Liquid-based Cytology Preparations Research Articles

Liquid-based cytology features of pancreatic acinar cell carcinoma: comparison with other non-ductal neoplasms of the pancreas.

Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens. We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9). Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC. ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound-guided fine needle aspiration cytology would have impact on the management of the patient.

Digital Image Comparison of Cellular Yield in Bronchial Brushing: Pre- and Post-Biopsy Lavage Cytology.

Bronchoscopy is a useful diagnostic tool capable of performing core biopsy, forceps biopsy, bronchoalveolar lavage, and bronchial brushing. This study compares the cellularity of bronchial cytology including pre- and post-biopsy lavage by digital image analysis, aiming to increase diagnostic and tumor yield by optimizing the sequence and combination of bronchial biopsy and cytology. Alveolar macrophage, bronchial epithelium, and tumor cell cellularity from liquid-based cytology preparations of bronchial brushing and pre-biopsy and post-biopsy bronchoalveolar lavage were annotated on digitized whole-slide images and compared. Secondary analysis on the relationship of tumor cell and non-lesional cell yield was performed. Overall, 118 cytology specimens from 43 patients were retrieved in total. Bronchial epithelium count was higher in pre-biopsy than post-biopsy lavage (p < 0.01) but not for alveolar macrophages nor tumor cell (p > 0.05). Tumor cell count was higher for bronchial brushing cytology samples than lavage (p = 0.018). The alveolar macrophage count was higher in post-biopsy lavage than bronchial brushing (p = 0.033); otherwise, brushing showed consistently higher bronchial epithelium and tumor cell counts. There were 33 false negative (tumor cell absent) specimens, and the combination of bronchial brushing and pre-biopsy lavage yielded the lowest false negative cases. Correlation between bronchial epithelium and alveolar macrophage counts with tumor cell count was weak (correlation coefficient = -0.168-0.203) except for post-biopsy lavage (correlation coefficient = 0.412-0.479, p < 0.05). Bronchial brushing yields a greater amount of tumor cell than lavage, and timing lavage before or after core biopsy does not affect tumor cell yield. Combining bronchial brushing and pre-biopsy lavage results in the lowest false negative rate.

Cytomorphological comparison of ThinPrep and SurePath liquid-based cytology in thyroid fine-needle aspiration.

The two widely established systems for liquid-based cytology (LBC), ThinPrep and SurePath, employ different principles. The aim of this study was to compare the cytomorphology of thyroid lesions prepared by the two techniques. We retrospectively reviewed 44 thyroid FNA specimens prepared by LBC, including 20 ThinPrep and 22 SurePath. Cytologic diagnoses were made according to the Bethesda system and cytomorphologic parameters were evaluated. Acellular smears were significantly frequent in ThinPrep than SurePath (10% vs. 0%). Both techniques produced a clean background, well cell preservation, and not apparent cell shrinkage. ThinPrep showed significantly lower cellularity than SurePath (25% vs. 4.3%). ThinPrep produced considerable flattening and fragmented clusters, while SurePath contained larger clusters in a three-dimensional configuration. Colloid was significantly reduced in amount and fragmented in ThinPrep, and was easily observed in SurePath. In cases of Hashimoto's thyroiditis, ThinPrep produced much less leukocytes in background than SurePath. Aggregates of fibrin and leukocytes were frequently present in 10/16 cases (62.5%) processed by ThinPrep. Air-dry artifact at periphery of the ring was present in 6/16 cases (37.5%) processed by ThinPrep. The nuclear features of papillary carcinoma were similarly evident in both LBC preparations. SurePath seems to be superior to ThinPrep for diagnosing benign entities based on adequate representation of colloid and lymphocytes. The cell quality of both techniques in thyroid FNA was comparable, while each method introduces its own unique cytologic artifacts related to its methodology. We should recognize the cytomorphologic alterations to avoid misinterpretations.

