Fine Needle Aspiration Of Thyroid Nodules Research Articles

Pilot imaging study of o-BMVC foci for discrimination of indeterminate cytology in diagnosing fine-needle aspiration of thyroid nodules

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.

Clinicopathologic features of thyroid neoplasm with THADA-IGF2BP3 fusion

Abstract Introduction/Objective Thyroid adenoma-associated (THADA)-IGF2BP3 fusions is related to strong overexpression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA and protein, increased IGF2 translation and IGF1 receptor signaling via PI3K and MAPK pathways. THADA-IGF2BP3 have been identified as an oncogenic event in thyroid neoplasms, but the clinicopathologic features have not been greatly evaluated. The purpose of this cases review is to describe the clinical and pathologic findings of thyroid nodules with THADA-IGF2BP3 fusion on molecular testing. Methods/Case Report Surgical Pathology 220 cases of total and hemithyroidectomy from January 2018 to December 2019 were reviewed for cytology fine needle aspiration (FNA), molecular testing results and surgical resection pathology. Results (if a Case Study enter NA) Three cases of THADA-IGF2BP3 fusion identified by Thyroseq testing from FNA of thyroid nodules with all diagnosed as atypia of undetermined significance, Bethesda category 3. No other mutations or gene fusions are identified. Successive surgical interventions are performed. Case 1 is a 49-year-old female right hemithyroidectomy with pathologic diagnosis of papillary thyroid carcinoma (PTC) follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathological stage is pT1b pN0. Case 2 is a 71-year-old female total thyroidectomy and the pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, one lymph node evaluated is not involved by tumor and pathologic stage is pT1b pN0. Case 3 is a 76-year-old male left hemithyroidectomy and pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathologic stage is pT1b pN0. Conclusion THADA-GF2BP3 fusion is uncommon in thyroid neoplasms and only three cases are detected in 220 cases evaluated. The three cases of thyroid nodules are all diagnosed as AUS by FNA, and all are diagnosed as PTC follicular variant with capsular invasion upon resection without lymphvascular invasion or lymph node involvement. THADA-F2BP3 fusion is associated with thyroid carcinoma, with low-risk non-aggressive behavior, conservative surgery appears necessary and lobectomy is likely adequate.

NTRK3-rearranged thyroid carcinoma, clinical and pathologic features

Abstract Introduction/Objective NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions. Methods/Case Report The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021. Results (if a Case Study enter NA) Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b. Conclusion Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.

Diagnostic Accuracy of Fine Needle Aspiration Cytology in Thyroid Nodules in Thammasat University Hospital

Background: Fine needle aspiration (FNA) cytology is a key investigation of thyroid nodules. There are several reports of FNA accuracy, which ranges from 75.0% to 94.8%, while false negative rates are 5.8% to 21.5%. In Thailand, there is no available data of FNA accuracy according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The present study reported single-institute data of FNA accuracy, that could be used in thyroid nodule management. Objective: To determine the diagnostic accuracy of FNA cytology results of thyroid nodules collected in Thammasat University (TU) Hospital. Materials and Methods: The present study was a retrospective study collected cytologic results of all thyroid nodules that subsequently had definitive histopathologic diagnoses. The data were gathered from clinics at TU Hospital that performed thyroid nodule FNA between May 2011 and November 2014. The FNA cytology results were classified according to TBSRTC. Each cytopathologic result was compared with its postoperative tissue histopathology. The malignancy rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: The present study included 197 thyroid nodule FNA cytology results. The sensitivity and specificity were 77.8% and 65.4%, respectively. The calculated PPV was found to be 47.7%, and the NPV was 87.9%. The accuracy of these results was 69.0%. The malignancy rate of the unsatisfactory group was 6.25%, benign group 8.05%, atypia of undetermined significance or follicular lesion of unknown significance 22.22%, follicular neoplasm/suspicious for follicular neoplasm 14.20%, suspicious for malignancy 73.68%, and malignant 100%. Conclusion: The FNA cytology in TU Hospital has comparable sensitivity to the other studies. Interestingly, the malignancy rate in the follicular neoplasm category is lower than that of the other institutes because of a high false positive rate in this category. This causes lower specificity and accuracy, which may cause a higher rate of unnecessary operations. Keywords: FNA; Thyroid nodule; Diagnostic accuracy

