Gardezi M, Fakhari M, Libert D
… +7 more, Dey R, Phan T, Shiu T, Adeniyi AM, Martin C, Snowball B, Lowe AC
Cancer Cytopathol
· 2025 Dec · PMID 41258809
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BACKGROUND: The high cost of professional-quality microscopes for pathology labs can create a barrier to the availability of diagnostic services, especially in resource-constrained settings. Low-cost portable microscopes...BACKGROUND: The high cost of professional-quality microscopes for pathology labs can create a barrier to the availability of diagnostic services, especially in resource-constrained settings. Low-cost portable microscopes (LCPMs) are popular for recreational use and widely available. To our knowledge, they have not been evaluated for use in rapid on-site evaluation (ROSE). The aim of this study was to identify which LCPMs have the potential for clinical use. METHODS: In this investigation, five LCPMs were evaluated by 18 pathology professionals to determine the adequacy of fine-needle aspiration (FNA) biopsy readings using patient-generated material. Participants were surveyed to systematically assess preferred and undesirable characteristics of LCPMs and to provide feedback on their use. RESULTS: Most expressed that though LCPMs were not a comparable replacement for standard microscopes, they were a better option than nothing and could be helpful in instances with highly cellular and relatively flat slide preparations. Most participants believed that LCPMs could be used for ROSE in resource-limited environments. CONCLUSIONS: Pathology professional evaluated LCPMs on simulated fine-needle aspiration biopsy smear slides. The feedback they provided in this study suggests that LCPMs may be a feasible alternative to standard microscopes for ROSE in resource-limited settings.
Mericoz CA, Caylak G, Sanioglu ES
… +3 more, Satilmis ZS, Dur Karasayar AH, Kulac I
Cancer Cytopathol
· 2025 Dec · PMID 41217814
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BACKGROUND: High-quality RNA is essential for accurate molecular testing. This study evaluates the impact of cytological preparation techniques (May-Grünwald-Giemsa [MGG], Papanicolaou [PAP], Diff-Quik, and air-dried) on...BACKGROUND: High-quality RNA is essential for accurate molecular testing. This study evaluates the impact of cytological preparation techniques (May-Grünwald-Giemsa [MGG], Papanicolaou [PAP], Diff-Quik, and air-dried) on RNA quality in smear slides. METHODS: A total of 182 smears were prepared from fresh surgical specimens of 26 patients using seven different techniques. RNA was isolated, reverse-transcribed, and analyzed using quantitative polymerase chain reaction (qPCR). RNA quality was assessed using ΔCt (ΔCt = 45 - Ct, cycle threshold), where higher ΔCt indicates better RNA quality. RESULTS: RNA quality, measured by ΔCt, showed clear differences (p < .001) in-between preparation methods, whereas RNA concentration did not differ significantly among smear types (p = .07). MGG-stained smears (both film- and coverslip-mounted) demonstrated the highest and most consistent ΔCt values. PAP-stained smears yielded the lowest ΔCt values, indicating the poorest RNA quality. Air-dried unstained smears showed highly variable ΔCt values and frequent amplification failures. Diff-Quik preparations had intermediate performance. Mounting method (film vs. coverslip) did not significantly affect RNA quality. CONCLUSION: Among cytology smear techniques, MGG provided the best RNA preservation, PAP the worst, and air-dried slides yielded inconsistent results. These findings highlight the critical role of smear preparation in preserving RNA for molecular testing, especially RNA-based next-generation sequencing.
