Repeat Fine-needle Aspiration Research Articles

An innovative synthetic support for immunocytochemical assessment of cytologically indeterminate (Bethesda III) thyroid nodules.

Fine needle aspiration (FNA) is the procedure of choice in the evaluation of thyroid nodules. Nodules with indeterminate cytological categories, Bethesda III and IV, pose challenges in clinical practice and are frequently submitted to diagnostic surgery. CytoFoam Core (CFCS) uses an absorbent foam device inserted into the needle hub to collect the cytological sample aspirated during FNA. Specimen is formalin-fixed and paraffin-embedded. Assessing diagnostic efficacy of CFCS, compared to traditional cytology, in re-evaluating thyroid nodules classified as Bethesda III, using post-surgical histology as reference standard. Retrospective study on 89 patients with a first indeterminate cytological report who were referred to the Department of Endocrinology of Regina Apostolorum Hospital (Albano L. Rome, Italy) for a second FNA. FNA was performed after at least one month under ultrasound guidance with a 23G needle according to the established procedure. During the second procedure, both traditional cytological (TC) smears and a single-pass CFCS specimen were obtained for each patient. On CFCS samples immunocytochemical staining for Galectin-3, HBME-1, and CK-19 was also performed. 51 patients eventually underwent surgery, and their histological diagnoses were compared to the TC and CFCS reports. Four parameters were evaluated: inadequacy rate, rate of persistent indeterminate (Bethesda III and IV) reports, rate of malignancy in persistently indeterminate nodules, and rate of cancer in lesions cytologically classified as malignant. Non-diagnostic samples were 6 (11.8%) in TC vs 3 (5.9%) in CFCS (p=0.4). Persistent indeterminate samples were 31 (60.8%) in TC vs 19 (37.2%) in CFCS (p=0.01). Rate of malignancy in persistently indeterminate nodules was 8/19 (42.1%) in CFCS vs 9/31 (29%) in TC group (p=0.3). Nine/51 (17.6%) samples were classified as benign by TC vs 21/51 (41.2%) samples by CFCS (p<0.01). All nodules resulted benign at post-surgical evaluation. Five/51 (9.8%) samples were classified as suspicious for malignancy/malignant in TC group against 8/51 (15.7%) samples in CFCS (p=0.5). Post-surgical evaluation confirmed malignancy in all these cases. CFCS demonstrated greater diagnostic accuracy than TC in repeat FNA assessment of cytologically indeterminate nodules. CFCS increased the conclusive diagnosis rate and decreased the number of cytologically indeterminate cases.

ODP474 Critical Analysis of the Thyroid Cytopathologic Diagnosis of Atypia of Undetermined Significance and Associated Clinical Outcomes

Abstract Introduction FNA is the optimal test for classifying concerning thyroid nodules. Approximately 15-30% of FNAs are indeterminate, representing diagnostic challenge with intra- and inter-observer variability among cytologists. The Bethesda System (BS) for cytopathology was created in 2007 to standardize thyroid cytology with corresponding malignancy risk. Our goal is to identify the incidence of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS) and the percent of malignant AUS/FLUS cases at our institution. Methods Chart review of 3068 adult patients with FNA performed from 2003 to 2015 was completed, with attention to reports considered "indeterminant". BS for reporting thyroid cytology was not in use at our institution during that time. Cytopathology reports were evaluated for key descriptors concerning for AUS, FLUS, or follicular neoplasm. Results 461 cytology reports included language consistent with possible "indeterminate" cytology. These reports were reviewed with our institution's cytopathologist and retrospectively assigned an equivalent BS category. 241 cases were consistent with BS category III (7.86% of all thyroid nodule FNAs done during this time period). Molecular marker studies were not being performed at our institution on indeterminate thyroid cytology specimens during this time period. Of the patients who had indeterminate cytology consistent with BS category III, 66.3% (160/241) went for surgery. The malignancy rate was 27.5% (44/160) in the BS category III group. Conclusion Our data demonstrated that category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration. Molecular marker testing on indeterminate thyroid cytology specimens has been shown to be helpful in determining cases for surgery and is now being utilized at our institution. Presentation: No date and time listed

Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma

Purpose/Objective(s)Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. MethodsPathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. ResultsInitial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). ConclusionsFine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Optimization of the Management of Category III Thyroid Nodules Using Repeat FNA and TIRADS.

