Cancer Cytopathol
· 2026 Jun · PMID 42127125
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BACKGROUND: Pleomorphic adenoma (PA) is the most common benign salivary gland neoplasm detected by fine-needle aspiration (FNA). However, metaplastic changes within PA can complicate its cytologic interpretation. This st...BACKGROUND: Pleomorphic adenoma (PA) is the most common benign salivary gland neoplasm detected by fine-needle aspiration (FNA). However, metaplastic changes within PA can complicate its cytologic interpretation. This study evaluates the impact of metaplasia on the FNA interpretation in a large, multi-institutional cohort. METHODS: A two-armed study design was employed: one included 200 consecutive PA resections and the corresponding FNAs, and the second included 53 PA cases with known metaplastic features identified by cytologic or pathologic review. RESULTS: Histologic assessment revealed metaplasia in 16% of the 200 PA cases. Although the majority (83%) were cytologically classified as Neoplasm: Benign, indeterminate diagnoses were more common in cases with metaplasia (25%) than in those without (15.5%). Squamous metaplasia was frequently interpreted as indeterminate relative to other types of metaplasia, and a statistical trend was observed between the extent of metaplasia and indeterminate categorization. In the multicenter arm, FNA cases with metaplasia were more frequently interpreted as indeterminate compared to FNA cases without metaplasia (61.8% vs. 15.8%, p < .01). CONCLUSIONS: Metaplastic change in PA can pose diagnostic challenges. Although most FNA cases with limited metaplastic features are appropriately classified, extensive metaplasia is more likely to result in an indeterminate interpretation.
Wang CI, Zhang ML, Madrigal E
… +2 more, Faquin WC, Chebib I
Cancer Cytopathol
· 2026 Jun · PMID 42119039
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BACKGROUND: Gene fusion testing, essential for the diagnosis and classification of many salivary gland and soft tissue neoplasms, is typically performed on formalin-fixed paraffin-embedded material, which may be limited...BACKGROUND: Gene fusion testing, essential for the diagnosis and classification of many salivary gland and soft tissue neoplasms, is typically performed on formalin-fixed paraffin-embedded material, which may be limited or unavailable in cytology specimens. Although cytology smears have been validated for single-gene and DNA-based assays, evidence supporting routine diagnostic use of RNA-based next-generation sequencing fusion testing on smears remains limited. METHODS: The authors evaluated the clinical utility of a clinically validated anchored multiplex polymerase chain reaction (adenosine monophosphate)-based RNA fusion assay performed on digitized, scraped, and sacrificed cytology smears. Alcohol-fixed Papanicolaou-stained and air-dried modified Giemsa-stained smears meeting predefined cellularity thresholds were digitally archived, manually scraped, and processed for RNA extraction. Fusion testing targeted solid tumor-associated genes, and sequencing was performed on an Illumina platform. RESULTS: Of 8706 fusion assays performed during the study period, 807 (9.3%) were applied to cytology specimens, including 14 cases (1.7%) using sacrificed direct smears. Adequate nucleic acid was obtained in all cases. Gene fusions were detected in 64% (9/14), including MYB::NFIB, ACTB::PLAG1, NCALD::PLAG1, CRTC1::MAML2, COL1A1::PDGFB, COL1A2::USP6, and FGFR1::NOL4. Fusion results enabled definitive diagnosis for adenoid cystic carcinoma, mucoepidermoid carcinoma, pleomorphic adenoma, nodular fasciitis, and dermatofibrosarcoma protuberans. CONCLUSIONS: Adenosine monophosphate-based RNA fusion testing on sacrificed cytology smears is feasible, reliable, and diagnostically impactful, expanding the role of cytology specimens in definitive tumor classification.
