Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a "surgical" and a "cytological" series.

PURPOSE: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. METHODS: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a "Surgical series" of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a "Cytological series" of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. RESULTS: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. CONCLUSION: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

Routine Use of Preoperative Neck Ultrasound in Primary Hyperparathyroidism Identifies Coexisting Thyroid Disease and Improves Parathyroid Localization.

BACKGROUND: In Jan 2018, we began routinely obtaining neck ultrasound (US) with 123I/99Tc-sestamibi (MIBI) for parathyroid gland localization and to identify thyroid pathology in the setting of primary hyperparathyroidism (1HPT). The aim of this study is to assess if routine neck US is a useful adjunct to 123I/99Tc-MIBI in 1HPT. METHODS: Patients undergoing surgery for 1HPT with both 123I/99Tc-MIBI and US at our institution after implementation of routine US were reviewed. Biopsy and surgical management of thyroid pathology was evaluated. 123I/99Tc-MIBI and US results were compared to intraoperative findings to determine sensitivity and positive predictive value (PPV) for parathyroid localization. RESULTS: From January 2018 to September 2019, there were 423 patients (mean, 61 years) that met inclusion criteria (80% women). Thyroid nodules were found on US in 57%, mean size 1.3 + 0.8 cm. Fine needle aspiration (FNA) was performed in 87 patients with nodules (36%). 35 patients (8.5%) required total or partial thyroidectomy for diagnoses/treatment. Papillary thyroid cancer (PTC) was found in 3.5% of the cohort with micro-PTC 53% and PTC 1-2 cm 40%. A successful parathyroid operation for 1HPT was achieved in 98.6% of patients. Positive predictive value for localization of abnormal parathyroid glands was 97% when US and 123I/99Tc-MIBI had concordant findings. DISCUSSION: Routine use of US in 1HPT commonly identifies nodules that are benign or low-risk PTC. Ultrasound is less sensitive for parathyroid localization but when used with 123I/99Tc-MIBI, concordant imaging has a high PPV.

A Comparison of Two Widely Used Risk Stratification Systems for Thyroid Nodule Sonographic Evaluation.

BACKGROUND: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems. OBJECTIVES: To compare the two systems for accuracy of cancer risk prediction. METHODS: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared. RESULTS: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively. CONCLUSIONS: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems.

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

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Results: 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. Conclusions and Relevance: 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.

BRAF V600E mutation and the Bethesda System for Reporting Thyroid Cytopathology of fine-needle aspiration biopsy for distinguishing benign from malignant thyroid nodules.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) predicts the risk of malignancy for the different categories of the ultrasound-guided fine-needle aspiration biopsy (FNAB). The objective of this study is to investigate the efficiencies of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation test and the TBSRTC categories in distinguishing between benign and malignant thyroid nodules. METHODS: In this study, 362 ultrasound-guided fine-needle aspiration (FNA) samples from 344 patients aged from 17 to 76 years old were retrospectively reviewed. The patients were classified into six groups (I-VI) according to the TBSRTC system. The amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used to evaluate the BRAF V600E mutation level in total 362 samples. Among of the 344 patients, 128 patients (131 thyroid nodules) who underwent surgeries were followed by histopathological examination. The predictive values of the BRAF V600E mutation test and TBSRTC categories were evaluated in these 131 thyroid nodules. RESULTS: The median ages of the patients in the TBSRTC IV-VI group were smaller than those in the TBSRTC I-III groups. The proportion of nodules over 1 cm was larger than it in the TBSRTC IV group compared to the other groups. Significant differences in BRAF V600E mutation were observed (P < .001) among these six groups. The sensitivity (89.57%) for the detection of malignant thyroid nodules, negative predictive value (NPV; 45.45%) for the detection of benign nodules, and accuracy (86.26%) for distinguishing between benign and malignant thyroid nodules increased by combining the BRAF V600E mutation test and TBSRTC system when compared with the BRAF V600E mutation test and TBSRTC system respectively. The BRAF V600E mutation test alone demonstrated the increased positive predictive value (PPV; 98.91%) and specificity (93.75%) for the detection of malignant thyroid nodules compared to the TBSRTC method (alone or in combination with the BRAF V600E method). CONCLUSION: In summary, significant differences in age, nodule diameter, and BRAF V600E mutation were noted among the six categories of the TBSRTC system. The combination of the BRAF V600E mutation test and TBSRTC system demonstrated increases in the NPV, sensitivity, and accuracy, while the BRAF V600E method proved superiority to the TBSRTC system with regard to the PPV and specificity.

