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Background: Fine-needle aspiration (FNA) has been reported since 1912 beginning with the use of trocars and other specialized instruments that were impractical. Since then, FNA has proven to be a successful alternative technique to excisional biopsy for some assays despite a few limitations., Methods: In this study, we compared four different techniques for FNA in rhesus macaques by evaluating total live cells recovered and cell viability using a standard 6 mL syringe and 1.5-inch 22-gauge needle., Results: Technique B which was the only technique in which the needle was removed from the syringe after collection of the sample to allow forced air through the needle to expel the contents into media followed by flushing of the syringe and needle resulted in the highest total cell count and second highest cell viability in recovered cells., Conclusion: Based on our results, Technique B appears to be the superior method., (© 2023 The Authors. Journal of Medical Primatology published by John Wiley & Sons Ltd.)

Introduction: Telecytology offers a suitable solution to the cost and time efficiency questions on rapid onsite evaluation (ROSE). An increasing number of institutions are adopting new telecytology systems to meet the increasing ROSE requests, although there is no agreement on the details of how a telecytology validation study needs to be conducted. We propose a standardized approach for telecytology validation studies that could be done in a variety of practices., Materials and Methods: Consecutive cases from 6 months prior were chosen to reflect a case mix comparable to real life. A fellow assessed the slides at the ROSE site while 6 cytopathology faculty convened in a conference room with a television screen, and noted the adequacy, diagnostic category, and specific diagnoses. All participants were blinded to the original adequacy assessment and final diagnoses. For each case, evaluation time and the slides counts were noted., Results: Fine-needle aspiration specimens from 52 patients were included in the study. Of these, 13 cases were used in the first "test" session. The adequacy concordance rates ranged between 92.3% and 100%, with an overall concordance rate of 94.8%. The diagnostic category concordance rates ranged between 90.3% and 95.5%, with an overall concordance rate of 91.9%. The specific diagnosis concordance rates ranged between 84.6% and 92.9%, with an overall concordance rate of 88.1%., Conclusions: Validation of telecytology requires a standardized approach just like any other new technology. In this study, we propose an efficient and accurate method for cytopathology departments of various case volumes to conduct telecytology validation studies., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Fine-needle aspiration cytology (FNAC) under ultrasound guidance is clinically useful, but there is a risk of spreading infection by generating droplets of contaminated fluids during the procedure. Risk assessment to better control infection remains to be established. The aim of this study was to estimate infection risks during FNAC by visualization of droplet production and deposition using a simulation model., Methods: The simulation comprised a puncture needle, a device for holding the needle, and a fluid specimen containing fluorescent particles as a model. Simulating each step of FNAC (removal of the inner and outer cylinder and transferring the specimen onto a glass slide), the generation and deposition of droplets were visualized using a laser., Results: After removal of the inner cylinder, an aerosol of droplets in the air surrounding the needle was observed. After removal of the outer cylinder, several large droplets precipitating onto the circumjacent surface were observed. From the beginning of transferring the specimen, a large amount of sizeable droplets first moving away and then precipitating was observed, followed by the production of a cluster of fine droplets drifting and spreading through the air., Conclusions: Here, the generation of droplets at each step of FNAC, precipitation of large droplets onto the circumjacent surface, and drifting and spreading through the air of fine droplets was visualized. These results emphasize the need for precautions to prevent the transmission of infectious agents during FNAC., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Background: This meta-analysis was conducted to compare the safety and diagnostic performance between computed tomography (CT)-guided core needle biopsy (CNB) and fine-needle aspiration biopsy (FNAB) in lung nodules/masses patients., Methods: All relevant studies in the Pubmed, Embase, and Cochrane Library databases that were published as of June 2020 were identified. RevMan version 5.3 was used for all data analyses., Results: In total, 9 relevant studies were included in the present meta-analysis. These studies were all retrospective and analyzed outcomes associated with 2175 procedures, including both CT-guided CNB (n = 819) and FNAB (n = 1356) procedures. CNB was associated with significantly higher sample adequacy rates than was FNAB (95.7% vs 85.8%, OR: 0.26; P < .00001), while diagnostic accuracy rates did not differ between these groups (90.1% vs 87.6%, OR: 0.8; P = .46). In addition, no differences in rates of pneumothorax (28.6% vs 23.0%, OR: 1.15; P = .71), hemorrhage (17.3% vs 20.1%, OR: 0.91; P = .62), and chest tube insertion (5.9% vs 4.9%, OR: 1.01; P = .97) were detected between these groups. Significant heterogeneity among included studies was detected for the diagnostic accuracy (I2 = 57%) and pneumothorax (I2 = 77%) endpoints. There were no significant differences between CNB and FNAB with respect to diagnostic accuracy rates for lung nodules (P = .90). In addition, we detected no evidence of significant publication bias., Conclusions: CT-guided CNB could achieve better sample adequacy than FNAB did during the lung biopsy procedure. However, the CNB did not show any superiorities in items of diagnostic accuracy and safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Despite the important role of the community in the assessment and risk stratification of patients with thyroid nodules, evidence-based data on the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) performance in community clinics is lacking. We aim to evaluate BSRTC performance of aspirations taken in community clinics compared with primary referral center., Methods: Patients who underwent thyroid surgery between 2013 and 2018 at our institution were divided according to the fine needle aspirations (FNA) settings: community FNA (cFNA) vs. institutional FNA (iFNA). Demographics, BSRTC results and final pathology were collected. Diagnostic values were calculated for BSRTC categories (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), and were compared between the groups., Results: A total of 268 nodules were included in the study; 77% (207) cFNA and 23% (61) iFNA. Patients in the community were younger (51.7 ± 15.1 vs. 56.6 years±14.8, p = 0.03) and with less epidemiology risk factors for thyroid cancer (1.9% vs 13.1%, p < 0.001). cFNA malignancy rate for BSRTC I-VI was 0%, 6.4%, 11.8%, 32.1%, 91.6% and 93.8% respectively. Best sensitivity was found for BSRTC III-VI in both groups (88% and 83%, cFNAs and iFNAs, respectively). Overall best performance was obtained for BSRTC V-VI for both groups (cfNA: 85%, 97%, 93%, 94% and 93%; iFNAs: 81%, 100%, 100%, 87% and 91%, for sensitivity, specificity, PPV, NPV and accuracy, respectively)., Conclusions: Community-performed FNAs demonstrate acceptable BSRTC distribution and malignancy rates, comparable with a primary referral academic hospital. This supports the universality of the BSRTC 2017 and its recommendations also in the community., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA)., Objectives: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA., Methods: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics., Results: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient., Conclusions: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