Ramseyer TG, Batson B, Wu D
… +4 more, Matsko JL, Colaizzi AK, Khader SN, Zhao C
Cancer Cytopathol
· 2026 May · PMID 42080588
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BACKGROUND: Current professional guidelines recommend discontinuing Papanicolaou (Pap) test screening in women aged 65 years and older who have had adequate prior negative testing. However, limited data exist on Pap test...BACKGROUND: Current professional guidelines recommend discontinuing Papanicolaou (Pap) test screening in women aged 65 years and older who have had adequate prior negative testing. However, limited data exist on Pap test performance and histologic outcomes in this population. METHODS: Searches were performed for all Pap tests from women aged 65 years and older accessioned at a women's hospital between January 2023 and December 2024. Pap tests were performed using the liquid-based cytology ThinPrep test, and high-risk HPV testing was performed using Aptima high-risk human papillomavirus (HPV) assays. Surgical pathology follow-up within 6 months was recorded. A Pearson χ test was performed to compare HPV positivity among patients who had abnormal Pap tests. RESULTS: In total, 1536 women aged 65 years and older underwent Pap testing during the study period. The overall HPV-positivity rate was 24.2%. Abnormal Pap results (atypical squamous cells of undetermined significance or worse) comprised 939 of 1536 cases (61.1%). Histologic follow-up was available for 402 cases. Lesions categorized as cervical intraepithelial neoplasia grade 2 (CIN2) or more severe disease were identified in 94 cases (23.3%), including 11 squamous cell carcinomas, three endocervical carcinomas, 40 CIN2/3 lesions, and 40 endometrial carcinomas. Notably, three of 11 squamous cell carcinomas (27.3%) and 12 of 40 CIN2/3 lesions (30%) were HPV-negative. CONCLUSIONS: The abnormal Pap rate in women aged 65 years and older was high (61.1%), whereas HPV positivity remained low. CIN2 or more severe disease and endometrial lesions after negative HPV testing occurred at a substantial rate (33.8%). The rate for detecting atypical glandular cells was also elevated (3.0%), correlating with a significant number of endometrial carcinoma diagnoses. These findings underscore the need for additional research and suggest that continued screening with Pap and HPV cotesting may benefit older women.
Azad S, Graham TE, Levy S
… +9 more, Velanzuela-Sheker E, Bimston D, Ferenczi A, Chen Y, Alshalalfa M, Hao Y, Klopper JP, Kloos RT, Kotwal A
Cancer Cytopathol
· 2026 May · PMID 42080574
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Indeterminate thyroid nodules carry a wide range of malignancy prevalence, necessitating incorporation of molecular testing to guide management. Molecular test results help guide prognosis to a certain extent, but additi...Indeterminate thyroid nodules carry a wide range of malignancy prevalence, necessitating incorporation of molecular testing to guide management. Molecular test results help guide prognosis to a certain extent, but additional prognostic factors need to be identified. Limited data have linked PLEKHS1 promoter (PLEKHS1p) mutations with higher aggressiveness of thyroid cancer. Hence, we aimed to evaluate the diagnostic and prognostic value of PLEKHS1p mutations in preoperative thyroid nodules undergoing molecular testing. We assessed PLEKHS1p mutations in 9279 patient samples from April 2023 to June 2024 among indeterminate thyroid nodules ((B)ethesda III/IV) with Afirma GSC-(S)uspicious results as well as among B V/VI cytology thyroid nodules. We also analyzed a subset of 20 consecutive cases positive for PLEKHS1p mutations with surgical resection for histology and for co-occurring molecular alterations from the Afirma testing. PLEKHS1p mutations were positive in 60/9279 (0.6%) of patient samples with three times higher frequency in B VI compared to B III cytology nodules (1.36% vs 0.47%, p < .01). Among the 60 samples harboring PLEKHS1p mutations, 28 had the C593T hotspot mutation, 38 the G590A mutation, and six samples had both; four samples had concomitant TERTp mutations and 18 samples had concomitant BRAFp.V600E alterations. Our study demonstrated an overall low frequency of PLEKHS1p mutations, but this frequency was highest among malignant (B VI) cytology thyroid nodules. The frequency of PLEKHS1p mutations did not strongly correlate with the severity of thyroid cancer but the surgical sample size was limited. Further research is needed to clarify the role of PLEKHS1p mutations in thyroid nodules and cancer.