Dual Sec62/Ki67 immunocytochemistry of liquid-based cytological preparations represents a highly valid biomarker for non-invasive detection of head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid-based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non-invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions. 104 HNSCC patients and 28 control patients, including healthy patients (n = 17), papilloma (n = 1) and leukoplakia patients (n = 10), were included in this study. For all patients, an LBC swab followed by simultaneous immunocytochemical detection of Sec62 and Ki67 was performed. Immunocytochemical as well as cytopathological results were correlated with histological diagnoses and clinical findings. All HNSCC patients (100%) showed dual Sec62/Ki67 positivity, and all control patients except for the papilloma patient were negative for Sec62/Ki67 (96.4%), resulting in a 100% sensitivity and 96.4% specificity of Sec62/Ki67 dual stain for non-invasive detection of HNSCC. The positive predictive value was 99% and the negative predictive value was 100%. Sec62 expression levels showed a positive correlation with tumour de-differentiation (p = 0.0489). Simultaneous immunocytochemical detection of Sec62/Ki67 using LBC represents a promising non-invasive and easy-to-apply tool for the early detection of HNSCC in routine clinical practice. This novel technique can help to avoid incisional biopsies and reduce the frequency with which general anaesthesia is used in diagnostic procedures in patients with suspicious oral lesions.

Distribution of human papillomavirus prevalence, genotype, and PAP test results in women in the southeast of Turkey.

The aim of this study was to investigate the prevalence, genotype, and distribution of cervical human papillomavirus (HPV) in women living in southeast Turkey. A total of 13,300 cervical smear materials were scanned and 899 cases found to be HPV-positive were included in the study. Cases were divided into seven groups according to age (under 19 years of age, 20-24, 25-29, 30-39, 40-49, 50-59, and over 60 years old) and six groups according to HPV types (HPV type 16, HPV type 18, HPV type 16-18 association, HPV type 16-high risk (HR) association, HPV Type 18-HR association, and HPV HR [31,33,35,39,45, 51,52,56,58,59,66, and 68]). SurePath liquid-based cytology preparations were evaluated, and HPV tests were performed using real-time-polymerase chain reaction. A total of 6.7% of cervical smear samples were positive for HPV DNA. The mean age of these cases was 41 years (range 15-78 years). All HPV types showed the highest rate of positivity in the 30-39 age groups. Regarding the distribution of HPV types, most of the cases were in the HPV HR group (66%). The most common atypia category detected in cytological examination was "Atypical squamous cells of undetermined significance" (ASC-US) (27%). It was determined that the prevalence of HPV in the southeast of Turkey is lower than the world average, the most common HPV type in our region is HPV-HR, and HPV peaks at older ages compared to what has been reported for other regions of the world.

Effect of Specimen Processing Technique on Cell Detection and Classification by Artificial Intelligence.

Cytomorphology is known to differ depending on the processing technique, and these differences pose a problem for automated diagnosis using deep learning. We examined the as-yet unclarified relationship between cell detection or classification using artificial intelligence (AI) and the AutoSmear (Sakura Finetek Japan) and liquid-based cytology (LBC) processing techniques. The "You Only Look Once" (YOLO), version 5x, algorithm was trained on the AutoSmear and LBC preparations of 4 cell lines: lung cancer (LC), cervical cancer (CC), malignant pleural mesothelioma (MM), and esophageal cancer (EC). Detection and classification rates were used to evaluate the accuracy of cell detection. When preparations of the same processing technique were used for training and detection in the 1-cell (1C) model, the AutoSmear model had a higher detection rate than the LBC model. When different processing techniques were used for training and detection, detection rates of LC and CC were significantly lower in the 4-cell (4C) model than in the 1C model, and those of MM and EC were approximately 10% lower in the 4C model. In AI-based cell detection and classification, attention should be paid to cells whose morphologies change significantly depending on the processing technique, further suggesting the creation of a training model.