The Bethesda System for Reporting Thyroid Cytopathology: A Retrospective Review of its Diagnostic Utility at Johns Hopkins Aramco Healthcare, Saudi Arabia.

PURPOSE: Fine needle aspiration (FNA) is the gold standard for assessment of thyroid nodules, with the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) used to predict the malignancy risk of these nodules. Our aim was to evaluate the diagnostic utility of the TBSRTC for a Saudi population, by comparing the malignancy risk based on histopathology to FNA-based diagnosis of each of the TBSRTC categories and to previously published malignancy risk in other population. MATERIALS AND METHODS: This was a retrospective study of the data of 241 patients who underwent FNA assessment of thyroid nodules and surgical resection with histopathology at John Hopkins Aramco Healthcare, Dhahran, Saudi Arabia, between January 2016 and December 2019. RESULTS: The malignancy risk for each of the TBSRTC categories was as follows: non-diagnostic, 25%, benign; 5.74%; atypia of undetermined significance, 37%; suspicious for follicular neoplasm, 38%; suspicious for malignancy, 100%; and malignant, 95%. Our finding were comparable to previously published malignancy risks, except for a higher rate of malignancy in the benign category at 18% compared to 0-3%. CONCLUSION: Our findings validate the diagnostic reproducibility of the TBSRTC for a Saudi population, with the risk of malignancy confirmed by histopathological assessment being consistent with those previously reported for other populations.

[Is preoperative axillary radio-cytology justified after ACOSOG Z001?] / La radio-cytologie axillaire préopératoire est-elle justifiée après l'ACOSOG Z001 ?

INTRODUCTION: Invasive breast cancer without clinical adenopathy (cN0) is currently explored by the sentinel node (GS) technique, except in the case of positive preoperative radio-cytological screening, where axillary curage (CA) remains systematic from the outset. Since the publication of the ACOSOG-Z0011 trial, abstention from CA is possible in patients presenting less than three metastatic GS. As a result, the value of axillary radio-cytological screening is being questioned as it could potentially lead to axillary surgical over-treatment. The objective of this study was to study clinically N0 patients with positive axillary cytology and to compare it to a group of patients with positive GS. METHOD: One hundred and forty-seven patients with cN0 pN+ breast cancer treated between 2014 and 2016 were selected retrospectively. Two groups were constituted according to the initial radio-cytological evaluation. A CA was systematically performed. RESULTS: Thirty-one patients with positive axillary cytology (n=31 vs. n=116) had more metastatic lymph nodes (P=0.01) in the AC, larger (P<0.001), less differentiated (P<0.001) tumours, and shorter recurrence-free survival (P=0.0114). It also appeared that 38.7 % of patients with a positive cytology had at most two metastatic nodes and could, according to the results of ACOSOG, benefit from therapeutic de-escalation. CONCLUSION: X-ray cytological screening remains essential in order to select a subgroup of patients with a high lymph node tumour load. Additional studies are necessary in order to be able to offer therapeutic de-escalation to 1/3 of these patients without the risk of under-treatment for the remaining 2/3.

Comparison of British Thyroid Association, American College of Radiology TIRADS and Artificial Intelligence TIRADS with histological correlation: diagnostic performance for predicting thyroid malignancy and unnecessary fine needle aspiration rate.

OBJECTIVES: To compare diagnostic performance of British Thyroid Association (BTA), American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) and Artificial Intelligence TIRADS (AI-TIRADS) for thyroid nodule malignancy. To determine comparative unnecessary fine needle aspiration (FNA) rates. METHODS: 218 thyroid nodules with definitive histology obtained during 2017 were included. Ultrasound images were reviewed retrospectively in consensus by two subspecialist radiologists, blinded to histopathology, and nodules assigned a BTA, ACR-TIRADS and AI-TIRADS grade. Nodule laterality and size were recorded to allow accurate histopathological correlation and determine which nodules met criteria for FNA. RESULTS: 77 (35.3%) nodules were malignant. Deeming ultrasound Grade 4-5 as test-positive and 1-2 as test-negative, sensitivity and specificity for BTA was 98.28 and 42.55%, for ACR-TIRADS: 95.24 and 40.57% and for AI-TIRADS: 93.44 and 45.71%. FNA was indicated in 101 (71.6%), 67 (47.5%) and 65 (46.1%) benign nodules utilising BTA, ACR-TIRADS and AI-TIRADS respectively. The unnecessary FNA rate was significantly higher with BTA (46.3%) compared to ACR-TIRADS (30.7%) and AI-TIRADS (29.8%) p < 0.001. CONCLUSION: BTA, ACR-TIRADS and AI-TIRADS had similar diagnostic performance for predicting thyroid nodule malignancy with sensitivity >93% for all systems when considering ultrasound Grade 4-5 as malignant and Grade 1-2 as benign. ACR-TIRADS and AI-TIRADS both had a significantly lower rate of recommended FNA in benign nodules compared to BTA. ADVANCES IN KNOWLEDGE: BTA, ACR-TIRADS and AI-TIRADS have comparable diagnostic performance with high sensitivity but relatively low specificity for predicting thyroid nodule malignancy in this cohort using histology as gold-standard. Using Grade 1-2 as benign and 4-5 as malignant there were more false negatives with TIRADS but this improved when taking other features into account while BTA had a significantly higher rate of unnecessary FNA.

