Background Cervical cancer remains a leading cause of cancer-related mortality in Central Asia, yet Bethesda 2014-classified population-level cytological data from this region are virtually absent from the indexed literature. We describe the distribution of cervical cytological findings and identify independent risk factors for high-grade squamous intraepithelial lesion (HSIL) in a large consecutive urban cohort from Tashkent, Uzbekistan. Methods A retrospective cross-sectional study of 28,310 consecutive cervical cytology specimens collected at a single teritary cytopathology referral center between January 2022 and December 2024. All specimens were classified according to the Bethesda 2014 system. Statistical analysis used IBM SPSS v.26; chi-square tests, Cramer's V, Mann-Whitney U, Spearman correlation, and binary logistic regression were applied. As histological follow-up was not available in this cytology-only dataset, diagnostic accuracy metrics for individual Bethesda categories are presented as literature-derived reference benchmarks. Results Specimen adequacy was 99.5%. NILM was found in 88.3% (n=25,008) of cases. Squamous epithelial atypia was identified in 9.7% (n=2,751) and glandular abnormalities in 2.9% (n=823); overall, at least one epithelial abnormality was present in 11.7% (n=3,302) of specimens. HSIL rates rose from 0.3% (<30 years) to 2.7% (>60 years; p<0.001). ASCUS detection nearly tripled from 4.1% (2022) to 11.3% (2024; linear-by-linear χ2=285.70, p<0.001). On multivariate logistic regression, older age (OR=0.105–0.463 for younger groups vs. >60 years), cervical inflammation (OR=16.890; 95% CI 8.795–32.438), and district of residence were independent associated or relevant factors of cytological HSIL. The ASCUS-to-SIL ratio was 2.6, below the established upper threshold of 3.0 derived from College of American Pathologists interlaboratory comparison data. Conclusions This is the largest Bethesda 2014-classified cervical cytology cohort reported from Central Asia. Older age and cervical inflammation are the strongest independent risk factors for HSIL. The elevated AGC rate (2.8%) and rising atypia detection trends have direct implications for screening policy and HPV co-testing implementation in Uzbekistan.
INTRODUCTION:To evaluate histopathological outcomes following a diagnosis of atypical glandular cells (AGC) and identify independent predictors of neoplastic pathology. MATERIALS AND METHODS:This retrospective cohort study included patients diagnosed with AGC on cervical cytology between January 2013 and December 2023 at a tertiary gynecologic oncology center. Cases with histopathological follow-up within 12 months were included. Cytology slides were rereviewed according to the 2014 Bethesda System. Clinical characteristics, cytomorphological features, p16/Ki67 immunohistochemical status on follow-up tissue specimens, and histopathological outcomes were analyzed. Multivariable logistic regression and receiver operating characteristic analyses were performed. RESULTS:AGC was identified in 141 of 128,022 cytology specimens (0.11%). After exclusions, 119 patients were analyzed. Neoplastic pathology was detected in 28 cases (23.5%), including endometrial carcinoma (39.3%), cervical neoplasia (35.7%), metastatic malignancies (17.9%), and ovarian high-grade serous carcinoma (7.1%). Neoplastic outcomes were significantly associated with increasing age, postmenopausal status, p16/Ki67 positivity, increased nuclear-to-cytoplasmic ratio, nuclear enlargement, and loss of polarity. Multivariable analysis identified increasing age (odds ratio [OR]: 1.141, 95% confidence interval [CI]: 1.072-1.214; P < 0.001), p16/Ki67 positivity (OR: 7.321, 95% CI: 1.828-29.318; P = 0.005), and loss of polarity (OR: 16.873, 95% CI: 4.012-70.953; P < 0.001) as independent predictors of neoplastic pathology. The predictive model demonstrated excellent discrimination (area under the curve = 0.918). CONCLUSIONS:Nearly one-quarter of AGC cases harbored neoplastic pathology. Increasing age, p16/Ki67 positivity, and loss of polarity independently predicted neoplastic outcomes. Integration of these parameters with thorough clinical history may improve risk stratification and clinical management of patients with AGC.