Pighi C, Settanni G, Angelini M
… +7 more, Bortesi L, Viassolo V, Ceccaroni M, Bruni F, Gori S, Zannoni GF, Pesci A
Cancer Cytopathol
· 2026 May · PMID 42046206
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BACKGROUND: BRCA1/2 testing is currently recommended at diagnosis for high-grade serous ovarian carcinoma (HGSOC) because of its impact on patients' survival when treated with poly(adenosine diphosphate ribose) polymeras...BACKGROUND: BRCA1/2 testing is currently recommended at diagnosis for high-grade serous ovarian carcinoma (HGSOC) because of its impact on patients' survival when treated with poly(adenosine diphosphate ribose) polymerase inhibitors. Standard clinical practice involves analyzing BRCA1/2 genes in formalin-fixed, paraffin-embedded (FFPE) histological specimens. However, because neoplastic ascites is a common clinical presentation in HGSOC and provides a good source of neoplastic cells via a less invasive procedure, it is worthwhile to explore the feasibility of BRCA1/2 testing on cytological specimens obtained from malignant ascites. METHODS: BRCA1/2 status was analyzed in 34 ascites-derived cytological samples via an amplicon-based next-generation sequencing (NGS) approach, and the results were compared with those from FFPE tissues previously tested in routine clinical practice. RESULTS: A perfect match was observed between BRCA1/2 testing results from neoplastic ascites and surgical samples (100% concordance) for all pathogenic variants, including both germline and somatic mutations. This is the first study to report such high concordance within the largest collection of somatic variants analyzed to date. Additionally, molecular NGS testing was demonstrated to be feasible even in malignant ascites with a low tumor fraction and with archived material. CONCLUSIONS: This study shows that ascites can be a suitable specimen for BRCA1/2 NGS testing, and provides a minimally invasive option for disease diagnosis and the early detection of key molecular biomarkers essential for the clinical management of women with HGSOC.
Cancer Cytopathol
· 2026 May · PMID 42018436
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The nucleus of papillary thyroid carcinoma (PTC) has had a fascinating history since its early descriptions by Lindsay in 1960 and his designation of follicular variant papillary thyroid carcinoma (FVPTC) as a subtype of...The nucleus of papillary thyroid carcinoma (PTC) has had a fascinating history since its early descriptions by Lindsay in 1960 and his designation of follicular variant papillary thyroid carcinoma (FVPTC) as a subtype of follicular carcinoma (FC). Later, Chen and Rosai revived the awareness of FVPTC and aligned this neoplasm with PTC. From this era, PTC became a “nuclear” diagnosis and was expanded to include FVPTC, even when noninvasive and encapsulated. However, this practice was prone to interobserver variability. The main issue centered on the interpretation of two types of nuclei – the widely accepted “classical papillary nucleus” with well‐developed features such as nuclear pseudoinclusions and grooves and the other “papillary‐like nucleus” with subtle and delicate nuclear features. Subsequently, some individuals recognized “papillary‐like nucleus” in most follicular‐patterned neoplasms and diagnosed them as FVPTC, while others diagnosed them as follicular adenoma or FC. In the 2000s, noninvasive, encapsulated FVPTC was recognized as an indolent entity, and later relabeled as noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). Molecular analyses revealed two main families of drivers for PTC ‐ BRAF V600E or BRAF V600E–like mutations which aligned with “classical papillary nucleus”, papillary architecture, and conventional PTC outcomes, and RAS or RAS–like mutations that were associated with “papillary‐like nucleus”, follicular architecture, and follicular‐patterned neoplasm outcomes. The story has made full circle and the recent proposal to incorporate FVPTC into FC is in keeping with Lindsay’s original concept. By our current understanding, these nuclei are classified better by molecular associations.
