Cytology Specimens Research Articles

Reliability of assessing morphologic features with prognostic significance in cytology specimens of epithelioid diffuse pleural mesothelioma and implications for cytopathology reporting.

The World Health Organization incorporates morphologic features with prognostic significance in the 2021 classification of epithelioid diffuse pleural mesothelioma (E-DPM). Although cytology specimens are often the first and occasionally the only specimen available for patients with DPM, these features have not yet been investigated in cytology. Nuclear atypia, pleomorphic features, necrosis, and architectural patterns were retrospectively assessed in 35 paired cytology and concurrent/consecutive surgical pathology specimens of E-DPM. Agreement between pairs was determined via unweighted κ scores. Discordant cases were re-reviewed to determine the reasons for disagreement. Interpretation of nuclear atypia in cytology was concordant with histology in all cases (κ=1.000; p<.001). The presence of pleomorphic features and necrosis was concordant in 97.1% (κ=0.842; p<.001) and 85.7% (κ=0.481; p=.001) of paired cases, respectively. Assessment of architectural patterns in cytology showed only slight agreement with histology (κ=0.127; p=.037). In cytology cases (n=23) with cell block material available, assessment of nuclear atypia and the presence of pleomorphic features showed perfect agreement (κ=1.000; p<.001, each), the presence of necrosis showed moderate agreement (κ=0.465; p=.008), and assessment of architectural patterns showed slight agreement (κ=0.162; p=.15) in paired specimens. Most disagreements were due to sampling differences between cytology and histology specimens. Although complete nuclear grading of E-DPM is not possible given the unreliability of mitotic counts in cytology, assessment of nuclear atypia in cytology specimens is shown to be reliable. Identification of pleomorphic features and necrosis is also reliable despite occasional sampling issues. Assessment of architectural patterns is more limited in cytology.

Efficacy of categorization of urothelial malignancy in atypical urine samples by the Paris system for reporting urinary cytology

Background: Urine cytology is an important screening tool of patients for urothelial carcinoma and follow-up of patients. Ease of procurement, cost-effectiveness, and lower turnaround time are the advantages. Aims and Objectives: The aim of the study was to identify the accuracy of TPS criteria in diagnosing HGUC, considering biopsy as the gold standard and to describe the cytomorphological features in atypical urine specimens and categorization as per reference to TPS of reporting urine cytology. Definition – Atypical urine sample: Urine samples of patients with macroscopic hematuria and other unexplained urinary symptoms, suspicious of urothelial malignancy. Materials and Methods: The study was performed on patients attending urology OPD with macroscopic hematuria and other unexplained urinary symptoms, which were suspicious of urothelial malignancy and whose urine cytology and subsequent biopsy specimens were submitted to the Department of Pathology. Continuous sampling of 56 patients was done. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to compare TPS with histopathology. SPSS was used to assess correlation, done by diagnostic test evaluation. Results: Age group of study population ranges from 40 to 84 years with mean age of population as 62 years. Sensitivity, specificity, PPV, and NPV of TPS for reporting urinary cytology in the investigation were 85%, 75%, 65.38%, and 90%. Combination of elevated nuclear-to-cytoplasmic ratio, irregular nuclear border, and hyperchromasia was predictive of malignancy. Conclusion: The criteria outlined by TPS facilitated the standardization of urine cytology reporting and significantly increased the sensitivity of diagnosing HGUC.

Use of proliferative markers in cytological specimens for diagnosis and prognostication of cutaneous canine mast cell tumours

Use of proliferative markers in cytological specimens for diagnosis and prognostication of cutaneous canine mast cell tumours

Pax8 as a useful adjunct marker to differentiate pancreatic serous cystadenoma from clear cell renal cell carcinoma in both cytologic and surgical specimens

