Correlation of immediate prevalence of cervical precancers and cancers with HPV genotype and age in women with ASC-US/hrHPV+: a retrospective analysis of 2292 cases.

AIMS: To stratify the risk of cervical precancers (high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)) and cancers (squamous cell carcinoma (SCC) and adenocarcinoma) based on distinct high-risk human papillomavirus (hrHPV) genotypes as well as age groups among women with atypical squamous cells of undetermined significance (ASC-US) and hrHPV+results. METHODS: In total, 2292 cases of ASC-US/hrHPV+ with immediate follow-up biopsy results were included in the study for prevalence analysis. RESULTS: Overall, 12.2% women with ASC-US /hrHPV+ had HSIL+ while 0.22% had AIS+ lesions. The HPV-16+ group (31.6%) showed significantly higher prevalence of HSIL+ squamous lesions than other genotype groups (p<0.0001). The prevalence of SCC is significantly higher in HPV-16+ (1.8%) or HPV-18/45+ (1.1%) group than women in other genotype groups (0.1%) (p<0.0001). The HPV-18/45+ group (1.7%) showed significantly higher prevalence of AIS+ glandular lesions than other genotype groups (p=0.003). In addition, SCC prevalence was significantly higher in age over 50 group than that in age under 50 group (1.2% vs 0.2%, p=0.012). CONCLUSION: Women with ASC-US/hrHPV+ are at significant risk of cervical precancers and cancers; notably, HPV-16+ group has a higher risk of HSIL squamous lesions and SCC while HPV-18/45+ group has a higher risk of AIS+ glandular lesions. In addition, the older patient group (>50 years) has a significantly higher risk of SCC. Therefore, HPV genotyping as well as patient age need to be considered in the clinical management of patient.

Does an electronic pathology ordering system change the volume and pattern of routine testing in hospital? An interrupted time series analysis.

AIMS: Identifying and reducing low-value care is a vital issue in Australia, with pathology test ordering a common focus in this field. This study builds on previous research and aimed to quantify the impact of the implementation of an electronic ordering (e-ordering) system on the volume of pathology testing, compared with manual (paper based) ordering. METHODS: An audit and analysis of pathology test data were conducted, using an interrupted time series design to investigate the impact of the e-ordering system on pathology ordering patterns. All medical and surgical adult inpatients at a tertiary referral hospital in Newcastle, Australia, were included over a 3-year period. RESULTS: Overall, there were no statistically significant differences in the volume of orders due to the implementation of the e-ordering system. There was a slight increase in the aggregated volume (tests per admission and tests per bed day) of tests ordered across the entire study period, reflecting a secular trend. CONCLUSIONS: Despite providing greater visibility and tracking of orders, we conclude that the implementation of an e-ordering system does not, in and of itself, reduce ordering volume. Efforts to identify and reduce low-value care will require intentional effort and specifically designed educational programmes or hard-wired algorithms.

Unusual fusion gene rearrangements in patients with nodular fasciitis: a study of rare and novel USP6 fusion partners with a review of the literature.

AIMS: This retrospective non-randomised study aims to identify new and rare fusion partners with USP6 in the setting of nodular fasciitis. It has been proven, that nodular fasciitis can harbour different variants of USP6 fusions, which can be used in routine diagnostics and even determine the biological behaviour of the process. METHODS: A total of 19 cases of nodular fasciitis examined between 2011 and 2022 at Motol University Hospital in Prague were included into this study. Next to the histopathological evaluation, all cases were assessed using immunohistochemistry, RT-PCR and Anchored multiplex RNA methods. Patient's main demographic characteristics and corresponding clinical data were also analysed. RESULTS: This study presents one novel (KIF1A) and five rare examples (TMP4, SPARC, EIF5A, MIR22HG, COL1A2) of fusion partners with USP6 among 19 cases of nodular fasciitis. CONCLUSION: Identification of USP6 fusion partners in nodular fasciitis helps to understand the biology of such lesions. Moreover, it can be useful in routine histopathological practice of soft-tissues diagnostics, especially in preventing possible misdiagnosis of malignancy.

Characterising the use of surgical pathology rush requests: a descriptive analysis and survey.