Yang R, Gereg C, Olave MC
… +2 more, Yoon E, Cai G
Cancer Cytopathol
· 2025 Nov · PMID 41159799
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BACKGROUND: Accurate cytologic diagnosis of pancreatic ductal adenocarcinoma (PDAC) remains challenging. In this retrospective study, the authors assessed the utility of p53, SMAD4, and paraoxonase-2 (PON2) expression in...BACKGROUND: Accurate cytologic diagnosis of pancreatic ductal adenocarcinoma (PDAC) remains challenging. In this retrospective study, the authors assessed the utility of p53, SMAD4, and paraoxonase-2 (PON2) expression in fine-needle aspiration (FNA) diagnosis of PDAC. METHODS: Cytologic cases with sufficient cell block material were retrieved from pathology archives. p53 and SMAD4 immunostains were performed in two separate cohorts, primary cohort (10 benign and 23 PDAC cases) and indeterminate cohort (3 atypical and 17 suspicious cases). PON2 immunostain was performed in the primary cohort (10 benign and 23 PDAC cases). p53 and SMAD4 immunostains were qualitatively assessed and PON2 test was evaluated by semiquantitative H-score. RESULTS: In the primary cohort, p53 aberrant expression and SMAD4 loss were identified in 74% and 48% of PDAC cases compared to none in benign lesions. The combination of p53 and SMAD4 achieved a superior performance with an area under the curve (AUC) value of 0.96, compared to either marker alone (AUC = 0.87 and 0.74, respectively). In the indeterminate cohort, p53 aberrant expression or SMAD4 loss was seen in 13 of 17 (76%) malignant follow-up cases. PON2 was variably expressed in PDAC cases with H-scores ranging from 110 to 290, significantly higher in PDACs compared to benign cases (p < .001). Furthermore, strong PON2 expression was seen in two PDAC cases with wild-type p53 and intact SMAD4 expression. CONCLUSIONS: Combined p53 and SMAD4 immunostaining could help improve FNA diagnosis of PDACs, particularly in challenging cases. PON2 is differentially expressed in PDAC cases and may serve as a potential biomarker, warranting further investigation.
Wang M, Abi-Raad R, Adeniran AJ
… +5 more, Krishnamurti U, Buza N, Hui P, Cai G, Sun T
Cancer Cytopathol
· 2025 Nov · PMID 41159755
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BACKGROUND: Pelvic washing (PW) cytology has been excluded from endometrial cancer staging by the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, and its prognostic significance in early stage...BACKGROUND: Pelvic washing (PW) cytology has been excluded from endometrial cancer staging by the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, and its prognostic significance in early stage disease remains controversial. In this study, the authors evaluated the clinicopathologic correlates and prognostic impact of positive PW cytology in a large institutional cohort using a matched case-control design. METHODS: A retrospective case-control cohort was created by reviewing PWs for endometrial cancer from 2013 to 2023 in the authors' pathology database. Cases with positive PW were retrieved from consecutive patients who had FIGO 2009 stage I or II endometrial cancer. The control group was comprised of randomly selected patients with negative PWs who were matched to patients in the positive PW group on patient age, tumor histologic subtype, FIGO grade, and disease stage. Cox proportional hazards models and multivariable logistic regression analyses were used to correlate survival outcomes and to identify predictors of cytologic positivity. RESULTS: The cohort included 88 patients who had positive PW cytology and 223 matched controls. Positive PW cytology was independently associated with significantly worse disease-free survival (hazard ratio, 4.33; p < .001) and demonstrated borderline significance for overall survival (hazard ratio, 1.67; p = .05). The presence of free-floating tumor cells in the fallopian tubes was an independent predictor of positive PW cytology (p < .001). CONCLUSIONS: The current study demonstrates that positive PW cytology is an independent adverse prognostic factor in patients with stage I/II endometrial cancer and suggests that PW cytology status should be considered for accurate risk stratification of patients who have early stage endometrial cancer although it is not part of the current FIGO staging criteria.