Simple SummaryThyroid nodules of category III in the Bethesda system do not constitute a uniform group, so it is still a challenge to produce a recommendation for the management of patients with such nodules. The aim of the study was to examine the benefits of the joint use of repeat FNA and a sonographic risk stratification system in category III nodules in relation to the kind of atypia: cytologic/nuclear vs. architectural. Our results indicate that in both kinds of these nodules, the joint evaluation of repeat FNA outcome and sonographic risk of malignancy shows better effectiveness than any of these methods separately. Such a combination allows the identification of patients with a high risk of malignancy as well as a group of patients in which surgical treatment may be safely put aside.The aim of the study was to examine the benefits of the joint use of repeat FNA (rFNA) and EU-TIRADS in category III nodules in relation to the kind of atypia: nuclear vs. architectural (denoted by AUS and FLUS respectively). The study included 127 AUS and 1739 FLUS nodules with a known category of EU-TIRADS. Repeat FNA was performed in 82 AUS and 934 FLUS nodules of which 57 and 515 were excised, respectively. AUS nodules had higher malignancy risk than FLUS nodules. EU-TIRADS showed higher accuracy for AUS nodules, the opposite to rFNA, that had higher accuracy for FLUS nodules. The combined criterion for AUS nodules (at least rFNA-V or EU-TIRADS-4) maximized sensitivity (92.3%) with acceptable specificity (70.0%); OR: 28.0. In the case of FLUS nodules, the combined criterion (rFNA-V or EU-TIRADS-5) maximized specificity (95.2%) with 57.7% sensitivity and a low percentage (13.9%) of positive nodules, OR: 27.0. In both types of nodules, the low risk category in EU-TIRADS and benign result of rFNA excluded cancer. Concluding, category III nodules with and without nuclear atypia differ in their risk of malignancy and, consequently, diagnostic criteria adopted for the evaluation of these nodules with rFNA and EU-TIRADS should be specific to AUS and FLUS nodules.

Clinicopathologic features of thyroid nodules with PTEN mutations on preoperative testing.

The incidence of cancer in thyroid nodules carrying germline or somatic phosphatase and tensin homolog (PTEN) mutations is not well-defined. This study characterizes the clinical and histopathologic features of thyroid nodules with preoperatively detected PTEN mutations and their impact on management. Thyroid nodules with PTEN mutations on molecular testing of fine-needle aspiration (FNA) specimens from November 2017 to July 2020 at our institution were included. Demographic and clinicopathologic data were obtained through retrospective chart review. We identified 49 PTEN mutation-positive nodules from 48 patients. Surveillance was pursued for 28 patients and surgery for 20 patients. There were 14 follicular adenomas (FA), 4 oncocytic adenomas, 1 oncocytic hyperplastic nodule, and 1 encapsulated follicular variant papillary thyroid carcinoma (EFVPTC). The EFVPTC had two somatic PTEN mutations, an NRAS mutation, and was a low-risk tumor with capsular but no angiolymphatic invasion. Four patients, all with multiple nodules, had PTEN hamartoma syndrome (PHTS) with germline mutations or a clinical diagnosis of Cowden syndrome (CS); two had surgery finding FAs, and one previously had follicular carcinoma removed. Among surveillance patients, 1/20 had a significant increase in the size of the thyroid nodule and underwent repeat FNA, and no thyroid malignancy was found with a mean of 1.77 years of follow-up (range 1.00-2.78). Thyroid nodules with isolated somatic PTEN mutations are primarily benign and unlikely to grow at a high rate, at least on short-term follow-up. About 8% of patients with PTEN mutations may have PHTS or CS, which should be suspected in younger patients with multiple thyroid nodules.

Repeat Fine Needle Aspiration Cytology (FNAC) in Thyroid Does Not Help in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)

Repeat Fine Needle Aspiration Cytology (FNAC) in Thyroid Does Not Help in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)

Clinical utility of histogram analysis of grayscale sonograms in assessing sonographic suspicious malignant thyroid nodules.

