The Value of Gross Visual Assessment of Specimen Adequacy for Liquid-Based Cytology During Ultrasound-Guided,Fine-Needle Aspiration of Thyroid Nodules

Objective: Major problems of fine-needle aspiration (FNA) of thyroid nodules arise due to nondiagnostic results caused by inadequately obtained FNA specimens. The purpose of this study was to evaluate the value of visual assessment of liquid-based cytology specimens during FNA of thyroid nodules for predicting sampling adequacy.Methods: For 3 months, visual assessment of FNA specimens was used for 534 consecutive nodules in 534 patients. The FNA specimens were visually graded immediately following aspiration for each nodule, and the visual grades were classified into 2 categories: inadequate (<6 cell groups) and adequate (>6 cell groups). The cytology results were classified as diagnostic or nondiagnostic based on the Bethesda system. We compared the ultrasound features and FNA characteristics between the diagnostic and nondiagnostic results. Multiple logistic regression analysis was used to determine factors independently predictive of nondiagnostic results. We also evaluated the interobserver agreement regarding the visual assessment.Results: Visual assessment was feasible in all patients, and the nondiagnostic rate was 11.6% (62 of 534). Nondiagnostic results were more frequent in the inadequate visual assessment group (38.1%) than in the adequate visual assessment group (10.5%) (P = .001). Independent predictive factors for nondiagnostic results were inadequate visual assessment (odds ratio, 5.18), >50% vascularity (odds ratio, 3.98), and macrocalcification (odds ratio, 3.60). Interobserver agreement for the prediction of visual assessment was good (κ value, 0.767; P<.001).Conclusion: Immediate visual assessment of a specimen during FNA of a thyroid nodule is a feasible method for predicting sampling adequacy.Abbreviations: FNA = fine-needle aspiration LBC = liquid-based cytology US = ultrasound     

Prediction of Nondiagnostic Results in Fine-Needle Aspiration of Thyroid Nodules: utility of On-Site Gross Visual Assessment of Specimens for Liquid-Based Cytology

Objective: To explore a comprehensive approach for on-site gross visual assessments of liquid-based cytology (LBC) specimens of thyroid nodules and determine morphologic criteria that help predict nondiagnostic rates.Methods: Two-hundred nodules from 165 patients who underwent fine-needle aspiration (FNA) at our hospital were included in this prospectively designed, retrospective analysis. Specimens were visually assessed on-site for three morphologic categories (specimen color, specimen volume, and particle count) using a 5-point grading.Results: Twenty-two nodules (11%) showed nondiagnostic results. Regarding specimen color, nondiagnostic rates tended to be higher in grades 1 (75%) and 5 (100%) than in grades 2 (18%), 3 (8%), or 4 (17%), with a significant difference between grade 1 and grade 3 (P = .003). For specimen volume, nondiagnostic results were significantly more common in grade 1 (33%) and 5 (33%) than in grades 3 (5%) or 4 (1%) (P<.005). There was a significant negative correlation between the grading of the particle count and the nondiagnostic rate (Spearman ρ = -1.000; P<.001). The sensitivity and specificity in the prediction of nondiagnostic results were 77% and 76%, respectively, at the optimal cutoff value of 2 (grade 2 or lower).Conclusion: Particle count was an important morphologic criterion that helped predict nondiagnostic rates in LBC specimens of thyroid nodules, and the specimen color and volume were also useful adjuncts. In routine practice, on-site gross visual assessment followed by resampling (if necessary) may potentially help reduce the rates of nondiagnostic results, repeat FNAs, and the number of unnecessary needle passes.Abbreviations: FNA = fine-needle aspiration; LBC = liquid-based cytology; ROC = receiver operating characteristic; US = ultrasonography     

Comparison of Ultrasound-Guided Fine-Needle Aspiration Biopsy with Core-Needle Biopsy in the Evaluation of Thyroid Nodules