Spindle cell neoplasms of the upper gastrointestinal tract, hepatobiliary tract, and pancreas by fine needle aspiration: A single institutional experience of 15 years with follow-up data.

BACKGROUND: The diagnosis of spindle cell neoplasms (SCN) of the upper gastrointestinal (GI) tract, hepatobiliary tract, and pancreas detected by fine needle aspiration (FNA) is challenging. We describe a single-center experience of these samples with follow-up data and characterization of the morphologic findings. METHODS: We retrospectively reviewed pathology records for all FNAs diagnostic for or suggestive of SCN on esophagus, stomach, small bowel, liver, and pancreas in a 15 year period. All cases with at least 6 month follow-up were included. Surgical material (biopsy or resection) was the diagnostic gold standard. All FNAs with subsequent surgical specimens were reviewed and assessed for cellularity, architectural features, and nuclear features. RESULTS: In 15 years, 5101 FNAs of the upper GI tract, hepatobiliary tract, and pancreas were performed. SCN was diagnosed in 98 (2%) patients. Seventy-two patients had definitive pathologic diagnoses: 68 were neoplastic and four were non-neoplastic. Cytomorphologic review in relationship to final diagnosis revealed three statistically significant features: low cellularity favors a benign process (P = .00544), epithelioid nuclear morphology favors malignancy (P = .00278), and identification of perinuclear vacuoles favors a diagnosis of GIST over non-GIST SCN (P = .04236). CONCLUSIONS: Among cases with follow-up, final pathologic diagnoses were SCN in 94% of cases diagnosed as SCN on FNA of upper GI, hepatobiliary tract, and pancreas. Although some cytomorphologic criteria are more suggestive of malignancy, arriving at a specific diagnosis relies on collaboration of clinical, radiologic, cytomorphologic, and immunohistochemical data.

Cytopathology practice during the COVID-19 postlockdown: An Italian experience.

BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, the cytopathology workload has decreased remarkably worldwide as all screening and elective procedures have been postponed to prioritize the clinical management of patients at high oncological risk. In the current study, the authors provide data on the lasting impact of COVID-19 on cytopathology practice during the initial phases of the Italian postlockdown period. METHODS: The percentages of the cytological sample types processed at the University of Naples Federico II during the first 12 weeks of the Italian postlockdown period were compared with those of the same period in 2019. The study period was divided into four 3-week periods. Differences in the rates of malignant diagnoses were also assessed. RESULTS: During the 12-week study period, the overall cytological sample workload decreased by 41.6% in comparison with 2019. In particular, the workload significantly declined for each sample type: Pap smears, -33.3%; urine, -42.8%; serous fluids, -14.4%; thyroid, -54.5%; breast, -43%; lymph node, -27.3%; and salivary gland, -61%. By contrast, the overall malignancy rate was significantly increased (P = .0011). CONCLUSIONS: The reduction in the cytological sample workload during the postlockdown period still represents an ongoing effect of the COVID-19 pandemic. On the other hand, the rise in the overall malignancy rate reflects the importance of prioritizing diagnostic procedures for patients at high oncological risk.

Association of the Implementation of a Standardized Thyroid Ultrasonography Reporting Program With Documentation of Nodule Characteristics.

