Although the overall number of cervical cancer cases is declining worldwide, the incidence of this type of cancer is increasing in regions with low human papillomavirus (HPV) vaccination and cancer screening rates. In such regions, screening pregnant women can help improve the overall screening rate. Worldwide, cervical cancer screening is shifting from cervical cytology to HPV testing, which reduces the incidence of cervical cancer and, when negative, allows for longer screening intervals. Although HPV-based screening has been shown to be at least as effective as cytology screening for lesion detection in the general population, its performance during pregnancy remains poorly characterized due to the exclusion of pregnant women in previous clinical trials. The aim of this trial is to evaluate the effectiveness of an HPV testing protocol compared with that of a cervical cytology protocol for cervical cancer screening in pregnant women. This study is a multicenter, nonrandomized, single-arm comparative trial. In total, 5000 pregnant women aged 30 years and older in their first trimester will undergo both cervical cytology and HPV testing, with follow-up at 1 year. The primary end point is to assess the noninferiority of the HPV testing protocol compared with the cytology protocol for detecting cervical intraepithelial neoplasia grade 2 or higher, adenocarcinoma in situ, and invasive cervical cancer (CIN2+) in early pregnancy. In the cytology protocol, CIN2+ cases will be defined as those detected in cytology-positive participants. In the HPV protocol, CIN2+ cases will be defined as those detected in HPV-positive and cytology-positive participants. The primary end point analysis will use a one-sided 10% noninferiority test using the method by Tango, and with 5000 cases, the study can achieve a statistical power of at least 80%. Secondary end points will include an evaluation of the persistence of negative results post partum to determine the optimal screening interval in this population. The trial was funded in April 2024 and has already started. Data collection commenced in September 2024 and is scheduled to be completed by December 2026. As of March 2026, a total of 1906 participants have been recruited. Data analysis is currently planned to begin in December 2027, and the study findings are expected to be published in 2028. The results of this trial will clarify whether the HPV testing protocol should be adopted as the primary cervical cancer screening method for pregnant women or whether cervical cytology should remain the standard of care. DERR1-10.2196/86397.
To explore the effect of electroacupuncture (EA) at front-mu and back-shu points of large intestine on autophagy of Cajal interstitial cells (ICCs) in the colon of rats with slow transit constipation (STC), and to analyze the mechanism of EA for mitigating STC. Thirty-six SD rats were randomly divided into a blank group, a model group, an EA group, a mosapride group, an EA+rapamycin (RAPA) group and an EA+3-methyladenine (3-MA) group, with 6 rats in each group. The STC model was established by intragastric administration with loperamide hydrochloride. In the EA group, the EA+RAPA group and the EA+3-MA group, EA was operated at bilateral "Tianshu" (ST25) and "Dachangshu" (BL25), with dense-disperse waves (2 Hz/15 Hz in frequency), for 15 min each time. In the mosapride group, intragastric administration with mosapride solution was operated. In the EA+RAPA group and the EA+3-MA group, 30 min before acupuncture, the intraperitoneal injection was administered with RAPA and 3-MA solution, respectively. The intervention was delivered once daily and for