Evaluation of Breast, Lymph Node, and Thyroid Fine Needle Aspiration Cytology by Liquid Based Smears and Conventional Smears

Introduction: Fine needle aspiration cytology (FNAC) is a first-line investigation for palpable lumps and is a highly cost-effective and accurate investigative technique. It is a safe, simple, rapid, minimally invasive technique. Liquid-based cytology (LBC) has been used in gynecologic-cytology for over three decades. Many laboratories have adopted LBC technique for exfoliative and FNA samples. We undertook the present study to compare the advantages and disadvantages of conventional and liquid based cytology preparations. Aim of the study: To evaluate the diagnostic accuracy of LBC and Conventional smears in fine needle aspiration cytology samples from breast, lymph nodes, and thyroid tissue. Materials and methods: FNA material from accessible sites such as palpable breast lumps, thyroid, and lymph nodes were collected from 100 patients and was processed by two different methods, i.e., Conventional smears and by LBC. Various parameters on the slides were considered and compared for both the preparations. Out of 100 FNA samples, 51% were of Thyroid, 34% were of lymph node and 15% were of breast lumps. Observations and results: Adequate cellularity and better architecture was present in conventional smears than LBC preparations. Background material was less, and monolayers were better in the LBC preparations. Informative background material (i.e. Colloid, lymphoglandular bodies, etc) was more in cases of Conventional smears. The nuclear and cytoplasmic details were nearly equally good in both the preparations. Conclusion: Both these methods have their own advantages and disadvantages. Before incorporating LBC as a routine method, pathologists should familiarize themselves with all the aspects of LBC.

Assessment of the diagnostic usefulness of liquid-based cytology. The impact of modifications.

The technique of liquid-based cytology (LBC) is of increasing diagnostic value in non-gynecological cytology. The purpose of the present study was to validate modifications to stages of the LBC process and to assess the diagnostic usefulness of the LBC technique. Between May 2021 and January 2022, atotal of 484 samples were prepared from routine cytology tests carried out in the Department of Tumor Pathology of The Greater Poland Cancer Center. The material was obtained from fine-needle aspiration biopsies and fluid samples. One hundred cases were selected for the research described in the article. The slides were prepared using the Becton Dickinson Totalys SlidePrep device. Based on the research, it was concluded that predominantly the LBC technique gives better results than aconventional smear because the background, which would otherwise make it difficult to assess preparations, was eliminated. Additionally, in LBC preparations the cellularity was increased, and the cells were arranged in amonolayer system, which improves the image quality. The introduction of modifications to the LBC method facilitated the process of sample preparation, without adversely affecting the quality of the obtained material.

Utility of high-risk HPV RNA chromogenic in situ hybridization in cytology smears and liquid-based preparations from metastatic head and neck squamous cell carcinoma.

High-risk human papillomavirus (HR-HPV) status is critical for the diagnosis, prognosis, and treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Patients often present with enlarged cervical nodes, and fine-needle aspiration cytology (FNAC) is frequently the initial diagnostic procedure. Although p16 is the most widely used surrogate marker, problems with interpretation can limit its utility in FNAC. HR-HPV RNA in situ hybridization (ISH) has emerged as a specific way to assess HPV status on cell block preparations of cervical nodes. The authors evaluated the utility of HR-HPV ISH in conventional smears and liquid-based cytology (LBC) preparations of metastatic head and neck squamous cell carcinoma (SCC). Thirty-one aspirates of proven, HPV-related SCC (confirmed by p16 and/or HR-HPV ISH in corresponding surgical specimens) were selected. Ten aspirates of HPV-negative SCC were also retrieved. HR-HPV ISH was performed on 27 smears and 14 LBC preparations. All results were scored as positive, equivocal, or negative. Eighty-four percent of metastatic, HPV-related SCCs were positive for HR-HPV RNA ISH, with high number of signals (n=19) and low number of signals (n=7), whereas five HPV-related SCCs were equivocal. All metastatic, HPV-negative SCCs were negative for HR-HPV ISH. HR-HPV ISH can be reliably performed on smears or LBC preparations, particularly when cell blocks are unavailable or paucicellular. Results were easy to interpret when high numbers of signals were present but were challenging in aspirates with low or rare number of signals. The current study suggests that HR-HPV ISH could be used as the initial testing modality for determining HPV status in FNAC specimens of metastatic SCC.

