Acta Cytologica最新文献

Introduction: Liquid biopsy, especially when performed by the isolation, expansion, and examination of circulating tumor cells (CTCs) from peripheral blood, has become an innovative and transforming diagnostic tool in Clinical Oncology. The CTCs have already entered the clinical practice as an alternative method to invasive tumor biopsy for detecting postsurgical and/or posttreatment minimal residual disease, to predict cancer recurrence and real-time treatment response. In this context, the retrospective observational project, known as CHARACTEX, has permitted to state that it is possible to exploit blood-based cytologic samples through short-term culture and in vitro CTC expansion.

Methods: This method is based initially on a gradient-sedimentation technique, which impoverishes without completely depriving the obtained sample from the hematological cells, followed by short-term (14 days) in vitro culture and expansion and cytomorphological and flow cytometric analysis to investigate whether the expanded cell population possesses proliferative advantage and fits with criteria, which are consistent to the known primary tumor.

Results: The originality of this method is that, apart from the above exposed criteria, there is no selection bias for the isolation of the cells from peripheral blood (like immunomagnetic bead treatment or preliminary immunocytochemistry), which can potentially introduce some limitation to the cell population under evaluation.

Conclusion: The examination of the expanded cell population obtained by this method is very rewarding for both the pathologist - who can assess multiple tumor-related variables (like immunocytochemistry, flow cytometry of several parameters, and molecular pathology on cell suspensions and cell blocks obtained from them) - and the clinician.

Introduction: In 2020, the World Health Organization-International Agency for Research on Cancer/International Academy of Cytology (WHO-IARC IAC) joint project was commenced to develop standardized nomenclature and diagnostic criteria in cytopathology internationally. Our institution has been coding all respiratory cytological specimens in a similar fashion for over 10 years. Our aim was to analyse the effectiveness of our respiratory cytology coding system by calculating the estimated risk of malignancy (ROM) and rates of each diagnostic category.

Methods: Over a 2 year period, all endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), bronchial brushing, bronchial washing, bronchial lavage, and sputum specimens reported at our institution were analysed. For each specimen, the diagnostic code, the relevant indication for each diagnostic procedure, the diagnosis, and the presence or absence of a positive corresponding biopsy were recorded.

Results: In total, 1,432 respiratory cytological specimens from 945 patients over a 2-year period were analysed. 467 specimens were confirmed to be associated with a malignant process. The overall ROM for respiratory cytology specimens was 37.7% for nondiagnostic, 18.1% for benign, 46.7% for atypical, 85.7% for suspicious for malignancy, and 91.9% for malignant. For each diagnostic procedure, the ROM increased from the benign to malignant categories.

Discussion/conclusion: Our ROM rates for overall respiratory cytology specimens and for EBUS-TBNA, bronchial brushing, and bronchial washing specimens separately are concordant with other major international studies. With the WHO-IARC IAC joint project in progress and an international respiratory cytology coding system being developed, our study has the potential to add value by providing indicative ROM rates, which can be used to inform the development of this new classification system. Our rates of diagnostic accuracy are in keeping with international standards, which support the accuracy of our data.

Introduction: Lobular endocervical glandular hyperplasia (LEGH) is a benign lesion; however, it is considered to be the origin of gastric-type adenocarcinoma in the uterine cervix, and early diagnosis is important. At Shinshu University Hospital, screening of LEGH cells is based on the difference in color tone of cytoplasmic mucin on Papanicolaou staining and detection of gastric mucin using HIK1083-labeled latex agglutination assay. However, it is sometimes difficult to distinguish LEGH cells with subtle nuclear atypia from endocervical (EC) cells.

Methods: We calculated the Gabor filter features (mean signal value, standard deviation, skewness, kurtosis) from the nuclei of cytological specimens in EC cells (37 cases) and LEGH cells (33 cases) using microscopic images, and we performed statistical analysis and discriminant analysis by linear support vector machine (LSVM) using these features. A Gabor filter is a linear filter defined as a mathematical representation of the mammalian visual system. Gabor filters with three wavelengths and eight angles were used for analysis.

