Accuracy of ultrasound-guided fine-needle aspiration cytology in evaluation of thyroid nodules using different ultrasonographic and cytological features.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy. METHODS: We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015-2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis. RESULTS: The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%. CONCLUSION: Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid.

A cytodiagnosis of adenoid cystic carcinoma of the tracheobronchial tree through a systematic clinical case comparison and analysis.

BACKGROUND: Primary adenoid cystic carcinoma (AdCC) of the tracheobronchial tree is very rare with a high risk for recurrence and metastasis. The diagnosis of AdCC by histologic and immunohistochemical means has been well studied clinically. However, the identification of AdCC by cytologic features remains elusive due to the atypical features the cancer presents. This study aimed to describe the cytologic features of AdCC by using bronchial brushing, which could aid in distinguishing AdCC from other pulmonary carcinomas. METHODS: The cytopathological features of bronchial brushing smears collected from seven cases were histologically diagnosed as AdCC. The defined cytologic features, which could potentially be diagnostic, were systemically analyzed. RESULTS: Four out of the seven cytologic cases were inconcordance with the histologic diagnosis and cytologically classified as positive for malignant cells, small cell carcinoma, or atypical cells. Three cases showed a characteristic adenoid structure and magenta stroma forming globule, which was distinguished from the four cases. Cytologically, the above mentioned three cases were uniform with relatively small bland nuclei and little cytoplasm. In this study, only one case showed atypical polygonal medium-sized cells with conspicuous nucleoli. CONCLUSIONS: Unlike fine-needle aspiration cytology, magenta stroma globules might offer an alternate clue for cytodiagnosis of AdCC clinically. Bronchial brushings cytology was more present in bland uniform cells with high nuclear to cytoplasmic ratios and background mucoid substance. More cases should be collected and confirmed using histopathology with careful film reading to reduce the rate of misdiagnosis.

[Indications for fine-needle aspiration and core needle biopsy for diagnosis of salivary gland tumors]. / Indikation der Feinnadelpunktion und Grobnadelbiospie zur Diagnostik von Speicheldrüsentumoren.

BACKGROUND: Salivary gland malignancies are rare neoplasms of the head and neck area. Preoperative clinical and imaging assessment of salivary gland masses is challenging. However, preoperative identification of malignancy is crucial for further treatment and for the course of the disease. OBJECTIVE: This article presents the advantages and disadvantages of fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB). Additionally, the sensitivity and specificity of both methods for predicting malignancy were analyzed. Furthermore, it is discussed which procedure is suitable for the diagnostic work-up of salivary gland tumors. MATERIALS AND METHODS: This current article summarizes important and recent studies in the field of the diagnostic work-up for salivary gland lesions, with discussion of original articles, metanalyses, and systematic reviews concerning FNAC and CNB. RESULTS: The sensitivity and specificity of the predictive ability of FNAC for malignancy is described at between 70.0-80.0% and 87.5-97.9%. The pooled sensitivity and specificity for CNB were 92.0-98.0% and 95.0-100.0%, respectively. Tumor cell seeding or facial nerve palsy are very rare complications of both procedures. CONCLUSION: If malignancy is suspected based on clinical examination or imaging, FNAC or CNB should be performed. FNAC is easy to perform; however, an onsite cytologist is necessary. CNB has a higher sensitivity for routine diagnosis of malignancy; tumor typing and grading is facilitated by preserving the histological architecture. In conclusion, CNB is the procedure of choice in the diagnostic work-up for suspected malignant salivary gland tumors.

[Cytology of body cavity fluids - established methods and new developments]. / Zytologie der Körperhöhlenergüsse ­ Bewährtes und neue Entwicklungen.

BACKGROUND: Body cavity fluids are among the most frequently examined samples in cytology. Cytomorphology is supplemented by additive testing. An international system of terminology and classification has been recently presented. OBJECTIVES: Cytopreparation and staining techniques as well as some exemplary morphological patterns are presented. "The International System for Serous Fluid Cytopathology" (TIS) is briefly presented. MATERIALS AND METHODS: Pleural effusion, pericardial effusion, and ascites: special technical issues, immunocytochemistry, molecular diagnostics, and reporting system issues are discussed. RESULTS: Body cavity fluids are important samples that provide significant information. Additive testing is established for routine use. The form and structure of reports is widely divergent in practical use. DISCUSSION: A reporting system for serous fluid cytopathology that is easily applied and recognized internationally is highly desirable. TIS is a valuable approach to this goal.