INTRODUCTION:Few studies have compared robotic-assisted bronchoscopic (RAB) fine-needle aspiration (FNA) with RAB cryo-biopsy (CB) for the evaluation of peripheral pulmonary lesions. We compared performance between RAB-FNA and RAB-CB in the evaluation of peripheral pulmonary lesions. MATERIALS AND METHODS:From our pathology database, we identified patients who underwent RAB-FNA with rapid on-site evaluation and concurrent RAB-CB between January and December 2024. We recorded patient and lesion characteristics, RAB-CB and RAB-FNA diagnostic categorization (non-diagnostic, benign, atypical, suspicious, malignant), and specimen type used for molecular studies. RAB-FNA and RAB-CB results were compared with those of surgical resection and clinical follow-up as the gold standard. For both procedures, we evaluated diagnostic performance for establishing the diagnosis of the pulmonary lesion. RESULTS:We identified 240 cases including 148 malignant, 1 neoplasm with undetermined malignant potential and 91 benign diagnoses, based on the gold standard. The male-to-female ratio was 23:25; median patient age, 69 years; and median lesion size, 1.8 cm. Touch preparation of RAB-CB was performed in 26 (11%) cases. Compared with RAB-CB, RAB-FNA had lower sensitivity for malignant tumors (89% versus 91%) but higher sensitivity for metastasis (73% versus 70%) and lymphoma (86% versus 71%), and it was used less often for molecular testing (99% versus 1%). The RAB-FNA and RAB-CB diagnoses were discordant in 44 cases (18%). CONCLUSIONS:RAB-CB provided superior diagnostic performance overall compared with RAB-FNA for peripheral pulmonary lesions. However, the use of rapid on-site evaluation to evaluate RAB-FNA tissue yield guided the procurement and preservation of CB without touch preparation. Our findings support an integrated dual-sampling approach combining RAB-FNA and RAB-CB, as FNA aids in real-time confirmation of lesional targeting, thereby optimizing procedural adequacy while preserving cryobiopsy material for downstream studies.
Introduction Previous studies suggest that the adequacy rate of thyroid aspirates can be improved by modifying the adequacy criteria of the Bethesda System without loss of sensitivity. We sought to measure the impact of long-term implementation of these criteria. Methods Results from long-term implementation of modified Bethesda adequacy criteria (2024-2025) were compared with initial implementation (2018-2023). Adequacy was classified as Non diagnostic, Scant but Adequate, or Adequate. Results Long-term use of modified Bethesda adequacy criteria resulted in significantly lower Nondiagnostic rates (110/2812, 4%) than in initial implementation (506/5147,10%, p<.001). Overall, the suspicious rate for Afirma for Adequate cases (317/1492 21%) was significantly higher than for Scant but adequate cases (82/495 17% p = .02), and the Insufficient rate for Afirma in Adequate cases (59/1492 4%) was significantly lower than for Scant but adequate cases (53/495 11%, p <.001). The risk of Malignancy (ROM) was lower for the Adequate cases (49/165, 30%) compared to the Scant but Adequate cases (17/36, 47% p = .04).The percentage of cases requiring repeat aspiration (Nondiagnostic cases plus Scant but adequate cases with insufficient results on Afirma) decreased significantly with long term implementation (526/5147, 10% vs 143/2812, 5%, p <.001). Discussion Long term implementation of modified Bethesda adequacy criteria can significantly lower Nondiagnostic and repeat aspiration rates without lowering sensitivity. There are significant differences in how Afirma performs in Scant but Adequate cases compared with Adequate cases.