Cancer Cytopathol
· 2026 May · PMID 42018429
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BACKGROUND: The World Health Organization (WHO) Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (WHO System) offers a standardized five-category framework to enhance diagnostic consistency. Although glo...BACKGROUND: The World Health Organization (WHO) Reporting System for Lymph Node, Spleen, and Thymus Cytopathology (WHO System) offers a standardized five-category framework to enhance diagnostic consistency. Although globally applicable, its risk of malignancy (ROM) and management protocols are largely generalized. This study explores the system's specific applicability and clinical utility within the pediatric population. METHODS: The study presents a pediatric diagnostic pathway centered on fine-needle aspiration biopsy, implemented according to the protocols established by the WHO System. The methodology emphasizes the integration of a multidisciplinary approach. The five WHO categories are evaluated through the lens of pediatric-specific differential diagnoses. RESULTS: In pediatric practice, the Benign category often includes exuberant immunoblastic proliferation (e.g., Epstein-Barr virus) that mimics malignancy. Atypical and Suspicious categories represent a critical "gray zone" where the ROM is significantly influenced by the rarity of malignancy. Findings suggest that for Suspicious and Malignant categories, the use of rapid on-site evaluation (ROSE) under optimal conditions allows for an immediate transition to ancillary testing and clinical staging. DISCUSSION: Pediatric application requires shifted interpretive thresholds. Monotonous small cell populations, which might suggest low-grade B-cell lymphoma in adults, typically represent reactive processes or aggressive small round blue cell tumors in children. The interventional pathologist is vital in reducing "non-diagnostic" rates. Furthermore, a "malignant" or "suspicious" diagnosis should trigger immediate multidisciplinary intervention to prevent complications. CONCLUSION: The WHO System is a robust tool for pediatric evaluation when contextualized within pediatric-specific biological parameters. Integrating ROSE and interventional pathology minimizes invasive procedures and accelerates time-to-treatment for life-threatening malignancies.
Gutierrez Amezcua JM, Arcila ME, Ng DL
… +11 more, Feratovic R, Bilal KH, Cohen JM, Wei XJ, Kezlarian-Sachs B, Sigel CS, Agaram N, Nafa K, Salazar P, Lin O, Kim D
Cancer Cytopathol
· 2026 May · PMID 42018428
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BACKGROUND: For patients with aggressive thyroid cancer, including anaplastic thyroid carcinoma (ATC) and high-grade follicular cell-derived non-anaplastic thyroid carcinoma, rapid BRAF p.V600E testing is critical as tar...BACKGROUND: For patients with aggressive thyroid cancer, including anaplastic thyroid carcinoma (ATC) and high-grade follicular cell-derived non-anaplastic thyroid carcinoma, rapid BRAF p.V600E testing is critical as targeted therapy with BRAF/MEK inhibitors significantly improves outcomes. This study assesses the performance and turnaround time (TAT) of the Biocartis Idylla platform for ultrarapid BRAF p.V600E detection across various preparations, emphasizing the use of residual CytoLyt material (supernatant cell-free DNA [ScfDNA]). METHODS: All histologically confirmed cases of aggressive thyroid carcinomas received for Idylla testing were identified. Samples were prepared either as ScfDNA, formalin-fixed paraffin-embedded (FFPE) cell block (CB), Diff-Quik smear, or surgical FFPE samples. BRAF p.V600E testing was performed on the Idylla platform, and results were compared to a clinically validated reference method of either next-generation sequencing (NGS) or digital-droplet polymerase chain reaction (ddPCR). TAT for Idylla testing on ScfDNA samples was compared to FFPE preparations and to BRAF V600E immunocytochemistry (ICC). RESULTS: Fifty-seven samples (including 51 ATC) were tested by Idylla. The overall success rate for Idylla was 91%, with ScfDNA at 90% and surgical FFPE specimens at 100%. Of 42 samples that had NGS/ddPCR testing, concordance with the reference method showed 100% agreement (excluding failures) across all sample types. TAT for Idylla on ScfDNA samples was significantly shorter than ICC (median 2.86 vs. 46.7 hrs, p < .05). CONCLUSION: The Idylla BRAF assay delivers ultrarapid results that are both reliable and accurate with high success rates, particularly on ScfDNA samples. ScfDNA samples also have the fastest TAT because no histologic processing or pre-extraction are required for testing.