ObjectiveTo compare the diagnostic rate of ultrasound-guided fine-needle aspiration biopsy (FNAB) with the diagnostic rate of combined FNAB and core-needle biopsy in the evaluation of nodular thyroid disease.MethodsWe performed a retrospective case-control study by reviewing charts of patients who underwent ultrasound-guided FNAB and core-needle biopsy of the thyroid at a tertiary referral center from January 1999 to December 2001. Results were classified as diagnostic (negative, suspicious, or positive for malignancy) or nondiagnostic. These findings were compared with an age- and sex-matched control group who underwent only FNAB. Complications between the groups were reviewed.ResultsThe patient group consisted of 320 patients who underwent 340 ultrasound-guided fine-needle aspiration and core-needle biopsies of the thyroid; the control group consisted of 311 patients who underwent 340 FNABs. There was no significant difference in the nondiagnostic rates between groups—12.9% in patients who had FNAB–only compared with 10.9% in patients who had both procedures (proportion difference, -2.1%; 95% confidence interval, -7.0% to 2.9%; P = .41). There was a trend towards an increased incidence of hematoma and infection in the core biopsy group. In the group that underwent FNAB and core-needle biopsies, 10 patients (3.1%) developed biopsy-specific complications (hematomas in 8 patients, biopsy site infections in 2 patients). In the FNAB only group, 3 patients (1.0%) developed hematomas; there was no incidence of infection.ConclusionsIn the evaluation of thyroid nodules, the addition of core-needle biopsies to FNAB confers little benefit in decreasing the nondiagnostic rates and may be associated with increased complications. Core-needle biopsies should not be routinely performed in the evaluation of thyroid nodules, but rather, patient selection for the more invasive core biopsy should be done judiciously. (Endocr Pract. 2008;14:426-431)     

Thyroid Nodules with 2 Prior Inadequate Fine-Needle Aspiration Results: Effect of Increasing the Diameter of the Needle

Objective: The major limitation of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) procedures of thyroid nodules are the cytologically nondiagnostic results. The role of increasing the diameter of the needle in the third FNAB (FNAB#3) due to inadequate cytology has as yet not been investigated. The aim of the present study was to evaluate whether increasing the needle diameter could improve the cytologic sampling of thyroid nodules following 2 previous nondiagnostic US-FNAB results.Methods: Between July 2012 and December 2012, 140 consecutive patients with 2 prior nondiagnostic US-FNAB results were enrolled in this prospective investigation. Group 22G consisted of 70 patients (78.5% women; mean age, 52 years) having nodules examined with a 22-gauge (G) needle. Group 27G consisted of 70 patients (75.7% women; mean age, 53 years) having nodules examined with a 27-G needle.Results: The rate of nondiagnostic FNAB results was 42.8% (30 of 70) in group 22G and 64.3% (45 of 70) in group 27G, which was a significant difference (P = .011). The large-bore (22 G) needle was found to be statistically significantly superior compared with the small-bore (27 G) needle in diagnostic ability for predominantly solid (P = .014), irregular (P = .013), and halo-free (P = .021) nodules. The accuracy rate was 64.6 and 38% for large-bore (22 G) and small-bore (27 G) needles, respectively.Conclusion: The results of our study showed that increasing the needle lumen diameter significantly improves diagnostic performance in terms of adequate aspirated material and diagnostic accuracy rate following 2 prior nondiagnostic US-FNABs.Abbreviations: AUS = atypia of undetermined significance FNAB = fine-needle aspiration biopsy G = gauge NPV = negative predictive value PPV = positive predictive value US = ultrasound     

Utility of Ultrasound Versus Gene Expression Classifier in Thyroid Nodules with Atypia of Undetermined Significance

Objective: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset.Methods: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology.Results: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy.Conclusion: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder.Abbreviations:AUS = atypia of undetermined significanceFNA = fine-needle aspirationGEC = gene expression classifierGEC-B = GEC-benignGEC-S = GEC-suspicious for malignancyNPV = negative predictive valuePPV = positive predictive valueUSG = ultrasonography     

Do all Thyroid Nodules >4 cm need to be Removed? An Evaluation of Thyroid Fine-Needle Aspiration Biopsy in Large Thyroid Nodules