BackgroundWhen sonographic suspicious malignant thyroid nodules initially proven to be inconsistent by aspiration, repeat fine-needle aspiration cytology (FNAC) is commonly recommended. Although FNAC is simple and reliable, it is also an invasive operation with inevitable false negative results. To determine which sonographic features and histogram parameters based on gray-scale ultrasonic images need repeat aspiration.MethodsAll of the nodules were suspicious for malignancy by preoperative ultrasound (US), and their initial FNAC findings indicated Bethesda category II, or III. Histogram analyses were performed for gray-scale ultrasonic images. Mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th), and sonographic features were compared between pathological benign nodules and malignant ones. Thereafter, receiver operator characteristic (ROC) curves were analyzed for the valuable indicators.ResultsOne hundred and nineteen consecutive patients with 123 histopathologically diagnosed focal thyroid nodules were included in the cohort. The factors associated with malignancy were taller-than-wide shape [odds ratio (OR) =15.165; 95% confidence interval (CI): 3.157–72.854], irregular margins (OR =11.492; 95% CI: 1.747–75.573), microcalcifications (OR =5.107; 95% CI: 1.455–17.927) and skewness (OR =25.800; 95% CI: 1.034–76.422). The skewness of malignant thyroid nodules is higher than that of benign thyroid nodules and has an area under the curve (AUC) of 0.776 in the diagnosis.ConclusionsFor thyroid nodules suspicious on US but not on cytology, skewness, together with taller-than-wide shape, irregular margins and microcalcifications might be a promising marker for clinicians to perform repetitive FNACs.

Effects of Rapid On-Site Evaluation on Diagnostic Accuracy of Thyroid Fine-Needle Aspiration

Introduction: Fine-needle aspiration (FNA) is well-established for the evaluation of suspicious thyroid nodules. However, a significant proportion is nondiagnostic. Rapid on-site evaluation (ROSE) has been proposed to improve the overall adequacy of FNA. Methods: Retrospective cohort study comparing adequacy of thyroid FNA findings pre- and postimplementation of ROSE at a tertiary center in Switzerland. Patients undergoing thyroid FNA from January 2016 to December 2019 were included. The primary outcome was the rate of nondiagnostic findings (Bethesda System for Reporting Thyroid Cytopathology category I). Results: In total, 410 thyroid nodule FNAs were performed. Of those, 309 with standard FNA and 101 with ROSE. The majority of patients were female (71%), with a median age of 56 years (IQR 46–68) and a nodule diameter of 1.9 cm (IQR 1.2–2.9). Implementation of ROSE led to a decrease in nondiagnostic findings from 41.1% to 23.8%, with an odds ratio of 0.42 (95% CI: 0.24–0.72; p = 0.002). Implementation of ROSE was associated with significantly higher rates of Bethesda category III (27.7% vs. 19.1%), category IV (15.8% vs. 5.5%), and Bethesda category VI (6.9% vs. 2.3%). Repeated FNA was performed in 29.1% before and 20.8% after implementation of ROSE (p = 0.18). The mean number of FNA per nodule was reduced from 1.4 (0.6) to 1.2 (0.4) with ROSE (p = 0.04). Conclusions: Implementation of ROSE of thyroid nodule specimen improved diagnostic adequacy of FNA, reducing nondiagnostic findings. However, due to increased equivocal findings (Bethesda category III), there was no significant reduction of repeat FNA.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series

Background Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2).MethodsWe retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria.ResultsThe mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%).ConclusionsWith a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

Hashimoto's Thyroiditis Does Not Influence the Malignancy Risk in Nodules of Category III in the Bethesda System.