A Computer-Aided Diagnosis System and Thyroid Imaging Reporting and Data System for Dual Validation of Ultrasound-Guided Fine-Needle Aspiration of Indeterminate Thyroid Nodules.

PurposeThe fully automatic AI-Sonic computer-aided design (CAD) system was employed for the detection and diagnosis of benign and malignant thyroid nodules. The aim of this study was to investigate the efficiency of the AI-Sonic CAD system with the use of a deep learning algorithm to improve the diagnostic accuracy of ultrasound-guided fine-needle aspiration (FNA).MethodsA total of 138 thyroid nodules were collected from 124 patients and diagnosed by an expert, a novice, and the Thyroid Imaging Reporting and Data System (TI-RADS). Diagnostic efficiency and feasibility were compared among the expert, novice, and CAD system. The application of the CAD system to enhance the diagnostic efficiency of novices was assessed. Moreover, with the experience of the expert as the gold standard, the values of features detected by the CAD system were also analyzed. The efficiency of FNA was compared among the expert, novice, and CAD system to determine whether the CAD system is helpful for the management of FNA.ResultIn total, 56 malignant and 82 benign thyroid nodules were collected from the 124 patients (mean age, 46.4 ± 12.1 years; range, 12–70 years). The diagnostic area under the curve of the CAD system, expert, and novice were 0.919, 0.891, and 0.877, respectively (p < 0.05). In regard to feature detection, there was no significant differences in the margin and composition between the benign and malignant nodules (p > 0.05), while echogenicity and the existence of echogenic foci were of great significance (p < 0.05). For the recommendation of FNA, the results showed that the CAD system had better performance than the expert and novice (p < 0.05).ConclusionsPrecise diagnosis and recommendation of FNA are continuing hot topics for thyroid nodules. The CAD system based on deep learning had better accuracy and feasibility for the diagnosis of thyroid nodules, and was useful to avoid unnecessary FNA. The CAD system is potentially an effective auxiliary approach for diagnosis and asymptomatic screening, especially in developing areas.

Development of a Molecular Assay for Detection and Quantification of the BRAF Variation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens

Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/μL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy. This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

Ultrasonography and Fine-Needle Aspiration in Indeterminate Thyroid Nodules: A Systematic Review of Diagnostic Test Accuracy.

Sonographic risk criteria may assist in further prognostication of indeterminate thyroid nodules (ITNs). Our aim was to determine whether sonographic criteria could further delineate the post-test probability of malignancy in ITNs. Meta-analysis of diagnostic test accuracy. A systematic review of Web of Science, MEDLINE, EMBASE, and CINAHL was performed from inception to April 15, 2021. Eligible studies included those which reported ultrasonographic evaluations with the American Thyroid Association (ATA) or the Thyroid Imaging Reporting and Data System (TIRADS) in adult patients with ITNs. ATA or TIRADS were scored as low (negative) or high (positive) malignancy risk using a previously validated binary classification. Primary outcomes included pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio for all sonographic criteria. Studies were appraised using Quality Assessment of Diagnostic Accuracy Studies and the data were pooled using bivariate random-effects models. Seventeen studies were included in the analysis. For Bethesda III, ATA had a specificity (0.90, 95% confidence interval (CI): 0.74-0.94), but a sensitivity of 0.52 (95% CI: 0.25-0.77). Conversely, K-TIRADS had the highest sensitivity (0.78, 95% CI: 0.62-0.89) with a specificity of 0.53 (95% CI: 0.31-0.74). Furthermore, American College of Radiology and EU TIRADS had specificities of 0.60 (95% CI: 0.36-0.80) and 0.81 (95% CI: 0.73-0.87) with sensitivities of 0.70 (95% CI: 0.37-0.90) and 0.38 (95% CI: 0.20-0.60), respectively. There were few studies with Bethesda IV nodules. Though dependent on malignancy rates, Bethesda III nodules with low-suspicion TIRADS features may benefit from clinical observation, whereas nodules with high-suspicion ATA features may require molecular testing and/or surgery. NA Laryngoscope, 132:242-251, 2022.