Objective: Controversy exists regarding the ability of fine-needle aspiration (FNA) biopsy to rule out malignancy when thyroid nodules exceed 4 cm in diameter. The goal of this study was to provide data regarding FNA accuracy in a clinical setting for detecting/ruling out malignancy in large thyroid nodules (≥4 cm) and discuss FNA utility in guiding surgical decisions.Methods: All thyroid FNA cases performed at Marshfield Clinic from 1/1/2000 to 12/31/2010 followed by complete or partial thyroidectomy on nodules of at least 4 cm were identified. Demographics, medical history, nodule biopsy characteristics, surgical procedures, and diagnosis data were abstracted. FNA was compared to histologic evaluation of surgical specimens.Results: A total of 198 patients with large thyroid nodules were identified. Most had a single large nodule, but ~40% were multinodular, and 206 total nodules were assessed. Females outnumbered males, and the mean age was ~50 years. After surgery, cancer was histologically identified in 49/206 (23.8%) nodules, including 9/123 nodules that had been categorized as benign by FNA, corresponding to a false-negative rate of 7.3%. Sensitivity/specificity for detecting malignancy by FNA was ~80%. The positive predictive value (PPV) was just below 60%, and the negative predictive value (NPV) was 93% but rose to 96% when papillary microcarcinomas were excluded.Conclusion: While FNA sensitivity in large nodules was relatively low, NPV was high, especially if incidental papillary microcarcinomas were excluded. When cancer prevalence and NPV are known, FNA can be a reliable “rule out” test in nodules ≥4 cm. This information is critical and can help guide the surgery decision, especially in high-risk patients. The decision for surgery should not be solely based on nodule size but should consider additional factors including cancer prevalence, clinical history, ultrasound features, surgical risk, and life expectancy.Abbreviations:FNA = fine-needle aspirationNPV = negative predictive valuePPV = positive predictive value     

Same-Day Fine-Needle Aspiration Cytology Diagnosis for Thyroid Nodules Achieves Rapid Anxiety Decrease and High Diagnostic Accuracy

Objective: The time between the moment of referral for the diagnostic workup for thyroid nodules and the outcome can be worrisome for patients. In general, patients experience high levels of anxiety during the evaluation of a lesion suspicious for cancer. Therefore, the implementation of same-day fine-needle aspiration cytology (FNAC) diagnosis is becoming standard-of-care for many solid tumors. Our aim was to assess the feasibility of same-day FNAC diagnosis for thyroid nodules and to assess patient anxiety during the diagnostic process.Methods: For feasibility of same-day FNAC diagnosis, we assessed the proportion of patients receiving a diagnosis at the end of the visit. Accuracy was measured by comparing histology with the FNAC result. Patient anxiety was measured by the State Trait Anxiety Inventory at 6 moments during the diagnostic workup.Results: Of the 131 included patients, 112 (86%) were female, and the mean age was 53 years. All patients, except those with a nondiagnostic FNAC result (n = 26; 20%), had a diagnosis at the end of the day. There were only two discordant results. Anxiety levels at the beginning of the day were high throughout the group, State Trait Anxiety Inventory (STAI) score 43.1 (SD 2.0) and decreased significantly more in patients with a benign FNAC result (STAI score 30.2), compared to patients with a malignant or indeterminate result (STAI score 39.6).Conclusion: Distress of patients with a thyroid nodule undergoing same-day FNAC diagnostics was high. Same-day FNAC diagnosis is feasible and accurate for the evaluation of thyroid nodules. Therefore, same-day FNAC diagnosis seems a safer, more patient-friendly approach to diagnose thyroid nodules.Abbreviations:AUS = atypia of undetermined significanceCWS = Cancer Worry ScaleFNAC = fine-needle aspiration cytologySTAI = State Trait Anxiety InventoryTSH = thyroid-stimulating hormone     

Utility of Afirma Gene Expression Classifier for Evaluation of Indeterminate Thyroid Nodules and Correlation with Ultrasound Risk Assessment: Single Institutional Experience