INTRODUCTION:Secondary solid malignancies involving the gastrointestinal tract (GIT) are uncommon and often present as subepithelial or deeply seated lesions, limiting the diagnostic yield of endoscopic mucosal biopsy. The utility of fine-needle aspiration (FNA) in setting remains underexplored. MATERIALS AND METHODS:We retrospectively reviewed cases of secondary solid GIT malignancies diagnosed by FNA at a single institution from 2000 to 2025. Clinical, radiologic, and pathologic data were analyzed, and FNA performance was compared with endoscopic mucosal biopsy when both were performed. RESULTS:Fifty-nine patients (mean age, 64 years) were identified with the stomach as the most frequently involved site (49%). Breast carcinoma and pancreatobiliary tract carcinomas were the most common primary malignancy. Most patients had widespread metastatic disease and poor overall survival. Imaging demonstrated either intraluminal subepithelial nodules/masses or diffusely infiltrative wall thickening. Endoscopic mucosal biopsy was performed in 28 patients but yielded concordant results in only 29%, corresponding to a false-negative rate of 71%. Among 205 nondiagnostic or negative GIT FNA specimens with follow-up tissue sampling, 2 cases were subsequently diagnosed with metastatic carcinoma. Similarly, metastatic carcinoma was identified on follow-up in 2 of 55 atypical FNA cases. Using follow-up tissue diagnosis as the reference standard, FNA achieved a sensitivity of 93.7% and specificity of 100%. CONCLUSIONS:Secondary GIT tumors represent advanced systemic disease with poor prognosis. FNA is a reliable, minimally invasive diagnostic modality, particularly for deeply seated lesions where conventional endoscopic biopsy has a high false-negative rate.
INTRODUCTION:Amendment reports are a recognized but underutilized cytopathology quality assurance metric that can reveal diagnostic, reporting, and workflow vulnerabilities other indicators miss. Implementation of a new laboratory information system (LIS) is an underappreciated driver of amendments, as transitions introduce altered workflows, unfamiliar templates, and reconfigured terminology. The impact of LIS go-live events on amendment patterns has not been systematically studied. We characterized amendment frequency, categorization, and workflow implications during the early postimplementation period following an enterprise LIS migration. MATERIALS AND METHODS:All gynecologic and nongynecologic cytopathology amendments issued during the first 6 months after new LIS implementation were reviewed. Amendments were reviewed and reclassified into a standardized taxonomy distinguishing diagnostic from nondiagnostic changes, misassignment errors, and system-level causes. RESULTS:Fifty-five amendments were issued across 18,952 cases (0.29%), with half (50.9%) reclassified upon structured review. Rates peaked in the first full operational month (0.47%) and declined to 0.14% by month 6. Nondiagnostic amendments predominated (50.9%), most commonly corrected nondiagnostic information (27.3%), followed by diagnostic amendments (36.4%), of which corrected diagnostic information was most frequent (25.5%). One wrong-patient misassignment (1.8%) occurred in the go-live month, and 6 amendments (10.9%) reflected system-level errors. CONCLUSIONS:LIS go-live is associated with a characterizable, time-limited pattern of amendment activity concentrated in the earliest months. Structured, prospective amendment monitoring offers a low-cost, high-yield quality assurance tool for uncovering system-level errors requiring informatics or vendor intervention and for protecting patient safety during LIS transitions, supporting intensified surveillance during the earliest implementation window.
INTRODUCTION:Laboratory practices surrounding thyroid fine-needle aspiration (FNA) have shifted with the introduction of the Third Edition of The Bethesda System and the increasing utilization of molecular testing. The goal of this survey was to assess the current state of laboratory practices and ancillary molecular testing for thyroid FNA. MATERIAL AND METHODS:A 32 question online survey was developed by the Clinical Practice Committee of the American Society for Cytopathology (ASC) to assess thyroid FNA laboratory practices with an emphasis on ancillary molecular testing. The survey was distributed to the membership of the ASC and the International Academy of Cytology. Data was collected by SurveyMonkey, collated, and analyzed. RESULTS:A total of 220 responses were obtained with similar numbers of US and international participants. Utilization of rapid on-site evaluation (ROSE) for thyroid FNAs showed higher rates in the US, with nearly half of respondents evaluating adequacy on 76%-100% of FNAs, compared with 9% of international responses who reported similar rates. Molecular testing is offered by nearly all US-based respondents' laboratories whereas 38% of international respondents offered such testing. When molecular testing is performed, commercial assays designed to triage indeterminate results dominate US-based responses relative to international sites. CONCLUSIONS:Although there was good alignment between US and international responses around sample processing and reporting, distinct practice patterns surrounding ROSE and molecular testing were apparent, with notable opportunities to standardize or improve laboratory practices.