Introduction: Soft tissue myoepithelioma (STM), a rare mesenchymal neoplasm morphologically analogous to its more common salivary gland (SG) counterpart, is the subject of single case reports regarding its fine-needle aspiration (FNA) biopsy. To our knowledge, ours is the first case series of STM., Materials and Methods: A search was made of our pathology databases for cases diagnosed as STM. FNA biopsy smears and cell blocks were performed using standard techniques., Results: Seven cases were retrieved from 4 men and 3 women (M:F = 1.3:1; age range: 25-79 years, x = 54 years). All but 1 presented as a primary neoplasm. Six aspirates were from the extremities, and 1 from the abdominal wall. Mean tumor size was 5.7 cm. Cytologic diagnosis of STM or suspicious for STM was made in 3 cases (43%). Remaining FNA diagnoses were spindle cell neoplasm/lesion (2), spindle cell sarcoma (1), and extraskeletal myxoid chondrosarcoma (1). Three cases were composed primarily or solely of uniform spindle cells, 3 primarily of uniform epithelioid cells with plasmacytoid features, and 1 case a mixture of these 2 cell types. Myxoid/chondromyxoid stroma was relatively abundant except in the single hypocellular example. Immunohistochemical (IHC) testing performed in 71% was nonspecific, but positive with S-100 in 4 of 5, EMA in 3 of 3, calponin in 2 of 2, and keratin in 1 of 3 examples., Conclusion: FNA biopsy smears of STM are remarkably similar cytomorphologically to their SG equivalent. However, STM can be misidentified principally as extraskeletal myxoid chondrosarcoma, thus requiring a relatively broad IHC panel for a specific diagnosis., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To assess the impact of aspiration on cytologic quality of fine-needle specimens obtained from lymph nodes of dogs and to compare the level of agreement of the cytologic diagnosis between the two sampling techniques., Materials and Methods: Fifty-three client-owned dogs were prospectively enrolled. Client-owned dogs were prospectively enrolled in the study if cytologic examination of lymph nodes was indicated in the course of their clinical diagnostic work-up. In each dog, two superficial, palpably accessible lymph nodes were sampled: one by fine-needle aspiration and the other by fine-needle non-aspiration, using a 21-Gauge needle with or without a 5-mL syringe. Cytologic quality was assessed in duplicate smears assessed by two observers who rated cellularity, blood contamination, thickness, cell preservation and cytoplasmic fragmentation using a predefined scoring system., Results: Fifty-three client-owned dogs were included in the study. No significant difference was found in rating scores between the two sampling techniques for any of the cytologic quality parameters assessed. Cohen's kappa coefficient was 0.84 (95% confidence interval 0.68-1.00), indicating diagnostic agreement between the sampling techniques., Clinical Significance: In this study, both fine-needle aspiration and fine-needle non-aspiration techniques yielded lymph node specimens of comparable cytologic quality and with acceptable agreement in cytologic diagnosis., (© 2021 British Small Animal Veterinary Association.)

Purpose: Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules., Methods: Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements., Results: At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03)., Conclusion: US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules., (© 2021. The Author(s).)

Introduction: Splenic fine needle aspiration (FNA) and core needle biopsies (CNB) are rare specimen types, potentially avoided due to clinical concern for hemorrhagic complications. The safety and utility of splenic FNA, the role of rapid onsite evaluation (ROSE), as well as the diagnostic utility of CNB versus FNA have not been recently reviewed., Materials and Methods: A 10-year retrospective review was performed of percutaneous image-guided FNA and CNB of the spleen. Clinical indications, outcomes, ROSE findings, and final diagnoses were reviewed and correlated., Results: Forty-four specimens from 39 patients were identified. The commonest indication for biopsy was a radiographic mass found during assessment for patient complaint (45%, 20/44), evaluation for malignancy (primary or metastatic) (39%, 17/44), and incidentally (16%, 7/44). Malignant diagnoses were rendered in 10 cases, 80% hematolymphoid and 20% nonhematolymphoid. Thirty-one cases were nonneoplastic and identified as infectious/inflammatory processes 39%, cysts 10%, vascular lesions 13%, benign splenic elements 22%, accessory or atrophic spleen 10%, and extramedullary hematopoiesis 6%. The nondiagnostic rate was 7%. Cases with subsequent splenectomy showed 100% specificity and 86% sensitivity. The concordance of ROSE and final interpretation was 90% within the neoplastic category. Finally, the significant complication rate was 6.8% with no bias to occurrence following FNA or CNB., Conclusions: This series affirms the safety and efficacy of splenic FNA and CNB by complication rates comparable to prior studies and high rate of concordance. The diagnostic accuracy may be further improved by ROSE, and CNB in cases reliant on staining and tissue architecture., (© 2021 Wiley Periodicals LLC.)

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.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Background: The guideline for managing pediatric thyroid nodules has not been established. We investigated the appropriateness of the Korean Society of Thyroid Radiology (KSThR) guidelines and the need to consider risk factors for managing pediatric thyroid nodules. Methods: From August 2007 to February 2020, a database of thyroid nodules in patients younger than 19 years who underwent fine-needle aspiration (FNA) was analyzed. Two radiologists retrospectively reviewed ultrasound images to characterize the nodules according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) criteria. Thyroid nodules were divided into benign and malignant nodules. Clinical risk factors were identified, including familial thyroid cancer, history of radiation therapy, and underlying thyroiditis. According to the K-TIRADS categories and the presence of risk factors, malignancy rates were calculated. We compared the diagnostic performance of the original KSThR guidelines and newly suggested criteria for FNA derived by simulation tests with variable size cutoffs in the total study population, a group with risk factors, and a group without risk factors. Results: A total of 107 patients (mean age, 13.9 years; range, 4-18 years; 83 females; 50 patients with risk factors) with 133 nodules (71 benign and 62 malignant) were included. The malignancy rate of thyroid nodules was higher in the group with risk factors (64.0%) than in the group without risk factors (43.9%; p  = 0.037). Compared with the KSThR guideline (≥1.0 cm for K-TIRADS 4 and 5), the accuracy was higher (62.4% vs. 56.4%) and the unnecessary biopsy rate was lower (44.0% vs. 47.4%) when the new criteria (≥0.6 cm for K-TIRADS 4 and ≥0.5 cm for K-TIRADS 5) were used in the total study population. In particular, in the group with risk factors, the newly suggested size criteria had a much higher accuracy (73.1% vs. 59.7%) and lower unnecessary biopsy rate (30.4% vs. 35.5%) than the KSThR guideline. Conclusions: For the management of thyroid nodules in children, it is necessary to consider risk factors and adjust the criteria values for FNA. FNA should be considered in children with risk factors for thyroid cancer even if thyroid nodules are small.

