Testagem Molecular para Detecção de HPV e rastreamento do câncer do colo do útero / Molecular Testing for HPV Detection and Uterus Colon Cancer Tracking

INTRODUÇÃO: Evidências científicas robustas indicam que o rastreamento com testes moleculares para detecção de HPV oncogênico é mais sensível, eficaz/efetivo e eficiente, em termos do aumento de detecção de lesões precursoras e da redução da incidência e mortalidade por CCU, do que o rastreio com exame citopatológico. Outro aspecto fundamental é a maior detecção de casos de CCU em estágio inicial, precedendo em até 10 anos o diagnóstico pelo exame citopatológico. A detecção precoce leva a tratamentos menos mutilantes e onerosos, com excelente prognóstico e até com possibilidade de cura, impactando positivamente a custo-efetividade do rastreamento. Ademais, por apresentarem maior sensibilidade e valor preditivo negativo (VPN), quando comparados à citologia, os testes para detecção de HPV de alto risco permitem o aumento da idade de início do rastreio e do intervalo de testagem, melhorando a eficiência e otimizando o desempenho dos programas. PERGUNTA: "A testagem molecular para detecção de HPV

Quality Assessment of Cervical Cytology Practices in Estonia From 2007 to 2018.

BACKGROUND: Cervical cancer incidence and mortality in Estonia are among the highest in Europe, although the overall coverage with cervical cytology is high. This indicates potential issues with the quality of collection and/or laboratory evaluation of cervical cytology. OBJECTIVES: The aim of the retrospective observational study was to assess the quality of cervical cytology specimen collection, evaluation, and reporting using laboratory reports in Estonia. METHODS: The study included women with a cervical cancer diagnosis in 2017-2018. Cervical cytology and histology reports for these women in 2007-2018 were obtained from ten laboratories. We described the quality of cytology specimen collection and reporting of cytology results. Multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) to identify factors associated with NILM as the last cervical cytology result within 5 or 2 years before the cervical cancer diagnosis. Also, we calculated cytology-histology correlation (CHC). RESULTS: We identified 503 cytology and 100 histology reports from 138 women. The laboratories differed greatly regarding human resources, work capacity and volume. Differences between local and regional laboratories were observed in reporting specimen adequacy (P < .001). We found that local laboratories had 3 times higher odds (OR = 2.95, 95% CI: 1.05-8.33) of reporting normal results 2 years before cancer diagnosis than regional laboratories. According to the CHC, 58.9% of pairs were in agreement. CONCLUSIONS: The study showed considerable heterogeneity and suboptimal performance of cervical cytology practices in Estonia, particularly at local laboratories. Efforts to improve laboratory quality assurance are crucial.

Oral brush biopsy using liquid-based cytology is a reliable tool for oral cancer screening: A cost-utility analysis: Oral brush biopsy for oral cancer screening.

BACKGROUND: This study aimed to assess the diagnostic utility and associated cost of oral liquid-based brush cytology (OLBC) in the diagnosis of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: A total of 284 patients with oral mucosal lesions were included. OLBC samples were collected from all patients immediately before undergoing surgical biopsies. A liquid-based cytology slide was prepared from each OLBC sample for cytological evaluation using the modified 2014 Bethesda cytology system. The results and the cost were compared with the histopathological outcomes. RESULTS: The level of agreement between the two approaches was very good (weighted kappa = 0.824). The accuracy of OLBC in differentiating between the different diagnostic groups was 91.69%, whereas the associated sensitivity and specificity were 79.23% and 94.81%, respectively. The estimated cost of each OLBC sample was at least 26% less than the cost of a single biopsy and more than 42% less in cases of multiple biopsied lesions. CONCLUSIONS: The proposed modifications of the Bethesda system can be adopted as a standardized system for oral cytological assessment. Our findings support OLBC as a reliable adjunct to surgical biopsy in the diagnosis of OPMDs. This tool has potential for oral cancer-finding and surveillance programs.