consecutive 14 days in each group. After model establishment, the defecation time of the first red fecal particle was recorded in each group. After modeling and intervention, the number of fecal particles and fecal quality were recorded in each group over a 24-hour period. After intervention, the small intestinal propulsion rate was calculated in each group. HE staining was used to observe the histological morphology of colonic tissue, transmission electron microscopy was used to observe the ultrastructure of ICCs in the colon tissues, the immunofluorescence assay was used to observe the positive expression of the ICCs marker tyrosine kinase receptor (C-kit) in colonic tissue, the real-time quantitative PCR assay was used to detect C-kit mRNA expression, and Western-blot was used to detect C-kit and autophagy-related protein expression in each group. After modeling, compared with the blank group, the model group exhibited the prolonged defecation time of the first red fecal particle and the reduced number of fecal particles, and the decline of fecal quality and small intestinal propulsion rate (P<0.01). After intervention, compared with the model group, the EA group and the mosapride group showed the increase in the number of fecal particles, fecal quality, and small intestinal propulsion rate (P<0.01). Compared with the EA group, fecal quality and small intestinal propulsion rate were reduced in the EA+RAPA group (P<0.01). Compared with the blank group, the model group showed the impaired colonic mucosal structure and reduced goblet cell count; and autophagosomes and mitochondrial swelling were markedly observed in the cytoplasm of ICCs. The average fluorescence intensity of C-kit, the mRNA expression of C-kit, and the protein expression of C-kit and P62 all decreased, while the protein expression of LC3 and ATG5 increased in the model group (P<0.01). Compared with the model group, all other groups showed the improvements in colonic mucosal structure and ICCs ultrastructure, with the increase in average C-kit fluorescence intensity (P<0.01); the mRNA expression of C-kit and the protein expression of C-kit and P62 were elevated (P<0.01), while the protein expression LC3 and ATG5 were reduced in the EA group (P<0.01). When compared with the EA group, the protein expression of P62 decreased in the EA+3-MA group (P<0.01). Electroacupuncture at front-mu and back-shu point of large intestine can effectively alleviate intestinal motility disorder in rats with slow transit constipation, which may be related to inhibiting excessive autophagy of ICCs and repairing the structure and quantity of ICCs. 目的：观察电针大肠俞募穴对慢传输型便秘（STC）大鼠结肠Cajal间质细胞（ICCs）自噬的影响，探讨电针改善STC的作用机制。 方法：将36只SD大鼠随机分为空白组、模型组、电针组、莫沙必利组、电针+雷帕霉素（RAPA）组及电针+3-甲基腺嘌呤（3-MA）组，每组6只。采用盐酸洛哌丁胺灌胃法建立STC模型。电针组、电针+3-MA组、电针+RAPA组予以电针双侧“天枢”“大肠俞”干预，选择疏密波（频率2 Hz/15 Hz），每次15 min；莫沙必利组予莫沙必利溶液灌胃；电针+RAPA组在针刺前30 min予RAPA溶液腹腔注射；电针+3-MA组在针刺前30 min予3-MA溶液腹腔注射，以上干预均每日1次，连续14 d。造模后，记录各组大鼠首粒红便排出时间；造模后和干预后，记录各组大鼠24 h排便粒数和粪便质量；干预后，计算各组大鼠小肠推进率，HE染色观察各组大鼠结肠组织形态，透射电镜观察各组大鼠结肠组织ICCs超微结构，免疫荧光法观察各组大鼠结肠组织ICCs标志物酪氨酸激酶受体（C-kit）阳性表达，实时荧光定量PCR法检测各组大鼠结肠组织C-kit mRNA表达，Western-blot法检测各组大鼠结肠组织C-kit及自噬相关蛋白表达。 结果：造模后，与空白组比较，模型组大鼠首粒红便排出时间延长，24 h排便粒数、粪便质量及小肠推进率降低（P<0.01）。干预后，与模型组比较，电针组、莫沙必利组大鼠24 h排便粒数增加、粪便质量及小肠推进率升高（P<0.01）。与电针组比较，电针+RAPA组粪便质量及小肠推进率降低（P<0.01）。与空白组比较，模型组结肠黏膜结构受损，杯状细胞数量减少，ICCs细胞质内可见明显自噬体、线粒体肿胀，C-kit平均荧光强度、C-kit mRNA、C-kit及P62蛋白表达均降低，LC3、ATG5蛋白表达升高（P<0.01）。与模型组比较，其余各组结肠黏膜结构及ICCs超微结构均有所改善，C-kit平均荧光强度升高（P<0.01）；电针组C-kit mRNA、C-kit及P62蛋白表达升高（P<0.01），LC3、ATG5蛋白表达降低（P<0.01）。与电针组比较，电针+RAPA组C-kit mRNA表达升高（P<0.01）；电针+3-MA组P62蛋白表达降低（P<0.01）。 结论：电针大肠俞募穴可有效改善STC大鼠的肠道动力障碍，其作用机制可能为抑制ICCs过度自噬，修复ICCs结构与数量。.