Fine-needle aspiration (FNA) biopsy reliably diagnoses parotid gland lesions preoperatively, whereas intraoperative frozen section (FS) has the additional benefit of assessing surgical margins and refining diagnoses; however, the role of FS in the setting of prior FNA diagnosis is not well established. Our aim was to determine whether FS should still be performed after a prior FNA/ CNB diagnosis. Parotid gland resections from January 2009 to January 2020 were identified; however, only patients who had both FNA and FS constituted our study population. For the purpose of statistical analysis, FNA diagnoses were classified into non-diagnostic (ND), non-neoplastic (NN), benign neoplasm (BN), indeterminate, and malignant. FS diagnoses were classified into benign, indeterminate, or malignant. Resections were dichotomized into benign and malignant and regarded as the gold standard to subsequently calculate diagnostic accuracy of FNA and FS. A total of 167 parotid gland resections were identified, but only 76 patients (45.5%) had both FNA and FS. In 35 cases deemed as benign preoperatively, three (8.6%) were reclassified as malignant on FS. Out of 18 lesions reported as malignant on FNA, four (22.2%) were interpreted as benign on FS, with three of these benign lesions confirmed on permanent slides. In addition, in patients with both FNA and FS, compared to FNA, FS was able to provide a definitive diagnosis in all five ND cases and in 61.1% (11/18) of indeterminate tumors. Intraoperative assessment provided a relative increase of 33.3% in specificity and 38.5% in positive predictive value when compared to preoperative FNA. The addition of FS to FNA was helpful to further refine the diagnoses of parotid gland lesions, which may provide better guidance for surgical intervention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers., Research Question: Are the HAL and HOMER models valid across multiple centers?, Study Design and Methods: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test., Results: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error., Interpretation: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative., (Copyright © 2021. Published by Elsevier Inc.)

This study aimed to present the 2-year experience of the implementation of the Milan System for Reporting Salivary Gland Cytopathology at Alpha Prolipsis Medical Laboratories, a private medical laboratory located in Athens, Greece. A totaI of 102 Fine Needle Aspirations (FNAs) performed since 2018 were included in the study. Reports were issued according to the Milan System for Reporting Salivary Gland Cytopathology. Aspirates were prepared with both conventional and liquid-based cytological methods and were evaluated by two or three Board-certified cytopathologists. Diagnostic reproducibility and accuracy were evaluated. All cases included in this study had histologic follow-up. The diagnostic accuracy of FNA for differentiating between benign and malignant disease according to MSRSGC classification was 93.3%, the specificity was 97.5% and the sensitivity was 82.2%. The positive and negative predictive values were 93.2 and 87.2%, respectively. Our results show that FNA is a valuable examination technique in the preoperative evaluation of salivary gland lesions. The integration of the 2018 Milan System for Reporting Salivary Gland Cytopathology is effective, with an overall accuracy around 95%., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objectives/hypothesis: The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions., Study Design: The effectiveness evaluation of diagnostic methods., Methods: Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated., Results: The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P < .001). No severe complications occurred after FNAB., Conclusions: FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application., Level of Evidence: 4 Laryngoscope, 131:1798-1804, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Aim: Cost-effectiveness comparison between endoscopic ultrasound (EUS)-guided acquisition techniques by fine-needle aspiration (FNA) and fine needle biopsy (FNB) in gastrointestinal lesions is still scarce. EUS-FNB has been shown to be more cost-effective than EUS-FNA, however, when adding rapid on-site evaluation (ROSE) to EUS-FNA, it is unclear whether EUS-FNB remains more cost-effective. Our aim was to assess cost-efficacy of EUS-FNB as compared to EUS-FNA with ROSE in gastrointestinal lesions., Method: All patients who underwent EUS-FNA with ROSE or EUS-FNB at Galilee Medical Center were retrospectively reviewed. Cost-effectiveness analysis was based on the additional EUS sessions needed and on the average cost expenditure to achieve one final pathological diagnosis., Results: Seventy-four cases were included in the final analysis. Of them, 21 patients (28.4%) were in the EUS-FNB group (group A), as compared to 53 patients (71.6%) who underwent EUS-FNA with ROSE (group B). Additional EUS sessions needed to achieve one final pathological diagnosis were needed in 14.3% of group A patients vs 9.4% in group B patients (P = .5). and, the average cost for achieving one final pathological diagnosis was similar in both groups (1226 ± 369$ for group A vs 1158 ± 309.6.7$ for group B, P = .2). Notably, even after analyzing pancreatic and non-pancreatic gastrointestinal lesions separately, there was no cost benefit of EUS-FNB over EUS-FNA with ROSE., Conclusions: Cost-effectiveness analysis was not different between EUS-FNB vs EUS-FNA with ROSE. Thus, the preference of one modality over the other should be based on availability and local expertise., (© 2021 Wiley Periodicals LLC.)

Purpose: Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy., Methods: A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region., Results: Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013., Conclusions: The results of this population-based study describe recent variations over time and between surrounding areas of indicators of 'diagnostic pressure' on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas., (© 2021. The Author(s).)

Background: Molecular testing (MT) refines risk stratification for thyroid nodules that are indeterminate for cancer by fine needle aspiration (FNA) cytology. Criteria for selecting nodules for MT vary and remain largely untested, raising questions about the best strategy for maximizing the usefulness of MT while minimizing the harms of overtesting. We used a unique data set to examine the effects of repeat FNA cytology-based criteria for MT on management decisions and nodule outcomes. Methods: This was a study of adults (age 25-90 years; 281 women and 72 men) with cytologically indeterminate (Bethesda III/IV) thyroid nodules who underwent repeat FNA biopsy and Afirma Gene Expression Classifier (GEC) testing ( N  = 363 nodules from 353 patients) between June 2013 and October 2017 at a single institution, with follow-up data collected until December 2019. Subgroup analysis was performed based on classification of repeat FNA cytology. Outcomes of GEC testing, clinical/sonographic surveillance of unresected nodules, and histopathologic diagnoses of thyroidectomies were compared between three testing approaches: (i) Reflex (MT sent on the basis of the initial Bethesda III/IV FNA), (ii) SemiRestrictive (MT sent if repeat FNA is Bethesda I-IV), and (iii) Restrictive (MT sent only if repeat FNA is Bethesda III/IV) testing approaches. Results: Restricting MT to nodules that remain Bethesda III/IV on repeat FNA would have missed 4 low-risk cancers and 3 noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) (collectively 2% of the test population) but would have avoided diagnostic surgery for 42 benign nodules (12% of the test population). The Restrictive testing strategy was more specific (delta 0.126 confidence interval [CI 0.093 to 0.159] and 0.129 [CI 0.097 to 0.161], respectively) but less sensitive (delta -0.339 [CI -0.424 to -0.253] and -0.340 [CI -0.425 to -0.255], respectively) than the Reflex and SemiRestrictive approaches for detecting NIFTP or cancer. Conclusions: Repeat FNA cytology can guide the selection of cytologically indeterminate thyroid nodules that warrant MT. The Restrictive model of performing Afirma GEC only on nodules with two separate biopsies showing Bethesda III/IV cytology would reduce the rate of diagnostic surgery for histologically benign nodules while missing only rare low-risk tumors. Given the low but nontrivial risks of thyroidectomy, the higher specificity of the Restrictive testing approach disproportionately outweighs the potential harms.