INTRODUCTION:The International Medullary Thyroid Carcinoma Grading System stratifies medullary thyroid carcinoma (MTC) using Ki-67 proliferation index, mitotic index, and tumor necrosis. However, the ability to predict MTC grade using fine needle aspiration (FNA) specimens is unclear. Artificial intelligence (AI)-based quantification tools are increasingly being adopted. We therefore evaluated the concordance of MTC grading on cytology using manual counting and an AI-based digital quantification platform. MATERIALS AND METHODS:Eighteen MTC cases with paired FNA and surgical resections (2013-2022) were retrospectively identified. MTC grading was assessed on FNAs and resections according to the International Medullary Thyroid Carcinoma Grading System criteria. Manual cytologic Ki-67 proliferation index (MCPI) and manual surgical proliferation index (MSPI) were compared. Digital cytologic Ki-67 proliferation index (DCPI) was generated using DeepLIIF. Concordance between Ki-67 proliferation indices and overall MTC grade was evaluated using Cohen's kappa. RESULTS:Substantial agreement was observed between MCPI and MSPI (94% concordance; kappa = 0.77). Overall grade concordance between cytology and surgical specimens was 83% (kappa = 0.49), with discrepancies largely due to necrosis identified only in resections. Agreement between MCPI and DCPI was fair (61%; kappa = 0.22), with digital analysis frequently overestimating Ki-67 proliferation index. Concordance between DCPI and MSPI was 67% (kappa = 0.33), and overall grade agreement between digital cytology assessment and surgery was slight (56%; kappa = 0.11). CONCLUSIONS:Grading of MTC on cytology demonstrates substantial concordance for Ki-67 assessment but only modest agreement for overall grade, primarily because necrosis is often only focally present. The limited performance of the AI-based digital quantification platform emphasizes the need for specimen-specific development and validation prior to clinical implementation.
INTRODUCTION:Small tissue biopsies aid in diagnosing infections; however, workup of inflammatory processes varies widely. We assessed the performance of small biopsies in identifying bacterial, mycobacterial, and fungal infections in granulomatous inflammation, using cultures as the gold standard, and described practice patterns across large U.S. academic institutions. MATERIALS AND METHODS:A multi-institutional retrospective electronic medical record review identified small thoracic biopsies (January 1, 2021-December 31, 2021) diagnosed as "granulomatous inflammation,", "non-necrotizing granulomatous inflammation", "necrosis only", and "acute inflammation." Clinical data, pathologic diagnoses, and special stain and culture results were collected. RESULTS:All participating institutions perform rapid on-site examination and routinely order acid-fast bacilli stain (AFB) and Grocott's methenamine silver stain (GMS) for granulomatous inflammation. Of 584 patients, 358 were evaluated with special stains and cultures, 91 patients had an infectious organism on cultures, and 67 patients had positive stains. AFB and Fite sensitivities were 38.5% (95% CI: 20.2-59.4) and 11.1% (95% CI: 0.3-48.3), respectively with specificities of 97.4% (95% CI: 94.5-99.1) and 96.5% (95% CI: 87.9-99.6), respectively GMS sensitivity and specificity for fungal infection were 37.5% (95% CI: 15.2-64.6) and 92.1% (95% CI: 88.3-94.9). Special stains were more frequently positive with necrosis (P < 0.001) and cultures were more often positive in necrotic cases (P = 0.005). CONCLUSIONS:Microbiologic cultures used with special stains result in the best diagnostic performance. Detection of granulomatous inflammation on morphologic assessment should prompt pathologists to order special stains (AFB and/or Fite and GMS) regardless of the presence of necrosis, especially in cases where cultures were not collected or resulted as negative but clinical suspicion remains high.
