Bethesda System Research Articles

Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid.

This review addresses new reporting systems for lung and pancreatobiliary cytopathology as well as the most recent edition of The Bethesda Reporting System for Thyroid Cytopathology. The review spans past, present, and future aspects within the context of the intricate interplay between traditional morphological assessments and cutting-edge molecular diagnostics. For lung and pancreas, the authors discuss the evolution of reporting systems, emphasizing the bridge between past directives and more recent collaborative efforts of the International Academy of Cytology and the World Health Organization in shaping universal reporting systems. The review offers a brief overview of the structure of these novel systems, highlighting their strengths and pinpointing areas that require further refinement. For thyroid, the authors primarily focus on the third edition of The Bethesda System for Reporting Thyroid Cytopathology, also considering the two preceding editions. This review serves as an invaluable resource for cytopathologists, offering a panoramic view of the evolving landscape of cytopathology reporting and pointing out the integrative role of the cytopathologist in an era of rapid diagnostic and therapeutic advancements.

Association of albumin, neutrophil-lymphocyte ratio and lymphocytes with clinical stage in cervical cancer patients.

To determinate the association between of albumin, neutrophil-lymphocyte ratio and lymphocytes (NLR) with clinical stage in cervical cancers. Design a retrospective cross-sectional study of consecutive subjects diagnosed with cervical cancer for the first time. The Bethesda system was used for histological diagnosis and the subjects were stratified with the FIGO system, considering stages IA to IIB as localized; while, IIIA and IVB as advanced stages. Albumin, NLR and lymphocytes were evaluated as inflammatory biomarkers and the cut-off points generated by the ROC curves were albumin < 3mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul. The association was calculated by Odds Ratios (OR) with 95% confidence intervals. A total of 152 patients were analyzed, with mean age of 49.3 ± 14.0years. Epidermoid cancer was the most frequent in 70.6% and 51.3% were classified as advanced clinical stages. A bivariate analysis showed significant relationships between advanced clinical stages and albumin < 3mg/dL with OR 5.72 (CI95% 2.62-12.4; p < 0.001); for NLR ≥ 2.0 an OR 2.53 (CI95% 1.34-4.89; p = 0.005) and for lymphocytes < 1.2 103/ul of OR 3.39 (CI95% = 1.73-6.65; p < 0.001). Albumin levels < 3mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul, were associated with advanced stages in subjects with cervical cancer.

Accuracy of ultrasound-guided fine-needle aspiration cytology in evaluation of thyroid nodules using different ultrasonographic and cytological features.

Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy. We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015-2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis. The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%. Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid.

The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

Fine-needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US-guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade-long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next-generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports.

Copy Number Profiling Implicates Thin High-Grade Squamous Intraepithelial Lesions as a True Precursor of Cervical Human Papillomavirus-Induced Squamous Cell Cancer

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)–associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC.

Association of body mass index with anal human papillomavirus infection and histologically confirmed high-grade squamous intraepithelial lesions in people who receive services at the Anal Neoplasia Clinic in Puerto Rico

ObjectiveThis study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico. MethodsThis cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed. ResultsMean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 – 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 – 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity. ConclusionBMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.

Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against theSrc canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src(p < 0.001), phospho-Src(p < 0.001), Ras(p < 0.01), c-Raf(p < 0.001), ERK1(p < 0.001), phospho-ERK1(p < 0.001), phospho-ERK2(p < 0.01), phospho-Mnk1(p < 0.001), eIF4E(p < 0.01), phospho-eIF4E(p < 0.001), E6(p < 0.01), E7(p < 0.01), Rb(p < 0.01), phospho-Rb(p < 0.001), MDM2(p < 0.01), E2F1(p < 0.001), phospho-FAK(p < 0.001), phospho-p130 Cas(p < 0.001), Mcl-1(p < 0.01), and Bcl-2(p < 0.001), but upregulates cPARP(p < 0.001), and cPARP/fPARP(p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.

Cytological Spectrum of Pap Smears according to the Bethesda System and its Clinical Correlation in a tertiary care centre

Cytological Spectrum of Pap Smears according to the Bethesda System and its Clinical Correlation in a tertiary care centre

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea.Methylation of EPB41L3 (1–6 CpG-sites), hTERT (1–10 CpG-sites) and FAM19A4 (1–5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously.In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Study on the relationship between Methylation of Neuregulin (NRG) Gene and Cervical Carcinoma.

