Clinical impact of high-quality testing for peritoneal lavage cytology in pancreatic cancer.

In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.

Impression cytology of ocular surface in xeroderma pigmentosum.

PURPOSE: To describe cellular alterations detected by impression cytology of the ocular surface in patients with xeroderma pigmentosum. The secondary objective was to assess the reliability of impression cytology in diagnosing ocular surface squamous neoplasia. METHODS: Patients with xeroderma pigmentosum underwent a single-day complete ophthalmological examination and impression cytology for ocular surface evaluation using 13 mm diameter mixed cellulose esters membrane filters and combined staining with Periodic Acid Schiff, Hematoxylin and Eosin, and Papanicolaou stains followed by microscopic analysis. The cytological findings were correlated with the clinical diagnosis. The impression cytology findings at baseline and one-year follow-up were correlated with the clinical course (no tumor, treated tumor, residual tumor recurrent tumor, new tumor). RESULTS: Of the 42 patients examined, impression cytology was performed in 62 eyes of 34 participants (65% females). The mean age of patients was 29.6 ± 17 years (range 7-62). Fifteen eyes had a clinical diagnosis of ocular surface squamous neoplasia. Impression cytology showed goblet cells (47, 75%), inflammatory cells (12, 19%), keratinization (5, 8%), and squamous metaplasia (30, 48%). Impression cytology was positive for atypical cells in 18 patients (12 with and 6 without ocular surface squamous neoplasia). The sensitivity, specificity, positive predictive value, and negative predictive value of impression cytology (at baseline) for diagnosis of ocular surface squamous neoplasia were 80%, 87%, 67%, and 93%, respectively, using clinical diagnosis of ocular surface squamous neoplasia as the reference standard. CONCLUSION: Impression cytology has a moderate positive predictive value for the diagnosis of ocular surface squamous neoplasia in patients with xeroderma pigmentosum. However, the lack of detection of atypical cells on impression cytology has a high negative predictive value for ocular surface squamous neoplasia. Integration of impression cytology in the long-term management of high-risk patients, such as patients with xeroderma pigmentosum, can avoid unnecessary diagnostic biopsies.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Changing digital and telecytology practices post COVID-19 comparing ASC survey results from 2016 to 2023.

INTRODUCTION: During the COVID-19 pandemic, the need for digital pathology tools became more urgent. However, there needs to be more knowledge of the use in cytology. We aimed to evaluate current digital cytology practices and attitudes and compare the results with a pre-COVID-19 American Society of Cytopathology (ASC) survey. MATERIALS AND METHODS: Fourteen survey questions assessing current attitudes toward digital cytology were developed from a 2016 ASC Digital Pathology Survey. Ten new survey questions were also created to evaluate telecytology use. The survey was e-mailed to ASC members over 6 weeks in 2023. RESULTS: A total of 123 individuals responded (116 in 2016). Attitudes toward digital cytology were unchanged; most participants stated digital cytology is beneficial (87% 2023 versus 90% 2016). The percentage of individuals using digital cytology was unchanged (56% in 2016 and 2023). However, telecytology for rapid onsite assessment (ROSE) is now considered the best application (55% 2023 versus 31% 2016). Forty-three institutions reported using digital and telecytology tools; 40% made implementations after 2020; most did not feel that COVID-19 affected digital cytology (56%). Telecytology for ROSE is the most common application now (78%) compared with education (30%) in 2016. Limitations for implementing digital imaging in cytology included inability to focus (38%) and expense (33%). CONCLUSIONS: General attitudes toward digital tools by the cytology community have essentially remained the same between 2016 and now. However, telecytology for ROSE is increasingly being used, which supports a need for validation and competency guidelines.

[What contribution can make artificial intelligence to urinary cytology?] / Quel apport de l'intelligence artificielle en cytologie urinaire ?

Urinary cytology using the Paris system is still the method of choice for screening high-grade urothelial carcinomas. However, the use of the objective criteria described in this terminology shows a lack of inter- and intra-observer reproducibility. Moreover, if its sensitivity is excellent on instrumented urine, it remains insufficient on voided urine samples. Urinary cytology appears to be an excellent model for the application of artificial intelligence to improve performance, since the objective criteria of the Paris system are defined at cellular level, and the resulting diagnostic approach is presented in a highly "algorithmic" way. Nevertheless, there is no commercially available morphological diagnostic aid, and very few predictive devices are still undergoing clinical validation. The analysis of different systems using artificial intelligence in urinary cytology rises clear prospects for mutual contributions.

Comparison of Intraoperative Imprint Cytology versus Frozen Section for Sentinel Lymph Node Evaluation in Breast Cancer. A study along with Systematic Review and Meta-analysis of literature.