Análisis del impacto presupuestal en Colombia de la prueba de HPV con genotipificación comparada con la citología / Budget impact analysis of primary screening with the HPV test and genotyping against conventional cytology in Colombia

Introducción. La detección del virus del papiloma humano mediante la combinación de la prueba de HPV y otras técnicas como la citología, ha demostrado su eficacia en el diagnóstico y tratamiento oportuno de lesiones asociadas con el cáncer de cuello uterino. Objetivo. Estimar el impacto presupuestal de la estrategia de detección temprana del HPV mediante la prueba de genotipificación combinada con la citología en comparación con la citología convencional, en mujeres de 30 a 65 años participantes en el programa de tamizaje de cáncer de cuello uterino en una Entidad Administradora del Plan de Beneficios en salud (EAPB) en Colombia. Materiales y métodos. Utilizando un árbol de decisiones y un modelo de Markov, se estimaron las implicaciones clínicas y los costos directos anuales de dos ciclos de tamizaje, diagnóstico y tratamiento, en una cohorte de mujeres. Las prevalencias de los resultados clínicos y los costos se tomaron de la base de datos de una EAPB y la información de la progresión, persistencia y regresión de los estados de salud provinieron del estudio ATHENA. Resultados. El esquema de tamizaje con la prueba de HPV, la genotipificación y la citología resultó en un ahorro de costos comparado con la citología convencional. El costo promedio por ciclo de tamizaje con la prueba de HPV se estimó en COP $129'201.363 y con la citología en COP $186'309.952, es decir, un ahorro de COP $57'108.589 (30,7 %). Conclusión. La implementación de la estrategia de tamizaje evaluada sugiere que habría ahorros derivados de la detección temprana de los estados de salud asociados con el desarrollo de cáncer de cuello uterino.

Introduction: The detection of the human papillomavirus (HPV) through the combination of the HPV test and other techniques such as cytology has impacted the detection and timely treatment of lesions associated with cervical cancer. Objective: To estimate the budgetary impact of the strategy of early detection of HPV with DNA test genotyping with reflex cytology versus conventional cytology in women aged 30 to 65 years attending the cervical cancer screening program at a health benefit managing entity in Colombia. Materials and methods: Using a decision tree and a Markov model, the clinical implications and direct costs of screening, diagnosis, and treatment were estimated in a cohort of women. The analysis considered two screening cycles and their annual costs. The data on the prevalence of clinical results and the costs were taken from the health managing entity. The information on the progression, persistence, and regression of the health states were taken from the ATHENA study. Results: The screening scheme with the HPV test, genotyping, and reflex cytology compared to conventional cytology was cost-saving. The average cost per screening cycle with the HPV test was estimated at COP $ 129,201,363 and with cytology at COP $ 186,309,952, i.e., a saving of COP $ 57,108,589 (30.7%). Conclusion: The implementation of the screening strategy under evaluation suggests prospective savings derived from the early detection of health states associated with the development of cervical cancer.

Accuracy of definitive rapid onsite evaluation cytopathology diagnoses: Assessment of potentially critical diagnoses as a quality assurance measure.

INTRODUCTION: Intraprocedural rapid onsite evaluation (ROSE) of cytology specimens enhances cytopathology practice. More recently, ROSE diagnoses, like frozen section (FS) diagnoses, have guided immediate clinical decisions. In this study, we evaluated the diagnostic accuracy of definitive ROSE diagnoses in our quality assurance system over a 52-month period. MATERIALS AND METHODS: Cytopathology cases with ROSE from January 2017 to April 2021were retrieved from our laboratory information system. After excluding cases that were deferred or nondiagnostic/unsatisfactory, each definitive ROSE diagnosis (ie, negative for malignant cells or positive for malignant cells) was categorized as having agreement or disagreement with the final diagnosis. For comparison, concordance of FS diagnoses from the same time period were tabulated and compared to those of ROSE diagnoses by using χ2 testing with P < 0.05 considered statistically significant. RESULTS: Of the 1649 ROSE diagnoses, there were 15 disagreements (0.9%) with 1 final moderate interpretive disagreement (0.06%). By comparison, of the 17,469 FS diagnoses, there were 141 disagreements (0.8%) with 49 final moderate or major interpretive disagreements (0.3%). The remaining disagreements were minor. There were no statistically significant differences in the rates of final moderate and major interpretive disagreements. CONCLUSIONS: The final interpretive disagreement rates for definitive ROSE and FS diagnoses were similar in this study. Given the expanding role of ROSE and its use for immediate clinical decisions in some cases, monitoring the accuracy of definitive diagnoses may serve as an initial quality assurance measure.

The role of cytology as an effective tool in management of omental and peritoneal lesions: Experience of a large health care system.

