivity of the assay. All thyroid samples achieved high sequencing performance, with a mean base coverage depth ranging from 2228 × (in liquid-based FNA) to 3661 × (in FNA stained smears), and coverage uniformity ranging from 86% (in FFPE) to 95% (in FNA collected in preservative solution), with all target regions covered above the minimum depth required to call a variant (500×). The minimum nucleic acid input was 1 ng. Analytic sensitivity for mutation detection was 2-5% mutant allele frequency. This validation study of a novel NGS-based assay for thyroid nodules demonstrated that the assay can be reliably used on multiple thyroid sample types, including FNA from different sources and FF and FFPE thyroid samples, thus providing a robust and reliable assay to genotype thyroid nodules, which may improve thyroid cancer diagnosis and care.

Differences in cytopathologist thyroid nodule malignancy rate.

The accuracy of a cytological diagnosis obtained by fine needle aspiration is influenced by several factors including the technique used and the experience of both the aspirator as well as the cytologist. In this project we planned to evaluate the interobserver differences of thyroid nodule cytopathology in our medical centre. The study was conducted using retrospective pathology reports from a single academic centre from August 2013 to September 2017. We compared the sensitivity, specificity, negative and positive predictive values, malignancy rates, and accuracy of two cytopathologists who evaluated thyroid nodules. We included 287 fine needle aspirations of thyroid nodules in the study. Approximately one fifth (18.5%) of patients had surgery and the rate of malignancy was 40%. There was a similar frequency of use of all thyroid Bethesda system (TBS) categories with the exception of TBS 3 (8.0% and 21.2%, P=.01). As a consequence, the malignancy rate was different in TBS 3 category (40% vs 17%, P=.545). There are interobserver differences in the evaluation of thyroid nodules. Clinicians should be aware of such differences because they affect the malignancy rate in each TBS category.

OR28-05 Approaching Indeterminate Thyroid Nodules in the Absence of Molecular Markers. “The BETH-TR Score”

Context: Given the lack of easy access to molecular markers, for indeterminate thyroid nodules (Bethesda (BETH) category III, IV), the clinician can either decide to get a second opinion from an expert high volume thyroid cytopatholgist, re-do the FNAC after a period of 3-6 months or send the patient for a diagnostic hemithyroidectomy. Reviewing the sonographic risk features is also one way of triaging these nodules. The ACR-TIRADS (TR) is an objective method of sonographic risk assessment and is superior to other forms of sonographic classification. Aim: We propose combining the scoring of TR category and BETH category (both expressed as numerical value and summated) and look at the score which could potentially guide the clinician in deciding whom to send for surgery. Settings and Design: Observational Prospective collection of consecutive patient data from Thyroid FNAC clinic. Statistical analysis used: The BETH categories were represented numerically and summated with the TR category. The categorical outcome variables of Benign and Malignant nodules and the summated score was analysed using Kruskal-Wallis test. Results: We analysed 450 FNAC data, out of which 403 were thyroid nodule aspirates. Out of these nodules, 96 of them underwent surgery and 64% of these nodules were malignant on final histopathology (Malignant=62 and Benign=34). The mean (sd) size of the benign nodules was 3.6 (2.2)cm compared to 2.8 (1.8)cm of the malignant nodules. After excluding those with BETH 1 (n=4), the mean BETH-TR score for benign nodules was 6(1.4) and malignant nodules 9.4(2.1) (p<0.0001). The BETH-TR score progressively increased from 7.3(0.92) in Follicular thyroid cancers (FTC) to 8.6(1.4) in Follicular variant Papillary thyroid cancer (FVPTC) to 10(1.3) in classic Papillary thyroid cancers (PTC). Among the indeterminate nodules (BETH III & IV; n=40), the BETH-TR score of benign nodules was 6.75(1) and malignant nodules was 7.5(0.72) (p value=0.01). A BETH-TR score >=7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases (Likelihood ratio 3.5; ROC area: 0.8841; CI 0.79-0.94). Conclusion: A combined sono-cytological BETH-TR score is one way to triage management of indeterminate thyroid nodules. A BETH-TR score >=7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases.