Morphometrical Differences among Endometrial Endometrioid Carcinoma Grade 1, Grade 3, and Serous Carcinoma in Endometrial Liquid-Based Cytology Preparations

Introduction: In Japan, the direct smearing preparation (conventional preparation) has been widely used for cytological examination of the endometrium. Problems with the conventional preparation can be dissolved by liquid-based cytology (LBC) preparation. The Yokohama System is a method for reporting endometrial cytology, but the system lumps cancers together and does not distinguish between histological types. The objective of this study was to clarify morphometrical differences among endometrial endometrioid carcinoma grade 1 (G1), grade 3 (G3), and serous carcinoma (Serous) by image analysis of endometrial LBC. Methods: Using Papanicolaou smears prepared by LBC after sampling with a brush from 32 G1, 16 G3, and 16 Serous patients, image analysis was performed concerning the following 11 items: (1) number of layers of cluster, (2) area of cluster, (3) perimeter of cluster, (4) roundness of cluster, (5) complexity of cluster, (6) area of nucleus, (7) perimeter of nucleus, (8) roundness of nucleus, (9) complexity of nucleus, (10) area of nucleolus, and (11) nucleolus/nucleus (N/N) ratio. The data were statistically compared among G1, G3, and Serous. Results: Significant differences were observed in the number of layers of cluster (G1<G3<Serous), area of cluster (G1>G3<Serous), area of nucleus (G1<G3<Serous), area of nucleolus (G1<G3<Serous), roundness of cluster (G1>G3, G1>Serous), complexity of cluster (G1<G3, G1<Serous), roundness of nucleus (G1<Serous), complexity of nucleus (G1>Serous), and N/N ratio (G1>G3, G3<Serous). Conclusion: The number of layers and area of cluster, complexity of cluster, area and complexity of nucleus, area of nucleolus, and N/N ratio were suggested to be useful for the differentiation of histological types among G1, G3, and Serous. Particularly, differences in the number of layers of cluster, size of nucleus, and size of nucleolus among histological types were large and are considered to be potentially effective points of differential diagnosis.

Cell Block Method: An Imperative Tool for Cytological Diagnosis of Oral Potentially Malignant Lesions

Globally, oral squamous cell carcinoma (OSCC) is one of the commonest reported malignancies usually arising from oral potentially malignant lesions (OPMLs) such as leukoplakia, erythroplakia, oral submucous fibrosis (OSMF) and oral lichen planus (OLP). Hence timely and early diagnosis of these disorders is of prime importance to halt their malignant transformation. A search of published works was done using the online databases of PubMed, Scopus, Web of Science, and Cochrane Library”. Data from resource-constrained laboratory settings worldwide shows limited documentation of the efficacy of advanced cytological techniques, including LBC and cell block preparations. The oral mucosa can be a suitable area for regular cytological screening due to its easy accessibility. Liquid-based cytology (LBC) can preserve the cellular details and reduce the overlapping of cells, enabling precise interpretation, reducing false-negative results and aiding in the diagnosis of premalignant and malignant lesions of the oral cavity with more accuracy compared to exfoliative cytology. The remaining sample in LBC can be used in cell block formation and various ancillary tests like immunocytochemistry, immunofluorescence, and molecular studies. Literature showed a scarcity of data available regarding Pakistan. Therefore, the review is aimed to explore the cell block method as a minimally invasive technique for reducing morbidity and mortality associated with OSCC. Keywords: Cell Biology; Oral Squamous Cell Carcinoma; Malignancy.

Small cell carcinoma of the urinary bladder: Distinctive cytological characteristics and Cyto-histologic correlation

Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has not been described in detail in the literature. A 79-year old male presented at our institution with gross hematuria. He was accurately diagnosed with small cell carcinoma of the bladder on liquid-based cytology in urine. The patient subsequently proceeded to transurethral resection of the bladder tumor, confirming the diagnosis. In this article, we present a detailed report of primary urothelial carcinoma with dominant neuroendocrine differentiation of the bladder describing the cytologic and histologic morphologic features, its differential diagnosis with a review of the literature.

HIGH RISK HPV DETECTION IN PRECURSOR LESIONS OF CERVIX USING LBC SAMPLES.