Peritoneal washing (PW) cytology has become a widely accepted procedure for staging of gynecological malignancies. To compare conventional cytology, liquid-based cytology (LBC) and cell block in the evaluation of PWs. A total of 50 clinically suspected cases of gynecological malignancies were enrolled, which included 41 ovarian neoplasms, eight uterine, and one case of cervical malignancy. The age of the women ranged from 13 to 74 years. The PW samples obtained in all cases were subjected to conventional cytology, LBC, and cell block preparations. Immunohistochemistry (IHC) was applied on cell blocks and analyzed. A comparative evaluation and statistical correlation between the three techniques was performed. The number of cases reported as positive for malignancy on conventional smear and LBC were 9 (18%) and 11 (22%), respectively. Fifteen (30%) cases were reported as positive for malignancy on cell block after IHC analysis. All three cytological techniques showed a good correlation in diagnosing peritoneal metastasis on evaluation by Cohen's kappa score (≤ 1.00). However, the overall sensitivity, specificity, and diagnostic accuracy of PW cytology was 43.8%, 94.4%, and 62%, respectively, taking histopathology as the gold standard. The most common malignancy which led to peritoneal fluid involvement was high-grade serous carcinoma of the ovary. The study demonstrates the usefulness of combining the three cytological techniques to diagnose peritoneal metastasis in gynecological malignancies. Cell block with IHC can help in reducing the false-negative cases and further adds to objectivity in ambiguous cases.
Accurate preoperative diagnosis of papillary thyroid carcinoma (PTC) remains difficult, especially for small thyroid nodules and lesions with indeterminate cytology. This prospective diagnostic study evaluated the clinical value of serum-based v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation detection and its performance in combination with ultrasound-guided fine-needle aspiration cytology (US-FNAC). A total of 145 patients with thyroid nodules classified as TI-RADS 3 to 5 and measuring 3 cm or less were enrolled. All patients underwent US-FNAC and serum BRAF V600E testing using allele-specific quantitative PCR, with postoperative histopathology used as the reference standard. Among the enrolled patients, 64 were diagnosed with PTC and 81 had benign nodules. US-FNAC showed a sensitivity of 68.75% and specificity of 83.95%, while serum BRAF V600E testing showed a sensitivity of 62.50%, specificity of 81.48%, and an area under the curve (AUC) of 0.792. In patients with papillary thyroid microcarcinoma, serum BRAF V600E testing demonstrated higher sensitivity than US-FNAC, 94.12% versus 64.71%, with an AUC of 0.841. However, its diagnostic sensitivity remained limited in poorly differentiated PTC, at 57.14%. A combined model integrating US-FNAC and serum BRAF V600E testing improved diagnostic performance, with a sensitivity of 81.25%, specificity of 85.19%, and AUC of 0.873, significantly outperforming either method alone. These findings suggest that serum BRAF V600E detection is a useful complementary, minimally invasive approach for diagnosing PTC, particularly micro-PTC, and may improve early detection and risk stratification when combined with US-FNAC.
Crush/imprint cytology, a diagnostic technique within the realm of cytological examinations, has emerged as a powerful tool for rapid and minimally invasive tissue evaluation. Its simplicity, cost-effectiveness, and rapidity make it indispensable in pathology practice. The aims and objectives were as follows: (1) to evaluate the diagnostic utility of crush/imprint cytology and (2) to correlate cytomorphological and histopathological (HP) findings for comprehensive diagnostic evaluation. This prospective study was carried out in a tertiary health care hospital for a period of 1 year, and 56 cases were included in this study. Both benign and malignant lesions from different organ systems were included in this study. The cytological diagnosis was correlated with HP diagnosis to evaluate the sensitivity and specificity of crush cytology. This study showed a male predominance (69%). Most lesions were from the respiratory system (33.33%), followed by head and neck (24.07%), lymphoreticular system (16.66%), gastrointestinal system (11.11%), skin (9.25%), and genitourinary system (5.55%). Malignant lesions showed good (44%) cell yield on crush/imprint cytology. The sensitivity was 100%, with 94.12% specificity for detecting benign and malignant lesions, and the overall diagnostic accuracy was 98.15%. The crush/imprint cytology stands as a cornerstone in the realm of cellular diagnosis, offering a rapid, cost-effective, and minimally invasive approach to evaluating tissue specimens. It is an indispensable tool in intraoperative diagnostics, offering rapid and accurate assessments of tissue pathology. It acts as a good complement to histopathology and can be of benefit for rapid preliminary diagnosis and intraoperative surgical management planning. Its use is highly recommended routinely.