Simple SummaryThyroid nodules in patients with Hashimoto’s thyroiditis (HT) have a high prevalence of equivocal cytology, especially category III of the Bethesda system. The aim of this study was to evaluate the risk of malignancy (RoM) in category III thyroid nodules in patients with and without HT, and to analyze whether obtaining category III with a repeat FNA increases RoM. We found that RoM in category III nodules was not affected by the presence of HT. In patients with nodules that show nuclear atypia, irrespective of the presence of HT, there are stronger indications for surgical treatment than in patients with nodules presenting architectural atypia. The chances of obtaining category III once again, with repeat FNA, are higher in patients with HT than without it. If the repeated diagnosis of category III results again from the architectural atypia, without signs of nuclear atypia, then the risk of malignancy does not increase.The aim of this study was to evaluate the risk of malignancy (RoM) in category III thyroid nodules of the Bethesda system in patients with and without Hashimoto thyroiditis (HT) and to analyze whether obtaining category III with a repeat FNA (rFNA) increases RoM. The study included 563 HT and 1250 non-HT patients; rFNA was performed in 349 and 575 patients, and surgical treatment in 160 and 390, respectively. There was no difference in RoM between HT and non-HT patients in the whole examined population (lower limit of RoM), nor in operated patients (upper limit of RoM), HT: 5.0–17.5%, non-HT: 4.7–15.1%. RoM in patients with AUS nodules (with nuclear atypia) was similar in both groups (HT: 21.7–40.0%, non-HT: 16.9–41.4%), as it was in patients with FLUS nodules (with architectural atypia) (HT: 3.5–13.3%, non-HT: 4.0–13.0%). In patients from both groups together, with category III diagnosed twice and AUS identified at least once, RoM was 16.7–50.0% and it was higher than that in patients with FLUS nodule diagnosed twice: 3.2–13.0% (p < 0.005). Concluding, RoM in category III nodules is not affected by the presence of HT. Subcategorization of category III nodules (FLUS vs. AUS) may provide guidance toward further follow-up or surgery in both groups.

Nondiagnostic category of Milan System for Reporting Pediatric Salivary Gland Cytopathology: outcomes and root cause analysis.

Fine-needle aspiration (FNA) results classified as the nondiagnostic category of the Milan system for reporting salivary gland cytopathology (MSRSGC) may be infrequently encountered in children. Clinical management may be challenging due to lack of data regarding outcomes and underlying causes. We retrospectively analyzed 106 consecutive pediatric salivary gland FNAs (2000-2020; 45% performed under image guidance). The outcomes of patients with nondiagnostic results were analyzed. Clinical parameters, FNA procedural parameters, and histopathologic parameters were compared between diagnostic and nondiagnostic cases. A root cause analysis was performed using the fishbone diagram and the 5 Whys method. A total of 103 initial FNAs were identified. The nondiagnostic rates for initial and repeat biopsy were 16% (16/103) and 67% (2/3), respectively. Initial nondiagnostic FNAs were most frequently managed by clinical/radiologic follow-up only (56%, 9/16), followed by direct surgery (19%, 3/16) and repeat FNA (19%, 3/16). By histologic and clinical/radiologic follow-up, the risk of malignancy for nondiagnostic cases was zero. Palpation guidance (P < .05), inadequate sampling determined by rapid on-site evaluation (P < .01), and lesions with cystic, vascular, or diffuse nature (P < .05) were significantly associated with nondiagnostic results. By root cause analysis, proceduralist sampling error and lack of ultrasound guidance were the most common primary and secondary causes, respectively. Pediatric salivary gland lesions of the nondiagnostic MSRSGC category have minimal risk of malignancy and may be successfully managed by clinical/radiologic follow-up. The root causes for nondiagnostic results were often multifactorial and primarily related to proceduralist sampling, characteristics of the lesions, and lack of ultrasound guidance.