Background: Liquid-based cytology (LBC) was developed as an alternative to conventional cytology screening to improve specimen adequacy and sensitivity in detecting cervical abnormalities. High risk HPV (HR HPV) types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. Objectives: This study aimed (1) to compare the diagnostic efciency of liquid based cytology LBC and conventional tests in detecting cervical dysplasia and (2) detection of high risk HR HPV types 16 and 18 in cervical precursor lesions using liquid based cytology samples. Methods: A prospective comparative study was conducted from the year August 2014 – February 2019 at Basavatarakam Indoamerican Cancer Hospital and Research Institute, Hyderbad.A total of 200 women undergoing screening for cervical cancer were included in the study. HR-HPV 16 &amp; 18 detection was done by Nested Multiplex Polymerase Chain Reaction (NMPCR). Results: The area under the ROC curve for conventional Pap smear was 0.725 and LBC was 0.974, showing that the diagnostic accuracy of LBC method in diagnosing precursor lesions and carcinoma of cervix is better than the conventional Pap smear method. HR-HPV 16/18 were positive in 43/102 (42.2%) of cases. HPV 16 alone was positive in 32/43(74.4%), HPV 18 alone in 6/43 (13.9%) and both HPV-16 and HPV-18 were positive in 5/43 (11.6%) of the total HR-HPV positive cases. Conclusion: The detection rate of epithelial abnormalities and infections in LBC preparation was better than CPS. LBC samples can be used for HR-HPV genotype detection to explore new paradigms of screening strategies.

A Rapid Cytological Screening as pre-Endoscopy Screening for Early Esophageal Squamous Cell Lesions: A Prospective Pilot Study from a Chinese Academic Center.

Background: Cytological detection of early esophageal squamous cell carcinoma (ESCC) remains challenging. Therefore, we introduced a rapid cytological screening method and evaluated its efficacy as a pre-endoscopy screening for early ESCC and precursor lesions. Methods: This method consisted of a sponge sample retrieval, automatic liquid-based cytological treatment and slides preparation, computer-assisted screening and manual diagnosis. Efficacy for detection of early ESCC and precursor lesions was evaluated. Also, diagnostic efficiency was compared with manual diagnosis. Results: Eighty-three patients with early ESCC and precursor lesions and 2,090 asymptomatic participants with high risks of ESCC were enrolled. Whole procedure was accomplished within two working days. Abnormal cells were detected in all 83 patients, and in 272 (13.01%) subjects among 2,090 asymptomatic participants. Early ESCC, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia and reflux esophagitis and normal endoscopic findings were detected in 8, 13, 11, 187 and 53 participants with abnormal cells, respectively. The calculated sensitivity, specificity, positive predictive value and negative predictive value for detection of early ESCC and precursor lesions were 100%, 88.34%, 11.76%, and 100%, respectively. Compared with manual diagnosis, this method was accomplished in a shorter time duration (5.4 ± 0.45 min vs 320.2 ± 132.4 min, p < 0.001), a higher diagnostic accuracy (96.7% vs74.4%, p = 0.015) and a better inter-observer agreement (93.3% vs66.7%, K = 0.286, p < 0.001). Conclusions: Our study provides a promising methodology as pre-endoscopy screening for early ESCC and precursor lesions.

Comparison of Conventional Smear and Liquid-Based Cytology in Adequacy of Thyroid Fine-Needle Aspiration Biopsies without an Accompanying Cytopathologist.

ObjectivesIn this study, we aimed to compare the adequacy of conventional smear (CS) and liquid-based cytology (LBC) methods in thyroid fine-needle aspiration biopsy (FNAB) samples obtained without an accompanying cytopathologist during the procedure. Furthermore, we aimed to investigate the presence of a significant difference between the rates of nodules classified as Bethesda Category III and malignancy in both techniques and the features of the nodules affecting malignancy.MethodsA total of 625 nodules from 572 patients who were found suitable for biopsy were included in this retrospective study. FNABs were performed by interventional radiologists without an accompanying cytopathologist during the procedures. The specimens were either prepared using CS or LBC preparation methods. Cytopathological diagnostic adequacy and cytopathological results of the specimens were evaluated according to Bethesda category, and the relationship between the morphological findings was evaluated retrospectively.ResultsOf all the biopsy preparations, 338 (54.1%) of them were transferred to pathology in liquid-based solution and 287 (45.9%) were transferred as CS. Malignancy rates of the biopsy samples were found similar in both LBC and CS methods. Considering the nodules classified as Bethesda Category II, III, IV, V, and VI, there was no statistical difference between the results of both methods. Non-diagnostic biopsy rate was higher in the specimens prepared by CS method (p<0.001).ConclusionIn this study, the adequacy rate of FNAB was found significantly higher in LBC method compared to the CS method. LBC was more practical and faster than the CS method. We think that LBC method may be preferred in FNAB of thyroid nodules.