BACKGROUND: The aim of this study is to assess the efficacy of cytology in omental or peritoneal lesions. METHODS: A retrospective review of the pathology database for cytology cases of peritoneal or omental nodules over a 3-year period (2016-2018) was conducted. The cases consisted of either FNA only (FO); FNA and Core biopsy (FCB) or Touch prep and core biopsy (TCB). Cases were further divided based on the prior history of carcinoma. Concordance rates of cytologic diagnosis with histologic diagnosis were studied. RESULTS: Out of 104 cytology cases reviewed, 60 (57.7%) had prior history of cancer (PHC) and 44 (42.3%) had no prior history of cancer (NPHC). Of the cases with PHC, 43(71.66%) were recurrence, 10 (16.66%) were second cancer, and 7 (11.66%) were non-neoplastic lesions. Of the cases with NPHC, 38 (86.4%) had a second cancer diagnosis, while 6 (13.6%) were non-neoplastic. For FO only cases, 11 of 35 (31.4%) had follow up and 9 of 11 (81.8%) were concordant. For FCB cases, 6 out of 39 (15.4%) had follow up and 6 (100%) were concordant. For TCB cases, 9 out of 30 (30%) had follow up and 9 (100%) were concordant. A definite diagnosis was reached in 30/35, 39/39, and 29/30 cases in FO, FCB, and TCB, respectively. CONCLUSION: In summary, cytologic evaluation of omental lesions is an effective tool in providing accurate diagnosis and guiding further management. Also, the results based on our study show that the combined techniques are superior at reaching a definitive diagnosis.

HPV-specific risk assessment of cervical cytological abnormalities.

BACKGROUND: Cytology and HPV genotype screening play an important role in cervical cancer detection. Whether multiple HPV genotyping can predict cytological lesions remains to be further studied. METHODS: Two thousand two hundred twenty-four females were analyzed for cytology and HPV genotypes test. The possibility of predicting cytological lesions by HPV genotypes test was evaluated by multivariate logistic regression and area under the receiver operator characteristic curve (AUC). RESULT: Abnormal cytological results were found in 479 participants. A total of 688 patients were detected with HPV infection, 619 with HR-HPV infection and 112 with LR-HRV infection. HPV-52 was found to be the most common type among these patients, and a relatively higher risk of cervical lesions was found in HPV positive females. HPV-16, 31, 33 and 58 were found to have significantly higher infection rates in patients with HSIL and higher lesions. The prediction model was developed based on age and HPV-specific genotypes, with the AUC of 0.73 for cytological abnormalities and 0.82 for HSIL and higher lesions. CONCLUSION: HPV-16, 31, 33 and 58 infection are significant risk factors for cervical lesions. Combined HPV genotypes test can effectively predict cytological abnormalities.

Harmonization of training, training program requirements, board certification, and the practice of cytopathology: data from the American Board of Pathology surveys.

INTRODUCTION: The American Board of Pathology (ABPath) has ongoing efforts to better align certification with graduate medical education, training program requirements, and pathology practice. The present study focused on the subspecialty of cytopathology. We evaluated the current content and scope of fellowship programs, practice patterns and needs of diplomates, and program director (PD) and diplomate perceptions of the ABPath certification examination to identify gaps and provide an evidence base to guide harmonization in these areas. METHODS: Two surveys were administered: one directed to PDs of all 93 Accreditation Council for Graduate Medical Education (ACGME) cytopathology fellowship programs and the other to cytopathology diplomates submitting continuing certification reporting to the ABPath. RESULTS: Most (86%) cytopathology diplomates work in smaller groups. Only 11% do >50% cytopathology in practice. Diplomates' cytopathology-related practice tasks varied, as did their perception of the content of fellowship training aligning with practice needs. In fellowship training programs, the specimen types, volumes, techniques of specimen acquisition, and graduated responsibility varied significantly. We identified areas in which current training and certification requirements are challenging for some programs. Diplomates and PDs had differing perceptions of the cytopathology examination; diplomates regarded image-based and microscopic glass slide questions as the best assessment of their knowledge. CONCLUSIONS: First, fellowship training programs could benefit from shared resources and should provide more graduated responsibility for fellows. Second, the ACGME Review Committee could consider this data in future program requirement revisions. Finally, information from these surveys will be useful as the ABPath adjusts certification examination content and delivery.

Selective deployment of dynamic telecytology for rapid evaluation of cytology smears: assessment of workflow processes and role of cytopathology fellows as on-site operators.