Objective: We assessed our experience with Afirma gene expression classifier (GEC) combined with sono-graphic risk assessment, using both the American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TI-RADS) in evaluating indeterminate thyroid nodules.Methods: We identified 98 patients with 101 nodules who had a second fine needle aspiration biopsy (FNA) between January 1, 2014, and September 30, 2017, and sent to Veracyte for cytopathology and subsequent Afirma GEC testing. A second FNA biopsy was performed if the initial cytopathology was either Bethesda III or IV (n = 94) or nondiagnostic (n = 7). We correlated cytopathology, histopathology, and Afirma GEC results with sonographic risk assessment using both the ATA system and TI-RADS.Results: The mean age of the cohort was 57.4 ± 12.3 years; 84% women and 60% white. Repeat FNA was benign in 51 of 101 nodules, and of the remaining 50 nodules, 18 (36%) were GEC-benign and 32 (64%) GEC-suspicious. Eighteen of the 32 GEC-suspicious nodules underwent surgery with the following results: 7 benign (39%), 1 follicular thyroid carcinoma (6%), 6 follicular variant of papillary thyroid cancer (33%), and 4 noninvasive follicular tumor with papillary-like nuclear features (22%). The malignancy rate among the surgical cohort was 39% (without noninvasive follicular tumor with papillary-like nuclear features [NIFTP]) and 61% (with NIFTP) and about 50% and 20% of this group scored in the high suspicion category by ATA and TR5 by TI-RADS, respectively.Conclusion: Afirma GEC was useful in avoiding surgery in one-third of indeterminate nodules and performed similarly to ATA and TI-RADS. However, the use of echogenicity in scoring may underestimate the risk of malignancy in patients with indeterminate nodules.Abbreviations:ATA = American Thyroid Association; AUS = Atypia of Undetermined Significance; FLUS = Follicular Lesion of Undetermined Significance; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid cancer; GEC = Gene Expression Classifier; ND = nondiagnostic; NIFTP = noninvasive follicular tumor with papillary-like nuclear features; TI-RADS = Thyroid Imaging Reporting and Data System; TR = TI-RADS     

Value of Repeating A Nondiagnostic Thyroid Fine-Needle Aspiration Biopsy

ObjectiveTo assess the value of repeating a biopsy when the initial thyroid fine-needle aspiration (FNA) biopsy is nondiagnostic.MethodsBetween 1990 and 2003, 4,311 thyroid FNAs were performed at the Cleveland Clinic Foundation, of which 220 (5%) were nondiagnostic. Among 189 patients whose medical records were available for retrospective review, 106 underwent a repeated FNA (FNA #2), and 14 had a second repeated FNA (FNA #3). Thyroid ultrasonography was used in the evaluation in 113 FNAs.ResultsThe first and second repeated FNAs were diagnostic in 58% (62 of 106 patients) and 50% (7 of 14 patients), respectively. The rate of malignant disease in patients with no repeated FNAs versus 1 or more repeated FNAs was 4.8% (4 of 83) versus 11.3% (12 of 106), respectively. Ultrasound-guided FNA yielded a diagnosis among 33 of 113 biopsies (29.2%), and FNA without ultrasound guidance provided a diagnosis in 30 of 159 biopsies (18.9%). Thus, the use of thyroid ultrasonography significantly improved the likelihood of establishing a diagnosis (P = 0.017). We found that repeating the FNA up to 2 times provides a diagnosis in up to 60% of cases.ConclusionThe overall prevalence of thyroid cancer in patients with nondiagnostic FNA is not trivial—8.5% in our study group of 189 patients. An aggressive approach toward nondiagnostic FNA biopsies is recommended, with performance of at least 2 repeated FNA biopsies, preferably with the help of ultrasound guidance. (Endocr Pract. 2007;13:735-742)     

Thyroseq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules

Objective: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules.Methods: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy.Results: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy.Conclusion: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules.Abbreviations: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia     

Repeatedly nondiagnostic thyroid fine-needle aspirations do not modify malignancy risk