[New aspects in fine needle biopsies of the lymph nodes]. / Neue Aspekte zur Feinnadelpunktion von Lymphknoten.

BACKGROUND: The cytology of lymph nodes is a cost-effective method with a short turnaround time and low risk to patients that delivers valuable information on the cause of the lymphadenopathies. OBJECTIVES: To discuss the value of lymph node cytology in the diagnosis of lymph node swellings. METHODS: Analysis of the causes of the controversially discussed aspects of lymph node cytology. Presentation of the diagnostic groups of lymph node cytology according to the Sydney system. RESULTS: The technical aspects of lymph node sampling during fine needle biopsy, as well as the subsequent preparation of the correctly fixed direct smears and the triage of the sample for the auxiliary studies, may pose a significant challenge for some puncturers. The whole spectrum of modern pathologic auxiliary studies can be applied to correctly triaged cytologic samples. The diagnoses of fine needle biopsies of the lymph nodes can be divided into five groups according to the recently proposed Sydney reporting system: insufficient/non-diagnostic, benign, atypical, suspicious, and malignant. Further details concerning the diagnosis as well as recommendations on how to proceed are additionally included in cytologic reports. CONCLUSIONS: The improvement of lymph node sampling as well as the technical aspects of the sample handling, including the application of auxiliary studies, considerably increase the diagnostic value of fine needle biopsy of the lymph nodes. Wide implementation of the usage of the diagnostic groups for reporting fine needle biopsies of the lymph nodes can standardize reporting and improve communication with other clinical specialists.

Identification of Molecular Basis for Objective Discrimination of Breast Cancer Cells (MCF-7) from Normal Human Mammary Epithelial Cells by Raman Microspectroscopy and Multivariate Curve Resolution Analysis.

Raman spectroscopy (RS), a non-invasive and label-free method, has been suggested to improve accuracy of cytological and even histopathological diagnosis. To our knowledge, this novel technique tends to be employed without concrete knowledge of molecular changes in cells. Therefore, identification of Raman spectral markers for objective diagnosis is necessary for universal adoption of RS. As a model study, we investigated human mammary epithelial cells (HMEpC) and breast cancer cells (MCF-7) by RS and employed various multivariate analyses (MA) including principal components analysis (PCA), linear discriminant analysis (LDA), and support vector machine (SVM) to estimate diagnostic accuracy. Furthermore, to elucidate the underlying molecular changes in cancer cells, we utilized multivariate curve resolution analysis-alternating least squares (MCR-ALS) with non-negative constraints to extract physically meaningful spectra from complex cellular data. Unsupervised PCA and supervised MA, such as LDA and SVM, classified HMEpC and MCF-7 fairly well with high accuracy but without revealing molecular basis. Employing MCR-ALS analysis we identified five pure biomolecular spectra comprising DNA, proteins and three independent unsaturated lipid components. Relative abundance of lipid 1 seems to be strictly regulated between the two groups of cells and could be the basis for excellent discrimination by chemometrics-assisted RS. It was unambiguously assigned to linoleate rich glyceride and therefore serves as a Raman spectral marker for reliable diagnosis. This study successfully identified Raman spectral markers and demonstrated the potential of RS to become an excellent cytodiagnostic tool that can both accurately and objectively discriminates breast cancer from normal cells.

Chromosomal analyses of human giant diploid oocytes by next-generation sequencing.