BackgroundHistomorphological differentiation between pancreatic serous cystadenoma (SCA) and clear cell renal cell carcinoma (RCC) can be challenging. We aimed to study Paired box 8 protein (Pax8) expression profile in cytologic and surgical specimens with pancreatic SCA to assess its utility as a differentiating marker from clear cell RCC.MethodsWe characterized Pax8 immunohistochemistry in 33 patients with pancreatic SCA (23 surgical resections and 10 cytology specimens). Nine cytology specimens from metastatic clear cell RCC involving pancreas were used as control tissue. Electronic medical records were reviewed to retrieve clinical information.ResultsAll 10 pancreatic SCA cytology specimens, and 16 of 23 pancreatic SCA surgical resections showed absent Pax8 immunostaining, while the remaining 7 surgical resection specimens showed 1%-2% immunoreactivities. Islet and lymphoid cells adjacent to the pancreatic SCA expressed Pax8. In contrast, the proportion of Pax8 immunoreactivity ranged from 50 to 90% (average of 76%) in nine cases of metastatic clear cell RCC involving pancreas. Using a 5% immunoreactivity cutoff, all cases of pancreatic SCA are interpreted as negative for Pax8 immunostains while all cases of metastatic clear cell RCC involving pancreas are interpreted as positive for Pax8 immunostains.ConclusionsThese results suggest that Pax8 immunohistochemistry staining can be a useful adjunct marker to differentiate pancreatic SCA from clear cell RCC in clinical practice. To the best of our knowledge, this is the first large-scale study of Pax8 immunostaining on surgical and cytology specimens with pancreatic SCA.

Expression of Stemness Markers in the Cervical Smear of Patients with Cervical Insufficiency.

The presence of stem cells has been previously described in human precancerous and malignant cervical cultures. Previous studies have shown a direct interplay of the stem cell niche, which is present in practically every tissue with the extracellular matrix. In the present study, we sought to determine the expression of stemness markers in cytological specimens collected from the ectocervix among women with cervical insufficiency during the second trimester of pregnancy and women with normal cervical length. A prospective cohort of 59 women was enrolled of whom 41 were diagnosed with cervical insufficiency. The expression of OCT-4 and NANOG was higher in the cervical insufficiency group compared to the control group (-5.03 (-6.27, -3.72) vs. -5.81 (-7.67, -5.02) p = 0.040 for OCT4) and (-7.47 (-8.78, -6.27) vs. -8.5 (-10.75, -7.14), p = 0.035 for NANOG. Differences in the DAZL gene were not significantly different (5.94 (4.82, 7.14) vs. 6.98 (5.87, 7.43) p = 0.097). Pearson correlation analysis indicated the existence of a moderate correlation of OCT-4 and Nanog with cervical length. Considering this information, the enhanced activity of stemness biomarkers among pregnant women diagnosed with cervical insufficiency may be predisposed to cervical insufficiency, and its predictive accuracy remains to be noted in larger population sizes.

CDKN2A/p16 evaluation in cytology specimens.

CDKN2A/p16 evaluation in cytology specimens.

Relationship between a deep learning model and liquid-based cytological processing techniques.

Artificial intelligence (AI)-based cytopathology studies conducted using deep learning have enabled cell detection and classification. Liquid-based cytology (LBC) has facilitated the standardisation of specimen preparation; however, cytomorphology varies according to the LBC processing technique used. In this study, we elucidated the relationship between two LBC techniques and cell detection and classification using a deep learning model. Cytological specimens were prepared using the ThinPrep and SurePath methods. The accuracy of cell detection and cell classification was examined using the one- and five-cell models, which were trained with one and five cell types, respectively. When the same LBC processing techniques were used for the training and detection preparations, the cell detection and classification rates were high. The model trained on ThinPrep preparations was more accurate than that trained on SurePath. When the preparation types used for training and detection were different, the accuracy of cell detection and classification was significantly reduced (P < 0.01). The model trained on both ThinPrep and SurePath preparations exhibited slightly reduced cell detection and classification rates but was highly accurate. For the two LBC processing techniques, cytomorphology varied according to cell type; this difference affects the accuracy of cell detection and classification by deep learning. Therefore, for highly accurate cell detection and classification using AI, the same processing technique must be used for both training and detection. Our assessment also suggests that a deep learning model should be constructed using specimens prepared via a variety of processing techniques to construct a globally applicable AI model.

Uncommon case of cytopathological features of sialadenoma papilliferum.

Sialadenoma papilliferum, a benign and rare salivary gland neoplasm, accounts for 0.4%-1.2% of all salivary gland tumors and occurs primarily in minor salivary glands of the oral cavity. Here, we report a case of sialadenoma papilliferum and its associated cytological findings. A papillary tumor was incidentally detected on the palate of an 86-year-old Japanese man. Conventional oral exfoliative cytology was performed; the cytology smear exhibited epithelial clusters composed of atypical epithelial cells with a high nuclear/cytoplasm ratio and arranged in sheet or small papillary-like projections. Cytoplasmic vacuoles were also observed in the papillae. It was difficult to make a definitive diagnosis due to the presence of uncommon cytological features. The excisional biopsy specimen revealed histological features characteristic of sialadenoma papilliferum. Mutational analysis detected BRAFV600E mutation, which confirmed the diagnosis of sialadenoma papilliferum. To the best of our knowledge, no prior cytomorphological evaluations of sialadenoma papilliferum have been reported in detail. Oral exfoliative cytology specimens from salivary gland tumors can demonstrate uncommon cytomorphological features. A differential diagnosis of sialadenoma papilliferum can be based on the observation of mildly atypical epithelial cells that form small papillary-like structures.