Cancer Cytopathol
· 2026 May · PMID 41958111
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BACKGROUND: Nondiagnostic cytology for thyroid nodules, consistent with The Bethesda System for Reporting Thyroid Cytopathology category I (B1) poses a management dilemma for clinicians. The objective of this study was t...BACKGROUND: Nondiagnostic cytology for thyroid nodules, consistent with The Bethesda System for Reporting Thyroid Cytopathology category I (B1) poses a management dilemma for clinicians. The objective of this study was to define the malignancy risk of nodules with B1 cytology using American College of Radiology Thyroid Imaging Reporting & Data System (TI-RADS) and to assess whether TI-RADS can help guide the decision to perform a repeat biopsy of these nodules. MATERIALS AND METHODS: This retrospective cohort study evaluated 139 B1 nodules that had a definitive diagnosis on repeat biopsy or surgical excision. Sonographic features were evaluated and classified according to TI-RADS. TI-RADS category and total points were compared to the final diagnosis to determine the malignancy risk of B1 thyroid nodules. RESULTS: Of the 139 nodules, 11 (7.9%) were malignant. The malignancy risk of nodules assigned TI-RADS category 1 and 2 were both 0%, TI-RADS 3 was 2.9%, whereas TI-RADS 4 and 5 were 5.9% and 46.2%, respectively. The optimal cutoff for TI-RADS points predicting malignancy was 5 points. CONCLUSION: B1 thyroid nodules in TI-RADS categories 1-3 may not require repeat biopsy given low malignancy risk. However, B1 nodules in TI-RADS categories 4 and 5 have a higher malignancy risk and thus should undergo repeat biopsy.
Dai M, San Lucas FA, Alvarez H
… +14 more, Ballester L, Chen H, Patel KP, Rashid A, Rao S, Routbort MJ, Sura G, Sweeney K, Toruner G, Wei P, Yang R, Dang H, Luthra R, Roy-Chowdhuri S
Cancer Cytopathol
· 2026 Apr · PMID 41891376
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BACKGROUND: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have li...BACKGROUND: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored. METHODS: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations. RESULTS: Of the 312 cases evaluated, 192 harbored NSCLC-specific oncogenic alterations. Relative to EGFR-mutated tumors, TMB was significantly higher in KRAS (p = 2.7 × 10), ERBB2 (p = .023), and BRAF (p = .023) -mutated tumors but lower in ALK-rearranged tumors (p = .005). Significantly higher PD-L1 expression was seen in tumors with KRAS (p = .002) and MET exon 14 (p = 1.06 × 10) when compared to EGFR-mutated tumors. Strong positive correlations between TMB and PD-L1 were observed in ERBB2-, KRAS-, and BRAF-mutated tumors when evaluated as continuous variables. TP53 mutations further enhanced immunogenicity when co-occurring with KRAS, ERBB2, or BRAF mutations but this effect was not observed in EGFR-mutated tumors. CONCLUSIONS: These findings demonstrate distinct TMB and PD-L1 profiles that may identify patients who will benefit from ICI therapy. Cytology specimens provide adequate material for biomarker testing, which underscores their value in guiding immunotherapy decisions.
BACKGROUND: Spindle cell lesions can be challenging to diagnose on cytology alone. The World Health Organization (WHO) is publishing a new WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). The authors examin...BACKGROUND: Spindle cell lesions can be challenging to diagnose on cytology alone. The World Health Organization (WHO) is publishing a new WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). The authors examined the performance characteristics of spindle cell lesion diagnoses at their institution when reclassifying according to the WHORSSTC. METHODS: Spindle cell fine-needle aspirations or fine-needle core biopsies diagnosed on cytology were collected from August 2021 through July 2024. Clinical information, procedural data, cytologic diagnoses, and surgical pathology diagnoses were obtained from the electronic medical records. Cases were reclassified according to the WHORSSTC, and relevant metrics were calculated. RESULTS: In total, 296 cases were identified from 164 women, 131 men, and one transgender female. The average age was 60 years. Biopsies were obtained as fine-needle core biopsies (n = 152), fine-needle aspirations (n = 130), or both (n = 12); and 127 patients (43%) had subsequent surgical pathology follow-up. Most lesions (n = 94; 74%) were mesenchymal on resection. These were initially diagnosed as negative (n = 3; 2%), atypical (n = 14; 11%), suspicious (n = 5; 4%), malignant (n = 35; 28%), and descriptive (n = 70; 55%), with absolute risks of malignancy of 0%, 43%, 80%, 100%, and 44%, respectively. To align with the WHORSSTC, these cases were recategorized as insufficient/nondiagnostic (n = 7; 6%), benign (n = 13; 10%), atypical (n = 12; 9%), soft tissue neoplasm of uncertain malignant potential (n = 54; 43%), suspicious for malignancy (n = 5; 4%), and malignant (n = 36; 28%), with absolute risks of malignancy of 0%, 0%, 42%, 57%, 80%, and 100%, respectively. CONCLUSIONS: Although not all spindle cell lesions prove to be mesenchymal, they can be effectively categorized by the upcoming WHORSSTC with increasing risks of malignancy that better predict biologic potential.
