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BACKGROUND: Cytological samples play a critical role in diagnosing advanced-stage tumors and those arising in difficult-to-reach anatomical sites such as the pancreatobiliary tract, lung, thyroid, suprarenal, pelvis, and others such as salivary glands. These samples are often the only available material for accurate diagnosis and for performing ancillary studies, such as immunocytochemistry (ICC) or the detection of molecular biomarkers. SUMMARY: While the use of immunohistochemistry is well established and standardized on formalin-fixed-paraffin-embedded histological tissue, in cytological samples, it presents unique challenges. Methods used for obtaining and processing these specimens are complex and are not standardized among laboratories. Moreover, there is also diversity in the types of cytological samples potentially suitable for ICC. KEY MESSAGES: This review explores the current landscape of ICC practices in European and North American laboratories, highlighting variability in methods and the need for standardization to ensure reliable results and reproducibility of ICC on cytological specimens.

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For over a century, the need to identify malaria in the peripheral blood has been the driving force behind the development of fundamental clinical microscopy techniques. In the study by Moysis et al., artificial intelligence-based model was utilized to identify and provide quantitative morphological characteristics of red blood cells typical to severe malaria anaemia, irrespective to the actual presence of visible parasites. Commentary on: Moysis et al. Leveraging deep learning for detecting red blood cell morphological changes in blood films from children with severe malaria anaemia. Br J Haematol 2024;205:699-710.

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Inteligencia Artificial , Eritrocitos , Malaria , Humanos , Malaria/sangre , Malaria/diagnóstico , Eritrocitos/parasitología , Anemia/sangre , Anemia/diagnóstico , Niño

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Our study compared the diagnostic accuracy of the 10% alcohol-formalin cell-block (CB) technique against traditional smears (CS) in serous effusions over 1 year. CB outperformed CS by detecting 7 missed cases and diagnosing 177 benign, 5 suspicious and 26 malignant cases compared to CS's 180 benign, 9 suspicious and 19 malignant cases. Using histopathology as a gold standard, CB showed a sensitivity of 96.4%, specificity of 98.3% and diagnostic accuracy of 98.1%, significantly higher than CS's 79.3% sensitivity, specificity of 97.7% and 95.2% accuracy. Using a 10% alcohol-formalin method, CB also excelled in cytomorphological characterization, especially in background elements, cellularity and cellular architecture. CB offered improved diagnostic accuracy and allowed extra sections for additional tests. In resource-constrained settings, combining CS and CB enhances cytological assessment.

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OBJECTIVE: Immunocytochemistry (ICC) is essential for enhancing diagnostic accuracy and identifying markers for diagnosis, prognosis and targeted therapies. While cell blocks (CBs) are preferred for standardization and optimized staining, cytological smears are an alternative when CBs are unavailable. However, the literature on ICC protocols for smears is sparse. This review addresses preparation, fixation and protocols for nuclear and cytoplasmic antibodies on smears, drawing from our laboratory's experience. METHODS: We reviewed procedures for ICC on cytological smears using existing literature and practical insights from our laboratory. RESULTS: Commercially available antibodies were found to be reliable for ICC on smears if specimens are properly prepared and fixed. Protocols developed in our laboratory maintained antigenicity and provided clear staining results. CONCLUSIONS: Although ICC on CBs is the gold standard for standardization, cytological smears are a viable alternative when CBs are unavailable. Success in ICC on smears depends on proper preparation and fixation. This review offers practical protocols and insights to help laboratories optimize ICC on cytological smears. Further research and standardization are necessary to enhance reproducibility and reliability of ICC on smears. The practical information provided is based on personal experience in our laboratory.

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Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions.

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Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/terapia , Femenino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Detección Precoz del Cáncer/métodos , Papillomaviridae , Lesiones Precancerosas/terapia , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/etiología , Lesiones Precancerosas/prevención & control