INTRODUCTION: The deployment of telecytology (TC) requires a substantial investment of financial and human resources. To offset the high demand for rapid on-site evaluation, we performed a limited deployment of dynamic TC and have detailed the workflow processes and the role of trainees. MATERIALS AND METHODS: TC systems were installed in radiology suites with a high volume of cases. Validation was performed using retrospective and prospective cases. Cytotechnologists and cytopathology fellows were the operators of the instrument. TC malignant and benign diagnoses were correlated with the final sign-out diagnoses. RESULTS: Of the 120 cases, 50 (41.6%) were fine needle aspirations and 70 (58.3%) were touch imprint smears of core biopsy specimens. The cytotechnologists were the operators for 34 cases (28.3%) and cytology fellows for 86 cases (71.6%). Adequacy concordance with the final diagnosis was 100% and 98.5% in the retrospective and prospective cases, respectively. In the prospective cases, concordance of TC with the final diagnosis of malignancy was 42 of 45 (93.3%), with 2 of 45 (4.4%) discordant and a downgrade rate of 2.7%. For the benign diagnoses, the concordance was 90%. For the malignant diagnoses, the sensitivity of TC was 97.67% (95% confidence interval [CI], 87.71 to 99.94%; specificity, 81.82%; 95% CI, 48.22% to 97.72%). The positive predictive value was 95.45% (95% CI, 85.69% to 98.66%), the negative predictive value was 90.00% (95% CI, 55.98% to 98.45%), and the accuracy was 94.44% (95% CI, 84.61% to 98.84%). CONCLUSIONS: TC can be deployed in a limited fashion as an option for cytopathologists to offset the high demand for rapid on-site evaluations. Trainee participation in TC service is important for building confidence and honing their cytology skills.

Comparison of quantitative internal and external measures of performance for trainees in cytopathology fellowships.

INTRODUCTION: Cytopathology fellowships need measures to assess performance of fellows. We sought to compare several internal quantitative assessment metrics in our fellowship with external metrics, such as performance on the American Society of Cytopathology (ASC) Progressive Evaluation of Competency (PEC) examination and United States Medical Licensing Examination (USMLE). METHODS: Quantitative parameters generated from our laboratory information system (LIS) on cytopathology fellows were evaluated over 6 years, including case volume and diagnostic discrepancies, in addition to ASC PEC and USMLE scores. For discrepancy reports, interpretations made by the fellow were compared with that of the cytopathologist, and classified as none (concordant), minor (<2-levels) or major (≥2-levels). RESULTS: We evaluated internal and external metrics on 13 fellows over 6 years. The program average diagnostic concordance rate was 89.9%, with an average major discrepancy rate of 1.5%, and an average monthly case volume of 260 cases. More fellows with above-average ASC PEC performance showed above-average concordant diagnoses and lower case volume, while below-average PEC scores were seen more often with higher major discrepancy rates. More fellows with above-average USMLE scores had higher case volumes, while low USMLE scores showed a trend towards higher major discrepancy rates. CONCLUSION: Our fellowship program has used a variety of internal and external measures of performance for cytopathology fellows. Although the findings show no statistically significant finding correlating performance, these quantitative parameters generated from our LIS were helpful to identify areas of improvement, facilitate comparison to peers, and provide case volume documentation.

Trends in cytopathology fellowship positions and vacancies over the past decade.

INTRODUCTION: Cytopathology is one of the most sought-after fellowships within pathology, with a lower fellowship vacancy rate compared with most other subspecialties. The Accreditation Council for Graduate Medical Education (ACGME) actively tracks annual program data for cytopathology fellowship programs, and evaluating this longitudinal data looking at trends in programs and positions over the past 10 years could provide insights into the future of cytopathology and its training programs. METHODS: Data obtained from the ACGME was examined in detail for all ACGME-accredited cytopathology fellowship programs over the past decade (2011-2021). Additional responses from program directors (PDs) from a 2021 American Society of Cytopathology (ASC) survey are also included. RESULTS: The total number of ACGME-approved cytopathology training programs and cytopathology fellowship positions remained relatively constant over the past 10 years, but the vacancy rate and number of programs with 1-2 unfilled spots has gradually but steadily risen over the past 6 years. In a 2021 ASC PD survey with 66% response rate, 53% of PDs reported having recruitment problems at least occasionally and 46% reported an increase in unexpected fellowship openings. CONCLUSIONS: Although the number of cytopathology positions has been relatively constant over the past decade, there has been a recent increase in cytopathology fellowship vacancies that may indicate changes in career choices or the job market, with fellows choosing jobs over additional fellowships, and potentially signal a growing shortage of fellowship-trained, Board-certified cytopathologists in the coming years.