Factors Responsible for Non-Diagnostic Cytology on Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

IntroductionFine-needle aspiration (FNA) is a well-recognized procedure for the diagnosis of thyroid nodules, with the advantage of being safe and inexpensive. Fine-needle aspiration cytology (FNAC) is mainly performed for nodules showing suspicious sonographic features that may require thyroidectomy. Even when FNAC is performed under sonographic guidance, the cytological specimen obtained may be inadequate, leading to a non-diagnostic outcome. The aim of this study is to determine the sonographic and technical factors influencing the outcome of FNAC.Material and methodsThis cross-sectional study was conducted prospectively at the radiology department, Dr. Ziauddin Hospital, Karachi, from January 1, 2019, to December 31, 2020. This study was approved by the Ethical Review Committee (ERC) of Ziauddin University. All the patients undergoing ultrasound (US)-guided FNAC of thyroid nodules were included. Patients with a history of previous thyroid surgery, very large thyroid lesions (>5 cm), and those with adjacent soft tissue pathology obscuring the assessment of thyroid nodules were excluded from this study.ResultOut of 176 nodules studied, 14 were non-diagnostic and 162 were diagnostic. A 22G needle was used in most of the patients, i.e. 102 (57.3%), which demonstrated no relationship with the non-diagnostic results. According to Bethesda, 136 (77.3%) patients were benign, 22 (12.5%) had lesions with atypia/follicular lesions of undetermined significance, 14 (8%) were non-diagnostic and four (2.3%) were suspicious for malignancy. A subset, including 76 nodules, was categorized according to Thyroid Imaging Reporting and Data System (TIRADS) as follows: 28 (36.8%) nodules were moderately suspicious, 24 (31.6%) were mildly suspicious, 20 (26.3%) were not suspicious, and four (5.3%) nodules were benign. It was also observed that none of the hypoechoic nodules yielded non-diagnostic cytology.ConclusionThis study concludes that radiologists must be aware of the technical details, cytologic preparation, and procedure-related complications associated with US-guided FNA to optimize patient care and the diagnostic outcome.

Inadvertent Excessive Soy Intake as Part of a Weight Loss Program Leading to Rapid Growth of Multinodular Goiter

Background: Over the past few decades consumption of soy products has gained popularity in the U.S. in part due to reports of potential health and weight loss benefits. However, concerns have emerged regarding soy as a potential endocrine-disrupting chemical (EDC) leading to thyroid dysfunction amongst other health issues. Studies have shown a potential association of high soy intake with risk of hypothyroidism and simple goiter (1), but less is known regarding its impact on multinodular goiter. Clinical Case: A 33-year-old female originally from Bolivia without significant medical history presented to our endocrine clinic with complaints of right-sided neck swelling. The swelling was insidious in onset, had gradually increased in size over the past 3-4 months, and become uncomfortable. She denied dysphagia, cough, or shortness of breath. Prior to the onset of symptoms, she had enrolled in a commercial weight loss program. The diet program consisted of limiting caloric intake to multiple meal replacement bars during the day followed by a light dinner of fish and non-starchy vegetables. Examination revealed a palpable right-sided thyroid mass and enlarged thyroid gland. Lab work showed normal TSH, fT4, and T3 levels, positive anti-thyroid peroxidase antibody (anti-TPO Ab) 588 (<=35.0 IU/ml), and negative thyroid-stimulating immunoglobulins (TSI). Ultrasound of the thyroid confirmed the presence of a 4 cm dominant right thyroid nodule and multinodular goiter. Subsequent fine-needle aspiration of thyroid nodule was consistent with benign nodular goiter. Upon further investigation, it was discovered that the meal replacement bars contained a significant amount of soy protein resulting in an excessive intake of 20-40 grams of soy protein daily. We discussed treatment options, and the patient declined thyroid surgery in favor of surveillance following discontinuation of the weight loss products. The patient was advised to consume a varied diet and given follow-up appointments for monitoring. Conclusion: Inadvertent excessive soy intake via meal replacement bars may have triggered the rapid growth of a multinodular goiter in our patient despite reported adequate dietary iodine intake. Soy products often contain isoflavones that may exert an adverse effect on the thyroid by inhibition of TPO, disruption of iodine metabolism, and/or estrogenic activity. We advise that caution be exercised with high soy protein consumption especially in patients with underlying risk factors for multinodular goiter.