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Leukemia-associated structural chromosomal abnormalities (SCA) can be identified either by karyotyping or interphase-fluorescence in-situ hybridization (i-FISH) assays. Both karyotyping and i-FISH on mononuclear cell suspension are time, resource, and manpower-consuming assays. In this study, we have compared the results of specific leukemia-associated SCAs identified by i-FISH on air-dried bone marrow (BM)/peripheral blood (PB) smears and BM karyotyping. The study was conducted among pediatric patients (age ≤ 18 years) diagnosed with acute leukemias between January 2018 to December 2022. The results of i-FISH on air-dried BM/PB smears and BM-karyotyping for our SCA of interest (BCR::ABL1, ETV6::RUNX1, TCF3::PBX1, KMT2A rearrangement, RUNX1::RUNX1T1, CBFB::MYH11, and PML::RARA) were entered in a contingency table and the agreement of results was calculated. The strength of agreement was assessed by Cramer's V test. Among 270 patients, SCA of interest was identified among 26% and 17% of patients by i-FISH on air-dried smears and karyotyping, respectively. Excluding 53 patients with metaphase failure, the remaining 217 patients had 92% agreement (Cramer's V of 0.931 with p < 0.000) between the results for specific SCAs identified by both techniques. On excluding samples with cryptic cytogenetic aberrancies, there was 99% agreement (Cramer's V of 0.953 with p < 0.000) for gross SCA identified by both techniques. In addition, i-FISH on air-dried smears identified SCA in 30% of patients with metaphase failure. I-FISH on air-dried PB/BMA smears is a less-labor and  resource-consuming assay. It can be considered an efficient alternative to conventional karyotyping for  identifying specific SCA of interest in under-resourced laboratories. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01699-2.

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Background: Rapidity and reliability are the major advantages of cytopathology in tumor diagnosis. The need for minimal turnaround time for assessing cytological smears has encouraged innovations in staining techniques that require lesser staining time with unequivocal cell morphology. Rapid Pap staining was introduced as a hybrid to conventional Pap stain. It improves staining quality, gets over the staining time in restriction, and is a more efficient technique financially. In the present study, a modified staining technique was adopted where phloxine is added as one of the cytoplasmic stain components in rapid Pap stain kits. Objective: The aim of this study was to assess whether the modification of the existing procedure by adding phloxine as one of the components of the cytoplasmic stain intensifies the cytoplasmic differentiation and cytoplasmic staining in gynecological smears. Materials and Methods: This was a prospective study done on 50 cases of gynecological smears. Two smears were collected from each patient and fixed in 100% propanol and stained with the rapid Pap stain kit procedure and modified rapid Pap stain with phloxine. Slides were then analyzed by two pathologists blinded to the staining method used. Five parameters were considered and scored (background, cell morphology, nuclear staining, cytoplasmic differentiation, and cytoplasmic staining). The quality index for each method was calculated by finding out the ratio of the actual score obtained to the maximum score possible. Results: Both the staining methods had comparable results. For both pathologists, the quality index calculated for modified Pap stain was found to be marginally higher than the quality index for rapid Pap. The mean quality index was comparable for modified Pap (0.91) and rapid Pap (0.89). Conclusions: The efficacy of modified Pap stain with phloxine to distinctly stain the cytoplasm is comparable with that of rapid Pap stain. In addition, the intensity of staining can be enhanced with little cost outlay, and this can be especially beneficial in low-resource settings.

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Background: The role of rapid on-site evaluation (ROSE) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is debatable. In this study, we aimed to compare the diagnostic yield of ROSE vs. non-ROSE in solid pancreatic lesions. Methods: This retrospective single-center study included patients undergoing EUS-FNA of solid pancreatic lesions from 2019-2021. Patients with cystic lesions, those undergoing fine-needle core biopsy, those undergoing repeat procedures, and patients with non-diagnostic smears with less than 6-month follow up were excluded. The diagnostic yield, need for repeat procedures and number of passes required with and without ROSE were analyzed in these patients. Results: Of the 111 patients included, 56 underwent ROSE. The majority of lesions were malignant in both groups (79.6% ROSE vs. 75% non-ROSE). The diagnostic yield was 96.4% in the ROSE group and 94.5% in the non-ROSE group. Repeat samples were needed in 1 ROSE and 2 non-ROSE patients. The median number of passes made was significantly fewer in the ROSE group (3.5, interquartile range - 3,4) compared with the non-ROSE group (4, interquartile range - 3,5) P=0.01. However, the frequency of procedure-related complications was similar in both groups. Conclusion: The utilization of ROSE during EUS-FNA of solid pancreatic lesions does not affect the diagnostic yield or the need for repeat samples, but reduces the number of passes needed for acquiring samples.