Importance: Although most thyroid nodules are benign, the potential for malignant neoplasms is associated with unnecessary workup in the form of imaging, fine-needle aspiration, and diagnostic surgery. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) is commonly used to assess the malignant neoplasm risk potential of thyroid nodules imaged by ultrasonography. However, standardized reporting of ACR TI-RADS descriptors is inconsistent. Objective: To increase the documentation rate of ACR TI-RADS thyroid nodule characteristics to 80% in 18 months. Design, Setting, and Participants: This prospective interrupted time series quality improvement study was conducted from December 1, 2018, to March 31, 2020, at a tertiary outpatient head and neck clinic among 229 patients who had at least 1 documented thyroid nodule identified on bedside clinic ultrasonography. Data analysis was performed throughout the entire study period because this was a quality improvement study with iterative small cycle changes; final analysis of the data was performed in April 2020. Main Outcomes and Measures: The primary outcome was the documentation rates of 6 ACR TI-RADS ultrasonographic descriptors. Secondary outcomes included nodule fine-needle aspiration biopsy rate and physician-reported clinic flow efficiency. Results: A total of 229 patients had at least 1 documented thyroid nodule and were included in the analysis. Size was the most frequently documented nodule characteristic (72 of 74 [97.3%]) at baseline, followed by echogenic foci (31 of 74 [41.9%]), composition (23 of 74 [31.1%]), echogenicity (17 of 74 [23.0%]), margin (6 of 74 [8.1%]), and shape (1 of 74 [1.4%]). After 3 Plan, Do, Study, Act (PDSA) cycles, the final intervention consisted of a standardized ultrasonography reporting form and educational initiatives for surgical trainees. After the third PDSA cycle (n = 36), reporting of nodule size, echogenic foci, and composition increased to 100%. Similarly, reporting of echogenicity (34 of 36 [94.4%]), shape (28 of 36 [77.8%]), and margin (25 of 36 [69.4%]) all increased. This represented a cumulative 90.3% documentation rate (195 of 216), a 56.5% increase from baseline (95% CI, 50.0%-61.9%). The standardized reporting form was used in 83.3% of eligible thyroid ultrasonography cases (30 of 36) after PDSA cycle 3, demonstrating good fidelity of implementation. There were no unintended consequences associated with clinic workflow, as a balancing measure, reported by staff surgeons. Conclusions and Relevance: This study suggests that implementation of an ACR TI-RADS-based reporting form in conjunction with educational initiatives improved documentation of ultrasonographic thyroid nodule characteristics, potentially allowing for improved bedside risk stratification and communication among clinicians.

Thyroid surgery during coronavirus-19 pandemic phases I, II and III: lessons learned in China, South Korea, Iran and Italy.

OBJECTIVE: We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019. METHODS: The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25-February 25, 2020), phase II (February 26-March 19), phase III (March 20-April 20). RESULTS: There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (P = 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital. CONCLUSION: The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).

Malignancy is in the eye of the beholder: Pathologic diagnosis of challenging follicular neoplasms in the era of noninvasive follicular thyroid neoplasms with papillary-like nuclear features and immunohistochemical and molecular adjuncts.

BACKGROUND: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts. METHODS: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient. RESULTS: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%). CONCLUSION: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge.

A New Device for Fine-Needle Aspiration Cytology Consisting of a Vibrating Linear Resonant Actuator.

OBJECTIVE: To evaluate the efficacy of a new device for fine-needle aspiration cytology (FNAC) consisting of a vibrating linear resonant actuator (LRA). STUDY DESIGN: Prospective clinical study. METHODS: The LRA frequency was optimized by visualization of the needle motion using a high-speed camera. The FNAC device consists of a vibrating motor fixed to the stopper of a 5-ml syringe and piston. Upon insertion of the syringe needle into a thyroid nodule (with the stopper attached to the syringe piston), sufficient negative pressure with 1-ml suction was maintained. Subsequently, samples were obtained using vibration generated by an LRA or an eccentric rotating mass (ERM). Surgically resected thyroid specimens from 10 patients were evaluated. The number of follicular groups required for adequate diagnosis and the number of larger follicular groups were counted. Next, 254 thyroid nodules from 187 patients were also evaluated by FNAC. The inadequacy rate was determined, and final cytology was classified according to thyroid Bethesda categories. RESULTS: The optimized LRA frequency was 155 Hz. Both the LRA and ERM devices resulted in sufficient amounts of diagnostic material and achieved low inadequacy rates. The number of large follicular groups obtained was significantly greater with the LRA device compared with the ERM device. CONCLUSIONS: The vibrating device using an LRA for thyroid FNAC resulted in sufficient amounts of thyroid follicular groups and achieved low inadequacy rates. In addition, the LRA device allowed for collection of larger follicular groups sufficient to diagnose appropriate thyroid Bethesda categories. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1393-E1399, 2021.

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations.

INTRODUCTION: Reoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies. MATERIALS AND METHODS: Retrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B). RESULTS: From over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B. CONCLUSION: Optimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.

Accuracy of fine-needle aspiration cytology in the diagnosis of salivary gland masses according to the Milan reporting system and to an in-house system.