Aims: With ongoing intensive vaccination programme against COVID-19, numerous cases of adverse reactions occur, some of which represent rare events. Enlargement of the injection site&rsquo;s draining lymph nodes is increasingly reported, but is not yet widely recognised as being possibly associated with recent vaccination. As patients at risk of a severe course of COVID-19, indicated by their medical history such as a previous diagnosis of malignancy, receive priority vaccination, newly palpable lymph nodes raise concerns of disease progression. In this case series, we report on five patients who presented with enlarged lymph nodes after COVID-19 vaccination., Methods: Sonography guided fine needle aspiration (FNA) was performed in five patients presenting with PET-positive and/or enlarged lymph nodes after COVID-19 vaccination with either the Pfizer-BioNTech or Moderna vaccine., Results: COVID-19 vaccination had been carried out in all cases, with an interval of between 3 and 33 days prior to FNA. Three of five patients had a history of neoplasms. The vaccine was administered into the deltoid muscle, with subsequent enlargement of either the cervical, supra-, infra- or retroclavicular, or axillary lymph nodes, in four out of five cases ipsilaterally. In all cases, cytology and additional analyses showed a reactive lymphadenopathy without any sign of malignancy., Conclusions: Evidence of newly enlarged lymph nodes after recent COVID-19 vaccination should be considered reactive in the first instance, occurring owing to stimulation of the immune system. A clinical follow-up according to the patient&rsquo;s risk profile without further diagnostic measures is justified. In the case of preexisting unilateral cancer, vaccination should be given contralaterally whenever possible. Persistently enlarged lymph nodes should be re-evaluated (2 to) 6 weeks after the second dose, with additional diagnostic tests tailored to the clinical context. Fine needle aspiration is a well established, safe, rapid and cost-effective method to investigate an underlying malignancy, especially metastasis. Recording vaccination history, including date of injection, site and vaccine type, as well as communicating this information to treating physicians of different specialties is paramount for properly handling COVID-19 vaccine-associated lymphadenopathy.

Introduction: Background The aim of the paper is related to our experience defining the diagnostic accuracy of breast elastosonog-raphy., Objective: The aim of our study is therefore to define the diagnostic accuracy of breast elastosonography in the differential diagnosis of nodular breast neoformations to improve the characterization of the solid lesion and reduce the number of needle aspiration unnecessary for benign formations., Material and Methods: A total of 88 patients were enrolled, who came to the Department with an ultrasound diagnosis of a breast lesion. Each lesion was subjected to mammography and B-mode ultrasonogra-phy with an evaluation of size, echogenicity, and vascularization pres-ence or absence. The use of the ultrasound machine and the respective probe has made it possible to make the measurements. All nodules were subjected to ultrasound-guided FNAC. These data were compared with the results of elastosonographic examination., Results: FNAC results were as follows: CIN 1 in 18 nodules, CIN 2 in 22 nodules, CIN 3 in 36 nodules, CIN 4 in 6 nodules, and CIN 5 in 6 nodules. The sensitivity and specificity of elastosonography found in our case series reported values in line with data reported in the literature, confirming the method's high reliability., Conclusions: The elastosonography could become a complemen-tary technique to mammography and ultrasonography in the future, reducing the costs and risks of additional examinations. Therefore, we believe it is essential to contribute with this additional finding to increasingly accredit this pathway and reduce the discomfort to patients of more invasive methods.

Background: Cytomorphologic distinction of hepatocellular carcinoma (HCC) from its mimics on fine-needle aspiration cytology (FNAC) is often problematic. The present study evaluates the strength of cytomorphology and the utility of an immuno-panel of arginase-1, glypican-3, HepPar-1, thyroid transcription factor (TTF-1) and CK-19 in resolving this diagnostic issue., Methods: FNAC features of 71 nodular hepatic lesions were studied with an immunocyto/ histochemical (ICC/IHC) panel of arginase-1, glypican-3, HepPar-1, TTF-1 taking 10% positivity as "cut-off." Cytomorpholologic diagnoses were compared with diagnoses made on combined cytomorphologic and ICC/IHC approach., Results: Of 71 cases, 32, 10 and 29 had histopathologic, cell block and clinico-radiologic correlation respectively with 55 metastatic adenocarcinomas (MAC), 13 HCCs and one case each of hepatic adenoma (HA), cirrhotic nodule (CN) and intrahepatic cholangiocarcinoma (CC). Cytoplasmic positivity of HepPar-1 and glypican-3 were noted in 11/13 and 8/13 HCCs respectively; while only 3/13 and 1/13 HCCs revealed cytoplasmic positivity for arginase-1 and TTF-1 respectively. Benign hepatic lesions were negative for glypican-3 and TTF-1, but expressed both arginase-1and HepPar-1. Twenty-one of 55 MACs and the lone case of CC were positive for CK-19; however, all MACs and CC cases were negative for HepPar-1, arginase-1, glypican-3 and TTF-1. The immune-panel had sensitivity, specificity and diagnostic accuracy of 100%, 88.9% and 90.6%, respectively, for differentiating HCC from its morphologic mimics., Conclusion: Though a meticulous cytologic evaluation in conjunction with clinicoradiologic profile helps in distinguishing HCC from its benign and malignant mimics; an immunopanel of arginase-1, glypican-3, HepPar-1, TTF-1 and CK-19 drastically improves the diagnostic accuracy., (© 2021 Wiley Periodicals LLC.)

Background: In Fine-needle aspiration cytology (FNAC) of lymph nodes, tissue fragments derived from follicular structures may be observed in specimens. We defined such tissue fragments as follicular tissue fragments (FTF), and investigated differences in cytological findings for FTFs of each histological type., Method: A total of 41 cases with FNAC of lymph nodes were examined. In these cases, the histopathological diagnoses were reactive lymphoid hyperplasia (RLH) (n = 17), follicular lymphoma (FL) (n = 13), diffuse large B-cell lymphoma (DLBCL) (n = 18), and Burkitt lymphoma (n = 1). Specimens were analyzed for the presence of FTFs, and for tingible-body macrophages (TBMs) and monomorphism of lymphocytes in FTFs. FTFs with a maximum diameter of >500 μm were defined as large-FTFs., Results: FTFs were identified in RLH (14/17, 82.4%), FL (13/13, 100%), and DLBCL (3/18, 16.7%). In the RLH subtypes, FTFs were present only in follicular hyperplasia (FH) (14/15, 93.3%) and not in paracortical hyperplasia (0/2). The number of cases with large FTFs among those with FTFs were as follows: RLH (10/14, 71.4%), FL (11/13, 84.6%), and DLBCL (0/3). Similarly, those with TBMs in FTFs were as follows: RLH (13/14, 92.9%), FL (0/13) and DLBCL (2/3, 66.7%). Monomorphism was observed in RLH (1/14, 7.1%) and FL (11/13, 84.6%), but not in DLBCL (0/3)., Conclusions: Distinction between FL and FH is possible by identifying large-FTFs. In FL, TBMs are absent in FTFs and lymphocytes often show monomorphism. Therefore, recognizing FTFs and observing details inside the FTFs are useful for identification and differential diagnosis of FL and FH in FNAC of lymph nodes., (© 2021 Wiley Periodicals LLC.)