Cytopathology fellowship recruitment: Has the time come to consider a unified approach?

INTRODUCTION: Cytopathology (CYP) fellowship training is a critical component of maintaining a skilled group of cytopathologists. For years, the recruitment process for CYP fellowship programs has remained unchanged, with individual programs outlining their own requirements and timeline, and applicants bearing the cost of travel and dealing with the variable processes outlined by individual programs. However, there has been renewed interest in analyzing the recruitment process for CYP fellowships to look for areas of potential improvement and uniformity. METHODS: With the goal of gauging the interest of CYP fellowship program directors (PDs) in a more unified approach to recruitment or a formal match process, the ASC Cytopathology Program Directors Committee (CPDC) surveyed PDs via SurveyMonkey and organized special webinars with polling over a 4-year time frame (2017-2021), and examined Qualtrics survey data collected by the American Board of Pathology (ABPath) in 2020. RESULTS: The response rate for PDs was greatest in a formal survey by the ABPath (66 respondents; 71% of PDs) conducted in 2020, and lower for an ASC survey in 2021 (61 respondents, 66% of PDs) and 2017 (19 respondents; 21% of PDs) and two recent ASC webinars (10 and 26 respondents; 11% and 28% of PDs). Support for a fellowship match process varied from 29% to 77%, respondent uncertainty ranged from 13% to 50%, and a lack of support ranged from 10% to 60%. In aggregate, approximately 56% of respondents would be in favor of a more standardized process. Recently, after hearing about other fellowships experimenting with a standardized process, the interest in a unified approach doubled from approximately 29% to 60%, and the percentage of PDs with uncertainty decreased from 50% to 26%. In the most recent follow up survey, interest reached the highest level of 77% among PDs. CONCLUSIONS: Herein we present several years of feedback from the CYP fellowship PD community regarding a more standardized approach to CYP fellowship recruitment, culminating in the latest survey with 77% of CYP fellowship PDs expressing interest. Thus, details about what a unified timeframe may look like for CYP fellowships is presented to show how this may improve the recruitment process for the mutual benefit for programs and applicants.

The p16/ki-67 assay is a safe, effective and rapid approach to triage women with mild cervical lesions.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy and efficiency of p16/ki-67 dual stain in the identification of CIN2+ lesions, in Greek women with ASCUS or LSIL cytology. METHODS: A total of 200 women, 20 to 60 years old, were enrolled in the study. All samples were cytologically evaluated and performed for p16/ki-67 and high-risk HPV (HR-HPV) test. All patients were referred to colposcopy for biopsy and histological evaluation. Three cervical cancer (CC) screening strategies were designed and the total direct medical costs of the procedures during our clinical trial were evaluated, from a healthcare perspective. RESULTS: HPV 16 as expected was the most common HR-HPV type followed by HPV 31 and HPV 51. The risk for CIN2+ was significantly higher in HPV 16/18 positive cases. p16/ki-67 demonstrated a high sensitivity for CIN2+ identification in both ASCUS and LSIL groups (90.4% and 95%, respectively). HR-HPV test with sensitivity 52.3% and 65.5%, as well as colposcopy with sensitivity 14.3% and 36% respectively in ASCUS and LSIL group, showed inferior results compared to p16/ki-67. The specificity of p16/ki-67 for ASCUS and LSIL was 97.2% and 95.2% respectively, inferior only to colposcopy: 100% and 100%, lacking however statistical significance. HR-HPV test instead, presented the lowest specificity: 76.4% and 71.4% respectively in comparison to the other two methods. From a healthcare perspective, the costs and benefits of the tests implementation for the annual screening and triaging, in three CC screening strategies, were also calculated and discussed. CONCLUSIONS: The results of the study indicate that p16/ki-67 is a safe and rapid assay that could be used to detect CIN2+ among women with mild cervical lesions, presenting both high sensitivity and specificity and could minimize the psychological and economic burden of HPV screening.

Algorithmic assessment of cellular senescence in experimental and clinical specimens.