Diagnostic Accuracy of FNA to Determine HPV Status in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) changes prognosis and can alter the treatment plan. Biopsy with fine needle aspiration (FNA) of cervical adenopathy is often performed during initial workup for OPSCC patients. FNA is limited by the amount of tissue obtained via small needle diameter and frequently requires repeat biopsies to determine HPV status. We evaluated the diagnostic accuracy of FNA biopsies to determine HPV status. <h3>Materials/Methods</h3> Consecutive patients with known HPV-associated OPSCC at a single institution between 2015 and 2021 were retrospectively analyzed. Demographic, clinical, and pathologic details were extracted from the electronic medical record for descriptive statistics. Patients with lymph node metastases undergoing initial biopsy with FNA were included. Pathology samples underwent central review and immunohistochemistry staining for p16 was used as a surrogate marker for HPV status. <h3>Results</h3> Two hundred ninety new cases of OPSCC were evaluated. FNA of lymph node metastases was the initial diagnostic procedure in 153 (52.8%) patients with median age at diagnosis of 57.0 (range 31.7 – 82.0). The population was mostly male (90.2%) with tumors most commonly located in the base of tongue (45.1%) and tonsil (42.5%). Initial FNA was positive for malignancy in 115/153 (75.2%) patients and non-diagnostic in 38/153 (24.8%). P16 staining on diagnostic FNA showed: 54/115 (47.0%) p16 positive, 6/115 (5.2%) p16 negative, 55/115 (47.8%) p16 indeterminate. In patients without a diagnosis of malignancy or p16 indeterminate, repeat FNA was performed in 30/93 (32.3%) patients. Of the repeat FNA patients: 7/30 (23.3%) remained non-diagnostic for malignancy, 16/30 (53.3%) p16 positive, 7/30 (23.3%) p16 indeterminate. In summary, 93/153 (60.8%) patients undergoing initial FNA and 14/30 (46.7%) undergoing repeat FNA were non-diagnostic of malignancy or p16 indeterminate. The final yield of FNA biopsies to determine malignancy status or p16 status was 76/153 (49.7%). <h3>Conclusion</h3> HPV-associated OPSCC patients undergoing FNA for initial diagnosis frequently are not diagnostic for malignancy or are indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Subtype of atypia on cytology and risk of malignancy in pediatric thyroid nodules.

Thyroid nodules with atypia of undetermined significance (AUS) are challenging to manage because of their intermediate risk of malignancy. Subclassification of atypia can refine malignancy risk in adult AUS nodules but has not been evaluated in children. This was a retrospective cohort study of pediatric patients (<19 years old) who underwent fine-needle aspiration (FNA) of a thyroid nodule with resulting AUS cytology. Atypia was subclassified as nuclear only, architectural only, nuclear and architectural, or oncocytic. The primary outcome was the association between atypia subtype and malignancy. A secondary outcome was the association of atypia subtype with repeat FNA cytology. Sixty-eight AUS nodules in 61 patients were analyzed. The median age at FNA was 16.2 years (range, 9.8-18.9 years). Twenty-four nodules (35%) were malignant. Nuclear atypia only was present in 17 nodules (25%), architectural atypia only was present in 27 nodules (40%), nuclear and architectural atypia was present in 20 nodules (29%), and predominantly oncocytic features were present in 4 nodules (6%). The presence of nuclear atypia was associated with a significantly increased rate of malignancy (22 of 37 [59%] vs 2 of 31 [6.5%]; P < .001), whereas architectural atypia was not associated with malignancy (P = .8). Repeat FNA was performed in 42 of 68 nodules (62%). In nodules with initial nuclear and architectural atypia, benign repeat cytology had a high false-negative rate (3 of 6; 50%). Pediatric AUS nodules with nuclear atypia have a high rate of malignancy, but architectural atypia is not associated with malignancy. In nodules with nuclear atypia, repeat FNA may inform clinical decisions regarding the need for resection. In the absence of suspicious clinical features, nodules without nuclear atypia might be considered for observation rather than resection or repeat FNA.

Performance of repeat cytology with reflex ThyroSeq genomic classifier for indeterminant thyroid cytology.

The American Thyroid Association recommends either repeat fine-needle aspiration biopsy (FNAB) or molecular testing (eg, ThyroSeq) of Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) nodules to provide further risk stratification. How a testing algorithm that uses ancillary molecular tests performs as a reflex test for repeat sampling of indeterminant nodules remains unclear. Thyroid FNABs performed over a 24-month period that received a diagnosis of AUS/FLUS and underwent subsequent FNAB were analyzed. In total, 187 patients were identified who received an FNAB diagnosis of AUS/FLUS and had repeat sampling. Of these patients, 64% received a subsequent indeterminant diagnosis on repeat biopsy: 7 (3.7%) repeat biopsies were diagnosed as nondiagnostic/unsatisfactory, 104 (55.6%) were diagnosed as AUS/FLUS, and 8 (4.3%) were diagnosed as follicular neoplasm/suspicious for follicular neoplasm. Of the repeat biopsied nodules, 63% underwent subsequent testing with ThyroSeq version 3. The diagnostic performance was calculated using only surgically confirmed nodules (sensitivity, 100%; specificity, 30%; positive predictive value, 41%; negative predictive value, 100%) and by assigning nonresected nodules with negative ThyroSeq or benign cytology results as benign (sensitivity, 100%; specificity, 88%; positive predictive value, 41%; negative predictive value, 100%). In the majority of patients, repeat FNAB for AUS/FLUS did not preclude subsequent molecular ancillary testing because of the high rate of indeterminant results on repeat biopsy. The diagnostic performance of the testing algorithm reported here was very similar to other reports using either repeat biopsy or molecular testing alone. Ultimately, the algorithm of performing molecular testing on repeat indeterminant nodules increased the number of biopsies performed and lengthened the time to definitive risk stratification without a disproportionate decrease in the use of molecular testing or an appreciable improvement in diagnostic performance.