PURPOSE: Although giant oocytes (GOs) having about twice cytoplasmic volume compared with general oocytes in mammals including the human are rarely recovered, it is thought that GOs have potentially chromosomal abnormalities. The aim of the present study was to assess chromosome numbers in chromosome-spindle complexes (CSCs) and polar bodies of human GOs by using micromanipulation for sampling and next-generation sequencing (NGS) for analyses of the chromosome numbers. METHODS: When recovered oocytes whose cytoplasm has lager than 140 µm or above, the oocytes were defined as GOs, and recovered GOs were vitrified. After warming, the CSCs, polar bodies, and enucleated cytoplasm were collected by micromanipulation from 3 GOs. The collected samples were analyzed by NGS. RESULTS: Chromosomal aneuploidy in the GOs was confirmed in all the three GOs. Comparing the CSCs with the chromosomes from polar bodies, the deletion and overlapping chromosome numbers were complementary in each GO. CONCLUSIONS: The authors could collect the CSCs and the polar bodies from human GOs by micromanipulation, and then could analyze the chromosome numbers of the GOs by NGS method. As our data suggest that human GOs have chromosomal abnormalities, GOs should be excluded from clinical purpose as gamete sources for embryo transfer in the human.

Improving our departmental reporting of thyroid cytology specimens against national guidelines: A two-cycle retrospective audit.

INTRODUCTION: In the UK, guidelines from the Royal College of Pathologists (RCPath) facilitate consistent and reproducible reporting and classification of fine needle aspiration cytology (FNAC) thyroid specimens. The aim was to audit our department against RCPath guidelines to refine and improve our reporting process. METHODS: Two-cycle retrospective observational audit of all patients undergoing thyroid FNAC over a 2-year period (1 year for each cycle). Final histology was correlated. The positive predictive value (PPV) for malignant neoplastic lesions was calculated; for Thy1, Thy1c, Thy2 and Thy2c all cases without final histology were assumed to be benign, while for Thy3a, Thy3f, Thy4 and Thy5 samples the PPV calculation was based only on those cytology samples with corresponding histology. False positive and false negative cases were reviewed. RESULTS: In total, 288 cytology samples were included in the first cycle; 96 (33.3%) had corresponding histology. There were 287 samples included in the second cycle; 119 (41.5%) had follow-up histology. The rate of non-diagnostic samples (Thy1/1c) decreased from 39.6% to 30.0%. The PPV for malignant neoplastic lesions was Thy1/1c 2.6%, Thy2/2c 0.0%, Thy3a 40.0%, Thy3f 19.4%, Thy4 75.0%, Thy5 100.0% (first cycle); Thy1/1c 4.7%, Thy2/2c 0.7%, Thy3a 13.3%, Thy3f, 7.7%, Thy4, 50.0%, Thy5 100.0% (second cycle). CONCLUSIONS: Our department was able to reduce the rate of non-diagnostic FNAC samples and improve the diagnostic accuracy of FNAC. Auditing local outcomes helps refine and improve the reporting process. Review of false positive and false negative cases helps examine potential pitfalls of cytology.

[Molecular diagnostics of cytological specimens]. / Molekularpathologische Diagnostik an zytologischen Präparaten.

For lung carcinomas with certain molecular genetic alterations of the ALK, BRAF or EGFR gene, there are targeted therapies that are also approved as first-line therapy. Often, only limited sample material from biopsies is available for molecular pathological testing. In some cases, biopsies with standard and immunohistochemical staining have no or too low tumor content to be used for PCR-based examinations or fluorescence in situ hybridization (FISH) analyses. In such cases, cytological preparations such as bronchus brush smears, transbronchial needle aspiration (TBNA), bronchial lavage, puncture smears from lymph node or peripheral metastases, pleural effusion, ascites, and pericardial effusion can be used. Standard stainings such as HE, Pappenheim, and Papanicolaou as well as immunohistological preparations can be used after morphological analysis and confirmatory diagnosis in order to extract DNA from them or to use them for FISH analysis. A cytopathologist marks the tumor cell areas on the slide beforehand. It is only possible to dissect these areas and extract DNA if the proportion of tumor cells is sufficiently high. In order to carry out a FISH analysis with the cytological preparations, the cytopathologist must draw in areas as small as possible with more than 100 tumor cells. Already stained sections are destained before the hybridization reaction. The aim is to achieve comprehensive diagnostics even with limited starting material and to avoid re-biopsies. Between 2016 and July 2019, 1711 next generation sequencing (NGS) and FISH analyses were performed on cytological preparations at the Department of Pathology of the University Hospital of Cologne. The success rate of 85.9% for NGS examinations was slightly higher than the success rate of 82.8% for FISH analyses.