Real-life use of BRAF-V600E mutation analysis in thyroid nodule fine needle aspiration: consequences on clinical decision-making.

This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at -20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.

Impact of Electronic Consultation on Timeliness and Guideline Concordance of Workups Leading to Thyroid Nodule Fine-Needle Aspiration Biopsy

ObjectiveElectronic consultations (e-consults) are commonly used to obtain endocrinology input on clinical questions without a face-to-face visit, but sparse data exist on the resultant quality of care for specific conditions. We examined workups resulting in a thyroid nodule fine-needle aspiration (FNA) biopsy to investigate whether endocrinology e-consults were more timely and similarly guideline-concordant compared with endocrinology face-to-face visits and whether endocrinology e-consults were more guideline-concordant compared with workups without endocrinology input. MethodsWe retrospectively reviewed charts of 302 thyroid FNA biopsies conducted in the Veterans Affairs health system between May 1, 2017, and February 4, 2020 (e-consult, n = 99; face-to-face visit, n = 100; no endocrinology input, n = 103). We used t tests to compare timeliness, χ2 tests to compare the proportion of guideline-concordant workups, and multivariable linear and logistic models to control for demographic factors. ResultsFNAs preceded by an endocrinology e-consult had more timely workups compared with those preceded by endocrinology face-to-face visits in terms of days elapsed between referral and FNA biopsy (geometric mean 44.7 days vs 61.7 days, P = .01). The difference in the summary measure of guideline concordance across groups was not statistically significant (P =.38). ConclusionE-consults were faster than face-to-face consults and similarly guideline-concordant compared with both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about the appropriate use of e-consults for thyroid nodules should take into account these data while also considering the potential benefits of direct patient-endocrinologist interaction for complex situations.

Pediatric adaptions are needed to improve the diagnostic accuracy of thyroid ultrasound using TI-RADS

Background/PurposeThyroid Imaging Reporting and Data System (TI-RADS) is validated in adults but not yet in children. The purpose of this study was to determine the sensitivity, specificity, and accuracy of TI-RADS in predicting thyroid malignancy for pediatric nodules, and to compare the diagnostic accuracy to the current American Thyroid Association (ATA) guidelines. MethodsA single institution retrospective review was performed of patients younger than 21 years who underwent thyroid nodule fine needle aspiration biopsy (FNAB). Two radiologists were blinded to the pathology and independently classified all biopsied thyroid nodules based on TI-RADS. ATA and TI-RADS guidelines were analyzed to determine the diagnostic sensitivity and specificity of both scoring systems. Results115 patients (median age 15.5 years, 90 females) with 138 nodules were scored using TI-RADS. There was moderate inter-rater agreement between radiologists (Kappa = 0.51; p < 0.0001). Evaluating several potential TI-RADS criteria, 23.2%-68.1% of nodules were recommended for FNAB, compared to 82.6% of nodules using ATA guidelines. Using TI-RADS ≥ 3 (without size cutoff) as an indication for FNAB had 100% sensitivity with no missed suspicious or malignant nodules on cytology or pathology. ConclusionsUsing TI-RADS for diagnostic management of pediatric thyroid nodules improves accuracy in predicting malignancy.