BACKGROUND: Sentinel lymph node (SLN) is the first lymph node to drain the lymph from a particular region involved by cancer. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section (FS). The present study aimed to determine the sensitivity, specificity and accuracy of TIC and FS with histopathological diagnosis as gold standard. MATERIALS AND METHODS: The nodes were bissected along their long axis and wet surface was imprinted on to clean glass slides followed by toluidine blue and rapid Papanicolaou staining. Subsequently the lymph node slices were cut at three levels using the cryostat machine and stained with Hematoxylin and eosin stain. The cytological and FS findings were compared and the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of TIC and FS was evaluated taking histopathological diagnosis as gold standard. In addition, pooled sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for touch imprint cytology and frozen section were assessed for the studies included in the meta-analysis. RESULTS: The specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value of touch imprint cytology were 100%, 88.2%, 90%, 100% and 60% respectively. The specificity, sensitivity, diagnostic accuracy, PPV and NPV of frozen section were 100%, 94.1%, 95%, 100% and 75% respectively. The sensitivity of TIC and FS for detection of micrometastasis was 60% and 80% respectively. The pooled sensitivity and specificity for touch imprint cytology were 85.24% (95% CI, 83.46%-86.90%), and 98.99% (95% CI, 98.69%-99.23%) respectively. The pooled sensitivity and specificity for frozen section examination were 90.45% (95% CI, 85.15%-94.34%), and 100% (95% CI, 99.24%-100%) respectively. CONCLUSION: Even though the sensitivity of FS was better than imprint cytology in detection of micrometastasis, TIC is a rapid inexpensive technique which can be utilized in remote areas in absence of cryostat machine. The sensitivity of the two techniques with respect to detection of macrometastasis was comparable. This meta-analysis highlights the accuracy of the touch imprint cytology and frozen section examination in the intra-operative detection of malignancy in breast cancer.

Evaluation of nuclear morphometry in exfoliative cytology of buccal mucosa in patients with high risk of oral cancer.

BACKGROUND: Oral cancer poses a significant global health burden, with India having the highest prevalence. Effective detection is crucial in effective prevention. This study aimed to evaluate nuclear morphometric parameters (NMPs) in buccal mucosa cells of smokers, correlate NMPs with dysplasia, establish cut off values for grading dysplasia, and investigate the relationship between NMPs and smoking. METHODS: After obtaining ethical approval and informed consent, patients were recruited from the outpatient department of our institution. A target sample size of 250 was calculated. The data included smoking exposure quantified in pack-years, nuclear morphometric analysis (NMA) of buccal mucosa cells obtained through oral cytology using Image J, and the severity of dysplasia of the slides assessed by pathologists. Statistical analysis assessed the impact of dysplasia and the association between nuclear characteristics and smoking exposure. Receiver operating characteristic (ROC) plots determined the potential of these parameters to distinguish dysplasia levels. RESULTS: Significant differences in NMPs were observed among different smoking groups. Dysplasia severity had a significant correlation with NMPs, and strong correlations were found between NMPs and lifetime smoking exposure. ROC analysis established cut off values for NMPs with good sensitivity and specificity for classifying dysplasia severity. CONCLUSIONS: This study highlights the potential of NMA as a tool for oral cancer screening. NMPs can distinguish dysplasia severity and correlate with tobacco (smoking). The efficiency of NMA in a non-invasive oral cytology offers promise for patient-centered screening Additionally, the findings suggest future applications in telepathology and the potential for AI integration in automated screening after conducting multicentric large-scale studies.

[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

Knowledge of cytology results affects the performance of colposcopy: a crossover study.

OBJECTIVE: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). METHOD: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. RESULTS: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. CONCLUSIONS: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.

Diagnostic accuracy of fine needle aspiration cytology of bone lesions: A study of Tertiary Care Institute.

AIMS AND OBJECTIVES: The aim is to study the spectrum and cytomorphological features of bone lesions and find out the diagnostic accuracy of Fine needle aspiration cytology (FNAC) on the same. MATERIALS AND METHODS: The study was a cross-sectional study conducted in the Department of Pathology and Orthopedics in a tertiary institute in north India over a period of 1 year in 55 patients. All the patients were subjected to FNAC of bone lesions followed by tru-cut or open bone biopsy. Cytosmears were stained with May Grunwald Giemsa and Hematoxylin and Eosin were done on biopsy specimens. Sensitivity and specificity were calculated in percentage with a 95% confidence interval with reference to biopsy specimens. RESULTS: Two peaks were observed; one between 11 and 40 years with 32 cases and another at 51 and 60 years with 12 cases. The male to female ratio was 1.4:1. In the present study, inflammatory lesions were present in 17 (31%) cases, 2 were tumor-like conditions; 10 (18%) cases of primary benign tumors, 26 (47.2%) cases were malignant. Out of these, 15 (27.2%) were primary malignant bone tumors and 11 (20%) were secondary in nature. The sensitivity, specificity, and diagnostic accuracy of the FNA of bone lesions were 55.17%, 79.04%, and 73.46%, respectively. CONCLUSION: Although there are a few limitations of FNAC such as low cellularity, small representative sample, and hemorrhagic aspirate, it can still be used as an initial diagnostic modality with proper clinical context for the management of bone lesions.