[Liquid biopsy-a possible key player in immuno-oncology]. / "Liquid biopsy" als Schlüsselfigur in der Immunonkologie.

BACKGROUND: Clinical application of immune checkpoint inhibitors (ICI), whether as monotherapy or in combination with established methods, is revolutionizing treatment of head and neck cancer. However, this change in therapeutic concepts requires reevaluation and further development of predictive and prognostic markers, since the survival rates for advanced and particularly human papillomavirus (HPV)-negative disease remain poor. MATERIALS AND METHODS: A selective literature review was performed in PubMed. Literature found with the keywords "cytodiagnostics, circulating tumor cells, liquid biopsy, cfDNA, exosomes" in combination with "head and neck cancer" and/or "immune checkpoint inhibitor therapy" published until March 2020 was included. The articles were selected for their relevance for the current study by the authors. RESULTS: This work provides a review of the current literature and indicates possible applications in the field of head and neck cancers. Liquid biopsy refers to the analysis of circulating tumor cells or of tumor genetic material in body fluids. This minimally invasive analysis can support therapeutic decisions and enable a personalized approach to treating head and neck cancer. DISCUSSION: Before any of these approaches can be established in clinical routine, long-term data and standardization of the methods for isolating and analyzing the markers are needed.

Evaluation of Region of Interest Digital Cytology Compared to Light Microscopy for Veterinary Medicine.

Digital microscopy (DM) has been employed for primary diagnosis in human medicine and for research and teaching applications in veterinary medicine, but there are few veterinary DM validation studies. Region of interest (ROI) digital cytology is a subset of DM that uses image-stitching software to create a low-magnification image of a slide, then selected ROI at higher magnification, and stitches the images into a relatively small file of the embedded magnifications. This study evaluated the concordance of ROI-DM compared to traditional light microscopy (LM) between 2 blinded clinical pathologists. Sixty canine and feline cytology samples from a variety of anatomic sites, including 31 cases of malignant neoplasia, 15 cases of hyperplastic or benign neoplastic lesions, and 14 infectious/inflammatory lesions, were evaluated. Two separate nonblinded adjudicating clinical pathologists evaluated the reports and diagnoses and scored each paired case as fully concordant, partially concordant, or discordant. The average overall concordance (full and partial concordance) for both pathologists was 92%. Full concordance was significantly higher for malignant lesions than benign. For the 40 neoplastic lesions, ROI-DM and LM agreed on general category of tumor type in 78 of 80 cases (98%). ROI-DM cytology showed robust concordance with the current gold standard of LM cytology and is potentially a viable alternative to current LM cytology techniques.

Malignancy risk with atypia of undetermined significance finding on thyroid nodule FNA: clinical experience from a tertiary institution.

The Bethesda System for Reporting Thyroid Cytopathology from 2009 introduced a new category in thyroid nodule fine-needle aspiration (FNA) findings named atypia of undetermined significance (AUS), which usually appears in around 5% of FNA findings. Our study aimed to assess the utility of AUS finding in determining the risk of malignancy in thyroid nodules. In our study, 160 patients with AUS finding on initial FNA were regularly followed-up. Total and specific malignancy rates were calculated after receiving histopathologic confirmation or histopathologic/cytologic exclusion of malignancy. Eventually 80 (50%) patients were referred to surgery, with malignancy rate of 37.5% on histopathology. Another 52 (32.5%) patients were confirmed to have benign nodules on repeat FNA. After combining results obtained from histopathologic reports with those obtained from cytologic follow-up, total malignancy rate was 22.72%. However, malignancy was confirmed in only one (5.26%) of 19 patients with AUS finding on repeat FNA with surgical and histopathologic follow-up. In conclusion, FNA is an extremely useful tool for clinicians to discriminate patients to be referred to surgery and those that can be followed-up safely without the need for further invasive procedures.

Effect of HIV infection in the micronuclei frequency on the oral mucosa.