The development of genetic tools allowed for the validation of the pro-aging and pro-disease functions of senescent cells in vivo. These discoveries prompted the development of senotherapies-pharmaceutical interventions aimed at interfering with the detrimental effect of senescent cells-that are now entering the clinical stage. However, unequivocal identification and examination of cellular senescence remains highly difficult because of the lack of universal and specific markers. Here, to overcome the limitation of measuring individual markers, we describe a detailed two-phase algorithmic assessment to quantify various senescence-associated parameters in the same specimen. In the first phase, we combine the measurement of lysosomal and proliferative features with the expression of general senescence-associated genes to validate the presence of senescent cells. In the second phase we measure the levels of pro-inflammatory markers for specification of the type of senescence. The protocol can help graduate-level basic scientists to improve the characterization of senescence-associated phenotypes and the identification of specific senescent subtypes. Moreover, it can serve as an important tool for the clinical validation of the role of senescent cells and the effectiveness of anti-senescence therapies.

Assessment of the deep resection margin during oral cancer surgery: A systematic review.

The main challenge for radical resection in oral cancer surgery is to obtain adequate resection margins. Especially the deep margin, which can only be estimated based on palpation during surgery, is often reported inadequate. To increase the percentage of radical resections, there is a need for a quick, easy, minimal invasive method, which assesses the deep resection margin without interrupting or prolonging surgery. This systematic review provides an overview of technologies that are currently being studied with the aim of fulfilling this demand. A literature search was conducted through the databases Medline, Embase and the Cochrane Library. A total of 62 studies were included. The results were categorized according to the type of technique: 'Frozen Section Analysis', 'Fluorescence', 'Optical Imaging', 'Conventional imaging techniques', and 'Cytological assessment'. This systematic review gives for each technique an overview of the reported performance (accuracy, sensitivity, specificity, positive predictive value, negative predictive value, or a different outcome measure), acquisition time, and sampling depth. At the moment, the most prevailing technique remains frozen section analysis. In the search for other assessment methods to evaluate the deep resection margin, some technologies are very promising for future use when effectiveness has been shown in larger trials, e.g., fluorescence (real-time, sampling depth up to 6 mm) or optical techniques such as hyperspectral imaging (real-time, sampling depth few mm) for microscopic margin assessment and ultrasound (less than 10 min, sampling depth several cm) for assessment on a macroscopic scale.

A comparison of the analysis of 3 types of body fluids using the XN-350 hematology analyzer versus light microscopy assessment.

ABSTRACT: We evaluated the capacity of the XN-350 instrument to analyze 3 different types of body fluid samples under "body fluid mode."The performance of XN-350 was evaluated in terms of precision, carryover, limit of blank, limit of detection, limit of quantification, and linearity. Cell enumeration and differential data produced by the XN-350 were compared to manual chamber counting results in 63 cerebrospinal fluid (CSF), 51 ascitic fluid, and 51 pleural fluid (PF) samples. Comparisons between XN-350 versus Cytospin data were also performed in PF samples.The precision, carry-over, limit of blank, and linearity of the XN-350 were acceptable. The limits of detection for white blood cells (WBCs) and red blood cells were 1.0/µL, and 1,000.0/µL, respectively; the corresponding limits of quantitation (LOQs) were 5.0/µL and 2,000.0/µL, respectively. The XN-350's cell enumeration and differential counting correlated well with those of manual chamber counting for all 3 sample types (except for differential counting in CSF samples), particularly parameters involving monocytes (r = 0.33) and mononuclear cells (MO- body fluid [BF]; r = 0.26), as well as total cell (TC-BF) enumeration (r = 0.50) and WBC-BF (r = 0.50) in PF samples. The MO-BF in CSF samples differed significantly from manual chamber counting results, but neither TC-BF nor WBC-BF in PF samples did. The XN-350 also showed good correlations with Cytospin analyses for differential counting of neutrophils, lymphocytes, and monocytes in PF samples. The differential counting of eosinophils via the XN-350 and Cytospin were not significantly correlated, but the difference between them was not significant.The XN-350 is an acceptable alternative to manual fluid analysis. Samples with low cellularity around the LOQ should be checked manually. Moreover, manual differential counting should be performed on CSF samples, particularity those with low cell numbers.

Cytopathologic assessment of gloves and instruments after major head and neck surgery.