Fine needle aspiration despite being an inexpensive, rapid, accurate and non-invasive diagnostic practice, particularly when used in oncology, is frequently underutilized. The World Health Organization - International Academy of Cytology - International Agency of Research on Cancer initiated a series of Blue Books devoted solely to cytology and reporting methods in particular entities of different organs. The use of ancillary techniques such as immunocytochemistry, molecular biology and flow cytometry was defined in detail. In this review, we have focused on the role of ancillary techniques in the cytological diagnosis of soft tissue tumors. Combination of cytological and histological cellular material with ancillary techniques increases the number of accurate diagnoses and improves clinical management of patients.
The aim of this study was to evaluate the clinical, ultrasonographic, and elastographic parameters in the risk stratification of malignancy for thyroid nodules with indeterminate cytology according to The Bethesda System for Reporting Thyroid Cytology. This retrospective, single-center study analyzed 838 thyroid nodules from 716 consecutive patients for six years. The diagnostic performance of nodule size, Doppler ultrasonography features, American Thyroid Association risk of malignancy guidelines, and Tsukuba elasticity scores via strain elastography was assessed. A multinomial logistic regression analysis was employed to compare indeterminate categories (III, IV, and V) with benign cytology (II) to identify independent predictors of malignancy. Indeterminate nodules exhibited larger mean diameters compared to benign ones (20.83±9.89 vs. 18.65±9.08 mm; p<0.05), and significant associations were identified between III, IV, and V categories and increased peripheral/central vascularization, higher-risk American Thyroid Association risk of malignancy classifications, and elevated Tsukuba elasticity scores (4 and 5). Histopathological malignancy rates were higher in indeterminate groups (p<0.05), whereas patient age and nodule location demonstrated no significant predictive value. Integrated assessment of nodule size, Doppler vascularity, American Thyroid Association risk stratification, and strain elastography significantly enhances the predictive accuracy for malignancy in nodules with indeterminate cytology. These multiparametric indices provide essential guidance for optimizing surgical indications and clinical management in cases of diagnostic uncertainty.
To evaluate the performance of a soft-voting ensemble deep learning (DL) model incorporating five transfer learning (TL) architectures for categorizing cervical smears according to the Bethesda system. A total of 259 cervical cytology cases processed by SurePath liquid-based cytology were included, yielding 1016 representative microphotographs. Images were divided into training (70%), validation (15%), and test (15%) sets. An ensemble model comprising VGG16, ResNet50, InceptionV3, DenseNet121, and MobileNetV2 was trained using TL with soft-voting integration. Diagnostic performance was assessed using standard metrics, including 95% confidence intervals (CI). In the test set, the model correctly classified 27/31 negative for intraepithelial lesions and malignancy (NILM) images and 56/58 carcinoma images. For NILM, the sensitivity was 0.871 (95% CI: 0.72-0.95), specificity 0.977 (95% CI: 0.94-0.99), accuracy 0.956 (95% CI: 0.92-0.98), and area under the curve of receiver operating characteristic (AUROC) 0.98 (95% CI: 0.96-1.00). For carcinoma, the sensitivity was 0.966 (95% CI: 0.88-1.00), specificity 0.960 (95% CI: 0.87-0.99), accuracy 0.962 (95% CI: 0.93-0.99), and AUROC 0.99 (95% CI: 0.98-1.00). Intermediate categories demonstrated variable performance, with lower sensitivity for low-grade squamous intraepithelial lesion (0.20), though the specificity remained high (1.00). Overall, AUROC values were high across all categories (0.93-0.99). Among all the models, the ensemble learning (EL) model had the best performance. The proposed EL approach demonstrates high diagnostic accuracy and excellent discrimination for clinically critical categories such as high-grade squamous intraepithelial lesion (HSIL) and carcinoma. This model highlights the potential of DL-based ensemble frameworks in improving the reliability of cervical cytology interpretation. Larger datasets and whole-slide image analysis may further refine the performance for intermediate-grade lesions.