OR21-02 Impact of Nodule Size on the Probability of Hurthle Cell Carcinoma and Other Cancers in Thyroid Nodules with Multiple Chromosomal Copy Number Alterations

Fine-needle aspiration (FNA) of thyroid nodules yields indeterminate cytological diagnosis in ~20% of cases, confounding patient management. This includes Hurthle cell nodules, which typically yield Bethesda IV and III cytology. Chromosomal copy number alterations (CNA) are known to occur in thyroid tumors, particularly in Hurthle cell carcinomas (HCC) as well as in other typically follicular-patterned tumors including papillary thyroid carcinomas (PTC) and poorly differentiated thyroid carcinomas (PDTC). The aim of this study was to evaluate thyroid nodules tested positive for CNA but negative for all other genomic alterations using ThyroSeq v3 NGS assay in order to establish the probability of cancer in these nodules and find whether it is influenced by the pattern of CNA and nodule size. We evaluated 111 nodules with multiple CNA detected by ThyroSeq in FNA samples and available surgical pathology outcome. Of those, 69 (62%) nodules showed CNA changes consistent with genome near-haploidization (GNH) whereas 42 (38%) nodules had multiple chromosomal losses and gains (CLG). Nodule size ranged from 0.5-10.2 cm; cytology was Bethesda III in 54%, Bethesda IV in 43%, and Bethesda V-VI in 3% of cases, with Hurthle cells mentioned in the cytology report in 64% of cases. On surgical pathology, 38 (34%) of these nodules were malignant (including 24 HCC, 8 PTC, and 5 oncocytic PDTC) and 73 (66%) were benign (including 43 Hurthle cell and 18 follicular adenomas). No significant difference was observed in probability of malignancy between the two patterns of CNA (p=0.41). However, a significant correlation between the nodule size and probability of cancer was found (p=0.006). In specific CNA groups, correlation between cancer and nodule size remained significant for nodules with GNH pattern (P=0.0002), but not with CLG pattern (p=0.449). Specifically, cancer probability in nodules with GNH pattern and <2 cm in size was 14% (all cancers minimally-invasive), 2.0-2.9 cm was 33%, 3.0-3.9 cm was 50%, 4-4.9 cm was 67%, and ≥5 cm was 80%. Among high-risk cancers (widely-invasive or angioinvasive HCC, PDTC), all 10 tumors had the GNH pattern (p=0.01) and average nodule size of 4.9 cm (range, 2.1-8.5 cm). These findings suggest that CNA of both types are frequently found in Hurthle cell tumors, and probability of cancer in nodules with CNA and no other mutations increases with larger nodule size. This may help to refine the pre-operative assessment of cancer probability and risk of more aggressive disease and offer more tailored management to these patients.

Diagnostic value of ultrasound in comparison with the pathologic results of fine-needle aspiration of thyroid nodules for rapid diagnosis of thyroid malignancies in patients referred to Baqiyatallah Hospital

Background and Aim: Various studies have reported that 4-7 percent of adults with palpable thyroid nodules that 50-70 percent of it’s diagnosed with high-accuracy sonography. Although most thyroid nodules are non-cancerous and do not require treatment, a small percentage of them are associated with a potential risk of malignancy, which is an important early diagnosis by ultrasound or pathology. The present study aimed to compare the ultrasound with the pathologic results of fine-needle aspiration (FNA) of thyroid nodules for the rapid diagnosis of thyroid malignancies in patients referred to Baqiyatallah Hospital. Methods: The study population consisted of 100 (80 female, 20 male) patients with thyroid nodules in the age range of 19-82 years referred to the radiology ward of Baqiyatallah Hospital who were studied by the cross-sectional method. All patients were first scoring by ultrasound, then fine needle aspiration with thyroid nodule ultrasound was performed, and the specimens were referred to the pathology department for further evaluation. Results: The pathologic results from fine-needle aspiration showed that only 8 of the 100 patients studied had malignant nodules that, by ultrasound scoring, 7 patients had 4 scores and 1 patient had 3 scores. However, the other 92 patients with benign nodules 57.60% of patients had score 1, 30.43% of patients had score 2 and 11.97% of patients had score 3. Conclusion: According to the results of this study, it seems that ultrasound scoring is useful in the rapid diagnosis of thyroid nodules and prevent unnecessary thyroid nodule FNA.