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision‐making of thyroid nodules

A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAFV600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage. The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

Unraveling the significance of TSHR mutations in indeterminate thyroid cytology specimens.

We investigated the clinical significance of thyroid-stimulating hormone receptor (TSHR) mutations detected in thyroid fine needle aspiration (FNA) specimens. The pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations. A total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty-two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium-iodide transporter (NIS) mRNA was in the range of 0.01%-62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow-up was available in five cases (all benign except one). On follow-up available for 38 cases (mean: 24 months; range: 7-47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size. TSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.

The impact of war on cytopathological practice in Ukraine

Aim: To investigate the impact of Russian invasion on Ukrainian healthcare services related to cytopathology screening and diagnostics.Methods: The workload and output of the cytopathological laboratory located in Kyiv before and during 8 months of Russian invasion were analyzed. The laboratory performance was assessed by the total number of cytologic cases, the turn-around time (TAT) index, and the percentage of timely reported test results. The geographic distribution of cases was also analyzed.Results: There was a significant decline in the workload of the laboratory during the first two months of the war, and the numbers of cytopathology specimens fell to less than one third of prewar levels, and the TAT was prolonged. Since May 2022, the efficiency and quality of cytopathologic testing has been largely restored in most parts of Ukraine, only to be affected again by increased Russian bombardment toward the end of summer 2022. The number of cytology specimens was reduced and the source of cytology specimens changed from the prewar conditions reflecting the relocation of the CSD Lab to western Ukraine.Conclusion: Cytolopathological screening and diagnostics were seriously disrupted in Ukraine during the Russian invasion resulting in a decreased volume of cytology specimens received in the CSD Lab during the early months of the war. By adapting to the war conditions and reorganizing the cytology services, CSD Lab has continued providing cytology services at a level of efficiency similar to those of the prewar period. However, the volume of cytology specimens remains much smaller than before war, indicating that the cytology services have been adversely affected by the war.

Abstract 5414: Automated detection of high-grade urothelial carcinoma from urine cytology slides using attention-based deep learning

Abstract Urine cytology has long been an effective and non-invasive test for the detection of bladder urothelial carcinomas (UC) routinely performed in cases of unexplained hematuria or for monitoring patients with UC. In cytopathology practice, urine cytology specimens are examined manually with a light microscope to identify morphologic features associated with different diagnostic categories based on the Paris System (TPS) for Reporting Urinary Cytology. Specifically, the diagnosis of high-grade urothelial carcinoma (HGUC) requires the identification of &amp;gt; 5-10 cells with a nuclear/cytoplasm ratio of 0.7 or greater and hyperchromasia together with coarse chromatin or irregular nuclear membranes. However, the task of identifying HGUC involves a substantial degree of manual review and is often associated with intra-and inter-observer variability. To address this, we have designed an accurate and efficient deep learning system capable of automatically distinguishing between HGUC and non-HGUC using digitized cytology slides. Our model has been developed using a retrospective cohort of 158 digitized urine ThinPrep cytology slides consisting of HGUC (n=98) and negative for HGUC (n=60). The model was then prospectively validated on a cohort of 105 urine cytology slides that were also independently reviewed prospectively in a blinded manner by a cytopathologist and cytotechnologist. Our system uses Otsu’s method for automatic image thresholding followed by dividing images into non-overlapping tiles of 500 × 500 pixels at the highest magnification. Subsequently, we use a pre-trained ResNet50 model to extract features which are used for training our attention-based multiple instance learning framework. For the training task, our retrospective cohort (158 slides) has been divided into 10 different splits each consisting of training (70%), validation (15%), and testing (15%) sets. The training and validation sets were used for the model training and optimalization, respectively, while the testing set was used for assessing the performance. This process yielded 10 different models with an average Area Under the ROC Curve (AUC) of 0.80 in the testing set. The best performing model had an AUC of 0.90 and an accuracy of 0.88. This model was subsequently validated prospectively in an independent testing cohort with 105 slides. In the prospective testing cohort, the model was able to accurately distinguish between HGUC and non-HGUC with an AUC of 0.83, accuracy of 0.76, sensitivity of 0.89, and specificity of 0.62. Additionally, our system can detect slide regions with high attention score for HGUC which are enriched in atypical urothelial cells. These findings show that our system can be utilized to assist cytopathologists in assessing urine cytology slides and to detect regions with high-diagnostic relevance for further assessment which is expected to reduce the time needed for manual review. Citation Format: Mohamed Omar, David Kim, Luigi Marchionni, Momin T. Siddiqui. Automated detection of high-grade urothelial carcinoma from urine cytology slides using attention-based deep learning. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5414.