Emechebe DY, Patil SA, Collins T
… +3 more, Zhu LC, Silverman JF, Dodd LG
Cancer Cytopathol
· 2025 Nov · PMID 41139993
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BACKGROUND: Fine-needle aspiration cytology (FNAC) is a preferred method for evaluation of thyroid nodules. Under The Bethesda System for Reporting Thyroid Cytopathology, approximately 15%-30% of FNAC results fall into a...BACKGROUND: Fine-needle aspiration cytology (FNAC) is a preferred method for evaluation of thyroid nodules. Under The Bethesda System for Reporting Thyroid Cytopathology, approximately 15%-30% of FNAC results fall into an indeterminate category: atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM), Bethesda classes III, IV, and V respectively. Molecular testing of indeterminate nodules helps evaluate the risk of malignancy and guide management decisions. This retrospective study assesses the impact of molecular testing on thyroid nodule classification in our institution, with an emphasis on indeterminate results. METHODS: A 9-year retrospective analysis (January 2015-December 2023) was conducted at the University of North Carolina Health System. FNAC cases were classified per The Bethesda System. Molecular testing results and, when available, surgical pathology outcomes were reviewed. The study compared pre- and post-implementation data of routine reflex molecular testing of thyroid nodule diagnosis. RESULTS: A total of 3992 thyroid aspirates were evaluated: 490 (12.3%) nondiagnostic (class I), 2096 (52.5%) benign (class II), 1041 (26.1%) AUS (class III), 136 (3.4%) FN (class IV), 89 (2.2%) SFM (class V), and 140 (3.5%) malignant (class VI). Indeterminate cytology (classes III-V) accounted for 32% of all aspirates (n = 1266). Before molecular testing, the AUS rate was 19.8% with an AUS:malignant ratio of 5.4. Post-implementation, the AUS rate rose to 30.1%, with a ratio of 8.9. This increase was statistically significant (p = .029). CONCLUSION: Implementation of molecular testing was associated with a significant rise in indeterminate cytologic diagnoses, particularly AUS.
Furuhata A, Teramoto Y, Minamiguchi S
… +2 more, Hirata M, Haga H
Cancer Cytopathol
· 2025 Nov · PMID 41081342
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BACKGROUND: Urothelial carcinoma with squamous differentiation (UCSD) carries adverse outcomes, yet cytological recognition is challenging because keratinized atypical squamous cells (ASCs) often show deceptively low nuc...BACKGROUND: Urothelial carcinoma with squamous differentiation (UCSD) carries adverse outcomes, yet cytological recognition is challenging because keratinized atypical squamous cells (ASCs) often show deceptively low nuclear-to-cytoplasmic ratios. A size-based ASC classification anchored to neutrophils was evaluated as a biological internal reference. METHODS: All cytology specimens were prepared with the ThinPrep liquid-based cytology system. Seventeen urine cytology specimens from histologically confirmed UCSD and 79 cytologically benign (BE) specimens with squamous cells were retrospectively reviewed. ASCs with orangeophilic cytoplasm were subclassified by nuclear size relative to the adjacent neutrophils: ASC-S (small nuclei; >1× neutrophil) and ASC-L (large nuclei; >2× neutrophil). Counts were obtained from five high-power fields. UCSD was stratified by the extent of squamous differentiation (<50% vs. ≥50%). RESULTS: No ASC-S/L was identified in BE specimens, whereas either subtype was present in 15 of the 17 UCSD cases, which yielded a cohort-level sensitivity of 88% and specificity of 100% for UCSD detection (95% CI, 65.7%-96.7% and 95.4%-100%, respectively). ASC-S was more prevalent than ASC-L, and was observed across Paris System categories-including atypical urothelial cells (AUCs)-whereas ASC-L appeared mainly in suspicious for high-grade urothelial carcinoma/high-grade urothelial carcinoma. ASC-S counts tended to increase with greater histological squamous differentiation, and were detectable even when tissue involvement was <50%. CONCLUSIONS: Neutrophil-calibrated ASC classification provides an objective, biologically grounded framework that aligns cytology with histology in UCSD. Reporting ASC-S/L-particularly ASC-S in equivocal (AUC) specimens-may facilitate earlier recognition of squamous differentiation and inform subsequent tissue evaluation. Prospective, multi-institutional validation with interobserver agreement and receiver operating characteristic-based thresholds is warranted.