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BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

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Neoplasias Pulmonares , Linfadenopatía , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Mediastino/diagnóstico por imagen , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Ganglios Linfáticos/patología , Linfadenopatía/patología , Broncoscopía/métodos , Estadificación de Neoplasias , Estudios Retrospectivos

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BACKGROUND: Uganda has approximately 1.2 million people aged 15-64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a comparative cross-sectional study of 210 women aged 22-65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions. RESULTS: The overall prevalence of premalignant cervical lesions in the study population was 17% (n = 72; 95% C.I: 14.1-21.4), with 23% (n = 47; 95% C.I: 17.8-29.5) in women living with HIV and 12% (n = 25; 95% C.I: 8.2-17.1) in women not living with HIV (p < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n = 35) and women not living with HIV (80%; n = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27-4.42; p = 0.007). CONCLUSION: Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.

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Detección Precoz del Cáncer , Infecciones por VIH , Lesiones Precancerosas , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Estudios Transversales , Uganda/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Persona de Mediana Edad , Adulto Joven , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Prevalencia , Lesiones Precancerosas/epidemiología , Anciano , Prueba de Papanicolaou/estadística & datos numéricos , Centros de Atención Terciaria/estadística & datos numéricos , Seropositividad para VIH/epidemiología , Seropositividad para VIH/complicaciones , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Frotis Vaginal/estadística & datos numéricos

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Objective: In an era of minimally invasive and rapid diagnostic technologies, fine-needle aspiration cytology (FNAC) is most useful when it comes to patients with lymphadenopathies especially of the cervical region. Liquid-based cytology (LBC) is an alternative processing method which is used for both gynecological and non-gynecological samples. Because of the remarkable advantages of LBC smears in gynecological samples, nowadays, many studies have been done to assess its utility in various other lesions. Hereby, with the help of this study, we would like to evaluate the efficiency of LBC smears in comparison to conventional FNAC smears conventional smears (CS) on lymph node aspirates. Material and Methods: A retrospective study was done over a 1-year period in which 253 cases of lymph node aspirates were included in the study. The slides were prepared using standard conventional and LBC techniques and compared for adequacy, cellularity, cell architecture, necrosis, background debris, presence of cells in monolayer sheets, and nuclear/cytoplasmic details. Results: Of the total 253 cases, 171 (67.6%) were and 67 (26.5%) were diagnosed as non-neoplastic and malignant, respectively. Although the LBC smears were useful in the diagnosis of malignant cases, they did pose some challenges especially in the non-neoplastic lymph node aspirates due to loss of the background necrosis. In addition, the cellular yield in LBC smears was low in comparison to CS. Conclusion: LBC smears from lymph node aspirates results in better diagnostic accuracy for malignant cases due to better cellular and nuclear details. However, for non-neoplastic etiology, it should not be considered better than CS as loss of the background necrosis and inflammation may result in an incorrect diagnosis.

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BACKGROUND: To compare conventional smears (CSs) and liquid-based preparations (LBPs) for diagnosing thyroid malignant or suspicious lesions. METHODS: Studies in the PubMed, SCOPUS, Embase, Web of Science, and Cochrane database published up to December 2023. We reviewed 17 studies, including 15,861 samples. RESULTS: The diagnostic odds ratio (DOR) for CS was 23.6674. The area under the summary receiver operating characteristic curve (AUC) was 0.879, with sensitivity, specificity, negative predictive value, and positive predictive value of 0.8266, 0.8668, 0.8969, and 0.7841, respectively. The rate of inadequate specimens was 0.1280. For LBP, the DOR was 25.3587, with an AUC of 0.865. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.8190, 0.8833, 0.8515, and 0.8562. The rate of inadequate specimens was 0.1729. For CS plus LBP, the AUC was 0.813, with a lower DOR of 9.4557 compared to individual methods. Diagnostic accuracy did not significantly differ among CS, LBP, and CS plus LBP. Subgroup analysis was used to compare ThinPrep and SurePath. The DORs were 29.1494 and 19.7734. SurePath had a significantly higher AUC. CONCLUSIONS: There was no significant difference in diagnostic accuracy or proportion of inadequate smears between CS and LBP. SurePath demonstrated higher diagnostic accuracy than ThinPrep. Recommendations for fine-needle aspiration cytology should consider cost, feasibility, and accuracy.