Background: Classification of breast lesions into different cytological groups can accurately be done using the International Academy of Cytology (IAC) Yokohama System for reporting breast cytopathology. Fine needle aspiration biopsy (FNAB) of breast lesions has been considered to be the primary investigation in detecting breast cancers, especially in low-cost settings. The main objective of this study was to prospectively re-confirm the diagnostic accuracy of breast FNAB using the IAC Yokohama system. Additionally, separate secondary subgroup analysis was done to confirm the accuracy of breast FNAB excluding lymph-node positive and lymphadenopathy positive tumors., Material and Methods: A prospective study was done on patients undergoing biopsy of breast lesions between September 01, 2019 and November 30, 2020 (519 biopsies on 487 unique patients). Of these 519 histopathology biopsies, 505 had corresponding FNAB report of the same site. The FNAB was reported using the IAC Yokohama system and the most suitable category was allotted in every case. The rates of malignancy for each category and the accuracy of breast FNAB in diagnosing malignancy were calculated., Results: Of the total 487 patients, 120 cases were benign on histology, while 367 were malignant. The rates of malignancy in benign, atypical, suspicious and malignant categories were 5%, 25%, 71%, and 99.7%, respectively. The diagnostic accuracy of atypical, suspicious and malignant categories was calculated as 90.1%, 95.2%, and 93.3%, respectively., Conclusion: The high diagnostic accuracy for each BIRADS category suggest excellent accuracy for Breast FNAB using the IAC Yokohama system., (© 2021 Wiley Periodicals LLC.)

Background: Fine-needle aspiration (FNA) is a well-established modality for diagnosing salivary gland pathologies. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a standardized uniform framework leading to an evidence-based risk of malignancy (ROM). Based on the current literature, ROM in the 6-tier MSRSGC ranges from <5% for neoplasm-benign to >90% for the malignant category. Here, we report our institutional experience adopting MSRSGC., Methods: The cytopathology group at our institution implemented MSRSGC at the end of 2018. Through a query of our laboratory information system, we identified all salivary gland FNA cases from 27 November 2018 to 26 October 2020. The pertinent surgical pathology follow-up was also extracted. After manual curation, data was analyzed in Rv4.0.2., Results: Our cohort comprised of 315 patients undergoing 343 salivary gland FNA biopsies, predominantly on the parotid (90%), 162 with a surgical pathology follow-up. The risk of malignancy ranged from 3.2% in neoplasm-benign (IVA) to 100% in suspicious for malignancy (V) and malignant (VI) categories. ROM in the other categories was: 12.5% for non-diagnostic, 0 for non-neoplastic, 33.3% for atypia of undetermined significance, and 41.9% for salivary gland neoplasm of uncertain malignant potential (SUMP). Most SUMP cases had a basaloid or oncocytoid cytomorphology with similar ROM. In distinguishing benign and malignant salivary gland lesions, FNA had adequacy of 93.6%, a diagnostic yield of 62.2%, a sensitivity of 93.1% and a specificity of 100%., Conclusions: MSRSGC was successfully adopted by our cytology group and clinicians, with overall diagnostic performance similar to previous studies., (© 2021 Wiley Periodicals LLC.)

Introduction: breast lump is the commonest presentation for both benign and maligant breast conditions. Both ultrasound guided and conventional fine needle aspiration cytology (FNAC) have been used for diagnosing of breast malignancy among patients with palpable breast lumps. This study compared diagnostic utility of ultrasound guided versus conventional FNAC in diagnosing breast malignancies among patients with palpable breast lumps at Bugando Medical Centre., Methods: this was a hospital based cross sectional study with a follow up component that combined both retrospective data (from January 2017 to June 2018) and prospective data (from July 2018 to June 2019)., Results: during the study, total of 354 patients (male; female = 1: 32) were enrolled in the study. A total of 134 (37.9%) patients had malignant lesions while 220 (62.1%) of patients had benign lesions confirmed on histology. The diagnostic utility (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) for conventional FNAC was 86.7%, 95.7%, 93.5%, 91.1% and 92.0% with an 8% error margin versus ultrasound guided FNAC all were 100% with a 0% error margin respectively., Conclusion: both ultrasound guided and conventional FNAC show almost perfect agreement with histology. However, ultrasound guided FNAC has a higher diagnostic utility relative to conventional FNAC in diagnosing breast malignancies., Competing Interests: The authors declare no competing interests., (Copyright: Tresphory Bonephace Kamushaga et al.)

High cell viability and recovered cell concentration are typical quality control requirements for single-cell processing and quality data. This protocol describes procedures for sampling, live-cell biobanking, preprocessing for single-cell RNA sequencing, and analysis of fine-needle aspiration (FNA) samples of the skin. The minimally invasive nature of FNA collection is more accepted by patients and allows for frequent longitudinal sampling, resulting in high-quality single-cell sequencing data that capture cellular heterogeneity in clinical samples., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Rationale: Metastasis of neoplasms to the eye is quite uncommon. In this case report, we describe a patient where primary esophageal cancer was diagnosed by fine needle aspiration biopsy (FNAB) of an iris tumor., Patient Concerns: A 70-year-old male complained of redness and discomfort in the right eye., Diagnosis and Interventions: The patient's right eye was diagnosed as idiopathic uveitis, and a topical steroid was administered. As vitreous opacities were observed even after topical therapy, oral prednisolone was administered. On slit-lamp examination of the right eye, an iris mass with neovascularization was seen in the anterior chamber. A metastatic tumor was suspected, and FNAB was performed. Histology revealed squamous cell carcinoma. Systemic workup revealed esophageal cancer with several metastases. Best-corrected visual acuity decreased to 20/400, and intraocular pressure was 40 mmHg in the right eye. Two iris tumors with neovascularization were present extending into the anterior chamber with posterior iris synechiae and 360 degree peripheral anterior synechiae. Intraocular pressure in the right eye was medically managed with hypotensive eye drops and oral acetazolamide. Iris metastases were treated with 40 Gray of radiation therapy and concurrent chemotherapy., Outcomes: The tumor regressed, but intraocular pressure was refractory to treatment because of 360 degree goniosynechial closure. The right eye lost light perception six months after treatment commenced, and the patient died 9 months after the onset of therapy due to multiple systemic metastases., Lessons: This is a rare case of masquerade syndrome without systemic symptoms in which FNAB of an iris tumor led to a diagnosis of metastatic esophageal squamous cell carcinoma. Although the patient lost his sight due to uncontrollable ocular hypertension, systemic chemotherapy, and radiation therapy were initially effective in the treatment of the metastatic iris tumor. As the prognosis of patients with metastatic iris tumors is poor, it is important for ophthalmologists to consider such diagnoses and conduct systemic investigations when necessary., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Immuno-oncology therapies are now part of the standard of care for cancer in many indications. However, durable objective responses remain limited to a subset of patients. As such, there is a critical need to identify biomarkers that can predict or enrich for treatment response. So far, the majority of putative biomarkers consist of features of the tumor microenvironment (TME). However, in preclinical mouse models, the collection of tumor tissue for this type of analysis is a terminal procedure, obviating the ability to directly link potential biomarkers to long-term treatment outcomes., Methods: To address this, we developed and validated a novel non-terminal tumor sampling method to enable biopsy of the TME in mouse models based on fine needle aspiration., Results: We show that this technique enables repeated in-life sampling of subcutaneous flank tumors and yields sufficient material to support downstream analyses of tumor-infiltrating immune cells using methods such as flow cytometry and single-cell transcriptomics. Moreover, using this technique we demonstrate that we can link TME biomarkers to treatment response outcomes, which is not possible using the current method of terminal tumor sampling., Conclusion: Thus, this minimally invasive technique is an important refinement for the pharmacodynamic analysis of the TME facilitating paired evaluation of treatment response biomarkers with outcomes and reducing the number of animals used in preclinical research., Competing Interests: Competing interests: All authors were employees of and shareholders in AstraZeneca at the time of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of fine-needle aspiration (FNA) as a primary tool in the diagnosis of breast carcinoma provides opportunity for early proliferative characterization of the tumor. This study was undertaken to assess DNA ploidy and S-phase (SPF) fraction by flow cytometry in fine needle aspirates of patients with breast cancer., Method: Fifty patients of breast cancer diagnosed on fine needle aspiration cytology (FNAC) and who subsequently underwent either mastectomy or lumpectomy were included. Material obtained by FNAC was subjected to DNA ploidy and SPF analysis. Immunohistochemical estimation of Ki-67 was done on histopathology sections. The proliferation markers (SPF and Ki-67) were compared with each other and with the histopathologic parameters., Results: On DNA flow cytometry, 27 (54%) cases were aneuploid and 23 (46%) cases were diploid. The median SPF was 12.43% and 4.03% in aneuploid and diploid tumors respectively. Median Ki-67 among aneuploid tumors was 28.6% compared to 8.7% among diploid tumors. Aneuploid tumors were significantly associated with higher values of SPF and Ki-67, with Kappa 0.437 and agreement of 72%. Diploid tumors showed lower values of SPF and Ki-67, with Kappa 0.455 and agreement of 72.7%. Correlation among SPF and Ki-67 was highly significant with Kappa value 0.446, P value of .002 and agreement of 72.3%., Conclusion: DNA ploidy and proliferative activity by flow cytometric SPF estimation on fine needle aspirates from breast cancer can provide valuable prognostic and predictive information at the time of diagnosis in patients with breast cancer. This might help in selection of appropriate treatment modality., (© 2021 Wiley Periodicals LLC.)