Objective: Thyroid nodules with nondiagnostic (ND) fine-needle aspirations (FNA) typically undergo repeat sampling. While repeat FNA is often diagnostic, little is known regarding the significance of repeatedly ND aspirates. Limited data suggest there is very low, if any, risk of malignancy for repeatedly ND FNAs. Study Design: We performed a retrospective analysis of ND thyroid FNAs over a nearly 6-year period at our institution to further address this question. Results: There were 834 ND thyroid FNAs, representing 694 distinct thyroid nodules. Repeat FNA was performed after an initial ND aspirate in 52% of cases (363/694); 19% (70/363) had at least one additional ND diagnosis on repeat FNA. Surgical follow-up was available for 57 cases. Malignancy was identified histologically in 21% (9/42) of nodules after a single ND FNA and in 20% (3/15) of nodules with 2 or more repeatedly ND aspirates. Accounting for all benign cytologic follow-up, the overall risk of malignancy was 4% [12/303; 3.5% (9/255) following a single ND FNA and 6.3% (3/48) after repeated ND FNAs]. Conclusion: We observed no modification of malignancy risk when repeated FNAs were ND. Clinical management for an ND aspirate should remain repeat aspiration along with clinical and sonographic correlation.     

Incidental Thyroid Nodules: Race/Ethnicity Disparities and Outcomes

Objective: Black patients have a significantly lower incidence of well-differentiated thyroid cancer (WDTC) compared to all other race/ethnic groups, while white patients appear to be at greater risk. This study examines incidental thyroid nodules (ITNs) to assess whether racial disparities in WDTC arise from a differential discovery of ITNs—perhaps due to socioeconomic disparities—or reflect true differences in thyroid cancer rates.Methods: A retrospective review was performed of all patients who underwent fine-needle aspiration (FNA) of thyroid nodules by our academic medical center's endocrinology division between January 2006 and December 2010. Medical records were reviewed to identify whether the biopsied thyroid nodule was discovered incidentally through nonthyroid-related imaging or identified by palpation.Results: FNAs were performed on 1,369 total thyroid nodules in 1,141 study patients; 547 (48%) were classified as white, and 593 (52%) were classified as nonwhite. Among this cohort, 36.6% of patients underwent biopsy for an ITN. White patients were 1.6 times more likely to have undergone a biopsy for a nodule that was incidentally identified compared to nonwhites (P<.0001). Indicators of socioeconomic status (SES) did not have a significant association with ITNs. Within the ITN cohort, 4.9% of nonwhite patients were found to have a thyroid malignancy compared to 12.9% of white patients (P<.01).Conclusion: The higher incidence of thyroid cancer in white patients appears to be not only due to diagnostic bias, but also to a true difference in cancer prevalence.Abbreviations: FNA = fine-needle aspiration; ITN = incidental thyroid nodule; SEER = Surveillance Epidemiology and End Results; SES = socioeconomic status; WDTC = well-differentiated thyroid cancer     

Guideline Implementation on Fine-Needle Aspiration for Thyroid Nodules: Focusing on Micronodules

Objective: We investigated patients who were referred to our institution after fine-needle aspiration (FNA) was performed at outside clinics to evaluate how many nodules satisfied the FNA indications of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and compare that to the number of thyroid nodules that satisfy the FNA indications of the American College of Radiology (ACR)-TIRADS and American Thyroid Association (ATA) guidelines.Methods: Between January 2018 and December 2018, 2,628 patients were included in our study. The included patients were those referred for thyroid surgery after having a suspicious thyroid nodule. We retrospectively applied the three guidelines to each thyroid nodule and determined whether each nodule satisfied the FNA indications. We compared the proportion of nodules satisfying the FNA indications of each guideline using a generalized linear model and generalized estimating equation.Results: The median size of the 2,628 thyroid nodules was 0.9 cm (range, 0.2 to 9.5 cm). We found that FNA was not indicated for 54.1%, 47.7%, and 19.1% of nodules and 87.3%, 99.0%, and 97.8% among them were micronodules (<1 cm) according to the ACR-TIRADS, ATA guideline, and K-TIRADS, respectively. The proportion of micronodules which satisfied the FNA indications was significantly higher for the K-TIRADS (65.1%) compared to the ACR TIRADS (12.1%) and ATA guideline (12.1%) (P<.001).Conclusion: Among patients referred for thyroid surgery to our institutions, about 35% of the micronodules underwent FNA despite not being appropriate for indications by the K-TIRADS. Systematic training for physicians as well as modifications to increase the sensitivity of the guideline may be needed to reduce the overdiagnosis of thyroid cancers, especially for micronodules.     

