Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology.

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Stepwise analysis of thyroid diagnostic modalities with genomic imprinting detection.

BACKGROUND: The current preoperative malignancy risk evaluation for thyroid nodules involves stepwise diagnostic modalities including ultrasonography, thyroid function serology and fine-needle aspiration (FNA) cytopathology, respectively. We aimed to substantiate the stepwise contributions of each diagnostic step and additionally investigate the diagnostic significance of quantitative chromogenic imprinted gene in-situ hybridization (QCIGISH)-an adjunctive molecular test based on epigenetic imprinting alterations. METHODS: A total of 114 cytopathologically-diagnosed and histopathologically-confirmed thyroid nodules with complete ultrasonographic and serological examination records were evaluated using QCIGISH in the study. Logistic regression models for thyroid malignancy prediction were developed with the stepwise addition of each diagnostic modality and the contribution of each step evaluated in terms of discrimination performance and goodness-of-fit. RESULTS: From the baseline model using ultrasonography [area under the receiver operating characteristics curve (AUROC): 0.79; 95% confidence interval (CI): 0.71-0.86], significant improvements in thyroid malignancy discrimination were observed with the stepwise addition of thyroid function serology (AUROC: 0.82; 95% CI: 0.74-0.90; P=0.23) and FNA cytopathology (AUROC: 0.88; 95% CI: 0.81-0.94; P=0.02), respectively. The inclusion of QCIGISH as an adjunctive molecular test further advanced the preceding model's diagnostic performance (AUROC: 0.95; 95% CI: 0.91-1.00, P=0.007). CONCLUSIONS: Our study demonstrated the significant stepwise diagnostic contributions of standard clinical assessments in the malignancy risk stratification of thyroid nodules. However, the addition of molecular imprinting detection further enabled a more accurate and definitive preoperative evaluation especially for morphologically indeterminate thyroid nodules and cases with potentially discordant results among standard modalities.

Thyroid US-guided FNA techniques: A prospective,randomized controlled study.

BACKGROUND: Thyroid nodules are common in the general population. Ultrasonography is the most efficient diagnostic approach to evaluate thyroid nodules. The US FNAC procedure can be performed using either the short axis (perpendicular), or a long axis (parallel) approach to visualize the needle as it is advanced toward the desired nodule. The main aim of this study was to compare the percentage of non-diagnostic results between the long and short axis approach. METHODS: A prospective study that included a randomized controlled trial and was divided into two arms-the short axis and the long axis-was conducted. A total of 245 thyroid nodules were collected through the fine needle aspiration cytology, performed with ultrasound, from march 2021 to march 2022. The patient's demographic information were collected and also nodules characteristics. RESULTS: Of 245 nodules sampled, 122 were sampled with the long axis method, while 123 with the short axis method. There is not significantly less non diagnostic approach with either method compared to the other (11.5 % vs 16.3 % respectively). DISCUSSION: Previous studies came to the conclusion that the long axis method yields fewer non diagnostic samples. This study evaluated the two FNA approaches which were proceeded by the same physician who is expert in both techniques. CONCLUSION: The US FNAC performed in the long axis approach will not produce more conclusive results and less non diagnostic results (Bethesda category 1) than the short axis approach one.

Parathyroid fine needle aspiration with PTH washout: Can it lead to parathyroid cell seeding in primary hyperparathyroidism?