Introduction: Neuroblastoma (NB), Wilms tumor (WT), hepatoblastoma (HBL), germ cell tumors (GCT), rhabdomyosarcoma (RMS), and so forth are the commonly identified solid tumors in infants. Invasive diagnostic techniques are more challenging in infants than older children. fine needle aspiration cytology (FNAC) is a safe, minimally invasive and outpatient procedure which is time and cost-effective for solid tumor diagnosis. This study aims to evaluate the role of FNAC in the diagnosis of various infantile solid tumors., Methods: In this retrospective study, 61 cases of FNA of infant solid tumors were retrieved from the cytology archives over a period of 5 years from January 2013 to December 2017. Cytomorphology was studied and immunohistochemistry on cell block was performed wherever feasible. Histopathological correlation was done in 19 cases., Results: Of the 61 cases studied, 60 cases were included in the study of which 35 were male and 25 were female. Infantile solid tumors constituted 7.3% of all pediatric solid tumors reported in cytopathology division of our Institute. The most common final diagnosis was NB (15, 25%) followed by HBL (13, 21.6%), WT (10, 16.6%), RMS (nine, 15%) and GCT (nine, 15%). The commonest site was abdominal-pelvic (42, 70%). A definitive independent diagnosis could be made on FNA in 48 cases (80%). Follow-up was done for 1.5 to 4 years (mean 26 months). The highest and lowest mortality was noted in NB (64.3%) and WT (12.5%) respectively., Conclusion: This study concludes that FNAC can be adopted as a diagnostic modality in infant solid tumors., (© 2021 Wiley Periodicals LLC.)

Our organoid generation technique has allowed for the development of downstream organoid applications. Here, we detail an accessible, straightforward protocol for immunofluorescent staining and imaging of thyroid cancer organoids, particularly those with tumor de-differentiation. Immunofluorescence is a powerful tool to help understand the localization of cell types within organoids and determine the interactions between those cells. As organoids have been shown to recapitulate patient tumor morphology, immunofluorescent staining and imaging of organoids allows for enhanced understanding of near in vivo structures. For complete details on the use and execution of this protocol, please refer to Lee et al. (2020) and Vilgelm et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Recent advances in interventional radiology have resulted in the utilization of small lymph node biopsies, including fine-needle aspiration (FNA) and core needle biopsy (CNB) as an initial diagnostic tool in hematopathology. A major challenge to the utilization of FNA and CNB is the limited-to-scant tissue often available. We propose delegation of the task of handling biopsy specimens to the laboratory staff by the biopsy operators, in order to optimize the utilization of the specimen. Furthermore, in order to effectively diagnose hematolymphoid neoplasms a variety of ancillary tests including immunohistochemistry, flow cytometry, molecular analysis, florescence in situ hybridization (FISH) are necessary. We propose morphological evaluation coupled with careful utilization of ancillary studies along with clinical correlation to approach the correct diagnosis. Our morphological assessment considers the types of proliferating cell population: mainly small cells, sheets of large cells, or scattered large cells among small cells. This is followed by employment of the corresponding immunopanel to assess the differential diagnosis in each of the three categories. We also elaborate on the importance for pathologists to become proficient in understanding the limitations of small tissue biopsies as well as the differences in interpretation, and wording their reports to help clinicians and direct them to further investigate and/or to re-biopsy when necessary., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyze the diagnostic benefit of fine needle aspiration biopsy cytology (FNAB-C) and core needle biopsy tissue (CNB-T) with the addition of thyroglobulin (Tg) in the washout of the needle or BRAF V600E mutation assessment in assessing cervical lymph node metastasis (LNM) in papillary thyroid carcinoma., Materials and Methods: A total of 186 lymph nodes were punctured by fine or core needle. The diagnostic performance of FNAB-C and CNB-T with Tg in the washout or BRAF V600E mutation assessment was compared., Results: The optimal cutoff value of FNAB-Tg was 1.0 ng/ml, with an AUC of 0.976. The sensitivity and specificity of FNAB-C in predicting cervical LNM were 97.4% and 71.4%, respectively, and the addition of FNAB-Tg could contribute to a sensitivity of 100% and a specificity of 95%, but the introduction of BRAF V600E mutation assessment was associated with a decreased sensitivity of 96.3% and a decreased specificity of 50.0%. The FNAB-Tg level showed a comparable distribution in malignant lymph nodes with different TgAb statuses, serum TSH levels, and serum Tg levels. The sensitivity and specificity of CNB-T in predicting cervical LNM were 98.9% and 100%, respectively. The addition of CNB-Tg did not alter the diagnostic ability, but the introduction of BRAF V600E mutation assessment obtained the best performance, with a sensitivity of 100% and specificity of 100%., Conclusion: The sensitivity and specificity of FNAB-C could be increased if combined with FNAB-Tg. CNB-T alone could provide satisfactory diagnostic reliability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhang, Du, Dai, Luo, Fang and Ge.)