Comparative analysis of cytomorphology of thyroid lesion on conventional cytology versus liquid-based cytology and categorize the lesions according to The Bethesda System for Reporting Thyroid Cytopathology.

Thyroid nodules are a common disorder of the thyroid. Most of these are benign and only 5%-30% are malignant. Fine-needle aspiration cytology (FNAC) plays a vital role in differentiating benign from malignant and hence directing toward timely intervention. Liquid-based cytology (LBC) has been recently started in sampling thyroid lesions and has shown good results. The aim of our study was to compare the cytomorphology of thyroid lesions by conventional smear (CS) and LBC method and categorize the lesions according to TBSRTC (The Bethesda System for Reporting Thyroid Cytopathology). A prospective study was conducted from January 2018 to June 2019 on 131 patients. Thyroid FNAC samples were taken to prepare 2-5 slides for conventional reporting and one sample for LBC preparation by SurePath method. Staining with hematoxylin and eosin, May-Grünwald-Giemsa, and Papanicolaou stain was done. Cases were reported by TBSRTC and compared. The nonneoplastic lesions constituted the major proportion on both CS (83.2%) and LBC (73.2%). The neoplastic lesions constituted only 9.9% of all the diagnosis both on CS and LBC smear. The kappa agreement between CS and LBC cytology as per The Bethesda System for Reporting Thyroid Cytopathology came out to be 0.715, which was statistically significant. Colloid appearance was statistically significant on comparison by both methods. The comparison of ill formed epithelioid granulomas was statistically significant in autoimmune thyroiditis cases. In malignancy cases, nuclear and cytoplasmic details were crisper on CS. Cytoplasm appeared fragile and fragmented on LBC smears.

Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study

Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P< .0001). The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Morphological Differences between Liquid-Based Cytology and Conventional Preparation in Endometrial Endometrioid Carcinoma Grade 1 and Grade 3, and the Differentiation of Grades in Each Method

Introduction: Direct smearing preparation (conventional preparation [CP]) has been widely used for endometrial cytology in Japan. In CP, sampling and screening errors are problematic. In liquid-based cytology preparation (LBC), the problems of CP can be solved. But there is a problem that cytological findings of LBC are different from those of CP. The purpose of this study was to evaluate the differences of morphological findings of endometrial cytology between LBC and CP, and the usefulness of the endometrial LBC to differentiate endometrioid carcinoma grade 1 (G1) from grade 3 (G3). Methods: Thirteen cases of endometrioid carcinoma G1, and 5 cases of G3 collected by the Softcyte device and prepared by LBC and CP (split specimen) were used. We focused on the following items: (1) the number of clusters per cm², (2) the number of layers of clusters, (3) area of clusters, (4) perimeter of clusters, (5) roundness of clusters, (6) complexity of clusters, (7) area of nucleus, (8) perimeter of nucleus, (9) roundness of nucleus, (10) complexity of nucleus, (11) area of nucleolus, and (12) nucleolus-nucleus ratio (N/N). Results: Compared with CP, the number of clusters and layers of the clusters in LBC were significantly larger in G1. The area and perimeters of the clusters and the nucleus were significant smaller, and the N/N ratio was greater in LBC than that in CP in both G1 and G3. Regarding morphological differences between G1 and G3 in LBC and CP, the number of layers was significantly larger in G1 than in G3 in LBC and CP. The area of the clusters in LBC was significantly larger in G1 than in G3. The area and perimeters of the nucleus in CP and the area of the nucleolus and N/N ratio in LBC and CP were significantly smaller in G1 than in G3. Conclusion: In the endometrial cytology, it became clear that the cell image was different between LBC and CP and between G1 and G3. By microscopic examination understanding the characteristics of the cell image in LBC, endometrial LBC could be useful to diagnose endometrial carcinoma.