This study aimed to characterise priority or 'rush' surgical pathology requests and identify potentially targetable factors. We performed a retrospective descriptive analysis of rush requests at our institution from 2016 to 2019 and conducted a survey asking pathologists about their perspectives on rush cases. There were 3677 rush cases, with case characteristics generally stable over the study period. Two categories of requests were identified based on hospital status; outpatient requests more frequently provided a specific date for diagnosis, while inpatient rush requests generally required a diagnosis as soon as possible. Most pathologists found rush cases to be somewhat more stressful compared with routine cases (65.2%) and found it very or extremely useful to know when a result is needed (86.9%). The use of hospitalisation status, and identifying if results are required by a certain date, may help in more effective triaging of rush surgical pathology cases.

Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy.

AIMS: The aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value of KRAS and/or TP53 mutations in patients treated with immunotherapy. METHODS: This study is a retrospective cohort study of 519 patients with lung adenocarcinomas analysed for mutations and PD-L1 expression. Data were collected from electronic pathology record system, next-generation sequencing system, and clinical databases. Association between mutations and PD-L1 expression was investigated, as well as survival statistics of the 65 patients treated with immunotherapy. RESULTS: 41% of the samples contained a KRAS mutation, predominantly together with mutations in TP53 (41%) or STK11 (10%). Higher expression of PD-L1 was seen among patients with KRAS mutations (p=0.002) and EGFR wild type (p=0.006). For patients treated with immunotherapy, there was no statistically significant difference for overall survival (OS) and progression-free survival (PFS) according to KRAS mutation status, TP53 mutation status or PD-L1 expression. The HR for concomitant mutations in TP53 and KRAS was 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitant TP53 and KRAS mutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in either TP53 or KRAS. CONCLUSION: Mutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.

Impact of the transition to digital pathology in a clinical setting on histopathologists in training: experiences and perceived challenges within a UK training region.

AIMS: With increasing utility of digital pathology (DP), it is important to consider the experiences of histopathologists in training, particularly in view of the varied access to DP across a training region and the consequent need to remain competent in reporting on glass slides (GS), which is also relevant for the Fellowship of the Royal College of Pathologists part 2 examination. Understanding the impact of DP on training is limited but could aid development of guidance to support the transition. We sought to investigate the perceptions of histopathologists in training around the introduction of DP for clinical diagnosis within a training region, and the potential training benefits and challenges. METHODS: An anonymous online survey was circulated to 24 histopathologists in training within a UK training region, including a hospital which has been fully digitised since summer 2020. RESULTS: 19 of 24 histopathologists in training responded (79%). The results indicate that DP offers many benefits to training, including ease of access to cases to enhance individual learning and teaching in general. Utilisation of DP for diagnosis appears variable; almost half of the (10 of 19) respondents with DP experience using it only for ancillary purposes such as measurements, reporting varying levels of confidence in using DP clinically. For those yet to undergo the transition, there was a perceived anxiety regarding digital reporting despite experience with DP in other contexts. CONCLUSIONS: The survey evidences the need for provision of training and support for histopathologists in training during the transition to DP, and for consideration of their need to maintain competence and confidence with GS reporting.

Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study.

AIMS: The aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling (PMS), when compared with clinical assessment only. METHODS: This prospective observational study included deceased patients from the intensive care unit and internal medicine wards between October 2013 and August 2017. The primary outcome was percentage agreement on COD between the reference standard (autopsy) and the alternative postmortem examinations (clinical assessment vs PMCT or PMCT+PMS). In addition, the COD of patient groups with and without conventional autopsy were compared with respect to involved organ systems and pathologies. RESULTS: Of 730 eligible cases, 144 could be included for analysis: 63 underwent PCMT without autopsy and 81 underwent both PMCT and autopsy. Agreement with autopsy-determined COD was significantly higher for both PMCT with PMS (42/57, 74%), and PMCT alone (53/81, 65%) than for clinical assessment (40/81, 51%; p=0.007 and p=0.03, respectively). The difference in agreement between PMCT with PMS and PMCT alone was not significant (p=0.13). The group with autopsy had a significantly higher prevalence of circulatory system involvement and perfusion disorders, and a lower prevalence of pulmonary system involvement. CONCLUSION: PMCT and PMS confer additional diagnostic value in establishing the COD. Shortcomings in detecting vascular occlusions and perfusion disorders and susceptibility to pulmonary postmortem changes could in future be improved by additional techniques. Both PMCT and PMS are feasible in clinical practice and an alternative when autopsy cannot be performed.

Non-amplification genetic alterations of HER2 gene in non-small cell lung carcinoma.