Ye J, Goldhammer N, Vohra P
… +14 more, Warhadpande S, de Castro GC, Rodas CKM, Moasser MM, Ramalingam K, Abe SE, Alvarado M, Ewing C, Goodwin KM, Mukhtar RA, Wong JM, Esserman LJ, Balassanian R, Rosenbluth JM
Cancer Cytopathol
· 2025 Nov · PMID 41066221
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BACKGROUND: Patient-derived organoids (PDOs) generated from benign breast tissue and breast carcinomas have successfully recapitulated their in vivo counterparts. PDOs model tumorigenesis and allow for screening novel th...BACKGROUND: Patient-derived organoids (PDOs) generated from benign breast tissue and breast carcinomas have successfully recapitulated their in vivo counterparts. PDOs model tumorigenesis and allow for screening novel therapeutics personalized to individual patients. However, acquiring cells to generate PDOs is cumbersome. This study demonstrates the feasibility of fine-needle aspiration biopsy (FNAB) for harvesting cells for PDOs modeling ductal carcinoma in situ (DCIS) and compares the efficacy with core needle biopsy (CNB). METHODS: Surgical specimens from patients with biopsy-proven DCIS were used for this study. CNB was performed on fresh specimens in the operating room, and tissue was mechanically dissociated before culture in basement membrane extract (BME) and organoid medium to generate PDOs. FNAB was performed in the pathology gross room on fresh specimens, and the aspirate was similarly submitted for culture. RESULTS: PDOs were successfully generated in 15 of 18 specimens obtained by CNB and seven of 11 specimens obtained by FNAB. The average time to initial organoid growth was 4 days for FNAB specimens compared to 19.3 days for CNB specimens. Tumor cells were seen on seven of 11 FNAB smears and 16 of 18 CNB touch preps. Immunofluorescence staining confirmed the presence of both luminal and myoepithelial cells in derived PDOs. CONCLUSIONS: FNAB effectively obtains cells for PDOs modeling DCIS. CNB yielded PDOs with a high success rate, but they were slow to establish. The time to organoid growth was significantly shorter for FNAB specimens. Thus, FNAB offers an efficient alternative for breast PDO culture and can reduce the time and resources spent on generating PDO cultures.
Zhang X, Dong X, Starr D
… +9 more, Bai X, Li Y, Jones TE, Liu Y, Wang X, Li C, Wu X, Zeng X, Zhao C
Cancer Cytopathol
· 2025 Nov · PMID 41066206
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BACKGROUND: A diagnosis of atypical glandular cells (AGC) on Papanicolaou (Pap) slides is rare but has clinically significant findings associated with high-risk cervical and endometrial lesions. The authors evaluated the...BACKGROUND: A diagnosis of atypical glandular cells (AGC) on Papanicolaou (Pap) slides is rare but has clinically significant findings associated with high-risk cervical and endometrial lesions. The authors evaluated the efficiency and diagnostic performance of an artificial intelligence (AI)-assisted platform (Riuqian WSI-2400; with the registered trademark AICyte) in identifying AGCs on Pap slides. METHODS: A retrospective analysis of 485 Pap cases was conducted, including 185 cases with AGCs, 50 cases with high-grade squamous intraepithelial lesions, 50 cases with low-grade squamous intraepithelial lesions, and 200 negative cases; of these, 264 cases had histologic correlations. An experienced cytopathologist reviewed all slides using conventional microscopy and AICyte. Then, the same cases were evaluated by two other pathologists using the AICyte system. RESULTS: The initial study demonstrated a kappa value of 0.744, which indicated strong agreement of the Pap interpretation from the same pathologist between using microscopy and AICyte methods, whereas the average interpretation time was significantly reduced with AICyte (137 vs. 44 seconds). Diagnostic consensus among three pathologists using the AICyte system was strong, with a Kendall W coefficient of 0.802. The AICyte-pathologist consensus reached an exact match with original interpretations in 95.1% of cases. AICyte-assisted interpretations demonstrated improved specificity and diagnostic accuracy for glandular lesions compared with original interpretations while maintaining 100% sensitivity and negative predictive value. CONCLUSIONS: To the authors' knowledge, this is the first study focusing on assessment of AGCs on an artificial intelligence system. The findings demonstrated that the AICyte system offers substantial improvements in efficiency and diagnostic consistency for the interpretation of AGCs and significantly reduces slide reading time. These results support the potential of AI to augment performance, especially in resource-limited settings or high-volume screening environments.