Comparison of Core Needle Biopsy and Repeat Fine-Needle Aspiration in Avoiding Diagnostic Surgery for Thyroid Nodules Initially Diagnosed as Atypia/Follicular Lesion of Undetermined Significance.

ObjectiveTo compare core needle biopsy (CNB) and repeat fine-needle aspiration (rFNA) to reduce the rate of diagnostic surgery and prevent unnecessary surgery in nodules initially diagnosed as atypia/follicular lesions of undetermined significance (AUS/FLUS).Materials and MethodsThis study included 231 consecutive patients (150 female and 81 male; mean age ± standard deviation, 51.9 ± 11.7 years) with 235 thyroid nodules (≥ 1 cm) initially diagnosed as AUS/FLUS, who later underwent both rFNA and CNB. The nodules that required diagnostic surgery after the biopsy were defined using three different scenarios according to the rFNA and CNB results: criterion 1, surgery for low-risk indeterminate (categories I and III); criterion 2, surgery for high-risk indeterminate (categories IV and V); and criterion 3, surgery for all indeterminate nodules (categories I, III, IV, and V). We compared the expected rates of diagnostic surgery between CNB and rFNA in all 235 nodules using the three surgical criteria. In addition, the expected rates of unnecessary surgery (i.e., surgery for benign pathology) were compared in a subgroup of 182 nodules with available final diagnoses.ResultsCNB showed significantly lower rates of nondiagnostic, AUS/FLUS, and suspicious for malignancy diagnoses (p ≤ 0.016) and higher rates of follicular neoplasm or suspicious for a follicular neoplasm (p < 0.001) and malignant diagnoses (p = 0.031). CNB showed a significantly lower expected rate of diagnostic surgery than rFNA for criterion 1 (29.8% vs. 48.1%, p < 0.001) and criterion 3 (46.4% vs. 55.3%, p = 0.029), and a significantly higher rate for criterion 2 (16.6% vs. 7.2%, p = 0.001). CNB showed a significantly lower expected rate of unnecessary surgery than rFNA for criterion 1 (18.7% vs. 29.7%, p = 0.024).ConclusionCNB was superior to rFNA in reducing the rates of potential diagnostic surgery and unnecessary surgery for nodules initially diagnosed as AUS/FLUS in a scenario where nodules with low-risk indeterminate results (categories I and III) would undergo surgery.

Approach to Bethesda system category III thyroid nodules according to US-risk stratification.

This study evaluated how to manage Bethesda category III (Bethesda III) (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) thyroid nodules according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) to reduce unnecessary surgeries. A total of 161 thyroid nodules diagnosed as Bethesda III underwent surgery from 2016 to 2019. Ultrasonography-guided fine-needle aspiration (US-FNA) or core needle biopsy (CNB) was used for repeat examination. K-TIRADS category was assigned to the thyroid nodules. The proportion of malignancy in Bethesda III nodules confirmed by surgery were significantly increased in proportion relative to K-TIRADS with 60.0% low suspicion, 88.2% intermediate suspicion, and 100% high suspicion nodules (p < 0.001). The proportion of malignancy in AUS and FLUS were significantly different (94.2% vs. 40.0% p = 0.003). The proportion of malignancy in AUS increased with K-TIRADS categories, but there was no difference in FLUS. All K-TIRADS high suspicion nodules were AUS as papillary carcinomas (99%), while 80% of FLUS nodules and 50% of follicular carcinomas showed K-TIRADS low suspicion. In 116 nodules with repeat FNA or CNB after initial Bethesda III results, the conclusive result rate was significantly increased in proportion to K-TIRADS with 58.3% low suspicion, 83.3% intermediate suspicion, and 88.8% high suspicion nodules (p = 0.015). K-TIRADS low suspicion nodules of Bethesda III nodules should be managed after risk-benefit consideration rather than immediate surgery or repeat examination. K-TIRADS for Bethesda III nodules can predict papillary carcinoma well, but not follicular carcinoma.