Cancer Cytopathol
· 2026 Apr · PMID 41860812
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BACKGROUND: Nongynecologic (non-GYN) cytology plays an important role in cellular and molecular cancer diagnosis, although its use is limited by variability and interobserver discrepancies. Recent studies suggest that ar...BACKGROUND: Nongynecologic (non-GYN) cytology plays an important role in cellular and molecular cancer diagnosis, although its use is limited by variability and interobserver discrepancies. Recent studies suggest that artificial intelligence (AI) may improve diagnostic consistency and performance. BACKGROUND: This systematic review evaluated contemporary AI research in non-GYN cytology and examined commercially available systems. METHODS: MEDLINE, Embase, and the Cochrane Library were searched for English-language studies published from January 2010 to September 2024. Of ∼24,000 records screened, 71 met inclusion criteria. Commercial platforms (KFBIO, Landing Med, VitaDx/VisioCyt, AIxMED, and CellsVision) were assessed using publicly available regulatory documents, technical specifications, and vendor-reported validation data. RESULTS: Many studies reported high internal diagnostic performance, often exceeding 90% accuracy. Patch-level performance often reached ∼94%, exceeding whole slide image-level metrics. Reduced interobserver variability was frequently observed, with accuracies of 95.9% for senior and 94.4% for junior pathologists. Several studies documented shorter diagnostic time. Thyroid (37%) and urinary bladder (30%) cytology were most frequently studied. AI applications included categorization, segmentation, and atypia detection, with recent work exploring immunocytochemistry support, mutation-associated pattern recognition, and indirect prediction of histologic features. CONCLUSION: AI in non-GYN cytology shows promise but remains limited by data set quality, weak external validation, and regulatory barriers. At present, AI tools function primarily as decision-support systems. Advancing clinical adoption will require multicenter validation, standardized data sets, and careful integration with expert interpretation.
Cancer Cytopathol
· 2026 Apr · PMID 41854368
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BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (TIS) provides a standardized framework for classifying serous fluid cytology into five diagnostic categories: nondiagnostic, negative for mal...BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (TIS) provides a standardized framework for classifying serous fluid cytology into five diagnostic categories: nondiagnostic, negative for malignancy, atypical, suspicious for malignancy, and malignant. Although TIS has been widely adopted for pleural and peritoneal fluids, its application in pericardial effusion cytology remains limited. The objective of this study was to evaluate the use of TIS in pericardial effusion samples and estimate the associated risk of malignancy for each category. METHODS: A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies published between 2013 and 2023 were identified through a comprehensive PubMed search. Eligible studies applied TIS to pericardial effusion cytology. The analysis excluded case reports, case reviews, abstracts, comparative studies, and non-English publications. Furthermore, the authors omitted studies that did not explicitly categorize pericardial fluid samples using the TIS categorization. Ten studies met inclusion criteria, comprising 2976 pericardial fluid samples. RESULTS: The pooled distribution across TIS categories were: nondiagnostic (2.9%), negative for malignancy (60.2%), atypical (5.4%), suspicious for malignancy (2.4%), and malignant (23.4%). Risk of malignancy estimates based on histologic confirmation were: 10.8% for nondiagnostic, 8.7% for negative for malignancy, 34.0% for atypical, 64.1% for suspicious for malignancy, and 78.6% for malignant categories. CONCLUSIONS: TIS effectively stratifies pericardial effusion cytology samples by malignancy risk. The progressive increase in the risk of malignancy across categories supports its diagnostic utility. However, substantial heterogeneity, particularly in the negative for malignancy and malignant categories, highlights the need for standardized reporting and further prospective validation of TIS.