Although parathyroid fine-needle aspiration (P-FNA) with parathyroid hormone (PTH) washout is effective in detecting preoperative parathyroid lesions, it also presents risks such as fibrosis, hematoma, and, in rare cases, tumor seeding. This study aimed to investigate whether P-FNA with PTH washout leads to the seeding of parathyroid cells along the path of the needle. A retrospective analysis was conducted on patients undergoing minimally invasive parathyroidectomy guided by preoperative PTH washout. Permanent pathology reports, imaging data, and postoperative serum parathyroid hormone and calcium levels were assessed to determine the effectiveness and safety of the procedure. Complications following P-FNA with PTH washout were also reviewed using data from the patient registration system of Bulent Ecevit University. The procedure accurately localized parathyroid adenomas in 87 patients who underwent ultrasound-guided parathyroidectomy following preoperative P-FNA and PTH washout. Postoperatively, 75 patients showed normal parathyroid hormone and calcium levels. Two patients required secondary surgery for contralateral adenomas. Critically, there was no evidence of P-FNA with PTH washout-induced parathyromatosis or seeding during the follow-up. Effective adenoma localization is crucial for successful minimally invasive surgery of hyperparathyroidism. Our study indicates that combining preoperative P-FNAB with PTH washout and imaging enhances adenoma detection, especially when intraoperative PTH measurements are not available, thus improving surgical outcomes. Notably, we found no evidence of cell implantation after P-FNA, suggesting the safety and efficacy of this method for preventing parathyroid cell seeding.

Diagnostic value of transthoracic needle biopsy in lung tumors.

OBJECTIVE: Thoracic ultrasonography is widely used in imaging peripheral lesions and invasive interventional procedures. The aim of this study was to assess the diagnostic value of thoracic ultrasonography-guided transthoracic needle aspiration biopsy and the factors affecting the diagnosis of peripheral tumoral lung lesions. METHODS: The lesion size, biopsy needle type, number of blocks, complications, and pathology results were compared in 83 patients between January 2015 and July 2018. The cases with pathological non-diagnosis and definite pathological diagnosis were determined. For the assessment of the factors affecting diagnosis, the size of the lesions and the biopsy needle type were evaluated. Biopsy preparations containing non-diagnostic atypical cells were referred to a cytopathologist. The effect of the cytopathological examination on the diagnosis was also evaluated. RESULTS: Pathological diagnosis was made in 66.3% of the cases; cell type could not be determined in 22.9% of the cases, and they were referred to a cytopathologist. After the cytopathologist's examination, the diagnosis rate increased to 80.7%. Diagnosis rates were higher when using tru-cut than Chiba and higher in cases with tumor size >2 cm than smaller. CONCLUSION: Thoracic ultrasonography-guided transthoracic needle aspiration biopsy is a preferred approach to the diagnosis of peripheral tumoral lung lesions, given its high diagnostic rate, in addition to being cheap, highly suitable for bedside use, and safe, and the lack of radiation exposure.

Diagnostic value of high-frequency ultrasound combined with fine needle aspiration cytology and BRAF gene for papillary thyroid microcarcinoma.

We attempted to evaluate clinical application value of high-frequency ultrasound (HFUS), fine needle aspiration cytology (FNAC), BRAF gene, and combination of HFUS, FNAC, and BRAF gene in diagnosing papillary thyroid microcarcinoma (PTMC). The 150 patients with thyroid minimal lesions who underwent HFUS, FNAC and BRAF gene testing before surgery in our hospital from June 2020 to December 2021 were selected as research subjects. Patients were divided into two groups based on postoperative pathological results. The consistency of diagnostic results of HFUS, FNAC, and BRAF gene and their combination with those of pathological examination, diagnostic efficacy of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis, and diagnostic value of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis received analysis and comparison. The consistency of diagnostic results of combined detection with pathological examination exhibited elevation relative to that of HFUS, FNAC and BRAF gene detection alone (P < 0.05). The negative predictive value, sensitivity and accuracy of combined detection exhibited elevation relative to individual detection (P < 0.05). The AUC of combined detection in diagnosing PTMC lymph node metastasis exhibited elevation relative to that of HFUS and BRAF gene alone (P < 0.05). HFUS combined with FNAC and BRAF genes possesses high diagnostic value, with high diagnostic sensitivity, specificity, and accuracy. Thus, combined detection for PTMC before surgery can accurately determine whether lymph node metastasis occurs, reduce occurrence of missed diagnosis and misdiagnosis, and thus improve diagnostic precision.