AIMS: The present study investigated the incidence and spectrum of human epidermal growth factor receptor 2 (HER2) mutations, associated clinicopathological characteristics and the co-occurrence of HER2 gene amplification in the HER2 gene mutated cases in non-small cell lung cancer (NSCLC). METHODS: All patients with advanced lung adenocarcinoma (LUAD) who underwent broad genomic profiling by next generation sequencing (NGS) from 2015 to 2019 were included in the study. HER2 gene amplification was checked in all the HER2 gene mutated cases. Tumour tissues of all the mutated cases were examined by fluorescent in situ hybridisation (FISH). RESULTS: Fifty-four (37.2%) out of the 145 cases harboured tier 1 driver mutations comprising EGFR in 22.1%, ALK rearrangements in 7.6% cases, ROS1 rearrangements and BRAF V600E in 3.5% cases each, and NTRK fusion in 0.7% cases. Nine (6.2%) cases exhibited a significant genetic alteration in HER2 gene (tiers 2 and 3) on NGS. The most common alteration was exon 20 insertion of amino acid sequence AYVM in five cases (p.E770_A771insAYVM) followed by insertion of YVMA (p.A771_Y772insYVMA) in one case, insGSP (p.V777_G778insGSP) in one case and two missense mutations: p.G776C and p.QA795C (novel variant). The median copy number of the HER2 gene was 3.21 while on FISH, the median HER2/CEP17 ratio was 2.0. CONCLUSIONS: There is a relatively higher occurrence of HER2 exon 20 mutations as primary oncogenic driver in NSCLC especially LUAD. Our cohort has demonstrated (p.E770_A771insAYVM) as the strikingly dominant insertion mutation against the most often globally reported (p.A771_Y772insYVMA).

Current and future applications of artificial intelligence in pathology: a clinical perspective.

During the last decade, a dramatic rise in the development and application of artificial intelligence (AI) tools for use in pathology services has occurred. This trend is often expected to continue and reshape the field of pathology in the coming years. The deployment of computational pathology and applications of AI tools can be considered as a paradigm shift that will change pathology services, making them more efficient and capable of meeting the needs of this era of precision medicine. Despite the success of AI models, the translational process from discovery to clinical applications has been slow. The gap between self-contained research and clinical environment may be too wide and has been largely neglected. In this review, we cover the current and prospective applications of AI in pathology. We examine its applications in diagnosis and prognosis, and we offer insights for considerations that could improve clinical applicability of these tools. Then, we discuss its potential to improve workflow efficiency, and its benefits in pathologist education. Finally, we review the factors that could influence adoption in clinical practices and the associated regulatory processes.

Prueba diagnóstica entre la citología, biopsia por congelación e histopatología en el diagnóstico del Nódulo Tiroideo en pacientes atendidos en Solca desde el año 2009 ­2017 / Diagnostic Test between cytology, frozen biopsy and histopathology in the diagnosisof the thyroid nodule in patients treated at Solca from 2009 -2017

Introducción: La citología de nódulos tiroideos es una técnica que, evita procedimientos quirúrgicos innecesarios por lo que se lo ha determinado como primera línea dentro del algoritmo de diagnóstico, el objetivo del estudio fue determinar la sensibilidad y la especificidad de la citología y biopsia por congelación frente al estudio histopatológico en el diagnóstico de nódulos tiroideos en pacientes atendidos en Solca desde el año 2009 -2017. Métodos: Es un estudio de tipo observacional, retrospectivo y de correlación diagnóstica; los datos fueron obtenidos de las historias clínicas de pacientes intervenidos quirúrgicamente por nódulos tiroideos con biopsia por congelación, a quienes se les realizó previamente un estudio citológico en el Departamento de patología de SOLCA de la ciudad de Cuenca, Ecuador. El cálculo del tamaño de la muestra fue de 324 casos. Resultados:324 casos fueron incluidos. El 8.3% correspondió a hombres y el 91.7% a mujeres. La media de la edad fue 51.8 años; la gran mayoría provenían de la provincia Azuay con el 64.8%. En los estudios citológicos el 34.6% (112 casos)corresponden a lesiones inflamatorias benignas; el 11.1% [36 casos]a patologías malignas y 14.2% (46 casos)fueron insatisfactorios. En la biopsia por congelación el mayor porcentaje estuvo concentrado en enfermedades benignas con un 62.6% y 35.5% a lesiones malignas. Hubo 6 casos con el 1.9% en donde fue diferido el criterio diagnóstico. En el histopatológico definitivo el 60.2% (195 casos)fueron patologías benignas y el 39.8% (129 casos)fueron lesiones malignas. La sensibilidad de la PAAF frente a histopatológico es alta con un 91.79%, pero la especificidad es baja con un 51.94%. La sensibilidad y la especificidad de la biopsia por congelación frente a histopatológico es alta con un 98.97% y 90.70% respectivamente lo que le confiere una metodología óptima. Conclusiones: La PAAF de tiroides demuestra ser una metodología útil en el diagnóstico de nódulos, siempre y cuando sea realizada y observada por personal capacitado. La biopsia por congelación constituye una técnica con alta sensibilidad y especificidad que nos permite discriminar lesiones benignas de las malignas. Palabras claves: Nódulo tiroideo, Biopsia con Aguja, Servicio de Patología en Hospital, Oncología Médica, Agencias Voluntarias de Salud, Biología Celular, Biopsia con Aguja Fina