Comparison on the Use of Spinal (Stylet) Needle and Simple Needle in Ultrasound Guided Thyroid Nodule FNA; Does the Needle Affect Thyroid FNA Result?

Background: Thyroid fine needle aspiration (FNA) is currently the most acceptable method for evaluating thyroid nodules. Non-satisfactory sample is the main limitation of FNA. It has been shown that spinal needles can reduce the number of non-diagnostic samples. Objectives: In this study, we decided to compare the results obtained using spinal (stylet) needle and simple needle in thyroid nodule FNA according to the agreement between them and with the pathology results as the gold standard. Patients and Methods: Sampling of thyroid nodules of 156 patients was performed by a simple non-stylet 23 gauge needle (A) and a spinal 22 gauge needle with stylet (B). The samples were provided to the pathologist for blind examination. All samples were obtained by an expert radiologist and the pathology examination was also performed by a pathologist expert in thyroid gland diseases. Blind analysis was done using SPSS Statistics for Windows, version 16 (SPSS Inc., Chicago, Ill., USA). Results: The results of FNA with needles A and B were reported unsatisfactory in 11.51 (18 subjects) and 3.84 (six subjects), respectively (P = 0.01). The result in 63.46% (99 subjects) of the participants, in whom FNA was obtained by needle B was introduced as a better sample by the pathologist in comparison with 36.44% (57 subjects) (P &lt; 0.001). Cancer was diagnosed in 9.56 and 7.66 of the samples yielded by needles B and A, respectively, which was not statistically significant (P = 0.54). There was also a significant relationship between thyroid imaging reporting and data system (TI-RADS) score and FNA result. Conclusion: A significant relationship between the adequate sampling results, the qualitative examination result, TI-RADS score and the needle type indicates the importance of needle type on the results of thyroid FNA. Using spinal (stylet) needles may reduce the number of non-diagnostic samples in fine needle aspiration of thyroid nodules and therefore, can have a better effect on the results of this method.

Considerations for Thyroid Fine Needle Aspiration (FNA) Biopsies During the COVID-19 Pandemic

Considerations for Thyroid Fine Needle Aspiration (FNA) Biopsies During the COVID-19 Pandemic

Thyroid Nodule Size and Prediction of Cancer: A Study at Tertiary Care Hospital in Saudi Arabia.

BackgroundThyroid noduleshave become relatively common in clinical practice,and their prevalence increases with age. The majority of thyroid nodules are benign, with 5-15% being malignant. There are a number of well-established predictors of malignancy in thyroid nodules, but thyroid nodule size has been a cause for concern for many researchers and results of the studies are still controversial about their probability of malignancy. Up to the current knowledge, there is no published study that evaluates if thyroid nodule size is associated with the risk of malignancy in Saudi Arabia, so in this study, we aim to find that.MethodsThis is a retrospective study of 987 patients who underwent thyroid nodule fine-needle aspiration (FNA) and subsequent thyroidectomy for thyroid nodules measuring ≥ 1 cm.ResultsThyroid cancer was more prevalent in males than females, and in patients who were older than or equal to 45 years. Nodular size of 1 - 1.9 cm was more prevalent among cancer patients than in benign cases (p<0.001).ConclusionsThe highest malignancy risk was observed in nodules <2 cm and no increase in malignancy risk for nodules >2 cm. Nevertheless, when examined by type of thyroid malignancy, the rate of follicular carcinoma and other rare malignancy increased with increasing nodule size.