Radiofrequency ablation is an effective treatment for Bethesda III thyroid nodules without genetic alterations.

Background: Radiofrequency ablation (RFA) is effective in the treatment of thyroid nodules, leading to a 50-90% reduction with respect to baseline. Current guidelines indicate the need for a benign cytology prior to RFA, though, on the other side, this procedure is also successfully used for the treatment of papillary microcarcinomas. No specific indications are available for nodules with an indeterminate cytology (Bethesda III/IV). Aim: To evaluate the efficacy of RFA in Bethesda III nodules without genetic alterations as verified by means of a custom panel. Methods: We have treated 33 patients (mean delivered energy 1069 ± 1201 J/mL of basal volume) with Bethesda III cytology, EU-TIRADS 3-4, and negative genetic panel. The mean basal nodular volume was 17.3 ± 10.7 mL. Results: Considering the whole series, the mean volume reduction rate (VRR) was 36.8 ± 16.5% at 1 month, 59.9 ± 15.5% at 6 months, and 62 ± 15.7% at 1-year follow-up. The sub-analysis done in patients with 1 and 2 years follow-up data available (n = 20 and n = 5, respectively) confirmed a progressive nodular volume decrease. At all-time points, the rate of reduction was statistically significant (P < 0.0001), without significant correlation between the VRR and the basal volume. Neither cytological changes nor complications were observed after the procedure. Conclusion: RFA is effective in Bethesda III, oncogene-negative nodules, with reduction rates similar to those obtained in confirmed benign lesions. This procedure represents a good alternative to surgery or active surveillance in this particular class of nodules, regardless of their initial volume. A longer follow-up will allow to evaluate further reduction or possible regrowth.

Evaluation of abdominal fat pad aspiration highlighting challenges to interpretation.

INTRODUCTION: Fine-needle aspiration (FNA) of abdominal fibroadipose tissue is a commonly utilized method for the detection of amyloidosis. While generally regarded as an accurate and specific detection method, the sensitivity is variable. The objective of this study was to investigate the performance of fat pad FNAs in detecting amyloidosis relative to other tissue biopsies. MATERIALS AND METHODS: Fat pad FNA results from January 1, 2014, to December 31, 2022, were catalogued. Clinical data including FNA indication were ascertained for each case. The results of any subsequent tissue biopsy/biopsies evaluated for amyloidosis by Congo red staining were also assessed. Challenges to diagnostic interpretation were explored. RESULTS: A total of 334 fat pad FNAs were identified. The most common indications were peripheral neuropathy (29.3%), cardiomyopathy/heart failure (28.1%), monoclonal gammopathy (27.8%), and multiple myeloma/lymphoplasmacytic lymphoma (21.0%). Cytologic interpretations were: 7 (2.1%) nondiagnostic, 284 (85.0%) negative, 18 (5.4%) indeterminate, 16 (4.8%) suspicious, and 9 (2.7%) positive for amyloid deposition. In our sample, 103 (30.8%) patients had Congo red testing performed on a subsequent surgical specimen(s) including: 3 of 7 of nondiagnostic cases, none which were positive on the subsequent surgical; 70 of 284 negative cases, 27 which were positive on the subsequent surgical; 11 of 18 indeterminate cases, 7 which were positive on the subsequent surgical; 13 of 16 suspicious cases, 2 which were positive on the subsequent surgical; and 6 of 9 positive cases, 3 which were positive on the subsequent surgical. Challenges to FNA interpretation included scant cellularity, focal staining/birefringence, and overstaining. CONCLUSIONS: It is best to view fat pad aspiration versus other tissue biopsy results as complimentary diagnostic tests that should be interpreted in the context of the clinical setting and overall clinical suspicion for amyloidosis.

The role of fine-needle aspiration biopsy in the diagnosis of malignant tumors.