Urine Cytology Rarely Escalates Clinical Management in the Surveillance of Non-muscle-Invasive Bladder Cancer.

The use of urine cytology in the surveillance of non-muscle invasive bladder cancer (NMIBC) is widely variable in clinical practice. We studied the impact of surveillance urine cytology on clinical decision making during NMIBC surveillance. A retrospective chart review was conducted on patients surveilled for clinical NMIBC from 2013 to 2020 with at least one follow-up cytology result after diagnosis. Patients were classified into risk categories according to American Urological Association (AUA) NMIBC guidelines. Data were obtained regarding tumor recurrence pathology and the frequency and findings of surveillance cystoscopies and urine cytologies. Positive (suspicious, malignant) and negative (atypical or negative for malignant cells) cytology results were correlated with cystoscopy and pathology findings when obtained within 3 months of the cytology specimen to determine if cytology impacted plan of care. Two hundred fourteen patients with NMIBC were followed for a median of 34 months, with 1045 urine cytologies collectively obtained over the surveillance period. There were no positive urine cytologies among patients with low-risk NMIBC; therefore, cytology did not change management in this cohort. The potential for cytology to escalate management for patients of any risk group (ie, positive cytology in the absence of positive cystoscopy or pathology findings) occurred in 30 (2.9%) cases. However, clinical decision making was only altered in 4 cases (0.4% of all cytologies). Less than 1% of urine cytology specimens collected during NMIBC surveillance impacted clinical management, none of whom had low-risk disease. The use of urine cytology for surveillance of low-risk NMIBC should continue to be strongly discouraged, as it did not change management in any such cases.

Validation of cytopathology specimens for digital pathology.

Digital cytopathology is being progressively implemented in centres worldwide, but impediments such as the three-dimensionality of specimens and the size of scanned images have prevented its use from becoming widespread. This study aimed to validate the use of digital whole slide image scanning of cytopathology samples for routine sign-out. Specimens were scanned using the Leica Aperio GT 450 System. The following sample types were used: liquid-based cytology, direct conventional smears from fine needle aspirates and cytospins. Cases were validated by the same pathologist who originally rendered the conventional diagnosis, with a washout of at least 3 months. Final digital diagnoses were compared to the original analogical diagnoses, and cases were considered concordant up to a one-degree difference between the original and digital diagnoses. Reasons for the unsuccessful scanning of slides were also noted. The technical procedures followed the College of American Pathologists' guidelines for digital pathology validation. A total of 730 slides from 383 cases (337 female, 51 male; median age 42) were successfully scanned. These cases consisted of the following sample types: 81 (21.1%) conventional smears, 240 (62.7%) liquid-based cytology samples and 62 (16.2%) cytospins. There were only five discordant cases, with a 98.7% agreement between original and digital diagnoses using the difference rate of up to one degree. Seventy-seven slides (10.5%) had to be rescanned due to technical problems. The main reasons for unsuccessful scanning were paucicellular samples (44; 57.1%), the thickness of the smears (18; 23.4%) and issues with the coverslip (15; 19.5%). Cytological specimens can be successfully scanned and used for digital pathology, with excellent agreement with the original diagnoses.