Should Liquid Based Cytology (LBC) be Applied to Thyroid Fine Needle Aspiration Cytology Samples?: Comparative Analysis of Conventional and LBC Smears.

Context:Liquid-based cytology (LBC) is a cyto-preparatory technique that may be applied to fine-needle aspiration (FNA) samples. However, its efficacy over conventional smears (CS) in thyroid is controversial.Aims:The aim of this study was to compare CS versus LBC (SurePath, BD) preparations in thyroid FNA samples for diagnostic efficacy.Settings and Design:Prospective case-control study using split sample analysis in 200 non-consecutive cases of thyroid FNA reported as per the Bethesda system.Methods and Material:Detailed cytomorphological features were evaluated in CS and LBC preparations. Cellularity was scored as 0–3. Based on diagnostic efficacy, they were categorized into three groups:(i) CS and LBC equivalent for diagnosis, (ii) CS better than LBC, and (iii) LBC better than CS for providing the diagnosis.Statistical Analysis Used:Paired t test for cellularity scores and descriptive for diagnostic efficacy.Results:There were 7 unsatisfactory, 118 benign, 10 atypia or follicular lesion of undetermined significance, 25 follicular neoplasms, 6 suspicious for malignancy, and 34 malignant thyroid FNA cases based on routine conventional smears. Cellularity of conventional smears was significantly higher than paired LBC smears (paired t test, P < 0.005). Comparison of overall diagnostic efficacy showed that LBC and CS were equivalent in 59% of cases; CS was superior to LBC in 37% cases and LBC was better than CS in 4% cases only. LBC smears showed higher unsatisfactory rate as compared to CS (18% vs. 3.5%). In category 2, the two techniques were equivalent in 87% of cases. In categories 4 and 6, CS were superior to LBC.Conclusions:In thyroid FNA cases, conventional smears are superior to LBC preparation in terms of cellularity and diagnostic efficacy and hence, LBC preparations should not replace conventional smears for making a routine cytomorphological diagnosis.

How to obtain adequate biopsy specımen in suspected thymic tumors.

Pathologic diagnosis of thymic tumors (TTs) can be made by surgical or nonsurgical procedures. About 20% of TTs had been diagnosed by pretreatment biopsy methods while the rest had gone to surgery for diagnosis and treatment. However, in the last two decades there was an increase in pretreatment procedures for optimal management of locally advanced or metastatic TTs. Pretreatment tissue diagnosis of a noninvasive TT is not a standard option but is required if there is suspect or atypical clinical presentation and imaging, an invasive tumor requiring a nonsurgical approach or preoperative chemotherapy or chemo-radiotherapy, strong possibility of lymphoma or unclear differential diagnosis between lymphoma or other solid tumor by imaging studies, or suspicion of a metastatic lesion. In surgical diagnosis anterior mediastinotomy, video-assisted thoracic surgery or mediastinoscopy can be chosen for invasive TTs whereas total resection is performed for small, noninvasive tumors. Nonsurgical diagnosis can be made by transthoracic fine or core needle biopsies (TTFNA, TTCNB), conventional bronchoscopy, endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA), endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or medical thoracoscopy depending on procedural amenability according to tumor extension. TTFNA and TTCNB have been the most frequently used nonsurgical methods. However, there is an upward trend in using conventional bronchoscopy, EBUS-TBNA, EUS-FNA and medical thoracoscopy recently. To increase the diagnostic performance of these procedures in TTs, recommendations are (I) obtaining histologic specimens, (II) combining smears or liquid based cytology preparations and cell blocks, (III) obtaining multiple sufficient samples, (IV) combining histologic and cytologic specimens, (V) performing morphologic, immunohistochemical and molecular analyses on all specimens, (VI) using rapid onsite evaluation for cytologic specimens, (VII) correlating pathologic, clinical and radiologic findings, (VIII) consulting experienced pathologists.