Yu S, Wang M, Langdon J
… +6 more, Zhao J, Pai SI, Sinard J, Cai G, Prasad ML, Adeniran AJ
Cancer Cytopathol
· 2025 Oct · PMID 41021263
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BACKGROUND: Thyroid nodules, found in up to 68% of adults, can be risk-stratified by high-resolution ultrasound. This study evaluates the concordance between "suspicious" Thyroid Imaging Reporting and Data System (TI-RAD...BACKGROUND: Thyroid nodules, found in up to 68% of adults, can be risk-stratified by high-resolution ultrasound. This study evaluates the concordance between "suspicious" Thyroid Imaging Reporting and Data System (TI-RADS) 3-5 nodules and cytologic and molecular findings from fine-needle aspiration. METHODS: A total of 1199 suspicious thyroid nodules stratified as TI-RADS 3 (n = 384), TI-RADS 4 (n = 569), and TI-RADS 5 (n = 246) were studied. Cytopathologic and molecular results were correlated with clinical data from electronic medical records. RESULTS: Cytology, histology, and molecular testing revealed a lower risk of malignancy in TI-RADS 3 and 4 nodules compared to TI-RADS 5. Among TI-RADS 3 nodules, 75% (287 of 384) were cytologically benign, with only one case diagnosed as papillary thyroid carcinoma (PTC), and 8 of 48 resected nodules (17%) confirmed as carcinoma. In TI-RADS 4, 10% (56 of 569) were suspicious for or diagnosed as PTC by cytology, with 85 of 130 (65%) resected nodules confirmed as carcinoma. In TI-RADS 5, 44% (109 of 246) were cytologically suspicious for or diagnosed as PTC, and 129 of 154 (84%) resected nodules were malignant. High-risk mutations were more frequent in TI-RADS 5 than in TI-RADS 3 and 4. Overall malignancy rates were 2.0% (eight of 384) for TI-RADS 3, 14% (77 of 569) for TI-RADS 4, and 52% (129 of 246) for TI-RADS 5 nodules. CONCLUSION: TI-RADS 3, 4, and 5 nodules demonstrate distinct cytologic, molecular, and histologic features. TI-RADS 3 and 4 nodules are associated with lower malignancy risks, whereas TI-RADS 5 nodules exhibit a high risk of malignancy and are associated with higher mortality.
Karimkhan A, Xia R, Diaz D
… +7 more, Wald A, Hodak S, Givi B, Khader S, Pantanowitz L, Liu X, Brandler TC
Cancer Cytopathol
· 2025 Oct · PMID 40937607
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BACKGROUND: Mutations in DICER1 are uncommon, poorly understood, and infrequently found in thyroid nodules. METHODS: The objective of this study was to investigate category III/IV thyroid nodules according to The Bethesd...BACKGROUND: Mutations in DICER1 are uncommon, poorly understood, and infrequently found in thyroid nodules. METHODS: The objective of this study was to investigate category III/IV thyroid nodules according to The Bethesda System for Reporting Thyroid Cytopathology with DICER1 gene mutations detected in fine-needle aspiration cytology samples using ThyroSeq v3 molecular testing, with a focus on an exploration of the clinical and histopathologic outcomes of these nodules. In this multicenter study spanning more than 6 years, nodules were retrospectively analyzed for patient demographics, clinical course, cytologic features, and histopathology, where available. RESULTS: In total, 88 patients with somatic DICER1 mutations were included, with a mean age of 39.6 years and a female predominance. All mutations were in the somatic hotspot region, most commonly at the codon 5437 site. Most excised nodules showed benign histologic features (65.9%). Interestingly, the rate of malignancy was higher in this cohort compared with that in the national average. CONCLUSIONS: DICER1 mutations appear to confer a higher risk of malignancy, but are not associated with any specific cytological or histopathological distinguishing features.
Cancer Cytopathol
· 2025 Oct · PMID 40931696
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The current review article deals with the evaluation of the oncocytic/oncocytoid lesions in the salivary gland. The authors will focus on the diagnosis of Warthin tumor (WT) as a launching point to detail important morph...The current review article deals with the evaluation of the oncocytic/oncocytoid lesions in the salivary gland. The authors will focus on the diagnosis of Warthin tumor (WT) as a launching point to detail important morphologic findings that should prompt designation of an aspirate as oncocytic salivary gland neoplasm of uncertain malignant potential or other Milan categories. Oncocytic cells are defined as cells with a moderate to abundant amount of eosinophilic finely granular cytoplasm, round-to-oval nuclei, and large-distinct nucleoli. In contrast, the term oncocytoid is also frequently used in this discussion and indicates tumor cells with similarly abundant and sometimes granular cytoplasm but lacking all the definitive features of a true oncocyte. Several helpful tips are provided in hopes of improving an accurate diagnosis of WT on an aspirate sample. Using these types allows for consideration of important differential diagnoses, including both benign and malignant entities, when faced with an oncocytic salivary gland neoplasm. The morphological criteria as well as the possible application of ancillary techniques are also discussed.