May 25-31, International thyroid awareness week &amp; May 25, world thyroid day, 2022: Indetermination of indeterminate cytology, aus/flus, fn, susp, in thyroidology?

May 25, World Thyroid Day, WTD, was officially accepted at the Annual General Meeting of the European Thyroid Association (ETA) before the September 2007 Congress in Leipzig, Germany. Although the date also refers to the establishment day of ETA in 1965, the aim is to create awareness about thyroid diseases on this day. After World Thyroid Day was first celebrated by ETA, in 2010, the American Thyroid Association (ATA) declared its support for this day. In addition, on May 25-31, International Thyroid Awareness Week, ITAW, is celebrated worldwide with the mentorship of Thyroid Federation International. The "thyroid gland", commonly used terminology simply "thyroid", is an important endocrine organ localized in front of the neck, extending laterally on both sides. This butterfly-shaped and delicate (1) vital organ is responsible for many metabolic activities that are critical for the organism through the secretion of thyroid hormones. Therefore, "thyroid health" becomes extremely important. As such, thyroid gland disorders continue to affect all age groups globally and possess a wide spectrum of signs and symptoms. Among these, hypothyroidism (abnormally decreased thyroid activity), thyrotoxicosis with or without hyperthyroidism (abnormally increased thyroid activity), goiter (enlargement of the thyroid gland), congenital thyroid diseases, thyroiditis (inflammation of the thyroid gland), retro/substernal goiter (gland growth and extension behind the sternum), follicular nodular thyroid disease with primary and secondary thyroid carcinomas are noteworthy. Family history, genetic and familial predisposition, radiation exposure to the head &amp; neck and thorax region during the first two decades particularly in children and women (0-20 years of age), iodine deficiency, and some drugs such as amiodarone are known as the leading factors to the thyroid gland disorders. Nevertheless, the Public Health Update reported that more than 200 million people worldwide are facing thyroid disorders, and over 50% of them remain undiagnosed. To achieve an accurate diagnosis for disorders and also carcinomas with their metastasis and recurrences before histopathology and during postoperative follow-up of this small, delicate, and papillon vital organ that can affect the whole organism: (i) biochemical essays (fT3, fT4, tT3, tT4, TSH, Tg, antiTg, antiTPO, calcitonin, TSI/TRAb, US-guided-Tg/calcitonin washout); (ii) imaging modalities (sonography, strain, and shear wave elastography, SWE, scintigraphy and CT, MRI, 18-FDG PET/CT, and 131I-WBS, when necessary) and (iii) cytopathologic examinations have been utilized. However, thyroid and neck US and cytopathological examination, in particular, still maintain their importance today. Indeterminate cytology (Category III, IV, V, The Bethesda System for Reporting Thyroid Cytopathology, TBSRTC, 1st and 2nd ed.s) (2,3) in cytopathology and follicular nodular thyroid disease, in general, is one of the controversial topics which remains to be a significant topic in Thyroidology (4,5). The latest ATA guidelines, 2015 ATA Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (6), recommended repeat FNA cytology, molecular tests with further surveillance or diagnostic surgery, considering worrisome sonographic and clinical features with patient preference, as novel approaches in Endocrine Surgery, Endocrine Pathology, and Thyroidology to resolve the challenging issue, Category III, TBSRTC (AUS/FLUS, atypia of undetermined/follicular lesion of undetermined significance), which is at the center of the aforementioned controversion (Recommendation 15A, Weak recommendation, Moderate-quality evidence; 15B, Strong recommendation, Low-quality evidence). Of note, some authors and authorities have advocated the potential need for separation in TBSRTC in terms of Category III, AUS/FLUS (7,8,9). We very recently also postulated the so-called subdivision concept in Category III, TBSRTC, id est, (i) Category IIIA: AUS/FLUS without nuclear atypia (AUS/FLUS wo NA), and (ii) Category IIIB: AUS/FLUS with nuclear atypia (AUS/FLUS w NA) within the possible forthcoming 3rd ed., the 202X TBSRTC (10,11). Mater artium necessitas. Therefore, a novel risk of malignancy, ROM, for each diagnostic category of possible forthcoming TBSRTC would selectively enrich the different management proposals in Thyroidology. As a matter of fact that this issue merits further investigation. Bene diagnoscitur bene curatur.. Dum vivimus servimus..