INTRODUCTION:Molecular testing is increasingly integrated into the management of indeterminate thyroid fine-needle aspiration (FNA) diagnoses, particularly The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III. However, it remains unclear how increasing test availability has affected cytopathologists' use of this category and whether its expansion risks incorporating nodules that may not warrant surgery, particularly following the 2023 TBSRTC nomenclature updates. MATERIALS AND METHODS:We retrospectively queried all in-house thyroid FNAs from 2018 to 2024, assessing temporal trends in TBSRTC category distribution, with focused analysis of TBSRTC III cases and associated parameters including ThyroSeq utilization, atypia of undetermined significance:malignant ratio, and risk of malignancy (ROM). RESULTS:From 2018 to 2024, TBSRTC III interpretations increased significantly (6%-26% of FNAs), accompanied by increased ThyroSeq utilization in this category (5%-75%) and atypia of undetermined significance:malignant ratios (1.0-4.5). Meanwhile, the proportion of TBSRTC III cases undergoing surgery declined (40%-26%). Surgical selection became strongly influenced by molecular results, with 71% of ThyroSeq-positive TBSRTC III nodules undergoing resection in 2024 compared with only 3% of ThyroSeq-negative nodules. Increased use of TBSRTC III occurred primarily at the expense of category II, while categories IV-VI remained stable. ROM was not statistically different with and without molecular testing. Molecular changes were consistent with published ThyroSeq cohorts. CONCLUSIONS:These findings suggest that increased ThyroSeq utilization is associated with increased use of TBSRTC III and more selective surgical management without altering ROM or increasing the inclusion of lesions less likely to require surgery.
INTRODUCTION:Extramammary Paget disease (EMPD) is an uncommon intraepithelial neoplasm which typically involves the vulva or perineal skin. Documented involvement of the cervix or vagina is infrequent, but Paget disease involving cervical cytology (Pap test) has been rarely reported. We examined Pap tests from patients with known EMPD to better understand the frequency of involvement as well as to characterize the distinctive cytologic features. MATERIALS AND METHODS:Cases were identified via natural language search of our pathology LIS for biopsy/resection diagnoses of vulvar or vaginal EMPD at our institution over a 10-year period. Patient records were searched for concurrent or near metachronous Pap tests. Pap tests were retrospectively reviewed to identify cytologic features suspicious for involvement by Paget disease. RESULTS:We identified 98 surgical pathology cases of EMPD, affecting 40 patients, with 67 Pap tests taken concurrently or after initial diagnosis. After our review, 10 of 67 (10/67, 15%) of Pap tests showed possible involvement by EMPD. Suspicious features included: hyperchromatic nuclei lacking visible nucleoli, increased nuclear to cytoplasmic ratios, and anisonucleosis. CONCLUSIONS:Cervicovaginal involvement by EMPD is likely underappreciated on cytology. In our experience, EMPD likely has a constellation of cytomorphologic features that warrant further evaluation in future studies.
INTRODUCTION:The integration of digital whole slide imaging and artificial intelligence is poised to transform cytopathology practice. Our aim was to validate the Hologic Genius Digital Diagnostics System (GDDS) for clinical use in Papanicolaou (Pap) test interpretation by comparing digital interpretations using the GDDS to computer-assisted interpretations using the ThinPrep Imaging System (TIS). MATERIALS AND METHODS:The study set consisted of 1748 Pap tests, including 53 unsatisfactory for evaluation cases, 1450 negative for intraepithelial lesion or malignancy (NILM) cases, and 245 atypical squamous cells of undetermined significance or worse cases. Each Pap test was reviewed either retrospectively or prospectively by one of 29 cytologists, and results of review on the GDDS were compared to review on the TIS for concordance. Cases requiring hierarchical review were reviewed by one of 23 pathologists. Concordance was calculated between each method. Diagnostic concordance of 95% was required for validation. RESULTS:The GDDS interpretation was concordant with the TIS interpretation in 1722/1748 cases (98.5%). Of the 26 discordant cases, most (20) were discordances between unsatisfactory and NILM, while 5 were attributed to interpretation error, and one was a low-cellularity low-grade squamous intraepithelial lesion containing rare diagnostic cells in the GDDS tiles that was originally interpreted as NILM on the TIS. CONCLUSIONS:Pap test interpretation using the GDDS showed high concordance with interpretations using the TIS, achieving the 95% threshold for clinical validation. Discordances were mainly attributable to the ability of the GDDS to quantify cellularity in low/borderline cellularity cases, or rarely to identify significant abnormalities missed by the TIS.