Cytopathology and histopathology play a key role in the process of diagnosing oncological diseases and premalignant conditions. Fine-needle aspiration (FNA) is one of the techniques used for obtaining biopsy of a wide variety of body tissues, causing patients minimal discomfort. Therefore, it is often considered to be the best strategy for investigating and diagnosing some precancerous or potential malignant lesions. Being successful as a means of confirming the clinical suspicion of metastatic recurrence in the cases of an already known cancer, the interest has further focused on the preliminary diagnosis of various types of benign or malignant tumors. In cases of inoperable tumors, this technique is useful for formulating the final diagnosis. FNA biopsy proved its effectiveness as a highly accurate, cost-effective, and safe technique, with potential high diagnostic yield. Immunohistochemistry, used as an additional tool to classical histopathological examination, remains a very practical and reliable technique that promises good results especially in determining the site of origin within metastatic disease.

Ultrasound-guided fine needle aspiration thyroglobulin in the diagnosis of lymph node metastasis of differentiated papillary thyroid carcinoma and its influencing factors.

Background: Ultrasound-guided fine needle aspiration thyroglobulin (FNA-Tg) is recommended for the diagnosis of lymph node metastasis (LNM) in differentiated thyroid cancer (DTC), but its optimal cutoff value remains controversial, and the effect of potential influencing factors on FNA-Tg levels is unclear. Method: In this study, a retrospective analysis was conducted on 281 patients diagnosed with DTC, encompassing 333 lymph nodes. We analyze the optimal cutoff value and diagnostic efficacy of FNA-Tg, while also evaluating the potential influence of various factors on FNA-Tg. Results: For FNA-Tg, the optimal cutoff value was 16.1 ng/mL (area under the curve (AUC)= 0.942). The optimal cutoff value for FNA-Tg/sTg was 1.42 (AUC = 0.933). The AUC for FNA combined with FNA-Tg yielded the highest value compared to other combined diagnostic methods (AUC = 0.955). It has been found that serum thyroglobulin (sTg) is positively correlated with FNA-Tg (Rs = 0.318), while serum thyroglobulin antibodies (sTgAb) is negatively correlated with FNA-Tg (Rs = -0.147). In cases where the TNM stage indicated N1b, the presence of large or high volume lymph node metastasis(HVLNM), lymph node lateralization/suspicion (L/S) ratio ≤ 2, ultrasound findings indicating lymph node liquefaction, calcification, and increased blood flow, patients with coexisting Hashimoto's thyroiditis (HT), a tumor size ≥10 mm, and postoperative pathology confirming invasion of the thyroid capsule, higher levels of FNA-Tg were observed. However, the subgroup classification of DTC and the presence or absence of thyroid tissue did not demonstrate any significant impact on the levels of FNA-Tg. Conclusion: The findings of this study indicate that the utilization of FNA in conjunction with FNA-Tg is a crucial approach for detecting LNM in DTC. TNM stage indicated N1b, the presence of HVLNM, the presence of HT, lymph node L/S ratio, liquefaction, calcification, tumor diameter, sTg and sTgAb are factors that can impact FNA-Tg levels.In the context of clinical application, it is imperative to individualize the use of FNA-Tg.

Diagnostic utilities of washout CYFRA 21-1 combined with washout thyroglobulin for metastatic lymph nodes in thyroid cancer: a prospective study.