BACKGROUND: The majority of oral cancers are diagnosed at an advanced stage. It has been demonstrated that the implementation of screening programs reduces mortality rates. Oral cytology is a technique that is used in th...BACKGROUND: The majority of oral cancers are diagnosed at an advanced stage. It has been demonstrated that the implementation of screening programs reduces mortality rates. Oral cytology is a technique that is used in these programs. However, the accuracy of oral cytology remains controversial. Therefore, the objective of this meta-analysis was to validate the accuracy of oral cytology. METHODS: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases to identify eligible studies. The inclusion criteria were as follows: studies that evaluated the diagnostic accuracy of oral cytology for low-grade squamous intraepithelial lesion or worse. The article incorporated peer-reviewed articles. In addition, studies that provided sufficient data for conducting a meta-analysis were assessed. The meta-analysis was conducted using a bivariate random-effects model. RESULTS: In total, 26 articles comprising 8397 specimens were included in the study. The meta-analysis yielded a pooled sensitivity of 93.8% and a pooled specificity of 87.7% of oral cytology for identifying oral epithelia dysplasia or worse. A subgroup analysis of studies that evaluated oral cytology with Papanicolaou staining demonstrated a pooled sensitivity of 94.8%. The accuracy of oral cytology in detecting high-grade squamous intraepithelial lesion or worse was examined, resulting in a pooled sensitivity of 95.7%. CONCLUSIONS: This meta-analysis indicated that oral cytology exhibited high sensitivity and specificity in detecting oral epithelia dysplasia or worse, with slightly higher sensitivity for high-grade squamous intraepithelial lesion or worse. A notable advantage of using oral cytology with Papanicolaou staining is the potential for enhanced sensitivity.
D'Abbronzo G, Lucà S, Cozzolino I
… +9 more, Accardo M, Della Corte C, Iovino F, Parisi S, Tedesco I, Ingallinella F, Grasso F, Franco R, Montella M
Cancer Cytopathol
· 2026 Mar · PMID 41757801
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BACKGROUND: HER2-positive invasive breast carcinomas (IBCs) account for 15% of breast cancers and are driven by ERBB2 gene amplification. Although historically associated with aggressive behavior, HER2-targeted therapies...BACKGROUND: HER2-positive invasive breast carcinomas (IBCs) account for 15% of breast cancers and are driven by ERBB2 gene amplification. Although historically associated with aggressive behavior, HER2-targeted therapies have significantly improved outcomes. HER2 status is routinely assessed by immunohistochemistry (IHC) and in situ hybridization (ISH). Recently, tumors with low HER2 expression (IHC 1+ or 2+ without amplification), previously classified as HER2-negative, have emerged as a clinically relevant subgroup. Fine-needle aspiration cytology (FNAC) is a minimally invasive alternative to core needle biopsy, particularly useful in inoperable or metastatic settings. FNAC-derived cell blocks (CBs) allow immunocytochemical (ICC) evaluation of biomarkers. METHODS: This retrospective study included 46 FNAC-derived CBs from breast cancers (34 primary tumors and 12 metastases) collected at Vanvitelli University Hospital. ICC evaluation of HER2, estrogen receptor (ER), and progesterone receptor (PR) was independently performed by two expert pathologists and compared with corresponding histological assessments. Diagnostic performance was evaluated using sensitivity, specificity, predictive values, concordance rates, and receiver operating characteristic (ROC) curve analysis. RESULTS: ICC on FNAC-derived CBs showed good diagnostic performance for HER2-low tumors. Sensitivity ranged from 56.3% to 59.4%, whereas specificity was high (85.7%-92.9%). Positive predictive values reached 90.0%-95.0%, whereas negative predictive values were lower (46.2%-50.0%). Concordance between cytological and histological HER2-low assessment exceeded 90%, with ROC area under the curve values of 0.71-0.76. ER showed excellent concordance, whereas PR demonstrated moderate agreement. CONCLUSIONS: FNAC-derived CBs are a reliable tool for identifying HER2-low breast carcinomas when histological samples are unavailable or limited, emphasizing the need for standardized evaluation criteria.