Can ultrasound systems for risk stratification of thyroid nodules identify follicular carcinoma?

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. 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. Forty-five FTCs from 45 consecutive patients were included in the study. The median tumor diameter was 32mm (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. 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.

Approaching Indeterminate Thyroid Nodules in the Absence of Molecular Markers: "The BETH-TR Score".

Context:Given the lack of easy access to molecular markers for indeterminate thyroid nodules (Bethesda (BETH) category III, IV), the clinician can either decide to get a second opinion from an expert high-volume thyroid cytopathologist, redo the FNAC after a period of 3–6 months, or send the patient for a diagnostic hemithyroidectomy. Reviewing the sonographic risk features is also one way of triaging these nodules. The ACR-TIRADS (TR) is an objective method of sonographic risk assessment and is superior to other forms of sonographic classification.Aim:We propose combining the scoring of the TR category and BETH category (both expressed as a numerical value and summated) and look at the score which could potentially guide the clinician in deciding whom to send for surgery.Settings and Design:Observational prospective collection of consecutive patient data from the thyroid FNAC clinic.Statistical Analysis Used:The BETH categories were represented numerically and summated with the TR category. The categorical outcome variables of benign and malignant nodules and the summated score was analyzed using the Kruskal-Wallis test.Results:We analyzed 450 FNAC data, out of which 403 were thyroid nodule aspirates. Out of these nodules, 96 of them underwent surgery and 64% of these nodules were malignant on final histopathology (malignant = 62 and benign = 34). The mean size of the benign nodules was 3.6 ± 2.2 cm compared to 2.8 ± 1.8 cm of the malignant nodules. After excluding those with BETH 1 (n = 4), the mean BETH-TR score for benign nodules was 6 ± 1.4 and malignant nodules 9.4 ± 2.1 (P < 0.0001). The BETH-TR score progressively increased from 7.3 ± 0.92 in follicular thyroid cancers (FTC) to 8.6 ± 1.4 in follicular variant papillary thyroid cancer (FVPTC) to 10 ± 1.3 in classic papillary thyroid cancers (PTC). Among the indeterminate nodules (BETH III and IV; n = 40), the BETH-TR score of benign nodules was 6.75 ± 1 and malignant nodules was 7.5 ± 0.72 (P value = 0.01). A BETH-TR score ≥7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases (likelihood ratio 3.5; ROC area: 0.8841; CI 0.79–0.94).Conclusion:A combined sonocytological BETH-TR score is one way to triage the management of indeterminate thyroid nodules. A BETH-TR score ≥7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases.

Core-Needle Biopsy Does Not Show Superior Diagnostic Performance to Fine-Needle Aspiration for Diagnosing Thyroid Nodules.

PurposeTo compare the diagnostic performances of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for thyroid nodules according to nodule size.Materials and MethodsThis retrospective study included 320 thyroid nodules from 320 patients who underwent both FNA and CNB at outside clinics and proceeded with surgery in our institution between July 2012 and May 2019. According to nodule size, the diagnostic performances of FNA and CNB were calculated using various combinations of test-negatives and test-positives defined by the Bethesda categories and were compared using the generalized estimated equation and the Delong method.ResultsThere were 279 malignant nodules in 279 patients and 41 benign nodules in 41 patients. The diagnostic performance of FNA was mostly not different from CNB regardless of nodule size, except for negative predictive value, which was better for FNA than CNB when applying Criteria 1 and 2. When applying Criteria 3, the specificity and positive predictive value of FNA were superior to CNB regardless of size. When applying Criteria 4, diagnostic performance did not differ between FNA and CNB regardless of size. After applying Criteria 5, diagnostic performance did not differ between FNA and CNB in nodules ≥2 cm. However, in nodules ≥1 cm and all nodules, the sensitivity, accuracy, and negative predictive value of CNB were better than those of FNA.ConclusionCNB did not show superior diagnostic performance to FNA for diagnosing thyroid nodules.