INTRODUCTION:Genomic profiling for patients with solid tumors using conventional tissue-based next-generation sequencing (NGS) usually takes several weeks and can delay timely initiation of targeted therapies. Further, patients may often lack adequate tissue for NGS that is needed to guide therapeutic decisions. Fine needle aspiration supernatants (FNA-Sup), a routinely discarded component of cytology specimen processing, contains tumor-derived cell-free nucleic acids and offers an alternative liquid biopsy source that bypasses these limitations. This study validates a rapid NGS assay using FNA-Sup for clinical use. MATERIALS AND METHODS:We extended a previously validated plasma-based liquid biopsy assay to FNA-Sup samples (N = 22) utilizing the Oncomine Precision Assay on the Genexus Integrated Sequencer. For accuracy studies, results were compared to the patient's known tissue-based NGS profiling performed on the paired specimen. Performance metrics including sensitivity, specificity, accuracy, and precision for the detection of single-nucleotide variants, insertions/deletions, and gene fusions were evaluated. RESULTS:The assay demonstrated 100% sensitivity, specificity, and accuracy for single-nucleotide variants and insertions/deletions (variant allele frequencies ≥0.5%) and for gene fusions. All inter-run, intrarun, interinstrument, and interoperator precision studies met the acceptance criteria (≥90% concordance with reference method). Specimen stability of FNA-Sup was established up to day 7 postcollection. CONCLUSIONS:Our study shows FNA-Sup, a routinely discarded cytology substrate, are analytically suitable for NGS-based testing. Integration of cytology-derived liquid biopsy into the clinical workflow expands access to molecular testing when tissue is limited and when rapid test results are needed. The automated workflow of the platform can support rapid molecular diagnostics within a single day from specimen receipt to test results.
INTRODUCTION:Pleural mesothelioma (PM) is an aggressive malignancy that poses diagnostic challenges, particularly in cytological specimens. Checkpoint kinase 1 (CHK1); a pivotal mediator of genomic stability, has been identified as a promising therapeutic target. In this study, we investigate CHK1 protein expression in PM and evaluate its potential utility as a diagnostic biomarker. MATERIALS AND METHODS:This retrospective study included patients diagnosed with PM and control cases containing non-neoplastic mesothelial cells (NNMC). Tissue microarrays were immunostained for CHK1 protein. Diagnostic accuracy of CHK1 expression was assessed across tumor subtypes (epithelioid and nonepithelioid) and specimen types (cytology and histology), using dichotomized positivity. CHK1 expression levels were compared between tumor subtypes and specimen types using the histoscore method. RESULTS:A total of 152 pm cases were included (cytology, n = 74; histology, n = 78), along with 33 cytological control cases. CHK1 expression significantly distinguishes PM from NNMC (P < 0.001), with ranging sensitivities (67%-100%) and specificities (75%-91%), depending on subcellular localization and tumor subtypes. Nuclear expression contributes to high sensitivity whereas cytoplasmic expression confers the highest specificity. The histoscores were higher for total and nucleus in histology compared to cytology, while no significant differences in expression were observed between epithelioid and nonepithelioid PM. CONCLUSIONS:Immunohistochemical assessment of CHK1 expression may be useful for distinguishing PM from NNMC. Robust diagnostic sensitivity was observed across both epithelioid and nonepithelioid PM, independent of specimen type. These support CHK1 as a potential pan-mesothelioma diagnostic biomarker. Further validation is warranted in larger, independent cohorts.