Introduction:Cytology of thyroid nodules is a technique that avoids unnecessary surgical procedures and has therefore been determined as the first line within the diagnostic algorithm.General Objective:To determine the sensitivity and specificity of cytology and freezing biopsy versus histopathological study in the diagnosis of thyroid nodules in patients treated in Solca since 2009 -2017. Methods:This is an observational, retrospective and diagnostic correlation study; the data were obtained from the clinical histories of patients surgically treated by thyroid nodules with freeze biopsy, who underwent a cytological study in the Department of pathology of the city of Cuenca, Ecuador. The calculation of the sample size was 324 cases. Results:8.3% corresponded to men and 91.7% to women. The mean age was 51.8 years; The vast majority came from the province of Azuay with 64.8%. In cytological studies, 34.6% [112 cases]correspond to benign inflammatory lesions; 11.1% [36 cases]to malignant pathologies and 14.2% [46 cases]were unsatisfactory. In the freeze biopsy the greater percentage was concentrated in benign diseases with 62.6% and 35.5% to malignant lesions. There were 6 cases with 1.9% where the diagnostic criterion was deferred. In the definitive histopathological, 60.2% [195 cases]were benign pathologies and 39.8% [129 cases]were malignant lesions. The sensitivity of FNAB to histopathological is high with 91.79%, but the specificity is low with 51.94%. The sensitivity and specificity of freezing versus histopathological biopsy is high with 98.97% and 90.70% respectively, which gives it an optimal methodology. Conclusions: Thyroid PAAF proves to be a useful methodology in the diagnosis of nodules, as long as it is performed and observed by trained personnel. Freezing biopsy is a technique with high sensitivity and specificity that allows us to discriminate benign from malignant lesions. Key words:Thyroid Nodule; Biopsy, Needle;Pathology Department, Hospital; Medical Oncology; Voluntary Health Agencies; Cell Biology; Biopsy, Fine-Needle

Una visión peruana sobre los servicios de patología clínica: avances y agenda pendiente / A Peruvian view about clinical pathology services: progress and pending issues

RESUMEN Los países realizan muchos esfuerzos, para poder implementar los objetivos de desarrollo sostenible, en búsqueda de la cobertura universal de la salud. Sin embargo, el acceso o la oportunidad de los servicios de Patología Clínica de alta calidad y oportunos, son necesarios para respaldar los sistemas de atención médica que tienen la tarea de lograr estos objetivos. Este acceso es más difícil de lograr en los países de bajos y medianos ingresos. En este artículo especial, se realizó un análisis de la situación global y nacional de esta problemática, en esta especialidad médica. Se identifican las cuatro barreras clave para la provisión de servicios de calidad y óptimos: recursos humanos o capacidad de la fuerza laboral insuficiente, educación y capacitación inadecuada, infraestructura y equipamiento inadecuado, y calidad, normas y acreditación insuficientes.

ABSTRACT Countries do plenty of effort in order to implement the objectives for sustainable development, aiming to achieve universal health coverage. However, access or chances for having high quality Clinical Pathology services are both necessary for supporting medical care systems if such objectives are to be achieved. This access is much more difficult to achieve in low- and medium- income countries. This paper presents an analysis of both the global and local situation in this respect. Four key barriers for delivering high quality and optimal services were identified: insufficient human resources or limited capability of the working force, inadequate education and training, inadequate infrastructure and equipment, and insufficient quality, regulations, and accreditation strategies.