Evaluation of Thyroid Fine-Needle Aspiration Biopsies according to Cytological Methods and Comparison with Histopathological Diagnosis.

Objectives:In this study, we aim to compare the results of aspiration of thyroid nodules evaluated according to the Bethesda category (BC) with tissue diagnoses in the operation materials and to compare the sensitivity, specificity and accuracy rates according to cytology methods.Methods:The previous fine-needle aspiration biopsy (FNAB) of thyroid nodules of 879 cases diagnosed histopathologically between 2010 and 2017 was examined. The FNAB results determined according to the Bethesda system were matched with tissue diagnoses, sensitivity, specificity, and accuracy rates were investigated according to cytology methods.Results:Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy rates were found in all FNAB results (in units of %; Sensitivity; 84.7, Specificity; 81.1, PPV; 74.1, NPV; 89.2, Accuracy; 82.5). All of the cytological evaluation methods of thyroid FNABs were found to be reliable and effective (Generally, the results are 80% and above). Specificity and accuracy rates were close to the general average (82.5%) in all methods. However, in cases evaluated with liquid base cytology (LBC) method and in addition to LBC or conventional smear (CS), the sensitivity rates in cases where cell block (CB) were evaluated together were higher than cases in which LBC and CS were used alone (92.6% and 91.0%). When examined statistically, there was no significant difference concerning sensitivity, specificity and accuracy rates of cytological methods (p>0.05, respectively, p=0.576, 0.065, 0.643).Conclusion:In cytopathology, when evaluating thyroid aspirations, it is seen that the LBC method is used instead of CS. In our study, we recommend the use of the LBC method, which seems to have the highest sensitivity (taking into account its technical advantages), instead of CS. However, we think that both CS and LBC methods should be evaluated by supporting them with cell block sections.

Development and Analytical Validation of an Expanded Mutation Detection Panel for Next-Generation Sequencing of Thyroid Nodule Aspirates

Molecular analysis is used to evaluate the risk of malignancy for thyroid fine-needle aspirates, identified as indeterminate by microscopic cytology, on the basis of the detection of various oncogenic DNA mutations and fusion transcripts or on the use of various mRNAs or miRNA-based classifier algorithms. Our approach has been to use a combination test using the detection of oncogenic mutations/fusion transcripts and an miRNA expression-based classifier algorithm. To improve the performance of the combination test, the next-generation sequencing (NGS)-based mutational panel was expanded from the detection of 5 oncogenes to 10 oncogenes and tumor suppressor genes and the detection of fusion transcripts was increased from 6 to 38. Herein, we describe the assay development of the expanded panel NGS test and optimization of various steps for the library preparation of multiplexed target genes to maintain quality parameters for sequencing and to improve the robustness of the test for use in clinical testing in a College of American Pathologists/Clinical Laboratory Improvements Amendments-certified laboratory. Technical hurdles in NGS library preparation for the sequencing of both normal and high guanine-cytosine-rich regions, and balanced amplification of various amplicons in highly multiplexed PCRs, were successfully overcome. Analytical validation as a laboratory-developed test (ThyGeNEXT) included the demonstration of assay reproducibility, lower limit of detection, as well as other fundamental quality parameters.

BRAF mutation analysis by ARMS-PCR refines thyroid nodule management.