Pancreatic lesions range from benign cystic to premalignant and frankly malignant. The Papanicolaou Society of Cytopathology (PSC) was established in 2014 for pancreaticobiliary cytology, with a six-tiered system. Recently, the World Health Organization (WHO) proposed a reporting system for pancreaticobiliary cytopathology. This study aimed to apply PSC and WHO systems to pancreatic cytology samples and compare their risk assessment. The Institutional Hospital Information System was searched for all pancreatic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), transabdominal ultrasound-guided FNA (TUS-FNA), and pancreatic fluid cytology samples from January 2016 to April 2025, and cases were reassigned as per the PSC and WHO diagnostic categories by two cytopathologists. Risk of malignancy (ROM) in each diagnostic category was assessed using available histopathological, clinical, radiological, biochemical, and follow-up data. Of 281 pancreatic cytology cases via EUS (64.1%) and TUS-FNA (35.9%), 197 had complete follow-up records. The ROM for the PSC categories I-VI was 58.3%, 0%, 75%, 64.7%, 100%, and 100%. For WHO system categories I-IV, VI-VII, ROM values were 66.7%, 0%, 75%, 0%, 100%, and 100%. These findings indicate that the WHO system offers more effective risk stratification. Furthermore, compared with the PSC system, the WHO system showed an increase in sensitivity (89.2% vs. 81.4%), negative predictive value (NPV; 82.7% vs. 73.9%), and accuracy (92.9% vs. 87.8%), while specificity and positive predictive value (PPV) stayed consistent at 100%. The WHO reporting system for pancreatic cytology offers superior risk categorization, sensitivity, NPV, and accuracy compared with the PSC system, while maintaining comparable specificity and PPV.
Bladder cancer is a common and highly recurrent malignancy requiring lifelong surveillance. Urine cytology serves as a noninvasive triage tool to guide cystoscopy but is limited by variable sensitivity and manual review. Although deep learning enables quantitative cell-level assessment, limited work has examined three-dimensional urine cytology preparations (e.g., SurePath) containing residual cellular fragments, where restricting analysis to a single nominal focal plane may obscure diagnostically relevant features. This study aimed to quantify focal-plane heterogeneity, measure degradation of nuclear-to-cytoplasmic (NC) ratio and nuclear area estimates off plane, and evaluate focal-plane selection algorithms for performance recovery. A total of 325 SurePath whole-slide images scanned as 11-plane Z-stacks were analyzed that spanned negative through high-grade urothelial carcinoma cases. A detection model identified cells and clusters across planes, and 343 clusters (2435 urothelial cells) were reannotated at the optimal nuclear and cytoplasmic focal depths. Classical focus metrics and vision-transformer models were evaluated for focal-plane prediction. A U-Net segmentation model generated NC ratios and nuclear areas, and Spearman correlations compared annotated and predicted measurements across optimal, off-plane, and algorithm-selected conditions. Focal-plane prediction accuracy ranged from 42% to 88%, with classical focus metrics outperforming deep-learning approaches. NC ratio correlation was 0.774 at optimal focus and declined progressively off plane (∼0.50 at ±5 planes). Algorithm-selected planes partially recovered performance (up to 0.748). Similar trends were observed for nuclear area estimation. Accurate focal-plane selection is critical for artificial intelligence-based assessment of three-dimensional urine cytology. Future work will extend this analysis to cluster- and patient-level outcomes in multi-institutional validation studies.
Despite the availability of cervical cancer (CC) screening in Bolivia, coverage remains low and uneven across municipalities. This suggests the presence of barriers to effective secondary prevention, which involves early detection through screening and treatment of precancerous lesions. There is limited research on the perceptions of healthcare providers (HCPs) regarding the challenges that women in Bolivia face when accessing CC secondary prevention. This study therefore explored HCPs' perceptions of barriers and facilitators for women's access to CC secondary prevention in Cochabamba, Bolivia. Qualitative interviews were conducted with 30 HCPs working in CC secondary prevention, including gynaecologists, general practitioners, nurses, and auxiliary nurses. The interviews were analysed using reflexive thematic analysis. Levesque's access to healthcare framework informed the study design, and the socio-ecological model was used to discuss the findings across multiple levels. HCPs perceived numerous barriers and limited facilitators in access to CC secondary prevention at different levels. Barriers at the individual level included information gaps among women. Incentive-based campaigns were used to increase screening, but these did not address the actual treatment barriers or root causes. At the interpersonal-community level, barriers included family-transferred misconceptions, gender norms, and women's fear of intimate partner violence if attending screening. Facilitators included the use of the Quechua language during healthcare encounters, and material incentives to encourage attendance. Barriers at the organizational-structural level included a lack of clarity regarding which women should be screened and how often, the concentration of centralized cytology services in a single laboratory, unclear responsibilities among staff for sample collection and result delivery, and bureaucratic and administrative barriers that limited access to screening and timely results. These barriers led to long waiting times, generating mistrust and reluctance to engage with CC screening. HCPs perceive barriers to CC secondary prevention at the individual, community, and organizational levels, including women's lack of information, family-driven misconceptions, gender norms, unclear screening guidelines, centralized cytology services, and bureaucratic delays that erode trust. Facilitators include the use of Quechua language during care and material incentives to encourage screening attendance; however, these do not address treatment barriers or structural causes.