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Peripheral blood smear examination is one of the basic steps in the evaluation of different blood cells. It is a confirmatory step after an automated complete blood count analysis. Manual microscopy is time-consuming and requires professional laboratory expertise. Therefore, the turn-around time for peripheral smear in a health care center is approximately 3-4 hours. To avoid the traditional method of manual counting under the microscope a computerized automation of peripheral blood smear examination has been adopted, which is a challenging task in medical diagnostics. In recent times, deep learning techniques have overcome the challenges associated with human microscopic evaluation of peripheral smears and this has led to reduced cost and precise diagnosis. However, their application can be significantly improved by the availability of annotated datasets. This study presents a large customized annotated blood cell dataset (named the Bio-Net dataset from healthy individuals) and blood cell detection and counting in the peripheral blood smear images. A mini-version of the dataset for specialized WBC-based image processing tasks is also equipped to classify the healthy and mature WBCs in their respective classes. An object detection algorithm called You Only Look Once (YOLO) with a refashion disposition has been trained on the novel dataset to automatically detect and classify blood cells into RBCs, WBCs, and platelets and compare the results with other publicly available datasets to highlight the versatility. In short the introduction of the Bio-Net dataset and AI-powered detection and counting offers a significant potential for advancement in biomedical research for analyzing and understanding biological data.

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Procesamiento de Imagen Asistido por Computador , Leucocitos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Eritrocitos , Algoritmos , Plaquetas

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Immunotherapy has become a promising cancer treatment in the past decade, and IHC is the most commonly used testing method for PDL-1/PD1 evaluation. In general, PD-L1 assays can be performed on both FFPE specimens and cytological samples. However, their use on smears is not yet well-established or validated. Nowadays, digital images and advanced algorithms can aid in interpreting PD-L1 in cytological samples. Understanding the immune environment of non-small cell lung cancer (NSCLC) is critical in developing successful anticancer immunotherapies. The use of a multiplexed immunofluorescence (mIF) assay on cytological samples obtained through minimally invasive methods appears to be a viable option for investigating the immune environment of NSCLC. This review aims to briefly summarize the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.

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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/patología , Antígeno B7-H1 , Pulmón/patología , Inmunoterapia , Biomarcadores de Tumor/análisis

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Patient-derived organoid models hold promise for advancing clinical cancer research, including diagnosis and personalized and precision medicine approaches, and cytology, in particular, plays a pivotal role in this process. These three-dimensional multicellular structures are heterogeneous, potentially maintain the cancer phenotype, and conserve the genomic, transcriptomic, and epigenomic patterns of the parental tumors. To ensure that only tumor tissue is used for organoid development, cytologic validation is necessary before initiating the process of organoid generation. Here, we explore the technology of tumor organoids and discuss the fundamental application of cytology as a simple and cost-effective approach toward organoid development. We also underscore the potential application of organoid development in drug efficacy studies for lung cancer and head and neck tumors. Additionally, we stress the importance of using fine-needle aspiration to generate tumoroids.

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Neoplasias Pulmonares , Investigación Biomédica Traslacional , Humanos , Medicina de Precisión/métodos , Citodiagnóstico , Organoides/patología , Neoplasias Pulmonares/patología

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Leukocyte profiles are broadly used to assess the health status of many species. Reference intervals, and an understanding of the factors that may influence these intervals, are necessary for adequate interpretation of leukograms. Using a data set that spans over three decades, we investigated variation in leukocyte profile in several populations of the evolutionarily unique reptile, the tuatara (Sphenodon punctatus). To do this, we first established reference intervals for each leukocyte type according to best practices. Next, we determined that source population and sampling date were the two most important predictors of leukocyte makeup. We found significant differences in the ratio of heterophils: lymphocytes (H:L) between populations, with tuatara on the more resource-stressed sampling island having a significantly higher ratio of H:L. Finally, we found that sampling location, sex, and life stage did not explain variation in the responses of tuatara to stimulation with Concanavalin A and lipopolysaccharide in both 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide and Griess assay experiments. Our results offer important insight into the function of leukocytes in reptiles.

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Leucocitos , Reptiles , Animales