INTRODUCTION:Cell block (CB) preparation enhances morphological evaluation and enables ancillary testing in effusion cytology. Although HistoGel is widely used, the collodion bag method has been historically recognized for improved cellular recovery but remains underutilized. This study aimed to compare the diagnostic performance, technical quality, reproducibility, and downstream utility of the collodion bag and HistoGel CB methods. MATERIALS AND METHODS:A prospective cross-sectional study was conducted on 117 effusion specimens. Samples were processed in parallel using collodion bag and HistoGel methods. Slides were independently scored by 3 pathologists using a five-parameter system. Paired comparisons were performed using the Wilcoxon signed-rank test. Interobserver agreement was assessed using intraclass correlation coefficients (ICCs). DNA yield was analyzed in 25 paired cases. RESULTS:The collodion bag method yielded significantly higher scores for artifact reduction (P= 0.0058), tissue contamination (P= 0.0280), cell distribution (P< 0.0001), and tumor burden (P< 0.0001). No significant difference was observed in cell preservation. Interobserver agreement was good for tumor burden (ICC = 0.789) and moderate for total score (ICC = 0.587). DNA concentration was higher in the collodion bag method compared with HistoGel (31.5 versus 28.3 ng/μL, P= 0.048), with a median paired difference of 7.1 ng/μL. The collodion bag method required longer preparation time but only slightly higher material cost. CONCLUSIONS:The collodion bag method provides improved morphologic quality and higher DNA yield compared with the HistoGel method, supporting its utility in optimizing CB preparation, particularly for cases requiring ancillary and molecular testing.
Background Accurate evaluation of lymphadenopathy requires a multidisciplinary approach integrating clinical, laboratory, and imaging data, particularly ultrasound, before and during fine-needle aspiration biopsy (FNAB). Historically, the lack of standardized reporting systems has limited the reproducibility and clinical acceptance of lymph node FNAB. This review focuses on lymph node cytopathology, which currently is supported by a stronger evidence base and more consistent integration into diagnostic algorithms, than splenic or thymic lesions. Methods The Sydney System (2020) and the subsequent WHO Reporting System for Lymph Nodes, Spleen and Thymus Cytopathology (2024) (WHO System) provide a structured, evidence-based framework for cytopathological evaluation. The WHO System retains the five diagnostic categories of the Sydney System—Inadequate, Benign, Atypical, Suspicious for malignancy, and Malignant—while defining cytomorphological diagnostic criteria, standardizing terminology, and defining category-specific risks of malignancy (ROM). It emphasizes clinicopathological correlation and the use of ancillary techniques, including immunocytochemistry, flow cytometry, and molecular studies, and includes specific considerations for paediatric lymphadenopathy. Results Implementation of the WHO System improves diagnostic accuracy, interobserver reproducibility, and communication between cytopathologists and clinicians. The interventional cytopathologist plays a central role through image-guided FNAB and rapid on-site evaluation (ROSE), ensuring sample adequacy and appropriate triage for ancillary testing. Conclusions By integrating cytomorphological, clinical, imaging and ancillary data within a standardized, risk-based framework, the WHO System reinforces the pivotal role of FNAB in the diagnostic management of lymphadenopathy and establishes a globally harmonized standard for lymph node cytopathology.
INTRODUCTION:Peritoneal cytology (PC) is a useful predictor of ovarian surface involvement and intraperitoneal metastasis in epithelial malignancies. Most malignancies involving serous cavity effusions are adenocarcinomas; however, nonepithelial tumors such as lymphomas and germ cell tumors (GCTs) rarely cause malignant effusion. Data on PC in malignant ovarian germ cell tumor (MOGCT) are limited to isolated case reports with lack of systematic cytohistologic correlation, hence the need for this study. MATERIALS AND METHODS:All PC samples of surgically resected MOGCTs were classified using The International System (TIS) for the Reporting of Serous Cytopathology. Immunohistochemistry (IHC) was performed on cell blocks of all atypical and malignant cases. Tumor markers and histopathological parameters of surgical resection specimen were correlated with cytology findings using statistical tests. RESULTS:Nine (19%) of 48 MOGCTs showed features suspicious or definitive for metastasis on PC with three cases initially misdiagnosed as carcinomas. Spalt-like transcription factor 4 IHC resulted in upgradation of one TIS3 category case to TIS4/5. Cytological detection of metastasis correlated with intra-abdominal spread, omental involvement, and advanced pathological stage (P< 0.05). CONCLUSIONS:Cytological detection of intraperitoneal MOGCT metastases on PC correlates with other histopathological staging parameters. Cell blocks and Spalt-like transcription factor 4 IHC aided in confirming MOGCT origin in ambiguous and misdiagnosed cases. Further validation of atypia of undetermined significance is warranted to improve diagnostic accuracy.