<p><strong>Introduction:</strong> Fine-needle aspiration cytology (FNAC) is a standard preoperative diagnostic tool for salivary gland tumors, yet its sensitivity is widely debated.</p><p><strong>Aim:</strong> This study evaluates the diagnostic accuracy of FNAC compared to final histopathology, with a specific focus on institutional variability and the influence of tumor size on diagnostic yield.</p><p><strong>Methods:</strong> A retrospective, multicenter analysis was conducted on 1331 patients who underwent surgical resection for salivary gland tumors across five tertiary centers. After excluding incomplete records, 1031 patients with informative FNAC results were analyzed. Diagnostic performance (sensitivity, specificity, accuracy, and likelihood ratios) was calculated by comparing preoperative cytology with final histopathology. Statistical evaluations (Chi-square, Welch's t-test) assessed the impact of patient demographics, tumor dimensions (4 cm), and institutional location on diagnostic concordance.</p><p><strong>Results:</strong> The overall diagnostic accuracy of FNAC was 94.1%. The procedure demonstrated excellent specificity (98.4%) but suboptimal sensitivity (50.0%), confirming a high false-negative rate. Significant institutional variability was observed (p &lt; 0.001), with local sensitivities ranging from 16.7% to 69.2%. Tumor size significantly impacted diagnostic accuracy (p = 0.0258), peaking in intermediate lesions (2-4 cm; 95.0%) but declining in both smaller (&lt;2 cm; 93.7%) and larger&nbsp;neoplasms (&gt;4 cm; 91.9%). An independent review of 298 initially non-diagnostic aspirates revealed a substantial subset of histologically confirmed malignancies, demonstrating that non-informative cytological smears cannot be assumed benign.</p><p><strong>Conclusions:</strong> While FNAC provides highly specific evidence for salivary gland malignancies, its low sensitivity and susceptibility to institutional and size-dependent variables limit its reliability in ruling out cancer. High false-negative rates, particularly in tumors exceeding 4 cm, necessitate a multimodal diagnostic approach. Integrating core needle biopsy for challenging lesions and intraoperative frozen section analysis is crucial to mitigate cytopathological limitations and ensure appropriate surgical management.</p>.
Papillary lesions of the breast represent a diverse group of neoplasms with varying biological behavior, ranging from benign to malignant. Accurate diagnosis is critical for appropriate clinical management. This study aims to analyze the cytopathological features of papillary breast lesions to improve diagnostic accuracy. A retrospective study was performed on cases of papillary neoplasm of the breast diagnosed on cytology followed by histopathology during the study period, after procuring institutional ethical committee clearance. The clinical, pathologic, and follow-up details were retrieved from the hospital records and the pathology database and were analyzed. The study identified distinct benign and malignant papillary lesions, including intraductal papilloma, papillary ductal carcinoma in situ, encapsulated papillary carcinoma, and solid papillary carcinoma. The mean age of the study participants was 51.15 years. Benign neoplasms showed cohesive clusters and a clear background on cytology, while cases with atypical or malignant features demonstrated loss of myoepithelial cells, non-cohesive clusters, and necrotic/dirty background. Papillary breast lesions encompass a wide spectrum of pathology, necessitating precise cytologic and histopathologic evaluation. The presence or absence of myoepithelial markers aids in differentiating benign from malignant lesions. Identification of cytologic features of benign and malignant neoplasms can improve diagnostic accuracy, enhance patient management, and ensure timely intervention for malignant cases.
Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders requiring a multidisciplinary diagnostic approach. Bronchoalveolar lavage (BAL) is a minimally invasive procedure that provides cellular insights into lung pathology. This study evaluates the role of BAL cytology in ILD cases. This observational study was conducted at a tertiary care health care center, from April 2023 to June 2024. A total of 100 ILD patients were enrolled, out of which 31 patients who required multidisciplinary diagnosis (MDD) for a final diagnosis of ILD were included. BAL fluid was processed using cytocentrifugation and stained with Giemsa and Papanicolaou stains, and differential cell count patterns (cellular analysis) were assessed in 400 cells. In cases of sarcoidosis, endobronchial biopsy was performed in five cases, and endobronchial ultrasound-guided transbronchial needle aspiration was performed in nine cases. The MDD approach incorporated clinical features, high-resolution computed tomography, biochemical, microbiological, biopsy, and cytology findings. The mean age of patients was 41.2 ± 12.2 years, with a female predominance (74.2%). The distribution of ILD subtypes included sarcoidosis (45.2%), connective tissue disease-associated interstitial lung disease (CTD-ILD) (25.8%) idiopathic nonspecific interstitial pneumonia (6.5%), and hypersensitivity pneumonitis (HP) (22.6%). BAL cellular analysis showed lymphocytosis in sarcoidosis (41.8%) and chronic HP (56.7%) with neutrophilia (mean value >20%). The CTD-ILD cellular pattern is similar to that of sarcoidosis. BAL findings corroborated with the final diagnoses in cases with multiple differentials. BAL cellular analysis is a valuable tool in the MDD approach to ILD diagnosis. The presence of lymphocytosis in BAL commensurates with sarcoidosis and chronic HP diagnosis. The presence of concurrent neutrophilia in such cases may not necessarily be considered in lines of an infective etiology or acute exacerbation.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the images showing periodic acid‑Schiff staining in Fig. 5 on p. 1025, the 'PLKO‑SH' panel in Fig. 5A contained an overlapping section with the 'WB‑F344' panel in Fig. 5C, in spite of the experimental conditions reported for these figure parts being different. The authors have been contacted by the Editorial Office to offer an explanation for the apparent re‑use of the same data in Fig. 5 of this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 43: 1021‑1032, 2019; DOI: 10.3892/ijmm.2018.4010].
The study investigated the efficacy of internal thoracoscopy combined with multi-site biopsy and erbium nanoparticle-containing silica-indocyanine green composite covered (ErNP@SiO2-ICG) near-infrared fluorescent probe technology in the diagnosis of malignant pleural effusion. Internal medicine: This procedure was conducted on 90 patients with pleural effusion at the Department of Respiratory Medicine of the Second People's Hospital of Hefei City between January 2021 and October 2024. The procedure included pleural biopsy, pleural fluid staining, near-infrared fluorescence biopsy system analysis, and cytology of pleural effusion. Out of the 90 patients who had thoracoscopies, 20 had an unclear diagnosis, 35 had benign lesions, and 35 had malignant lesions. Thoracoscopy had a positive predictive value of 75.80%, a negative predictive value of 73.00%, a sensitivity of 71.40%, a specificity of 77.10%, and a concordance rate of 74.29% matched with pathological diagnosis for malignant lesions. The positive predictive value for the diagnosis of malignant pleural effusion increased to 80.00% when paired with an ErNP@SiO2-ICG near-infrared fluorescent probe. The negative predictive value was 82.90%, the degree of certainty was 82.40%, the specificity was 80.60%, and there was good concordance with the final pathological results (Kappa value of 0.629, p < 0.001). Internal thoracoscopy has a high detection rate and accuracy in the diagnosis of pleural effusion, and when combined with the ErNP@SiO₂-ICG near-infrared fluorescent probe technology, it improves the diagnostic accuracy of malignant pleural effusion.