BACKGROUND: This study aims to assess in our institutional experience the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland masses (SGM) according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and to an in-house system. METHODS: The study included 189 FNACs conducted between January 2011 and December 2019. The FNACs, classified according to the in-house system, were reclassified according the MSRSGC. Taking histopathology as gold standard, the measures of diagnostic accuracy of FNAC were determined for suspicion for malignancy (SFM) and malignant categories. RESULTS: According to the in house system, FNAC diagnoses were classified as: 23 (12.2%) non-diagnostic (ND), 23 (12.2%) non-neoplastic (NN), 119 (62.9%) benign neoplasm (BN), 10 (5.2%) indefinite neoplasm (IN), 2 (1.1%) SFM, and 12 (6.4%) malignant (M). Based on the MSRSGC, there were 3 (1.5%) cases of atypia of undetermined significance (AUS) and 7 (3.7%) neoplasms of uncertain malignant potential (SUMP). The number of ND, NN, BN, SFM, and M cases were identical in the two systems. For both systems, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy for malignancy diagnosis were 77.8%, 100%, 100%, 97.6%, and 97.8%, respectively. CONCLUSION: According to the MSRGC and to our in-house reporting system, FNAC is an accurate technique for the diagnosis of malignant salivary tumors with excellent specificity and good sensitivity. However, MSRGC has the advantage of standardization of salivary gland cytology reporting.

Thyroid fine-needle aspiration trends before, during, and after the lockdown: what we have learned so far from the COVID-19 pandemic.

PURPOSE: Nowadays, the clinical management of thyroid nodules needs to be multi-disciplinary. In particular, the crosstalk between endocrinologists and cytopathologists is key. When FNAs are properly requested by endocrinologists for nodules characterised by relevant clinical and ultrasound features, cytopathologists play a pivotal role in the diagnostic work-up. Conversely, improper FNA requests can lead to questionable diagnostic efficiency. Recently, recommendations to delay all non-urgent diagnostic procedures, such as thyroid FNAs, to contain the spread of COVID-19 infection, have made the interplay between endocrinologists and cytopathologists even more essential. The objective of this study was to assess the impact of COVID-19 pandemic on our practice by evaluating the total number of FNAs performed and the distribution of the Bethesda Categories before, during, and after the lockdown. METHODS: We analysed the FNA trends before (1st January 2019 to March 13th 2020), during (March 14th to May 15th), and after (May 16th to July 7th) the lockdown. RESULTS: Although the total number of weekly FNAs dropped from 62.1 to 23.1, our referring endocrinologists managed to prioritise patients with high-risk nodules. In fact, in the post-lockdown, the weekly proportion of benign diagnoses dropped on average by 12% and that of high-risk diagnoses increased by 6%. CONCLUSIONS: The lesson we have learned so far from this pandemic is that by applying safety protocols to avoid contagion and by increasing the threshold for FNA requests for thyroid nodules, we can continue to guarantee our services to high-risk patients even in times of a health crisis.

Cytopathology-histopathology correlation and the effect of nodule diameter on diagnostic performance in patients undergoing thyroid fine-needle aspiration biopsy.

INTRODUCTION: Although thyroid fine-needle aspiration biopsy (FNAB) is established to have a good overall sensitivity and specificity, various outcomes have been reported on its performance in large nodules. The aim of the study was to evaluate the diagnostic performance of FNAB and the effect of the nodule diameter on its diagnostic performance. MATERIALS AND METHODS: The outcomes of a total of 7319 patients who underwent FNAB over the course of 5 years were analyzed retrospectively and 648 patients who had undergone post-FNAB thyroidectomy or lobectomy were included in the study. FNAB results were classified according to the Bethesda system. After evaluating the compatibility between cytology and pathology results, all-nodules and diameter-based (<4 cm and ≥4 cm) sensitivity, specificity, false positivity, false negativity, and accuracy rates of FNAB were calculated. RESULTS: Sensitivity of FNAB was 85.4% for all nodules, 88.3% for nodules <4 cm, and 75.8% for nodules >4 cm (P < 0.001). Specificity was 58.4% for all nodules, 49.3% for nodules <4 cm, and 75.1% for nodules >4cm (P < 0.001). While false positivity was 41.6% for all nodules, it was 50.7% for nodules smaller than 4 cm and was 24.9% for nodules larger than 4 cm (P < 0.001). False negativity was 14.6% for all nodules and was 11.7% for nodules smaller than 4 cm and 24.2% for nodules larger than 4 cm (P < 0.001). Finally, among the entire set of nodules, the accuracy was 64.4%, which was 59.2% in nodules smaller than 4 cm, and 75.2% in nodules larger than 4 cm (P < 0.001). CONCLUSION: Despite a higher rate of false negativity, FNAB has higher specificity and accuracy in large nodules than those in the small nodules. Nodule diameter should not be used alone as a criterion to recommend thyroidectomy to the patient.