PURPOSE: To investigate the potential for cancer cells to be transferred between anatomic sites via instruments and other materials. MATERIALS AND METHODS: Pilot prospective study from April 2018-January 2019 at Rush University Medical Center. Glove and instrument washings were collected from 18 high-risk head and neck cancer resection cases (36 samples total). Each case maintained at least one of the following features in addition to a diagnosis of squamous cell carcinoma or sarcoma: palliative/salvage surgery, positive margins, extensive tumor burden, and/or extra capsular extension (ECE). Surgical gloves and four main instruments were placed through washings for blind cytological assessment (2 samples/case). RESULTS: 18 patients undergoing surgical tumor resection for biopsy-proven squamous cell carcinoma with at least one of the aforementioned characteristics were included. 26.7% of cases had ECE, 40.0% had positive final margins and 46.7% had close final margins. Tumor locations included: oral cavity (10), neck (4), parotid gland (2), and skin (2). Malignant cells were isolated on glove washings in 1 case (5.5%). No malignant cells were isolated from instrument washings. The single case of malignant cells on glove washings occurred in a recurrent, invasive squamous cell carcinoma of the scalp with intracranial extension. Anucleated squamous cells likely from surgeon skin were isolated from 94.4% of washings. Squamous cells were differentiated from mature cells by the absence of nuclei. CONCLUSIONS: Malignant squamous cells can be isolated from surgical glove washings, supporting the practice of changing of gloves after gross tumor resection during major head and neck cancer resections.

Impact of the Milan System for Reporting Salivary Gland Cytology on risk assessment when used in routine practice in a real-time setting.

INTRODUCTION: Several retrospective studies across the world have validated the role of the Milan System for Reporting Salivary Gland Cytology (MSRSGC) in improving communication between pathologists and clinicians. In this study, we evaluated the applications of MSRSGC in a real-time setting for 2 years. MATERIALS AND METHODS: All salivary gland lesions that underwent fine-needle aspiration (FNA) from January 2018 to December 2020 were categorized according to MSRSGC guidelines. The risk of malignancy (ROM) was calculated for each category and compared with the ROM proposed by MSRSGC and recent retrospective studies. RESULTS: A total of 160 FNA of salivary gland lesions were categorized as: nondiagnostic (ND) 30 (18%), non-neoplastic (NN) 7 (10.6%), atypia of undetermined significance (AUS) 5 (3.1%), benign neoplasm (BN) 59 (36.8%), salivary gland of uncertain malignant potential (SUMP) 21 (13%), suspicious for malignancy (SM) 3 (1.84%), and malignant (M) 25 (15.6%). Histopathologic follow-up was available for 94 (57.5%) cases. The ROM for each category was ND 54%, NN 0%, AUS 66%, BN 0%, SUMP 37.56%, SM 100%, and M 100%. CONCLUSION: With strict adherence to the diagnostic criteria and MSRSGC guidelines, a ROM of 100% in SM and M categories and a ROM of 0% in NN can be achieved in a real-time setting. The high ROM in the ND category in our study highlights the value of repeat FNA/biopsy for this category. High ROM for AUS indicates the tendency to classify high-grade tumors as AUS, calling for refinement in its criteria.

Comparative cytological and histological assessment of 828 primary soft tissue and bone lesions, and proposal for a system for reporting soft tissue cytopathology.

INTRODUCTION: The aim of the study was to evaluate the diagnostic utility of fine needle aspiration (FNA) cytology and core needle biopsies (CNBs) in a series of primary soft tissue and bone lesions and to test a possible system for reporting results of FNA cytology of soft tissue lesion. METHODS: This retrospective study encompassed 828 primary soft tissue and bone lesions, analysed with FNA, CNB and/or surgical specimen in order to perform sensitivity/specificity as well as accuracy analyses. The series was then used to test a system for reporting soft tissue cytopathology with six categories and the risk of malignancy in each category was calculated. RESULTS: With a malignant diagnosis defined as positive test result, FNA and CNB analysis showed sensitivity of 87% and 94%, respectively, and specificity of 89% and 95%, respectively. FNA and CNB analyses identified the correct histopathological entity of the examined lesion in 55% and 66%, respectively. The risk of malignancy within the tested categories was non-diagnostic 42%, non-neoplastic 0%, atypia of unknown significance 46%, neoplasm benign 3%, neoplasm of unknown malignant potential 27%, suspicious for malignancy 72% and malignant 97%. CONCLUSION: FNA cytology is a suitable tool to determine the malignant potential of a sampled soft tissue/bone lesion but is inferior to CNB in defining the correct entity. A standardised reporting system might improve the clinical management of patients with soft tissue tumours examined primarily by FNA cytology.