INTRODUCTION:Minimally invasive biopsies are ideal for procuring tumor tissue for cancer patients at various stages. With an expanding array of therapeutic agents and variable response of tumors to these agents, these small samples can also be valuable during or after treatment to determine response, residual disease, or new diagnosis. MATERIALS AND METHODS:In this narrative review, cytology and core biopsy cases mentioning therapy or treatment related changes were reviewed to look at different patterns that can arise with illustrative examples to provide morphologic clues to help when evaluating these specimens. RESULTS:The main patterns of morphological changes include epithelial atypia, epithelial and cellular degeneration, stromal changes, amorphous/foreign material, histiocytic and granulomatous inflammation, high-grade transformations, and immunophenotypic changes. Careful review of these cases with illustrative examples can help to maximize concordance between preliminary diagnoses at rapid on-site evaluation and final interpretations, in addition to providing guidance to the proceduralist during the procedure and helping to explain indeterminate imaging findings for cancer patients undergoing therapy. CONCLUSIONS:Given the increased use of novel therapies for cancer treatment and widespread use of imaging to follow-up cancer patients, cytopathology labs play an increasingly important role in evaluating specimens from these patients to exclude residual or recurrent tumor or to explain a mass lesion (eg, infection, new tumor, post-treatment changes). This review highlights the key patterns of changes that can be seen in tissue samples from patients who have had prior therapeutic intervention or are currently undergoing treatment, to demonstrate the impact of pathology review. Cytopathologists should be aware of these patterns and challenges when evaluating cytology and small biopsy specimens in the post-treatment setting to avoid overcalling malignancy and to understand clinical implications for the treating providers.
INTRODUCTION:Coccidioidomycosis is a fungal infection endemic to the southwestern United States, particularly Arizona. Fine needle aspiration biopsy (FNAB) is established as effective in diagnosing infectious diseases. However, existing literature evaluating FNAB of thoracic coccidiomycosis remains limited. We present a large single institution series of thoracic coccidioidomycosis cases diagnosed through FNAB. MATERIALS AND METHODS:The Mayo Clinic Arizona Pathology database was searched for all FNAB cases with a diagnosis of coccidioidomycosis from January 1, 2013, to December 31, 2025. Electronic medical records were reviewed to tabulate demographics, clinical history, serology, and radiologic findings. All key cytologic, histologic, and special stained slides were reviewed. RESULTS:One-hundred and one FNAB samples were obtained from 100 patients: 37 cases combined endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA) and robotic-assisted bronchoscopy (RAB), 31 cases RAB, 20 cases EBUS-TBNA, 12 cases percutaneous computed tomography-guided, 1 case endoscopic ultrasound-guided. Coccidioides organisms were identified during rapid on-site evaluation in 34 cases, saving 18 patients from unnecessary procedures. Coccidioides organisms were identified in 94.1% (95/104) of cytology slides and in 67.1% and 66.7% of tissue biopsies and cell blocks, respectively. For the 6 cases without Coccidioides organisms on cytology slides, concurrent tissue biopsies or cell blocks with or without Grocott's methenamine silver stains helped confirm the diagnosis. Of the 41 patients with a malignancy history, one had both Coccidioides and malignancy in the same specimen. CONCLUSIONS:FNAB is accurate at diagnosing thoracic coccidioidomycosis when combined with EBUS-TBNA and RAB. Rapid on-site evaluation is critical during interventional procedures and can eliminate the need for unnecessary procedures.