To investigate the relationship between the DNA methylation state of NRG1 promoter and its expression changes, and to analyze the clinical significance of its regulatory mechanism of DNA methylation in cervical carcinoma. This was a retrospective study. One-hundred and twenty patients from the Department of Gynecology of Cangzhou People's Hospital from September 2017 to September 2019 were selected, including 40 cases of cervical SCC, 40 cases of high grade squamous intraepithelial lesions(HSIL) and 40 cases of control cervical tissues. RT-qPCR, immunohistochemistry and DNA methylation-specific PCR(MSP) were used to detect the mRNA and protein expression of NRG1 and DNA methylation status in different tissue types. Immunohistochemical results showed that the positive protein expression rate of NRG1 gene in the SCC group was lower than that in both HSIL and Control groups. RT-qPCR results showed that the mRNA gene of NRG1 gradually decreased in expression with the increase of cervical tissue lesions, with a statistically significant difference. Similarly, it also found that the mRNA expression level of NRG1 in the SCC group was independent of patients' age (p>0.05), but significantly correlated with tumor pathological staging, surgical pathology staging and lymphatic metastasis (p<0.05). Furthermore, methylation-specific PCR results revealed a significantly higher DNA methylation rate of NRG1 gene in the SCC group than in both HSIL and Control groups, with a statistically significant difference. Moreover, the methylation degree of NRG1 gene in SCC tissues was negatively correlated with its mRNA expression (p<0.05). Abnormal DNA hypermethylation of NRG1 gene inhibits the expression of mRNA and protein in the progression of cervical tissue from normal to cancerous state, which is involved in the occurrence and development of cervical carcinoma.

Aptima HPV Genotypes in Abnormal Cervical Samples in Different Age Groups - Implication on Vaccination Strategies.

Persistent infection with high-risk human papillomavirus (hr-HPV) types is associated with high-grade cervical abnormalities. The aim of the study was to find most hr-HPV types causing persistent infection in abnormal cytological samples using Aptima HPV testing and discuss the compatibility of the Gardasil 9 vaccine in targeting most types. The study was conducted in a cytology laboratory in a tertiary hospital. This is a retrospective observational study. Cytology and HPV Aptima test reports were obtained for abnormal cervical samples for a 6-year period. Pearson Chi-square test. Reports of 2834 abnormal cervical samples were analyzed. Aptima testing was positive in 21% of samples, including 92% of squamous cell carcinoma (SCC), 76.4% of the high-grade squamous intraepithelial lesion (HSIL), 52% of low-grade squamous intraepithelial lesion (LSIL), 40% of adenocarcinoma (ADC), and 21% of atypical squamous cells that cannot exclude HSIL (ASC-H). The Aptima other hr-HPV group was most common (60%), HPV16 was 26%, HPV18/45 was 9.6%, and double HPV infection was 4.3%. HPV16 was the most common infection in HSIL+ cases. HPV infection was most common in age groups (30-39) and (40-49), and a shift to age groups (50-59) and ≥60 was seen in HSIL+ cases. This study is the first of its kind in correlating age with hr-HPV and cytology findings in the Middle East and adds to previous knowledge related to the prevalence and Aptima testing of HPV. The outcome could be used as a baseline for the Gardasil 9 vaccine and for the assessment of its effectiveness after three or five years from initiation.

Estudio retrospectivo que evalúa marcadores de riesgo de desarrollar lesión escamosa intraepitelial anal de alto grado en hombres que tiene sexo con hombres y viven con el virus de inmunodeficiencia humana

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Individual Ultrasonographic Characteristics of Thyroid Nodules and Their Cytopathological Correlation to Determine Malignancy Risk.