Background: High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT., Methods: The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed., Results: The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively., Conclusions: SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma., (© 2020 American Cancer Society.)

Background: Although 10% formalin is a standard preservative in pancreatic FNAs, the effect of CytoLyt on pancreatic tissue preservation has not been systematically explored., Methods: Smears and cell blocks from CytoLyt-fixed (CF-CBs) and formalin-fixed (FF-CBs) pancreatic FNAs were blindly reviewed without knowledge of the fixative used, and the presence of tissue/tumor autolysis was noted. Controls included FF-CBs from pancreatic FNAs, CF-CBs from nonpancreatic FNAs, and 4 pancreatic FNAs with matched CF-CBs and FF-CBs., Results: We found that 62 of 85 (73%) pancreatic FNAs with CF-CBs showed significant autolysis, which was most pronounced in acinar cells and/or tumor cells with benign acinar cells in the background, compared with 2 of 46 (4%) FF-CBs (P < .0001) and 3 of 26 (12%) CF-CBs from nonpancreatic FNAs (73% vs 12%; P < .0001). Of the 4 pancreatic FNAs with matched CF-CBs and FF-CBs, all 4 CF-CBs showed marked autolysis versus none of the matched FF-CBs. Of the 23 (27%) pancreatic FNAs with CF-CBs that did not show autolysis, 10 had no acinar cells, and 7 had only minute tissue fragments on CB., Conclusion: While CytoLyt is a useful fixative for nonpancreatic FNAs it is a suboptimal fixative for pancreatic FNAs and is associated with tissue/tumor autolysis in the majority of cases, influencing morphologic evaluation, and potentially immunocytochemical staining. Autolysis appears to be due to acinar enzymes whose effect is likely interrupted/inhibited by formalin fixation. Cytopathologists and cytotechnologists should be mindful of this pitfall and should avoid using CytoLyt as a fixative for pancreatic FNAs., (© 2020 American Cancer Society.)

Purpose: The clinical impact of the SIAPEC/SIE 2014 classification for thyroid cytology has been addressed in few studies that evaluated the malignancy rate and the relative prevalence of each category. No study analyzed its intra-observer and inter-observer reproducibility, so far., Methods: We retrospectively collected all "indeterminate" lesions diagnosed before (2011-2014) and after (2015-2018) the application of the SIAPEC/SIE 2014 classification at our Institution. Their relative malignancy risks were calculated based on available histological diagnoses. Cytological and clinical features of TIR3A were compared with the surgical outcome. Finally, a large set of samples was re-evaluated in blind of the original cytological and histological diagnoses by two pathologists, independently., Results: The prevalence of "indeterminate" diagnoses increased in years 2015-2018 (302/1482, 21% with 14% of TIR3A and 7% TIR3B categories) compared to years 2011-2014 (261/1680, 16%). Surgery was performed in 27% TIR3A and in 97% TIR3B cases. Malignancy rates were 40% for TIR3B and 17% for TIR3A, but were greatly influenced by the adoption of the WHO 2017 re-classification of encapsulated follicular-patterned lesions (decreasing to 28% and 6%, respectively). No criteria except for tumor size were associated to malignancy in TIR3A category. Intra-observer agreement of the experienced pathologist was 122/141 (86%), whereas inter-observer agreement between the expert and in-training pathologist was 95/141 (67%)., Conclusions: In this real-life experience, the sub-classification of TIR3A and TIR3B slightly increased the overall prevalence of "indeterminate" diagnoses. Malignancy rates were higher than estimated for both TIR3A and TIR3B categories. Agreement among observers highly depended on pathologist's training.

Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC., (© 2020 John Wiley & Sons Ltd.)

Introduction: Thyroid fine-needle aspiration (tFNA) is a powerful screening tool for assessing solitary thyroid nodules. Generally, morphologic evaluation of smears yields an accurate diagnosis; but, in some cases it is useful to have a cell block (CB) to conduct ancillary studies such as immunohistochemistry (IHC). Cytologic diagnoses guide clinical decisions, so it is important that accurate and efficient diagnoses be rendered. Our study evaluates the diagnostic utility of the CB in the evaluation of tFNAs., Materials and Methods: We performed a retrospective chart review of all tFNA specimens from January 2014 to July 2019. Data collected included TAT (in days), diagnosis, if a CB was prepared, and if it was diagnostically contributory. Descriptive statistics were calculated. Data were analyzed using the χ 2 test and the Mann-Whitney U-test., Results: Of the 2321 specimens, 40.2% (933) had CB and only 0.3% (7) were diagnostically contributory. IHC was used for 2 cases. For cases with CB, the median TAT was one day [0-18 days] and the median TAT without CB was 0 [0-9 days]. There was a significant difference in TAT between cases with a CB and those without. Most cases without a CB had same-day TAT (66.4%), whereas only 1.1% of those with a CB had same day TAT. Cases with CB were more likely to have a TAT >1 day (65% versus 12.1%) or >3 days (25.4% versus 10%) than those without a CB (P < 0.0001)., Conclusions: We found the diagnostic utility of CB for tFNAs to be very low. The addition of a CB added at least 1 day to the TAT in all diagnostic strata. The additional time causes patients to wait for results, even for nondiagnostic studies. The increased TAT, resources, and manpower use may be reduced if CB were produced only as needed-if the results of the smear were ambiguous or if ancillary tests were needed to confirm the diagnosis., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Orbital hematolymphoid lesions are rare and usually encountered in elderly patients. Orbital lesions are not easy to biopsy: hence fine needle aspiration cytology (FNAC) can be a very good diagnostic modality for these lesions., Materials and Methods: Cases of orbital masses subjected to FNAC dating from 2013 to 2020 were retrieved from our archives. A total of 16 cases with biopsy confirmation were included. All clinical details, the type of procedure, details of the immunocytochemistry (ICC) performed on smear, follow-up biopsy, and their haematological work-up were analysed in detail., Results: Sixteen biopsy-confirmed cases had been diagnosed as orbital haematolymphoid lesions on cytomorphology and further categorised with ancillary studies including ICC. In twelve instances, the cytology impression was congruent with the histopathological diagnosis and eight of the sixteen cases (50%) proved to be primary orbital lymphoma. Four were secondary orbital lymphomas and the remaining four included one case each of plasmacytoma, myeloid sarcoma, Rosai-Dorfman disease and angiolymphoid hyperplasia with eosinophilia., Conclusion: FNAC is a minimally invasive procedure for diagnosing most of the haematolymphoid orbital lesions and it has a rapid turnaround time. The accuracy of cytomorphology combined with ICC on smears/cell blocks can be as good as a biopsy for exact categorisation. Additionally, aspirate smears are preferred samples for cytogenetics compared to formalin-fixed tissue blocks, as molecular cytogenetics techniques are frequently employed for diagnostic, prognostic, and therapeutic purposes., (© 2020 John Wiley & Sons Ltd.)