Artificial intelligence assisted diagnoses of fine-needle aspiration of breast diseases: a single-center experience

Abstract: Purpose: Since 2010, physicians from Afghanistan have been uploading images of histological and cytological specimens to a telemedicine internet platform (iPath network) for expert evaluation. From this collective work, all cases with fine-needle aspirations (FNA) of mammary gland diseases were extracted and analyzed. The aim of the present retrospective feasibility study is to investigate the utility of artificial intelligence assisted diagnoses in fine-needle aspiration (FNA) of breast diseases.Material and Methods: A total of 3304 microphotographic images from 438 patients of smears from FNA of the mammary gland were available for this study. Telemedical expert diagnoses from 4 experienced cytopathologists were available in all 438 cases. Their diagnosis (malignant tumor of the mammary gland or benign mammary gland disease) was set as the gold standard. AI analysis was performed using i) clinical context data and ii) two different image recognition methods to determine the probability values for the presence of malignant breast tumor. Youden index and AUC (area under the curve) were used to evaluate test performance. Results: A score for invasive breast cancer (IBC) calculated from contextual variables agreed with the expert diagnosis (accuracy) in 85.2% and with the two image recognition systems in 78.4% and 65.2%. This simplifies health healthcare management of breast diseases in low income countries as in many patients the less expensive and less time-consuming technique of FNA may replace a histological examination.Conclusion: Image classification and analysis of context variables can be used to test the validity and plausibility of cytologic diagnoses, especially when cytologic interpretation has to be performed by people who are inexperienced in cytopathology.

Cytological features of stromal spindle cells and their prognostic significance in lung adenocarcinoma.

Cancer-associated fibroblasts (CAFs) in the tumour microenvironment play a key role in tumour development, proliferation, invasion, and metastasis. The cytological features of spindle cells including CAFs-defined as stromal spindle cells (SSCs) adjacent to cancer cells-are frequently encountered in pulmonary adenocarcinomas. This study aimed to investigate the association between the presence of SSCs in cytological specimens and the clinicopathological features. We evaluated 211 patients with pulmonary adenocarcinoma who underwent surgical resection. All participants had cytological specimens corresponding to the histological specimens available for review. Of the 211 cases examined, 89 were SSC-positive (SSC+ ) and 122 were SSC-negative (SSC- ). SSC+ cases were more frequently associated with higher pathological stage (P < 0.001), lymph node metastasis (P=0.002), anaplastic lymphoma kinase (ALK) gene rearrangement (P=0.04), high tumour grade (P < 0.001), solid and micropapillary predominant pattern (P=0.02), and lymphatic vessel (P=0.003), blood vessel (P < 0.001), and pleural invasion (P=0.03) as compared to SSC- cases. Patients with SSC+ adenocarcinoma had a significantly shorter recurrence-free survival than those with SSC- adenocarcinoma (P=0.009). Cytologically, necrotic background (P=0.002), mucinous cancer cells (P=0.02), pleomorphic cells (P < 0.001), and mutual cell inclusions (P=0.01) were observed more frequently in SSC+ adenocarcinomas. The presence of SSCs could be an important cytological feature for predicting poor prognosis in lung adenocarcinomas.

Evaluation of a commercial NGS service for detection of bacterial and fungal pathogens in infectious ulcerative keratitis.

To compare results from a commercial next-generation sequencing (NGS) service to corneal cytology and culture for identification of causative organisms in veterinary patients presenting for infectious ulcerative keratitis (IUK). Swabs for corneal aerobic and fungal cultures and DNA swabs for NGS were submitted for canine and equine normal controls (n=11 and n=4, respectively) and IUK patients (n=22 and n=8, respectively) for which microbrush cytology specimens confirmed the presence of infectious organisms. The sensitivity of the NGS results was compared with bacterial and fungal culture results. Concordance between the NGS and culture results was determined. The NGS results were positive for bacterial and fungal organisms in 5 and 1 normal and 18 and 1 IUK cases, respectively. Bacterial and fungal cultures were positive for 7 and 2 normal and 20 and 5 IUK cases, respectively. Sensitivity of NGS was 82.14% (95% confidence interval (CI), 63.11% to 93.94%) and specificity was 76.47% (95% CI, 50.10% to 93.19%). Concordance (complete and partial) between identified bacterial and fungal organisms was found in 79% and 100% of cases, respectively. NGS identified organisms in 3 culture-negative IUK samples. A commercial NGS service may be useful in the identification of causative agents in IUK cases with a sensitivity greater than the sensitivity previously reported for aerobic culture. Further testing is needed to determine the clinical significance of additional organisms isolated by NGS from infected cases, as well as organisms isolated from normal corneas.