A Novel Validated Real-World Dataset for the Diagnosis of Multiclass Serous Effusion Cytology according to the International System and Ground-Truth Validation Data.

INTRODUCTION: The application of artificial intelligence (AI) algorithms in serous fluid cytology is lacking due to the deficiency in standardized publicly available datasets. Here, we develop a novel public serous effusion cytology dataset. Furthermore, we apply AI algorithms on it to test its diagnostic utility and safety in clinical practice. METHODS: The work is divided into three phases. Phase 1 entails building the dataset based on the multitiered evidence-based classification system proposed by the International System (TIS) of serous fluid cytology along with ground-truth tissue diagnosis for malignancy. To ensure reliable results of future AI research on this dataset, we carefully consider all the steps of the preparation and staining from a real-world cytopathology perspective. In phase 2, we pay special consideration to the image acquisition pipeline to ensure image integrity. Then we utilize the power of transfer learning using the convolutional layers of the VGG16 deep learning model for feature extraction. Finally, in phase 3, we apply the random forest classifier on the constructed dataset. RESULTS: The dataset comprises 3,731 images distributed among the four TIS diagnostic categories. The model achieves 74% accuracy in this multiclass classification problem. Using a one-versus-all classifier, the fallout rate for images that are misclassified as negative for malignancy despite being a higher risk diagnosis is 0.13. Most of these misclassified images (77%) belong to the atypia of undetermined significance category in concordance with real-life statistics. CONCLUSION: This is the first and largest publicly available serous fluid cytology dataset based on a standardized diagnostic system. It is also the first dataset to include various types of effusions and pericardial fluid specimens. In addition, it is the first dataset to include the diagnostically challenging atypical categories. AI algorithms applied on this novel dataset show reliable results that can be incorporated into actual clinical practice with minimal risk of missing a diagnosis of malignancy. This work provides a foundation for researchers to develop and test further AI algorithms for the diagnosis of serous effusions.

Retrospective application of WHO reporting system for lung cytopathology with assessment of risk of malignancy.

INTRODUCTION: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category. MATERIALS AND METHODS: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually. RESULTS: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%. CONCLUSIONS: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy.

Reliably making the primary diagnosis of mesothelioma utilizing serous fluid cytology specimens: an institutional experience.

INTRODUCTION: The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy. MATERIALS AND METHODS: SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered. RESULTS: One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis. CONCLUSIONS: The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.

Intraoperative Touch Imprint Cytology of Brain Neoplasms: A Useful High-Diagnostic Tool in 93 Consecutive Cases; Differential Diagnoses, Pitfalls, and Traps.

Introduction: Intraoperative cytological examination of central nervous system (CNS) lesions was first introduced in 1920 by Eisenhardt and Cushing for rapid evaluation of neurosurgical specimens and to guide surgical treatment. It is recognized that this method not only confirms the adequacy of biopsy in CNS samples but also indicates the presence and preliminary diagnosis of lesional tissue. Methods: A total of 93 patients who underwent touch imprint cytology (TIC) for CNS tumors or lesions between 2018 and 2023 were included in the study. All cases were correlated with the final histopathological diagnosis, and pitfalls and difficulties encountered with discrepancies were noted. Result: The most common primary CNS tumors were gliomas and meningiomas, while secondary (metastatic) tumors were predominantly lung, breast, and gastrointestinal system carcinomas. Sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis with TIC were 94.1%, 100%, and 61.5%, respectively. Final histopathological diagnosis by TIC was made in 88 cases (94.6%) and the discrepancy was found in 5 cases (5.37%). Three of the five discrepancies (3.2%) were haematolymphoid malignancies (two lymphomas and one plasma cell neoplasia), one glioblastoma, and one hemangioblastoma case. Conclusion: TIC is a fast, safe, and inexpensive diagnostic tool used during intraoperative neuropathology consultation. Awareness of the pitfalls of using this method during intraoperative consultation will enable high-diagnostic accuracy.

Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions.

INTRODUCTION: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. METHODS: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. RESULTS: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. CONCLUSION: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.