Factors affecting thyroid nodule fine needle aspiration non\u2010diagnostic rates: a retrospective association study of 1975 thyroid biopsies

BackgroundThyroid nodules are common in clinical practice, and it is important to distinguish benign nodules, the vast majority, from malignant ones. Non-diagnostic (ND) samples have the potential to delay or mis-diagnose or lead to unnecessary surgeries, and it is important to examine what factors influence the ND rate. Prior literature has suggested that the impact of bedside cytology on ND rate is dependent on the initial adequacy rate, whereby higher ND rates benefit most from bedside cytology. We aim to compare the impact of bedside adequacy review between specialist groups who perform high volume thyroid biopsies with low initial ND rates.MethodsWe reviewed the cytopathology results of 1975 thyroid nodule FNAs performed between January 1, 2017 to December 31, 2017 in a multi-centre Canadian city, and the corresponding histopathology reports of 340 resected nodules. Descriptive variables were used to describe the data along with chi-squared testing and univariate logistic regression.ResultsThe FNA biopsies were performed by three different speciality groups, which differed by procedural volume: radiology performed the most at 1171, pathology performed 655 and surgery performed 103. We could not define the operator for 45 of the nodules. The ND rate was lowest in the speciality groups with highest procedural volume, 3.4 % in pathology and 8.3 % in radiology, compared to 37.9 % in surgery (p < 0.001). Completion of bedside cytology rapid onsite evaluation (ROSE) significantly reduced the ND rate from 16.7 to 4.2 % for all samples (p < 0.001). When ROSE was compared with non-ROSE within a high procedural group (radiology), it further reduced the ND rate from 12.5 to 5.1 % (p < 0.001). Of the 340 resected nodules, 10.7 % (18) were in the ND category, of which 28 % (5/18) of these were found to be malignant (4 papillary carcinoma and 1 lymphoma).ConclusionsThe results from this study demonstrate that thyroid FNAs performed with bedside ROSE can significantly reduce the ND rate compared with non-ROSE, even in experienced groups with low initial ND rates. It is therefore imperative that care providers managing patients with thyroid nodules ensure that thyroid FNAs are referred to specialized individuals/groups who do high volume, and ideally with the use of bedside ROSE, whether provided by a cytotechnologist or a pathologist.

Diagnostic Lobectomy for Bethesda III Thyroid Nodules: Pathological Outcomes and Risk Factors for Malignancy.

An indeterminate thyroid nodule fine-needle aspiration (FNA) presents a unique dilemma. We evaluated our institution's experience with Bethesda III thyroid nodules, including the risk of malignancy (ROM) of these nodules removed for diagnostic lobectomy and radiologic and clinical risk factors for malignancy. Retrospective chart review. San Antonio Military Medical Center (SAMMC; 483 bed Military Treatment Facility and Level 1 Trauma Center). We identified all patients with a Bethesda III thyroid FNA at our institution from 2010 to 2018 and determined which nodules were removed. The final histological diagnosis was recorded. Whether or not age, gender, body mass index (BMI), race, nodule size, margin regularity, rate of nodule growth, vascularity, internal calcifications, family history of thyroid cancer, personal history of radiation, and history of repeated AUS/FLUS on FNA had a significant impact on malignancy risk was evaluated with chi square and rank sum Wilcoxon tests. 492 patients had 1 or more AUS result. 52% (258/492) underwent repeat FNA. This resulted in Bethesda II or III in 90% (232/258). In 10% (26/258), the repeat FNA resulted in a higher Bethesda grade. 183 lobectomies were performed on the side containing an AUS nodule. The malignancy percentage was 38.3% (70/183). Age less than 30 was the only variable showing statistical significance for increased risk of malignancy (P = .04). The ROM of nodules characterized as AUS/FLUS on FNA may be higher than expected. Age may be a better predictor of malignancy than repeat FNA.

Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?

To verify the cytopathological Bethesda System classification of thyroid nodule fine-needle aspiration biopsy (FNAB) in MTC patients and to assess the role of preoperative serum calcitonin (CT) levels in the investigation of this neoplasm in medullary thyroid cancer (MTC) patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer). This is a cross-sectional review of medical records of patients monitored at the thyroid cancer outpatient clinic of Uopeccan. Clinical and demographic data, laboratory tests, ultrasound images, and cytopathological findings of MTC patients were evaluated. Among the 360 patients with thyroid cancer monitored in the outpatient clinic, 5.2% (n: 19/360) had MTC. The hereditary form was more prevalent (63.2%), and there was no sex preference. The most common ultrasound findings were hypoechogenicity, solid appearance and microcalcifications. The FNAB diagnoses showed a sensitivity of 47.1%, and the most common cytopathological report was Bethesda category III. Serum CT levels showed good sensitivity (84.6%) for the diagnosis of MTC, and sensitivity levels were directly associated with the size of the nodule and distant metastases. Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB.

The value of repeating fine-needle aspiration for thyroid nodules.

BACKGROUND: Fine-needle aspiration (FNA) is an invaluable technique used in the evaluation of thyroid nodules.OBJECTIVES: Evaluate the concordance of results for consecutive FNA readings.DESIGN: Retrospective, descriptive.SETTINGS: Two tertiary care centers.METHODS: Demographics were collected along with every FNA result and final pathology results for all patients (aged 9-90 years old) who underwent thyroid surgery from 2010 to 2017. The Bethesda system was used for cytology. Agreement levels were calculated and compared with final pathology.SAMPLE SIZE: Of 1237 initially included, 1134 had at least one FNA performed with results available for review.RESULTS: For the 1134 patients, demographic and clinical data were collection and a comparison was made between the three FNA results; the highest agreement was between FNA 2 and 3 (53.6%); however, the kappa value was consistently low for all comparisons, indicating a poor level of agreement overall. Also, the risk of malignancy was higher in this study than in the 2017 Bethesda system for reporting thyroid cytopathology in FNA cytology categories I and II.CONCLUSION: Repeating FNA biopsies yield different results every time; hence, there is a low level of agreement. The clinical decision should therefore include other important risk factors. Prospective studies could help shed more light on this topic.LIMITATIONS: Retrospective design.CONFLICT OF INTEREST: None.

Thyroid Cancer Identified After Positron Emission Tomography (PET) Shows Aggressive Histopathology

BackgroundIncidental thyroid nodules with focal uptake on positron emission tomography (PET) have an increased risk for malignancy, with the majority being differentiated thyroid cancer (DTC). It is unclear whether these cancers have more aggressive histopathology compared with DTC diagnosed via other means. MethodElectronic medical record of two medical centers was queried for the period of 2001-2016 to identify patients who underwent PET imaging for nonthyroid-related indications and who were found to have focal thyroid uptake. Patients who underwent thyroid nodule fine needle aspiration biopsy (FNAB) and subsequent thyroidectomy with a final diagnosis of DTC were further reviewed. A comparison group, matched for age, tumor type, and tumor size, was selected from consecutive patients who underwent surgery for DTC. ResultsAmong 35,124 PET scans reviewed, 227 (0.6%) patients were found to have focal thyroid uptake and underwent FNAB: Fourty-seven (21%) were found to have cancer (36 papillary thyroid cancer (PTC), 9 metastases, and 2 lymphoma). Sixty-seven patients proceeded to surgery: Thirty-one with FNAB of PTC and the rest with indeterminate FNAB necessitating diagnostic thyroidectomy. Compared with the control group, the PET PTC patients involved more men (54% versus 26%, P = 0.003), had more advanced tumor stage (P = 0.03), and had increased BRAF mutation on final pathology (78% versus 42%, P = 0.05). ConclusionsThis study demonstrates that DTC detected on PET is most commonly of the papillary type. Despite the small sample size, the results suggest that these PTC may be more aggressive than PTC detected through other means and more frequently harbor BRAF mutations.