Background Ultrasonographic evaluation of thyroid nodules is challenging due to their high frequency and low malignancy rate. The risk stratification system developed by the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) focuses on addressing the primary contemporary objectives for these lesions, aiming to decrease unnecessary biopsies while maintaining a similar specificity compared with other risk stratification systems. Generally, when indicative of malignancy by ultrasound findings, the next best step in management is an evaluation by fine needle aspiration biopsy (FNAB) and cytological analysis with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) resultsthat determine further evaluation requirements, actions that are based on the risk of malignancy (ROM) of the assigned category, which could include surgical intervention. Objectives To validate and analyze the individual impact of each ultrasonographic finding indicative of malignancy in the ACR TI-RADS guidelines based on their respective correlation with results obtained by TBSRTC. Materials and method Reports for 212 thyroid ultrasound-guided FNABs from 2018 to 2020 were assessed. Only 117 had both ACR TI-RADS and TBSRTC reports available and were analyzed. Nodules were divided into two groups: ROM < 5% (Bethesda 1, 2; n = 58), and ROM > 5% (Bethesda 3, 4, 5, 6; n = 59).Statistical analysis was performed using the x2 test and bivariate logistic regression model for each characteristic included in ACR TI-RADS. Results Individual ultrasound characteristics with a more pronounced distribution towards the Bethesda > 5% malignancy group were: solid or almost completely solid composition (n=53, 62.3%), very hypoechoic echogenicity (n=3, 75%), wider-than-tall shape (n=50, 50.5%), lobulated or irregular margin (n=23, 65.7%), punctate echogenic foci (n=18, 72%), and thyroid isthmus location (n=6, 75%). Statistically significant individual ultrasonographic characteristics indicative of malignancy included solid or almost completely solid (p = 0.005), very hypoechoic echogenicity (p = 0.046), margin lobulated or irregular (p = 0.031), and punctate echogenic foci (p = 0.015). No significant association was found in the taller-than-wide shape for differentiating malignant from benign lesions (p = 0.969). Conclusions Specific ultrasound characteristics identified in the ACR TI-RADS system demonstrate a stronger correlation with an increased risk of malignancy when compared with cytologic evaluation results. These characteristics include a solid composition, lobulated or irregular margins, punctate echogenic foci, and very hypoechoic echogenicity. Our findings revealedthat the scale points for the taller-than-wide characteristic do not adequately represent its true influence on the risk of malignancy.

Age and Peripheral Blood Values Relationship Evaluation of Trichomonas Vaginalis, Candida, and Gardnerella Vaginalis Frequency in Cervicovaginal Pap Smear Screening in Aksaray Province

This study aimed to explore the correlation between causative agents of vaginitis detected in Pap smear screenings and various hematological indices, alongside the severity of infections observed in Pap smears. We analyzed 348 Pap smear results, which were categorized into normal and abnormal findings and further subdivided into groups based on the presence of Vulvovaginal Candidiasis (VVC), Bacterial Vaginosis (BV), and Trichomoniasis (TV). The degree of inflammation (mild, moderate, severe) was assessed in relation to hematological indices (Platelet Index Value (PIV), Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Lymphocyte to Monocyte Ratio (LMR)), guided by the 2014 Bethesda System for evaluation. Out of 1654 patients screened, 348 met the inclusion criteria (253 aged below 45 years; 95 aged 45 years and above). In the under-45 age group, 83.3% had normal findings, with prevalence rates for VVC, BV, and TV at 73.4%, 60.2%, and 80.0%, respectively. In the over-45 group, these figures were 16.7% (normal), 26.6% (VVC), 39.8% (BV), and 20% (TV). The prevalence of moderate vaginitis in Pap smears was 45.3% for VVC, 96.1% for mild BV, and 53.3% for moderate TV. In cases of Atypical Squamous Cells of Undetermined Significance (ASCUS), BV was predominant, while VVC and TV were absent in Low-Grade Squamous Intraepithelial Lesion (LSIL) and High-Grade Squamous Intraepithelial Lesion (HSIL) cases. BV was present in 7.8% of normal smears. Significant associations were observed between hematological parameters and the severity of inflammation in the normal smear category (p&amp;lt;0.001). In squamous cell anomaly cases, especially ASCUS, differences in SII, NLR, PLR, SIRI, and PIV were noted between severe and mild infections, as well as between moderate and severe infection groups. This research underscores the linkage between the severity of infection and cellular abnormalities identified in cervical cytology, causative agents of vaginitis, and hematological indices with inflammatory parameters, potentially informing clinical management strategies