BRAFV600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

BackgroundThe BRAFV600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large‐scale analysis from a single institute to evaluate the accuracy of combined fine‐needle aspiration (FNA) and BRAFV600E mutation tests for PTC diagnosis.MethodsA total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAFV600E mutation analysis on FNA specimens were enrolled. The association between the BRAFV600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAFV600E mutation results. The diagnostic efficacy of the BRAFV600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results.ResultsThe cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I–VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAFV600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I–VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAFV600E‐positive and 4.3% of the BRAFV600E‐negative specimens with an initial indication of cytological non‐malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAFV600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAFV600E mutation test with cytology. BRAFV600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size.ConclusionsThe BRAFV600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA.

Clinical practice patterns in the management of thyroid nodules: The first survey from the Middle East and Africa

Objective: We sought to scope the practices in managing thyroid nodules in the Middle East and Africa (MEA). Materials and Methods: Survey of a convenience sample of physicians concerned with the management of thyroid disease. Results: Two hundred and twelve responses are included. Fine needle aspiration (FNA) is performed chiefly using ultrasound guidance (74.9%), generally by radiologists (47.1%). Respondents have a lower threshold for FNA than recommended. Management depends on the FNA cytology, with the follicular lesion of undetermined significance/atypia of undetermined significance resulting in repeat FNA for cytology (40.7%), immediate referral for thyroid surgery (32.9%), or molecular testing (13.2%). Follicular neoplasms are referred for lobectomy or total thyroidectomy by 81.6% of respondents. Nodules suspicious for malignancy are referred for thyroid surgery by 76.6% and for molecular testing by 20.1%. Respondents are less likely to perform FNA in an octogenarian than a younger patient with a comparable nodule. For a multinodular goiter, 29.9%, 25.9%, or 17.8% of respondents would, respectively, sample the largest 2–3 nodules, single largest nodule, or all nodules &gt;1 cm in size. During pregnancy, respondents would perform FNA with nodular growth (27.1%) in the absence of nodular growth (25.6%), but more respondents (35.2%) would defer FNA until after pregnancy. Conclusions: The physicians' survey revealed a practice pattern in managing thyroid nodules in the MEA region, including both agreements and deviations from current guidelines. Focused quality assurance exercises, education, and research are needed.

Value of Thyroid Imaging Reporting and Data System in Initial Bethesda Category III Thyroid Nodules

Background. To evaluate the role of Thyroid Imaging Reporting and Data System (TI-RADS) in predicting malignancy for cytological Bethesda system III nodules. Method. The study included 188 thyroid nodules with first Bethesda system III cytology on surgery or repeat FNA. Patients' clinicopathologic parameters and ultrasonographic (US) nodule characteristics were evaluated according to benignity and malignancy. Using the TI-RADS classification system, thyroid nodules were categorized. Results. The size of malignant nodules was significantly lower than that of benign nodules ( P &lt; 0.001). Thyroid nodules associated with concomitant thyroid carcinoma had a significantly increased risk of malignancy ( P &lt; 0.001). Univariate analysis indicated that there were significant differences in the images of benign and malignant nodules in terms of solid composition, hypoechogenicity or marked hypoechogenicity, a taller-than-wide or irregular shape, ill-defined margins, and microcalcifications presence ( P &lt; 0.05). TI-RADS categories 4c (OR = 8.3, 95% CI 3.8–18.1; P = 0.043) and 5 (OR = 9.4; 95% CI 1.2–74.2; P = 0.026) were predictive for malignancy. Conclusions. The TI-RADS US evaluation may assist the physician in deciding whether to proceed with follow-up, repeating FNA, or surgical intervention.