Results: Gabor filter features in EC cells were higher than in LEGH cells, demonstrating that the gradient of LEGH cell nuclei was milder than that of EC cell nuclei. The accuracy calculated using all Gabor filters was 91.0% and the accuracy of four Gabor filters (λ = 2/3π and θ = 0°, 45°, 90°, 135°) was 88.9%. High accuracy with low computation costs was achieved by reducing the number of features used for LSVM.

Conclusion: The application of a Gabor filter with convolutional processing resulted in the edges of LEGH cells being slightly rough and thick, whereas those of EC cells were fine and thin. Thus, it is thought that the frequency of abrupt gradients of pixels was higher in EC cells than in LEGH cells, and the gradient of chromatin distribution in LEGH cell nuclei was milder than that in EC cell nuclei. It was possible to evaluate nuclear findings of EC and LEGH cells objectively by quantifying morphological features of nuclei using Gabor filters. It was possible to differentiate EC cells from LEGH cells using LSVM using Gabor filter features.

Introduction: After the transition toward the HPV-based screening protocol, which has led to an increase in sensitivity, and in order to bring the specificity back to acceptable values, cytology underwent a change of approach, becoming a triage test. For these reasons, in the Tuscany region (after the recommendations of the GISCi document), it was decided to reduce, as much as possible, the use of ASC-US category in cytology triage, classifying these morphological cases as negative for intraepithelial lesion or malignancies (NILM) or LSIL, basing on the grade of nuclear atypia. So, in Italy, in a cytology triage context (HPV primary screening), a modified Bethesda system (TBS) is currently used. The aim of this study was to evaluate the performance of the review activity of 384 cytology triage cases and of the cervical cancer screening indicators (sensitivity and specificity for CIN2+ lesions) using the TBS 2014 or the modified TBS.

Materials and methods: 384 HPV positive cases at one-year recall (192 with a cytology result of NILM both at baseline and at one-year recall; 192 with a cytology result of NILM at baseline but abnormal at one-year recall), all with a histologically confirmed result (128 CIN2+, 256 ≤ CIN1), were selected, and their baseline Pap tests were reviewed in blind mode by 5 expert cytologists.

Results: The cytological results of NILM were confirmed for 92.5% and 83.8% of cases using TBS 2014 or modified TBS, respectively. 20/128 CIN2+ cases could have been reported at the baseline cytology triage, causing an anticipatory effect and an improvement in sensitivity of the screening protocol at baseline (+15.6%). Using TBS 2014, the number of false positives more than tripled with respect to the modified TBS 2014, with a significant increase in unnecessary colposcopies (+11.4%).

Conclusion: This work demonstrated that a greater expertise of cytologists, acquired during the following 3 years of experience with cytological triage, and a strong IQC system could lead to the identification of a significant number of lesions reported to baseline rather than at one-year recall (diagnostic anticipation).

Introduction: Fine needle aspiration biopsy (FNAB) is a routinely used investigation in the evaluation of lymph node pathologies. However, there exists a lack of uniformity in cytopathology reporting owing to the nonavailability of standard guidelines. Recently, a novel system for reporting lymph node cytopathology has been proposed. The present study aimed to analyze the utility of the proposed system in cytopathology reporting in our institution.

Materials: FNABs of lymph nodes performed over a period of 5 years were categorized as per the proposed Sydney system. The diagnoses on cytopathology were correlated with histopathologic diagnoses to assess the diagnostic accuracy. The rate of malignancy (ROM) for each category was calculated.

Results: A total of 747 lymph node FNABs were included in the study. Histopathology was available in 262 cases. ROM in categories I-V was 26.3%, 7.2%, 76.9%, 82.3%, and 100.0%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of FNAB when considering category L3 to represent benign cytopathology were 84.2%, 97.5%, 97.1%, and 86.2%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of FNAB when considering category L3 to represent malignant cytopathology were 92.56%, 95.08%, 94.9%, and 92.8%, respectively.

Conclusion: The study substantiates the usefulness of the proposed Sydney system in lymph node cytopathology in enhancing better communication between clinicians and cytopathologists. The use of ancillary techniques like immunocytochemistry and flow cytometry will aid in arriving at a more precise diagnosis.