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Introduction: Malaria is one of the most prevalent infectious diseases in sub-Saharan Africa, with 247 million cases reported worldwide in 2021 according to the World Health Organization. Optical microscopy remains the gold standard technique for malaria diagnosis, however, it requires expertise, is time-consuming and difficult to reproduce. Therefore, new diagnostic techniques based on digital image analysis using artificial intelligence tools can improve diagnosis and help automate it. Methods: In this study, a dataset of 2571 labeled thick blood smear images were created. YOLOv5x, Faster R-CNN, SSD, and RetinaNet object detection neural networks were trained on the same dataset to evaluate their performance in Plasmodium parasite detection. Attention modules were applied and compared with YOLOv5x results. To automate the entire diagnostic process, a prototype of 3D-printed pieces was designed for the robotization of conventional optical microscopy, capable of auto-focusing the sample and tracking the entire slide. Results: Comparative analysis yielded a performance for YOLOv5x on a test set of 92.10% precision, 93.50% recall, 92.79% F-score, and 94.40% mAP0.5 for leukocyte, early and mature Plasmodium trophozoites overall detection. F-score values of each category were 99.0% for leukocytes, 88.6% for early trophozoites and 87.3% for mature trophozoites detection. Attention modules performance show non-significant statistical differences when compared to YOLOv5x original trained model. The predictive models were integrated into a smartphone-computer application for the purpose of image-based diagnostics in the laboratory. The system can perform a fully automated diagnosis by the auto-focus and X-Y movements of the robotized microscope, the CNN models trained for digital image analysis, and the smartphone device. The new prototype would determine whether a Giemsa-stained thick blood smear sample is positive/negative for Plasmodium infection and its parasite levels. The whole system was integrated into the iMAGING smartphone application. Conclusion: The coalescence of the fully-automated system via auto-focus and slide movements and the autonomous detection of Plasmodium parasites in digital images with a smartphone software and AI algorithms confers the prototype the optimal features to join the global effort against malaria, neglected tropical diseases and other infectious diseases.

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BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. METHODS: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. RESULTS: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. CONCLUSIONS: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. CLINICAL TRIAL REGISTRATIONS: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

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Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Síndrome de Liberación de Citoquinas , Células Asesinas Naturales , Antígenos CD19

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Objectives: The objectives of the study were to assess the prevalence of abnormal Pap smears and their quality metrics in a tertiary health-care facility in the western region of Saudi Arabia and to share our data with other researchers in Saudi Arabia to potentially establish benchmark data based on a Saudi population. Material and Methods: A retrospective study was carried out by the Department of Pathology at King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia, on Pap smear statistics for 14,376 Pap smears of both conventional and liquid-based cytology (LBC) between 2010 and 2022. Results: The prevalence of abnormal Pap smears of both conventional and LBC was 3.05% (438 Pap smears). The percentages of adenocarcinoma and squamous cell carcinoma were 0.08% and 0.02%, respectively, and the ratio of atypical squamous cells (ASCs) to squamous intraepithelial lesions (SILs) (ASC/SIL) was 2.61. Conclusion: The prevalence of abnormal Pap smears and the ASC/SIL ratio were consistent with the international benchmark data provided by the College of American Pathologists for each preparation type and within the range of the data provided by published studies, highlighting the need for greater focus on glandular abnormalities.

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Context: The performance parameters of cervical cytology in any accredited cytology laboratory requires implementation of quality control exercise, which ensures acceptable performance by a laboratory. This study aims to assess the analytical aspect of quality control measures by evaluating the frequency and accuracy of epithelial abnormalities as detected in cervical Pap smears using histopathologic diagnosis as the gold standard. Methods: A retrospective diagnostic test study from 2018 to 2020 was conducted. Out of the total 6000 Pap smears, histopathologic correlation was available in 150 cases in the form of colposcopic-directed biopsy (CDB) and loop electrosurgical excision procedure (LEEP) tissue in 105 cases. The quality control measures analyzed were Atypical Squamous Cell: Squamous Intraepithelial Lesion (ASC: SIL) ratio, cyto-histo correlation, and study parameters like sensitivity, specificity, positive predictive value, and negative predictive value of Pap smears as against CDB and LEEP. Results: 4.5% smears were reported as inadequate, 92.3% as Negative for intraepithelial lesion or malignancy (NILM), followed by epithelial abnormality found in 3.21%. The ASC: SIL ratio was 1.3:1. Concordance rate against CDB was 100% in Squamous cell carcinoma (SCC), 82.35% in high-grade squamous intraepithelial lesion (HSIL), 82% in atypical squamous cells of undetermined significance (ASCUS), 65.6% in low-grade squamous intraepithelial lesion (LSIL), and 50% in Atypical Squamous Cell ,High grade Squamous Intraepithelial Lesion can not be ruled out (ASC-H). Total concordance rate was 84.15%. Sensitivity of Pap smear was 65% for LSIL and 82% for HSIL. Specificity, positive predictive value, and negative predictive value were 63.63%, 90%, and 75%, respectively. Concordance rate was 96% with LEEP. Conclusion: Quality control measures give an insight of performance of any accredited cytology laboratory. This exercise needs to be conducted on a regular basis, so that relevant steps can be taken in case of major discrepancy.