Cancer Cytopathol
· 2025 Oct · PMID 40931665
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Cystic lesions of the head and neck encompass a wide spectrum of benign and malignant entities, which often presents diagnostic challenges as a result of the region's complex anatomy. Despite extensive literature, variab...Cystic lesions of the head and neck encompass a wide spectrum of benign and malignant entities, which often presents diagnostic challenges as a result of the region's complex anatomy. Despite extensive literature, variability persists in diagnostic strategies and approaches. Fine-needle aspiration biopsy is a commonly used and highly effective method for the initial assessment of these lesions by offering a minimally invasive technique to collect cellular material for diagnostic evaluation. A multidisciplinary approach integrating clinical, radiologic, and cytologic findings is essential in diagnosing cystic lesions of the head and neck. This review provides readers with an organ-based algorithmic approach for integrating anatomic location (central vs. lateral neck), radiologic features, and cytomorphology to refine diagnoses and guide patient management.
Robledano R, Argueta A, Labiano T
… +1 more, Lozano MD
Cancer Cytopathol
· 2025 Sep · PMID 40900401
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Lung cancer continues to be the leading cause of cancer-related mortality, with cytologic samples often serving as the primary diagnostic tool. However, differentiating between benign and malignant processes in lung cyto...Lung cancer continues to be the leading cause of cancer-related mortality, with cytologic samples often serving as the primary diagnostic tool. However, differentiating between benign and malignant processes in lung cytology can be difficult because various non-neoplastic conditions closely resemble malignant lesions, which may lead to misdiagnosis. This review offers nine essential tips to help cytopathologists prevent false-positive diagnoses of malignancy in non-neoplastic processes. By examining common non-neoplastic entities that can mimic lung malignancies, this review emphasizes their key cytomorphologic features and distinguishing characteristics. The authors stress the importance of a thorough clinical and radiologic context, slide background evaluation, and identification of cytomorphologic features for an accurate diagnosis of these mimics. The objective of this review was to enhance diagnostic accuracy and prevent misdiagnosis, thereby improving patient management in lung cancer cytopathology.
Ahmed MS, Klippel-Almaraz D, Amin SE
… +6 more, Sura GH, Kundu UR, Yu W, Stewart JM, Gan Q, Krishnamurthy S
Cancer Cytopathol
· 2025 Sep · PMID 40889104
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BACKGROUND: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors ev...BACKGROUND: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center. METHODS: The authors evaluated 98 ultrasound-guided thyroid FNAB cases. Smears were stained with Papanicolaou and Diff-Quik and were scanned at ×20 magnification using a Leica Aperio CS2 scanner. Five cytopathologists evaluated specimen adequacy and Bethesda categorization using WSI followed by LM assessment after a 2-week washout. Intraobserver and interobserver agreements were calculated using Cohen and Fleiss kappa (κ) statistics. Scan time, interpretation time, and the need for ×40 magnification or z stacking were recorded. RESULTS: In total, 463 slides were scanned, with mean scan time of 5.48 minutes. WSI quality was acceptable in most cases. Z stacking and ×40 magnification were requested in 23% and 14% of reviews, respectively. Intrareader agreement between WSI and LM examination was excellent (κ = 0.86-0.95). Inter-reader agreement was moderate for both WSI (κ = 0.48) and LM examination (κ = 0.56). Concordance was highest for Bethesda categories I and VI and lowest for categories III-V. Interpretation with WSI took significantly longer than with LM examination (p < .0001). CONCLUSIONS: WSI is a feasible alternative to LM examination for ROSE of thyroid FNABs, with high intrareader agreement and comparable inter-reader agreement. The limited need for high magnification and z stacking supports its practical utility.