Pap Smears Cytology of Cervical Abnormalities in Derna, Libya

The study aimed to provide information about the prevalence of various cervical lesions diagnosed by Papanicolaou smear tests among women in the city of Derna, in eastern Libya. The reporting of the Pap smears is based on the 2014 Bethesda system. The study included seventy-two cervical Pap smears cytology received at the Noor-AL-Huda Medical Center Pathology Laboratory in Derna City, east of Libya, and processed using conventional smear techniques. The data was gathered retrospectively from March 2022 to August 2023. A total of 72 cervical Pap smears were included in the study. The majority of the cases reported were Negative for Intraepithelial Lesions or Malignancy (NILM) 54 (75%). Out of the 72 reports, 2 (2.7%) were unsatisfactory. Low-grade Squamous Intraepithelial Lesions (LSIL) were found in 8 cases (11.11%), and 4 (5.5%) were High-grade Intraepithelial Lesions (HSIL). Atypical Squamous Cells cannot exclude HSIL (ASC-H) were found in 4 cases (5.5%). LSIL and HSIL were more common among women aged 30-40 years. The age of the patients included in this study ranged from 30 to 56, with a mean age of 40 years. These findings emphasize the importance of a well-organized cervical screening program. In particular, women over 30 years should be educated about the importance of Pap smears and encouraged to undergo regular screening.

Role of Pap Smear Cervical Cytology in the Diagnosis of Extrauterine Malignancies: Largest Study of 104 Cases from Tertiary Care Cancer Centre in India

Introduction: Extrauterine malignancies in cervical samples are rarely seen. It is important to differentiate these cells from those of primary uterine malignancies to determine appropriate line of further investigations and management. Literature on these lesions is limited largely restricted to case reports. The aim of the present study was to study the spectrum and cytomorphological features of extrauterine malignancies in cervical Pap smears. Materials and Methods: It is a retrospective and descriptive study conducted in Department of Cytopathology from January 2019 to July 2023. All cases of extrauterine malignancies with available cytology material were included in this study. All cases of primary uterine malignancies, i.e., uterine corpus or cervix confirmed by clinical, radiological, and histopathological examination were excluded. Results: 104 out of 11,674 cytology Pap smears were those of extrauterine malignancy. Diagnosis of extrauterine malignancy was given in 47.1% cases, 30.9% were reported as positive for malignancy without giving the possibility of an extrauterine origin, and 22.0% were reported as atypical glandular cells only. In 56 cases where Pap smear was the first investigation which led to the diagnosis. Most common extrauterine malignancy was adenocarcinoma principally from ovarian, colorectal, and vaginal origin. Other epithelial malignancies noted were urothelial carcinoma and invasive breast carcinoma. Among non-epithelial malignancies, we reported vaginal mucosal melanoma, cutaneous melanoma, acute leukaemia, and anaplastic large cell lymphoma. Conclusion: High index of suspicion, presence of squamous and glandular elements with no atypical features, and occasional clusters of cells with marked atypia and usually no necrosis in the background are helpful cytomorphological clues to raise suspicion for extrauterine malignancy. Correlation with serology, radiology, and immunocytochemistry can help in reaching final diagnosis.

Clinical evaluation of an artificial intelligence-assisted cytological system among screening strategies for a cervical cancer high-risk population

BackgroundPrimary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China.MethodsA total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies.ResultsThe Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587–0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484–0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606–0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491–0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively).ConclusionsThese results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.

The Effect of Random Biopsy and Endo-Cervical Curettage in Diagnosis of Precancerous Cervical Lesions in Women With Normal Colposcopy.