Bronchial cytology of pulmonary adenoid cystic carcinoma – A multi-institute series with emphasis on immunocytochemistry

BackgroundPulmonary adenoid cystic carcinoma (AdCC) is a central and superficial primary lung neoplasm, well-suited for sampling by bronchial cytology. This study aims to review the cytologic features of pulmonary AdCC on bronchial cytology, and to report an experience of applying immunocytochemistry on this rare entity. MethodsA multi-institute review of bronchial cytology specimens from histologically proven pulmonary AdCCs was performed. Published cases of bronchial cytology of pulmonary AdCC were reviewed. The cytologic features and immunocytochemical profile for pulmonary AdCC was summarized and compared with pertinent differentials. ResultsA total of 16 specimens from eight patients were retrieved. The initial cytologic diagnoses were negative (n = 7), atypia (n = 6), suspicious (n = 2) and AdCC (n = 1). Retrospective review showed eight bronchial cytology specimens (including five cases of atypia) with tumor cells present. The tumor cells displayed small basaloid nuclei with occasional small nucleoli, mild nuclear atypia, and scanty cytoplasm. Architectural patterns observed included clusters, tubules, solid sheets, three-dimensional balls, papillary-like fronds, and complex cribriform structures. Basement-membrane-like material, free or associated with tumor cells, were seen in all cases. Immunocytochemistry was performed in one specimen. MYB was positive. TTF-1, synaptophysin and chromogranin were negative. Epithelial and basal markers demonstrated a dual cell population. Literature review yielded 28 cases. Cytologic features described were similar except for cytoplasmic vacuolation in one case. ConclusionBasement membrane-like material is specific for AdCC. MYB positivity, TTF-1 and neuroendocrine marker negativity, support a diagnosis of AdCC. Other immunocytochemistry and cytologic features overlap significantly with adenocarcinoma and small cell carcinoma of lung.

Paris system of reporting urine cytology: An important screening tool for urothelial neoplasms

Urine cytology is an important screening tool for detection of high grade urothelial carcinoma and follow-up of patients with treated disease. Ease of procurement, cost-effectiveness, and lower turnaround time are the major advantages of the system. We aim to determine the frequency of high grade and low grade urothelial carcinoma in urine cytology specimens and to evaluate the accuracy of Paris system. A retrospective study was conducted in the Department of Pathology (Cytology), GMCH from August 2020 to July 2022 where a total of 200 cases were included. Data along with the preserved slides of urine cytology of these cases were collected from the archives and examined for the presence of urothelial carcinoma. The results were calculated in Microsoft word and excel, and p value was calculated by using the Chi- square (χ2) test of significance, P values less than 0.05 was considered statistically significant. In our study, a total of 200 cases were analysed, 169 were males and 31 were females, the male to female ratio being 5.5: 1. The most commonly affected age group was 61-70 years, the mean age being 62 years. Of the 200 urine samples examined, 12.5% cases had High Grade Urothelial Carcinoma (HGUC), 13.5% cases had atypical urothelial cells, 9% cases were suspicious for HGUC and 2% cases had Low Grade Urothelial Neoplasm. : The Paris System is a highly sensitive and rapid tool for reporting urine cytology specimens and is particularly useful in diagnosing High Grade Urothelial Carcinoma thereby helping in early management of the patients with neoplastic lesions of the urinary bladder.

Next-Generation Sequencing Analysis of Pancreatic Cancer Using Residual Liquid Cytology Specimens from Endoscopic Ultrasound—Guided Fine-Needle Biopsy: A Prospective Comparative Study with Tissue Specimens

This study evaluated the feasibility and clinical utility of liquid-based cytology (LBC) specimens via endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for next-generation sequencing (NGS) of pancreatic cancer (PC). We prospectively evaluated the performance of DNA extraction and NGS using EUS-FNB samples obtained from PC. Thirty-three consecutive patients with PC who underwent EUS-FNB at our hospital were enrolled. DNA samples were obtained from 96.8% of the patients. When stratified with a variant allele frequency (VAF) > 10% tumor burden, the NGS success rate was 76.7% (n = 23) in formalin-fixed paraffin-embedded (FFPE), 83.3% (n = 25) in LBC, and 76.7% (n = 23) in frozen samples. The overall NGS success rate was 86.7% (n = 26) using FFPE, LBC, or frozen samples. The detection rates for the main mutated genes were as follows: 86.7% for KRAS, 73.3% for TP53, 66.7% for CDKN2A, 36.7% for SMAD4, and 16.7% for ARID1A. LBC had the highest median value of VAF (23.5%) for KRAS and TP53. PC mutation analysis using NGS was successfully performed using LBC compared with FFPE and frozen samples. This approach provides an alternative and affordable source of molecular testing materials.