The cytological features of granular cell tumour (GCT) are generally quite typical but, in some cases, the fine needle aspiration cytology (FNAC) diagnosis of GCT may be difficult or impossible because of unusual sites of onset or equivocal cytological features. In this report, two GCTs with atypical FNAC features are described in order to investigate the causes and provide possible diagnostic tips. From a series of nine histologically proven GCTs, two inconclusive FNAC cases were retrieved. Smears were poorly cellular showing isolated naked nuclei, anisonucleosis, granular chromatin and occasional small nucleoli. The background was finely granular in one case. Histological controls of these cases revealed marked fibrosis. Tumour-associated fibrosis in GCT is variable and does not seem to influence clinical behaviour but it influences the harvest and the integrity of granular cells collected by FNAC. When GCT smears are poorly cellular, attention should be paid to the granular background and to the few granular cells, if any, as they might be the only features to suggest a GCT., (© 2020 John Wiley & Sons Ltd.)

Background: In small animal medicine, ultrasound-guided fine-needle lymph node sampling plays a pivotal role in the diagnostic investigation of a range of pathologies including the staging of neoplastic disease. Traditionally fine needle aspiration cytology (FNAC) has been employed to produce samples, but fine needle non-aspiration cytology (FNNAC) has been suggested to generate superior sample quality and diagnosticity., Methods: In a randomised control trial, 104 canine and feline lymph nodes were each sampled by both techniques. The cytological samples were then submitted to pathologists who were blinded to the technique used to generate each sample. They determined if the sample was diagnostic or non-diagnostic and graded the sample in terms of the degree of cellularity, cellular preservation and haemodilution., Results: It was found that lymph node samples obtained using the FNAC technique were more likely to be diagnostic (p = 0.043) than samples obtained using the FNNAC technique. In addition, FNAC samples had significantly higher cellularity than FNNAC counterparts (P = 0.043). No significant difference in cell preservation or haemodilution was found between samples from the FNAC and FNNAC groups., Conclusion: In this study, FNAC was superior to non-aspiration cytology for the sampling of canine and feline lymph nodes as it generated a higher number of diagnostic samples with greater cellularity., (© 2021 British Veterinary Association.)

Objectives: This study aimed to evaluate benefits in terms of time and cost of percutaneous ultrasound-guided fine-needle aspiration biopsy/core-needle biopsy (US-FNAB/CNB) for the diagnosis of primary laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) in comparison with direct laryngoscopic biopsy (DLB) under general anesthesia., Study Design: Retrospective case-control study., Setting: Single operator of a single center., Subjects and Methods: From 2018 to 2019, 28 patients who underwent percutaneous US-FNAB/CNB for the diagnosis of untreated LHSCC were enrolled. All US-FNAB/CNBs were performed in the outpatient department by a single head and neck surgeon. Their results were compared with those of 27 patients who underwent DLB under general anesthesia., Results: No major complications occurred in the US-FNAB/CNB and DLB groups. Time to biopsy, time to pathologic diagnosis, and time to treatment initiation in the US-FNAB/CNB and DLB groups were 0 and 14 days ( P < .001), 7 and 20 days ( P < .001), and 24 and 35 days ( P = .001), respectively. Procedure-related costs were $368.5 and $981.0 in the US-FNAB/CNB and DLB groups ( P < .001)., Conclusions: US-FNAB/CNB offers true benefits in terms of time and cost over those given by conventional DLB for diagnosis of LHSCC in indicated patients.

Introduction: To evaluate the incidence, risk of malignancy, and management of "suspicious for malignancy" (SFM) for non-papillary carcinoma diagnoses according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)., Materials and Methods: A retrospective search was performed for all thyroid fine-needle aspirations (FNAs) with an SFM diagnosis in the electronic Pathology database at The Johns Hopkins Hospital from 2000 to 2019. During this period, a total of 644 cases were diagnosed as SFM. Of these, 55 cases of "suspicious for non-papillary thyroid carcinoma" (SNPTC) were identified. These 55 cases were then compared with 65 random cases of "suspicious for papillary thyroid carcinomas" (SPTC) diagnoses as a control group., Results: The SNPTC subgroup consisted of 28 cases of "suspicious for medullary thyroid carcinoma" (SMTC) (50.91%), 4 cases of "suspicious for metastasis" (SMET) (7.27%), 3 cases of "suspicious for malignant lymphoma" (SML) (5.45%), 2 cases of "suspicious for poorly-differentiated thyroid carcinoma" (SPDC) (3.64%), and 18 cases of "suspicious for malignancy, not otherwise specified" (SNOS) (32.73%). When compared to SPTC, SNPTC patients' average age was older (P = 0.004). Ancillary studies assisted in diagnosing SNPTC more so than SPTC (P < 0.001). Immunohistochemical studies were performed for 11 cases, molecular studies for 6 cases, and needle rinse calcitonin level for 1 case. When correlated with surgical follow-ups, the risk of malignancy (ROM) was 91.18% for SNPTC compared to 93.75 for SPTC%., Conclusions: SNPTC was rarely diagnosed when compared with SPTC. SMTC was the most commonly diagnosed SNPTC subgroup, followed by SNOS. The ROM of SNPTC was slightly lower than that of SPTC. Ancillary studies and previous clinical history, in addition to cytomorphology, was helpful when rendering the diagnosis of SNPTC., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Adrenal gland lesions span a range of entities from benign and malignant primary neoplasms to metastatic tumors. Fine-needle aspiration (FNA) provides a minimally invasive diagnostic tool to stage patients with known malignancy and procure material for molecular testing. This study characterizes the clinicopathologic associations of patients with adrenal gland FNA from 2 large hospitals., Materials and Methods: FNAs were identified by query of electronic medical record from 2002-2019. Clinical and pathological information was collated and correlated with corresponding surgical diagnosis when available., Results: Of 139 cases, the majority (n = 127, 91%) were adequate computed tomography-guided FNAs and included the following diagnoses: positive for malignancy (n = 77, 55%), negative for malignancy (n = 32, 23%), neoplastic cells present (n = 16, 12%), nondiagnostic (n = 12, 9%), atypical (n = 1, 1%), and suspicious for carcinoma (n = 1, 1%). The majority (94%, n = 72 of 77) of malignancies were metastatic tumors, most frequently carcinoma (n = 53 of 72, 74%), followed by melanoma (n = 11 of 72, 15%), lymphoma (n = 4 of 72, 6%), and sarcoma (n = 4 of 72, 6%). Metastatic carcinomas included lung (n = 21 of 72, 29%), genitourinary (n = 12 of 72, 17%), and hepatobiliary or gastrointestinal tract (n = 11 of 72, 15%) primaries. Primary adrenal neoplasms (n = 23) included adenomas (n = 11 of 23, 48%), pheochromocytomas (n = 4 of 23, 17%), and myelolipomas (n = 3 of 23, 13%). Thirty-two patients with metastases died of disease after median follow-up of 8 months., Conclusions: High specimen adequacy (n = 127, 91%) and low indeterminate rates (n = 2, 2%) are achieved with adrenal FNA. Most aspirated lesions represent metastases from primary lung carcinomas, but other primary sites including those below the diaphragm are part of the diagnostic differential. Adrenal metastasis was associated with a poor prognosis, with median survival of 8 months., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)