Cervical lymph node (LN) metastasis is common in differentiated thyroid cancer (DTC). This study evaluated the utility of the washout CYFRA 21-1 level, combined with the thyroglobulin (Tg) concentration, in terms of diagnosis of LN metastasis. We prospectively enrolled 53 patients who underwent thyroid surgery to treat DTC with lateral cervical LN metastases. Preoperative ultrasound guided needle localization was used to surgical sampling of specific LNs during the operation. The intraoperative washout Tg and CYFRA 21-1 levels were measured in such LNs. The Tg and CYFRA 21-1 levels differed significantly between metastatic and benign LNs. The cutoff values were 2.63 ng/mL for washout CYFRA 21-1 and 22.62 ng/mL for Tg. Combined use of the washout Tg and CYFRA 21-1 levels afforded the highest diagnostic accuracy (92.5%), better than that of individual markers. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 94.6%, 90.0%, 91.4%, 93.8%, respectively. The conjunction of the washout CYFRA21-1 and Tg levels enhances the diagnostic accuracy of LN metastasis in DTC patients. The washout CYFRA 21-1 level may be useful when malignancy is suspected, especially in cases where the cytology and washout Tg findings do not provide definitive results.

[A thyroid pathology: The great simulator]. / Une pathologie thyroïdienne : la grande simulatrice.

INTRODUCTION: Tuberculosis remains a major public health problem in developing countries. Thyroid localization is very rare, and often the cause of misdiagnosis. Pathological anatomy plays an important role in the diagnosis of certainty. The authors report a case of primary thyroid tuberculosis in a 22-year-old patient. We highlight the epidemiological particularities of this case, and discuss diagnostic methods and the contribution of pathological anatomy. OBSERVATION: A 22 year-old male patient, with no reported pathological history, was seen in the clinic for the management of an isolated anterior cervical swelling that had been evolving for two months. Clinical examination revealed only a small thyroid nodule, with no inflammatory or vascular features. Biological tests were unremarkable. Ultrasound revealed a 2.4cm hypoechoic, homogeneous, poorly vascularized tissue mass in the left lobe, classified as EU-TIRADS 3. Fine needle aspiration with cytopathological study revealed a necrotizing granulomatous lesion suggestive of tuberculosis. A lobo-isthmectomy was performed, and histopathology revealed thyroid parenchyma destroyed by tubercular granulomas. The postoperative course was straightforward, with an exeat on postoperative day 6. Anti-tuberculosis treatment was instituted for 6 months. Three- and six-month follow-up examinations were unremarkable. The evolution was favorable, with recovery after treatment. CONCLUSION: Primary thyroid tuberculosis is rare. Cytology is important for orientation, and often helps to avoid misdiagnosis. The diagnosis should be considered in the presence of any thyroid mass in a patient from a tuberculosis-endemic region.

Fungal infection mimicking soft tissue lesion: Role of on-site evaluation, special stain, and cellblock.

BACKGROUND: Fine-needle aspiration (FNA) cytology is a basic diagnostic method used for the investigation of superficial and deep lesions. The implementation of rapid on-site evaluation (ROSE) in cytological analysis can help in reducing the inadequacy rate and obtaining proper samples for further tests/analysis. CASE PRESENTATION: We report a case of 44-year-old male, who presented to our outpatient department with complaints of swelling in his right arm for the last 34 years. FNA with ROSE using 1% aq. toluidine blue helped identify the pathology (fungal lesion) in the patient with further confirmation by cellblock, periodic acid Schiff & Gomori methenamine silver stains. CONCLUSION: The role of FNA was significant in the above case, special stains prove their efficacy when sufficient sample is available. The differential diagnosis of fungal etiology should be considered in subcutaneous soft tissue lesions. There has been a major leap in diagnostic cytopathology with the advent of molecular testing. However, FNA still holds its charm.

Incidental detection of Cladosporium in cytology.

BACKGROUND: Fungal infection incidental detection is a common encounter in cytopathology practices. Detection of the fungal organisms and awareness of the morphological features are challenges for the cytopathologist. CASE PRESENTATION: We report a case of incidental detection of a fungal organism in a 67-year-old male patient with complaints of bilateral elbow joint swellings. Cytology was done and showed a fungal organism (Cladosporium sps.). CONCLUSION: Fine needle aspiration cytology (FNAC) along with Rapid on-site evaluation (ROSE) is a rapid, minimally invasive technique used for the diagnosis and detection of various fungi / parasites leading to early and definitive treatment.