Timing of repeat thyroid fine-needle aspiration in the management of thyroid nodules

Objective: The Bethesda System for reporting thyroid fine-needle aspirations (FNAs) recommends repeat aspirations be done at least 3 months following the initial aspiration to prevent false-positive misinterpretations due to reactive/reparative changes. Because limited data exists, we reviewed our own data to ascertain the recommendation. Study Design: We retrospectively reviewed thyroid FNAs accessioned in the Cytology Laboratory at Beth Israel Deaconess Medical Center in Boston, Mass., USA, from January 2006 to December 2008. We identified patients with repeat aspirates of a single lesion and those with thyroidectomy specimens. Cytologic and surgical diagnoses along with time between FNAs were recorded. Results: No statistically significant difference was detected in the distribution among nondiagnostic, suboptimal, and adequate categories with respect to the timing of repeat FNA (p = 0.25). Forty-six percent of the lesions that were nondiagnostic/suboptimal initially yielded the same results on repeat. Twenty-eight percent of initially adequate specimens were nondiagnostic/suboptimal on repeat (p = 0.04). Nine percent of those with an initial atypical diagnosis had the same diagnosis on repeat, while 2.6% of those who did not have an initial atypical diagnosis had an atypical diagnosis on repeat (p = 0.29). False positives between early (16%) and late (12%) repeats were not statistically significant (p = 0.74). Conclusion: The diagnostic yield and accuracy of repeat FNA is independent of the time interval between procedures but may be related to the original FNA diagnosis.     

Management of Nondiagnostic Thyroid Fine-Needle Aspiration Biopsy: Survey of Endocrinologists

ObjectiveTo evaluate the approach of endocrinologists in the setting of nondiagnostic thyroid fine-needle aspiration (FNA) biopsies.MethodsIn 2002, we surveyed physicians attending the national annual meetings of the American Association of Clinical Endocrinologists and the Endocrine Society of North America, using a 13-item questionnaire. The responses were tallied and analyzed.ResultsOf the 143 respondents, 139 were endocrinologists, with a male:female ratio of 2.5:1. Most respondents were involved in a medical practice in North America, but Europe, Asia, New Zealand, and Australia were also represented. Of those performing thyroid FNA biopsy, 31% used thyroid ultrasound guidance. Among the survey respondents, 16%, 49%, 20%, and 15% performed less than 2, 2 to 5, 6 to 10, and more than 10 thyroid FNA biopsies per month, respectively. Among the respondents, 13.5%, 44%, 28.5%, 10%, and 4% had nondiagnostic rates of less than 5%, 5 to 10%, 11 to 20%, 21 to 30%, and more than 30%, respectively. The approach of the respondents to an initially nondiagnostic FNA was repeated FNA biopsy in 87%, observation in 7%, levothyroxine suppression in 4%, and thyroid scintigraphy in 2%. Respondents believed that the most cost-effective approach in a patient with nondiagnostic FNA was repeated biopsy (82%), monitoring the size of the thyroid nodule (17%), and surgical referral (< 1%). No one was willing to repeat the thyroid biopsy more than three times.ConclusionOn the basis of findings in our survey, most endocrinologists repeat thyroid FNA at least once when confronted with a nondiagnostic result. No published studies have demonstrated the cost-effectiveness of this approach versus proceeding to surgical intervention or observation. We hope that this survey will encourage further studies on this issue. (Endocr Pract. 2004;10: 317-323)     

Comparison of Diagnostic Performance between the American College of Radiology Thyroid Imaging Reporting and Data System and American Thyroid Association Guidelines: A Systematic Review