This study aimed to evaluate the effect of random biopsy and endo-cervical curettage (ECC), alone and together, in the diagnosis of high-grade cervical lesions in women with normal colposcopy. This cross-sectional study was conducted on 356 women who underwent colposcopy examination in the gynecology-oncology clinic of Roointan-Arash Women's Hospital, affiliated with Tehran University of Medical Sciences. All eligible women underwent colposcopy. In colposcopy examination, up to four biopsy samples were randomly taken for each quartile of the cervix and ECC was performed. Finally, the rate of intraepithelial neoplasia (CIN) and the relation between random biopsy and ECC and CIN diagnosis was determined. In total, 27 (7.6%) low-grade squamous intraepithelial lesions (LSIL) and 19 (5.3%) high-grade squamous intraepithelial lesions (HSIL) were detected in cases that underwent random biopsy. There was a significant association between the abnormal random biopsy results and having multiple sexual partners (p=0.001), cigarette (p=0.041), and hookah (p=0.033) smoking. Furthermore, 31 (8.7%) LSIL and 42 (11.8%) HSIL were reported in women who underwent ECC. There was a significant relation between the abnormal results of ECC and hookah consumption (p=0.008) and human papillomavirus (HPV) infection (p=0.011). The concordance (p=0.001) between random biopsy and ECC result was 71.2% and only in 28.8% of the cases one of the methods was normal and the other was abnormal. The present study showed that the simultaneous use of ECC and random biopsy in women with normal colposcopy increases the detection rate of precancerous lesions by up to 28.8%.

Correlation Between the Thyroid Imaging Reporting and Data System and Bethesda System of Cytology in Thyroid Nodule Evaluation

Background: Accurate diagnosis of thyroid nodules is important for avoiding unnecessary surgeries and allowing timely treatment. Ultrasound and fine needle aspiration cytology (FNAC) are the most commonly used diagnostic procedures. Objective: To correlate ultrasonography with the FNAC report findings using the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in differentiating malignant from benign thyroid nodules. Patients and Methods: A prospective study conducted from January 2021 to January 2024 assessed 103 cases of thyroid nodules who underwent ultrasound examination and fine needle aspiration. Ultrasonography findings were analyzed and correlated with FNA cytology reports based on ACR-TIRADS and BSRTC. Results: Patients were predominantly female, n = 87 (84.4%). Most of the patients were in the 31–40 year group (n = 55, 53.39%). Most of the patient nodules had TIRADS 3 (n = 59, 57.28%), followed by TIRADS 2 (n = 20, 18.44%). When comparing the ACR TI-RADS scoring system with the TBSRTC, the percentage of malignancy for TR1, 2, 3, 4, and 5 was 0, 0, 1.6, 80, and 89%, respectively. In our study, the overall sensitivity and specificity of the TIRADS score were 94.11% and 96.51%, respectively. PPV: 84.21%; NPV: 98.80%; and accuracy: 96.11%. In addition, there was a significant association between TIRADS and the Bethesda system of classification (P &lt; 0.001). Conclusion: ACR-TIRADS scoring is highly sensitive and accurate for diagnosing thyroid malignant nodules. It is a sensitive tool and could be used alone to determine the nature of thyroid nodules. Keywords: Thyroid malignancies, Ultrasonography, Yemen

Correlation Between the Thyroid Imaging Reporting and Data System and Bethesda System of Cytology in Thyroid Nodule Evaluation

Background: Accurate diagnosis of thyroid nodules is important for avoiding unnecessary surgeries and allowing timely treatment. Ultrasound and fine needle aspiration cytology (FNAC) are the most commonly used diagnostic procedures. Objective: To correlate ultrasonography with the FNAC report findings using the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in differentiating malignant from benign thyroid nodules. Patients and Methods: A prospective study conducted from January 2021 to January 2024 assessed 103 cases of thyroid nodules who underwent ultrasound examination and fine needle aspiration. Ultrasonography findings were analyzed and correlated with FNA cytology reports based on ACR-TIRADS and BSRTC. Results: Patients were predominantly female, n = 87 (84.4%). Most of the patients were in the 31–40 year group (n = 55, 53.39%). Most of the patient nodules had TIRADS 3 (n = 59, 57.28%), followed by TIRADS 2 (n = 20, 18.44%). When comparing the ACR TI-RADS scoring system with the TBSRTC, the percentage of malignancy for TR1, 2, 3, 4, and 5 was 0, 0, 1.6, 80, and 89%, respectively. In our study, the overall sensitivity and specificity of the TIRADS score were 94.11% and 96.51%, respectively. PPV: 84.21%; NPV: 98.80%; and accuracy: 96.11%. In addition, there was a significant association between TIRADS and the Bethesda system of classification (P &lt; 0.001). Conclusion: ACR-TIRADS scoring is highly sensitive and accurate for diagnosing thyroid malignant nodules. It is a sensitive tool and could be used alone to determine the nature of thyroid nodules.