A comparative analysis of core needle biopsy and repeat fine needle aspiration in patients with inconclusive initial cytology of thyroid nodules.

Purpose: To assess and compare the effectiveness of ultrasound-guided core needle biopsy (CNB) in comparison to repeat fine-needle aspiration(rFNA) for thyroid nodules that yield inconclusive results following the initial fine-needle aspiration (FNA). Methods: A cohort of 471 patients who received an inconclusive cytological diagnosis following the initial FNA were included in this study. These patients subsequently underwent either CNB (n=242) or rFNA (n=229). The inconclusive FNA results encompassed categories I, III, and IV of The Bethesda System for Reporting Thyroid Cytopathology(TBSRTC), as well as the ultrasound images indicating malignancy despite FNA results falling under TBSRTC category II. This study assessed the sampling satisfaction rate, diagnostic efficacy, and complications associated with CNB compared to rFNA. Additionally, the impact of repeat puncture time and nodule size on diagnostic efficacy was analyzed. Results: Following repeat punctures, the satisfaction rate of the CNB sampling was found to be significantly higher than that of rFNA (83.9% vs 66.8%). The diagnostic rate in the CNB group was significantly greater compared to that of the rFNA group (70.7% vs 35.8%). In patients with nodule maximum diameters ranging from 5 mm to 20 mm, the diagnostic accuracy was significantly higher in the CNB group compared to that in the rFNA group. In patients with intervals less than 90 days, between 90 days and one year, the diagnostic rate in the CNB group was found to be higher compared to that in the rFNA group. In CNB, not immediately adjacent to the capsule was a risk factor for nodular puncture bleeding (37.0% vs 22.7%.). Conclusion: CNB demonstrated higher rates of satisfaction and diagnosis compared to the rFNA. The diagnostic effectiveness of CNB was not influenced by the time interval or the size of the thyroid nodule. Therefore, in cases where the initial FNA diagnosis of thyroid nodules is inconclusive, CNB should be considered as a viable option for re-puncture.

Telecytology - remote rapid on-site evaluation for ultrasound-guided head and neck fine needle aspiration utilising a clinical imaging assistant with an extended practice role.

OBJECTIVE: Rapid On-Site Evaluation (ROSE) of fine needle aspirations (FNA) is widely accepted as best practice, resulting in better outcomes and delivery of care for patients. However, it is not always practical for cytology laboratories to release staff. To increase the availability of ROSE, this study aimed to robustly test the effectiveness of Telecytology ROSE (TCROSE) utilising a clinical imaging assistant (CIA) to prepare the samples and operate the microscope. METHODS: The study was divided into 3 phases. Phase 1, equipment testing, validation and in-house training for the CIA and the Consultant Biomedical Scientist (CBMS) performing TCROSE. Phase 2, Verifying TCROSE on the same site as the cytology laboratory and phase 3, TCROSE utilising a clinic at a peripheral site away from the cytology laboratory. RESULTS: 78/80 (97% sensitivity, 95% accuracy) of TCROSE cases matched the final report for assessment of adequacy and sufficient sampling, demonstrating 94% reliability with a 95% confidence value. An appropriately trained CIA effectively prepared the samples and operated the microscope for remote interpretation. The samples were triaged effectively, and biopsy requests were appropriate to reduce the need for repeat procedures and delays in treatment. This approach received positive feedback from patients. CONCLUSION: TCROSE utilising a CIA provides a highly effective alternative to conventional ROSE, minimising the resources required from cytopathology services and improving patient care and access to best practice. This study supports the validity of trained CIAs for a more involved role in the ultrasound-guided FNA service.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

BACKGROUND: Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. DESIGN: Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). RESULTS: Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ = 0.73-0.91) and follow-up histopathology (κ = 0.66-0.85). The agreement was lowest in the inadequate (κ = 0.05) and atypical (κ = 0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). CONCLUSION: Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.