Objective: We aimed to compare the diagnostic accuracy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) with the American Thyroid Association (ATA) guidelines in risk stratification of thyroid nodules.Methods: We performed a computerized search of Medline, EMBASE, Web of Science, Cochrane Library, and Google Scholar to identify eligible articles published before July 31, 2019. We included studies providing head-to-head comparison between ACR TI-RADS and ATA guidelines, with fine-needle aspiration biopsy cytology results or pathology results as the reference standard. Quality assessment of included studies was conducted using the Quality Assessment of Diagnostic Accuracy Studies–2 tool. Summary estimates of sensitivity and specificity were calculated by bivariate modeling and hierarchical summary receiver operating characteristic modeling. We also performed multiple subgroup analyses and meta-regression.Results: Twelve original articles with 13,000 patients were included, involving a total of 14,867 thyroid nodules. The pooled sensitivity of ACR TI-RADS and ATA guidelines was 0.84 (95% confidence interval [CI], 0.76–0.89) and 0.89 (95% CI, 0.80–0.95), with specificity of 0.67 (95% CI, 0.56–0.76) and 0.46 (95% CI, 0.29–0.63), respectively. There were no significant differences between the two classification criteria in terms of both sensitivity (P = .26) and specificity (P = .05). For five studies providing direct comparison of ACR TI-RADS, ATA guidelines, and Korean TI-RADS, our analyses showed that the Korean TI-RADS yielded the highest sensitivity (0.89; 95% CI, 0.82–0.94), but at the cost of a significant decline in specificity (0.23; 95% CI, 0.17–0.30).Conclusion: Both classification criteria demonstrated favorable sensitivity and moderate specificity in the stratification of thyroid nodules. However, use of ACR TI-RADS could avoid a large number of biopsies at the cost of only a slight decrease in sensitivity.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; HSROC = hierarchical summary receiver operating characteristic; SROC = summary receiver operating characteristic; TI-RADS = Thyroid Imaging Reporting and Data System; US = ultrasonography     

ProGRP as a Novel Biomarker for the Differential Diagnosis of Medullary Thyroid Carcinoma in Patients with Thyroid Nodules

Objective: To investigate the release of progastrin-releasing peptide (ProGRP) in patients with thyroid nodules and the value of ProGRP in fine-needle aspirate washout fluid (FNA-ProGRP) in the differential diagnosis between medullary thyroid carcinoma (MTC) and non-MTC thyroid nodules.Methods: We investigated 2,446 healthy persons and 212 patients with 235 thyroid nodules. They were classified into healthy, nodular goiter, chronic thyroiditis, thyroid follicular neoplasm, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. The serum ProGRP and FNA-ProGRP were measured.Results: The serum ProGRP median concentration in MTC was 124.40 pg/mL, significantly higher than in other groups. The cutoff value of serum ProGRP was 68.30 pg/mL, leading to 53.85% sensitivity, 96.98% specificity, and 0.51 kappa value in MTC. The FNA-ProGRP median concentration in MTC nodules was 2,096.00 pg/mL, significantly higher than in other groups. A receiver operating characteristic analysis of MTC nodules and non-MTC nodules indicated that the cutoff value was 22.77 pg/mL, leading to 94.12% sensitivity, 98.27% specificity, and 0.85 kappa value.Conclusion: FNA-ProGRP measurement could be served as an ancillary method for the differential diagnosis between MTC and non-MTC thyroid nodules.Abbreviations: CEA = carcinoembryonic antigen; CT = calcitonin; FNAC = fine-needle aspiration cytology; FNA-CT = calcitonin in fine-needle aspirate washout fluid; FNA-ProGRP = ProGRP in fine-needle aspirate washout fluid; MTC = medullary thyroid carcinoma; ProGRP = progastrin-releasing peptide; SCLC = small-cell lung cancer; TM = tumor marker     

Should FNA be Performed in Patients with a Multinodular Goiter and Compressive Symptoms?

Objective: In this study, we aimed to determine whether preoperative thyroid fine-needle aspiration (FNA) in patients with multinodular goiter (MNG) and compressive symptoms influences the type of thyroid surgery performed, the incidence of recurrent thyroid cancer, or the need for successive surgery.Methods: We retrospectively reviewed the charts of 431 patients who underwent thyroidectomy at our institution from 2008 to 2011. Patients who presented with compressive symptoms and no prior FNA at initial presentation were included in this study.Results: Eighty patients met the criteria for our study, of which 46 (57.5%) underwent FNA prior to surgery and 34 (42.5%) were referred to surgery without FNA. The prevalence rates of malignancy (>1 cm) on surgical pathology in the FNA and non-FNA groups were 41% (n = 19) and 38% (n = 13), respectively. There was no statistically significant difference between the rate of total/subtotal thyroidectomies (71.7% in FNA vs. 79.4% in non-FNA, P = .31), lobectomies/partial thyroidectomies (28.3% in FNA vs. 20.5% in non-FNA, P = .43), neck lymph node dissections (P = .89) or subsequent surgeries (P = .72) between the 2 groups.Conclusion: Our findings show that preoperative FNA in patients with an MNG and compressive symptoms does not influence the type of surgery performed, short-term outcomes, or the need for subsequent surgeries. Further studies are needed to validate the need for preoperative FNA in such patients.Abbreviations:FNA = fine-needle aspirationMNG = multinodular goiterWHO = World Health Organization     