Fine-needle aspiration (FNA) of thyroid nodules leads to nearly 25% indeterminate nodules, while BRAFV600E mutation helps to predicting papillary thyroid carcinoma (PTC). However, the clinical validity and utility of the BRAFV600E mutation detected using preoperative FNA samples in a large cohort were rarely reported. To explore the clinical significance of the BRAFV600E mutation on preoperative diagnosis and decision-making in a large FNA cohort in China. This was a prospective study of BRAFV600E mutation analysis using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in FNA samples. The study involved 2640 samples from 2307 patients undergoing FNA procedures in a Chinese medical centre. A high mutation rate of 86.7% was found in the PTC population. For indeterminate thyroid nodules, the malignant rate of BRAFV600E+ and BRAFV600E- was 87.8% and 39.5% in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) III, and 88.2% and 31.8% in the BSRTC IV, respectively. A cost-effective diagnostic model combining both BSRTC grading and BRAFV600E mutation status showed the highest sensitivity of 82.9% and specificity of 85.4%. Central lymph node metastasis (CLNM) was independent of the BRAF mutation status and accounted for 34.2% of the patients with PTC. CT values of BRAFV600E of patients with PTMC were significantly lower in young patients and patients with CLNM. The combined analysis of cytological results and BRAFV600E mutation is highly recommended in BRAFV600E high-prevalence regions, including China. Prophylactic central neck dissection should be performed in selected patients without regard to the BRAF mutation status.

Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination: Diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results

Background and objectiveUltrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination may decrease the number of Bethesda category I cytologies. The study objective was to evaluate our second-year experience with this procedure to analyze diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results. Patients and methodA retrospective study was conducted of 279 nodules from 233 patients. Ultrasound-guided fine needle aspiration was performed according to the 2015 criteria of the American Thyroid Association. A specimen of each aspiration was air-fixed on site before Diff-Quik staining and microscopic examination to assess its suitability; otherwise, nodule aspiration was repeated up to 5 times. Diagnostic efficacy was assessed based on sensitivity and specificity on the cytological categories Bethesda II and Bethesda VI. ResultsDiagnostic sensitivity and specificity were both 100%, 5.4% Bethesda category I results were obtained, and variables independently associated were age (4.7% increase per year of life) and nodule volume (2.3% increase per each 1ml of volume). ConclusionsUltrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination allows for a high diagnostic efficacy and has been shown to be a highly relevant procedure because it has a very low rate of cytological results of Bethesda category I, whose risk has been higher in older subjects and with larger nodules.

Utility of Preoperative Ultrasonography in Transferred Patients with Suspicious Malignancy on Ultrasonography-Guided Fine-Needle Aspiration Cytology of Thyroid Nodules: A Single-Center Retrospective Study.

BackgroundThis study aimed to assess the utility and characteristics of preoperative ultrasonography (US) in patients transferred to referral hospitals from local clinics with a diagnosis of malignancy on US-guided fine-needle aspiration cytology of thyroid nodules.Material/MethodsFrom January 2018 to June 2018, 109 transferred patients underwent preoperative US in our hospital for suspected thyroid malignancy on cytological analysis after US-guided fine-needle aspiration of thyroid nodules in local clinics. Preoperative US was performed by a single radiologist in all patients. Among them, 6 were excluded from the study because of refusal of thyroid surgery. Preoperative US and histopathological results were compared in all patients.ResultsAfter thyroid surgery, pathological examination revealed papillary thyroid carcinoma (PTC) (n=98), follicular adenoma (n=1), and nodular hyperplasia (n=4). Of the 103 patients, 91 exhibited suspicious US findings on the preoperative US, whereas 12 did not. In the 91 patients with suspicious US findings, PTC (n=90) and follicular adenoma (n=1) were confirmed after thyroid surgery. In the 12 patients with no suspicious US findings, PTC (n=8) and nodular hyperplasia (n=4) were confirmed after thyroid surgery. On repeat analysis of the cytological slides of the 4 nodular hyperplasia cases from the local clinics, Bethesda category II (n=1) and III (n=3) were determined.ConclusionsIn the transferred patients with a malignant cytology, preoperative US might be helpful to detect false-positive cytology cases.