Patient Discomfort in Relation to Thyroid Nodule Fine-Needle Aspiration (FNA) Performed with or without Parenteral and/or Topical Anesthetic

There is much reported variation in the impact of local anesthesia on thyroid fine-needle aspiration (FNA) related discomfort. We compare patients undergoing thyroid FNA with subcutaneous injection or topical anesthetic to no anesthetic. We conducted a retrospective review of 585 sequential ultrasound guided thyroid FNA procedures in Mayo Clinic. Group 1 (n = 200), no anesthetic; Group 2 (n = 185), subcutaneous injection anesthetic; and Group 3 (n = 200), topical anesthetic. Patient demographics, number of FNA passes, needle gauge, and cytopathology were recorded plus a discomfort score (0 to 10) before and immediately post procedure in all 3 groups and peak discomfort during the FNA in Groups 1 and 2. There were no differences among the 3 groups in age, sex, FNA sufficiency rate, cytopathology, and FNA passes number. There was no significant difference between Groups 1 and 2 in peak discomfort score during the FNA: 0 (45%, 42.2%), 1 to 2 (19%, 24.9%), 3 to 5 (23.5%, 20.5%), 6 to 8 (9.5%, 10.8%), 9 to 10 (3%, 1.6%), respectively. Discomfort score post procedure: 0 (78.5%, 77.8%, 53.5%), 1 to 2 (13%, 13%, 36.5%), 3 to 5 (7%, 7%, 9%), 6 to 8 (1.5%, 2.2%, 1%), 9 to 10 (0%, 0%, 0%) for groups 1, 2, and 3, respectively. There were no significant differences among the 3 groups for a discomfort score ≥3. FNA associated patient discomfort was comparable during and after the procedure regardless of the use of anesthetic or the type utilized. Approximately 90% of patients experienced mild to moderate discomfort during the procedure. And 90% reported no more than a level 2 discomfort post procedure. End = endocrinology; FNA = fine-needle aspiration; MCF = Mayo Clinic Florida; MCR = Mayo Clinic Rochester.

Comparison of core-needle biopsy and repeat fine-needle aspiration for thyroid nodules with inconclusive initial cytology.

We aimed to compare the efficacy of ultrasound-guided core-needle biopsy (CNB) with repeat fine-needle aspiration (rFNA) cytology in thyroid nodules with inconclusive results in initial fine-needle aspiration cytology. We studied 402 patients who required a repeat biopsy of thyroid nodules using ultrasound-guided CNB (n = 192) or rFNA (n = 210) because of inconclusive results in initial FNA, corresponding to categories I, III, and IV of the Bethesda System for Reporting Thyroid Cytopathology. If repeat biopsy results were benign (category II), suspicious malignancy (category V), or malignancy (category VI), they were defined as "diagnostic results". The diagnostic yield and performances of repeat biopsy were analyzed and compared between the rFNA and CNB groups. The diagnostic results were obtained significantly higher in the CNB group than in the rFNA group (72.4% vs. 52.4%; P < 0.001). In the subgroup analysis, the diagnostic results were significantly higher in the CNB group than in the rFNA group for patients of categories I and III (P < 0.001 in both) in initial FNA. However, in patients with category IV nodules, there were no significant differences in diagnostic results between the two groups (P = 0.46). Compared to rFNA, ultrasound-guided CNB is useful and effective as a repeat biopsy option for thyroid nodules with non-diagnostic results (category I) and atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (category III) in initial FNA.

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.