Cervical cancer screening has evolved immensely with advances in molecular diagnostics and improved understanding of human papillomavirus (HPV)-mediated carcinogenesis. While conventional cervical cytology has historically played a pivotal role in reductions in cervical cancer incidence and mortality, its limitations have led to the development of liquid-based cytology (LBC) and HPV-based testing. LBC offers improved sample adequacy, better preservation of cellular morphology, and permits the use of residual material for ancillary testing. HPV DNA testing, particularly as a primary screening modality, provides high sensitivity for detecting high-grade cervical intraepithelial neoplasia. In addition, emerging biomarkers such as p16INK4a and Ki-67 dual staining enhance risk stratification and triage of HPV-positive women. Despite the growing adoption of primary HPV screening, cytology remains indispensable for morphologic assessment, detection of HPV-independent lesions, and clinical correlation. An integrated approach combining HPV testing, cytology, and biomarkers represents the most effective strategy for cervical cancer screening. Such a balanced model is essential for optimizing diagnostic accuracy, guiding management, and supporting global efforts toward cervical cancer elimination.
Polycomb repressive complex 2 (PRC2) represses genes through catalyzing H3K27me3, a histone modification essential for maintenance of cellular identity. The complex's catalytic activity, chromatin localization, and propagation along chromatin are modulated by accessory proteins such as AEBP2, MTF2, JARID2, and PALI, which is specifically required for mouse embryogenesis. AEBP2 exists in distinct isoforms: a short isoform that enhances PRC2 catalytic activity and promotes H3K27me3 spreading, facilitating robust gene repression, and a long isoform whose function has remained unclear. Here, we report that the N-terminal region of the long isoform contains conserved DE-motifs unique to this isoform that inhibit PRC2 activity, including both H3K27 methylation and EZH2 automethylation, suggesting that these motifs interfere with the automethylation loop proximal to the SET domain. Notably, re-expression of the long isoform in Mtf2/Jarid2/Aebp2 triple-knockout mouse embryonic stem cells failed to restore H3K27me3 and caused defective differentiation. These findings uncover an isoform-specific regulatory mechanism by which AEBP2 controls PRC2 activity and contributes to a broader understanding of the dynamic regulation of PRC2 during development.
The art of cytopathology lies not only in the interpretation of the slide but also careful consideration of demographic, clinical, radiological, and other relevant information of individual patients. While deep image learning may perform well in specific cytology image sets or uncover novel, significant cytomorphologic parameters, the lack of clinical context puts prediction models at a dangerous position where irrelevant and potentially harmful diagnoses may be issued. The increment in prediction accuracy by expanding the size of image sets diminishes and plateaus after reaching certain thresholds. This can be overcome by introducing multimodal data to deep learning, which has seen success in resection and small biopsy specimens from histopathological specimens and early adoption in cytopathology. In this study, a qualitative review on the current state of the potential sources of multimodal input-demographics, clinical investigations, and radiology; the diagnostic data that can be obtained in a cytology specimen-stains and preparations, immunocytochemistry, and molecular testing will be discussed with reference to the potential of multimodal deep learning in cytopathology.
Anal intraepithelial neoplasia (AIN) is a well-recognised precursor to invasive anal squamous cell carcinoma. The prevalence of anal cancer is increasing in people living with HIV. This hermeneutic phenomenology study explored the perceptions and experiences of patients and clinicians in anal cytology screening and high resolution anoscopy in sexual health clinics in the UK. The study was conducted using the interpretative paradigm using hermeneutic phenomenology informed by Heidegger. A purposive sample comprising 14 patients and 8 clinicians was recruited. In-depth unstructured interviews were conducted as part of a Doctorate in Nursing that was completed in 2020. Interpretive phenomenological analysis (IPA) was used to develop in-depth interpretations of participants' perceptions and experiences of anal cancer screening. Data were analysed using the six stages in the analysis process, that is, immersion; understanding; abstraction; synthesis and theme development; illumination and illustration of phenomena; integration and critique. Five themes emerged from the data from both patients and clinicians: psychological effects of anal cancer screening; screening procedures; education, knowledge and training; social and sexual activity; guidelines and practices. The study demonstrated that anal cancer screening is acceptable, but tolerability is variable; and education, knowledge and information on anal cancer screening is limited. Although the social life of most patients was not affected, their sexual activity was impacted. The author recommends introducing a screening programme as part of routine HIV care in outpatient sexual health clinics. Anal cancer screening benefits outweigh any psychological harm caused by tests and diagnostic procedures for people living with HIV. The emotional responses highlighted were not associated with significant psychological harm. Anal cancer screening should be considered in future guidelines in the UK for people living with HIV.