Agreement Between American and European Thyroid Imaging,Reporting, and Data System (TIRADS) in the Diagnosis of 473 Thyroid Nodules From a Single Center in Brazil

ObjectiveTo compare 2 ultrasound-based risk stratification systems in malignancy risk assessment of thyroid nodules and the clinical applicability of these guidelines in Brazil.MethodsWe retrospectively reviewed the ultrasound findings of 314 patients (473 thyroid nodules) who underwent fine-needle aspiration (FNA) biopsy and/or surgery between February 2018 and March 2019. All nodules were classified using 2 systems: the Thyroid Imaging, Reporting, and Data System (TIRADS) of the American College of Radiology (ACR-TIRADS) and the TIRADS of the European Thyroid Association (EU-TIRADS). Both risk stratification systems were analyzed. We identified the diagnostic predictive values that yielded optimal sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.ResultsOf the 473 nodules, all underwent FNA, and histopathology was performed for 332 nodules. The agreement between the ACR-TIRADS and EU-TIRADS results and that between cytology and histopathology findings was 92.6% (kappa = 0.84) and 86.7% (kappa = 0.73), respectively. The area under the curve for the ACR-TIRADS and EU-TIRADS was 0.871 and 0.828, respectively (P < .001). The EU-TIRADS had the best sensitivity and negative predictive value, whereas the ACR-TIRADS had the best specificity, positive predictive value, and accuracy. Of the 473 nodules studied, only 158 (33.4%) followed the FNA size criteria suggested by the ACR-TIRADS.ConclusionACR-TIRADS and EU-TIRADS had good diagnostic performances. However, most aspirated nodules did not follow the TIRADS indication; thus, the overuse of FNA as a diagnostic tool was observed.     

Thyroid Nodule Location on Ultrasonography as a Predictor of Malignancy

Objective: The diagnostic capacity of ultrasonography (US) for differentiating between malignant and benign thyroid nodules is crucial in preventing unnecessary invasive procedures. This is the first study to evaluate whether thyroid nodule location on US has predictive value for malignancy.Methods: We retrospectively reviewed data from 219 patients with thyroid nodules who underwent fine-needle aspiration biopsy in 1 year. Patients' demographics as well as nodule's laterality, polarity, morphology, and multinodularity were analyzed. All malignant lesions were confirmed by surgical pathology.Results: The majority of the patients were female (86.2%). Nodules were evenly distributed between the right lobe (46.3%) and left lobe (49.5%). Eight nodules (4.2%) were located in the isthmus. Most nodules (79.3%) were located in the lower pole, while 9.6% were located in the upper pole and 6.9% in the middle pole. Seventy-five patients (39.9%) had multiple nodules. Fourteen nodules were malignant, representing a prevalence of 7.4%. A significantly higher frequency of malignancy was observed in upper pole (22.2%) compared to lower pole (4.7%) and middle pole (15.4%). A multiple logistic regression model confirmed such association after adjusting for age, body mass index, multinodularity, and laterality. The odds of malignancy in the upper pole were 4 times higher than other locations (odds ratio, 4.6; P = .03).Conclusion: Our study is the first showing that thyroid nodules located in the upper pole can be considered as having higher risk for malignancy. It may enhance the predictive value of malignancy if it is included in thyroid nodule ultrasound classification guidelines.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; BMI = body mass index; FNA = fine-needle aspiration; TMS = total malignancy score; TTW = taller than wide; US = ultrasonography