Background: Up until recently, cervical cytology was the mainstay for cervical cancer screening. However, the established association between human papillomavirus (HPV) infection and cervical cancer has led to changes in preventive strategies, with cytology being replaced by the use of high-risk HPV (hrHPV) testing and primary prevention being achieved by HPV vaccination. In this context, the role of cervical cytology is shifting to secondary triage of HPV-positive women. As vaccination is leading to decreased HPV infections and significant cervical abnormalities (CIN2+), data on the impact of HPV vaccination on cervical cytology metrics, including positive predictive value (PPV) and negative predictive value (NPV), are starting to emerge.

Summary: This is a review of updates in cervical cancer screening, including the use of primary HPV testing and the impact of HPV vaccination on cytology as part of cervical cancer screening.

Key messages: Cervical cancer screening and prevention are undergoing significant changes as there is widespread implementation of HPV vaccination and hrHPV testing is becoming the entry point for secondary prevention. Optimal screening approaches and intervals in this setting are currently being analyzed including the use of cytology and other ancillary techniques for triage of positive cases, as well as the effect of vaccination on the PPV and NPV of cytology in the detection of CIN2+.

Background: Squamous intraepithelial lesions observed in Papanicolaou (Pap) test gynecologic cytology arise as a result of infection of the cervicovaginal tract by human papillomavirus (HPV). The viral cytopathic effect of HPV manifests as koilocytosis, also known as low-grade squamous intraepithelial lesion (LSIL) in The Bethesda System (TBS). Integration of HPV genetic material into the genome of squamous cells can, in some women, result in progressive accumulation of mutations and abnormalities of growth and maturation leading to high-grade squamous intraepithelial lesion (HSIL) and possibly invasive squamous cell carcinoma. Due to morphologic overlap between reactive processes and these changes related to HPV, TBS includes equivocal categories that may be applied to Pap tests with uncertain morphology: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells cannot exclude HSIL (ASC-H). Quality assurance (QA) measures in gynecologic cytology laboratories aim to maximize the sensitivity for LSIL and HSIL lesions while simultaneously keeping the use of ASC-US at reasonable levels.

Summary: TBS provides a comprehensive nomenclature for squamous abnormalities encountered in screening, but subjectivity in interpretation remains. QA practices attempt to identify problematic patterns of misinterpretation for correction.

Key message: This review aimed to provide practical recommendations for cytology practitioners seeking to alter their interpretive thresholds for ASC-US, LSIL, and HSIL in response to feedback from QA procedures indicating deviation from desired norms.

Introduction: Asbestos is a global occupational health hazard, and exposure to it by inhalation predisposes to interstitial as well as malignant pulmonary morbidity. Over time, asbestos fibers embedded in lung tissue can become coated with iron-rich proteins and mucopolysaccharides, after which they are called asbestos bodies (ABs) and can be detected in light microscopy (LM). Bronchoalveolar lavage, a cytological sample from the lower airways, is one of the methods for diagnosing lung asbestosis and related morbidity. Search for ABs in these samples is generally laborious and time-consuming. We describe a novel diagnostic method, which implements deep learning neural network technology for the detection of ABs in bronchoalveolar lavage samples (BALs).

Methods: BALs with suspicion of asbestos exposure were scanned as whole slide images (WSIs) and uploaded to a cloud-based virtual microscopy platform with a neural network training interface. The images were used for training and testing a neural network model capable of recognizing ABs. To prioritize the model's sensitivity, we allowed it to also make false-positive suggestions. To test the model, we compared its performance to standard LM diagnostic data as well as the ground truth (GT) number of ABs, which we established by a thorough manual search of the WSIs.

Results: We were able to reach overall sensitivity of 93.4% (95% CI: 90.3-95.7%) in the detection of ABs in comparison to their GT number. Compared to standard LM diagnostic data, our model showed equal to or higher sensitivity in most cases.

Conclusion: Our results indicate that deep learning neural network technology offers promising diagnostic tools for routine assessment of BALs. However, at this stage, a human expert is required to confirm the findings.