BACKGROUND: The genotoxic impact of HIV infection on the oral cavity malignancies is unknown. The aim of this study was to evaluate the effect of HIV infection in micronucleus (MN) frequency on the oral mucosa of HIV+ patients and establish a relationship with early cytogenetic changes in oral carcinogenesis. METHODS: Thirty HIV+ individuals who are under highly active antiretroviral therapy (HAART) and 30 non-HIV patients were evaluated. Two smears were taken from the lateral border of the tongue and mouth floor and stained by Feulgen. The frequency of MN was examined in 3000 cells per subject under common microscopy. RESULTS: MN analysis showed no significant difference between groups by Mann-Whitney U-test for total MNs (P = 0.178). The presence of single MN was greater in control group with statistical significance (P = 0.009), while in HIV group, multiple MNs were exhibited in higher mean. CONCLUSIONS: HIV patients under HAART therapy and low viral load values showed higher frequency of multiple MNs, which, although not statistically significant, may be caused by the action of the Vpr gene, an accessory gene of HIV. These results corroborate the theory of HIV infection cytogenetic damage.

[Study on clinical management of HPV(+)/Pap(-) during cervical cancer screening].

Objective: To study the clinical management way for HPV(+)/papanicolaou (Pap)(-) during cervical cancer screening. Methods: To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN) Ⅱ in Peking University People's Hospital from Jan. 2010 to Dec. 2014. Results: (1) For biopsy confirmed CIN Ⅱ, HPV positive rate was 98.5% (135/137), Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137), there was significant difference between them (χ(2)=43.32, P<0.01). (2) For the 42 patients with HPV(+)/Pap(-), whose cytology slides were reviewed again. Among them, the interpretations of there were 16 cases confirmed as the same before, while 26 cases were changed to abnormal (≥ASCUS). Cytology be misdiagnosed was 19.0% (26/137) at the first review. Among the 26 cases, 13 (50.0%) cases were missed for the little amount of abnormal cells, 8 (30.8%) cases for mild atypical morphology changed; the other 5 (19.2%) cases missed for stain problems. (3) For the cervical LEEP samples, 37 cases of the pathology diagnosis were upgrade to CIN Ⅲ(+), among them, 2 cases of microinvasive cervical carcinoma, 1 case of invasive cancer, 34 cases of CIN Ⅲ; 37 cases were CINⅠ or no lesion found; 63 cases were still CIN Ⅱ. Four to six months later after LEEP, the cytology abnormal rate was 11.7% (16/137), and the HR-HPV positive rate was 34.3% (47/137). Conclusions: Compared with cytology alone, cytology combined with HPV testing increase the sensitivity of cervical high grade lesion. For the cases of HPV(+)/Pap(-) cases, the cytology slides should be reviewed. The quality control of cervical exfoliate sample collection and interpretation should be strengthened. LEEP procedure is not only a treatment method, but also it could provide samples to confirm the diagnosis.

[Significance of p16/Ki-67 double immunocytochemical staining in cervical cytology ASCUS, LSIL, and ASC-H].

Objective: To investigate the application value of p16/cell proliferation associated nuclear antigen (Ki-67) double-staining and human papillomavirus mRNA in the cytological screening. Methods: Two hundred and fifty-one cases who suffered from atypical squamous cell of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cell-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in ThinPrep cytologic test (TCT) were collected in Peking University First Hospital between October 2015 and March 2016. And p16/Ki-67 double-staining and hybrid capture Ⅱ (HC-Ⅱ) detection were performed on the cervical cells. The result was compared with the pathological result of colposcope guided biopsy. All statistical analysis was completed by Stata 12.0 statistical software analysis. The results of diagnostic tests were described by using the sensitivity, specificity, positive predictive value,negative predictive value, and the area under the receiver operating characteristic (ROC) curve. Results: (1) One hundred and eight cases of liquid based cytology diagnosis of ASCUS patients, the positive rate of p16/Ki-67 was 13.9% (15/108), 102 cases of liquid based cytology diagnosis of LSIL patients, the positive rate of p16/Ki-67 was 21.6% (22/102), 41 cases of liquid based cytology diagnosis of ASC-H patients, the positive rate of p16/Ki-67 was 39.0% (16/41), compared amongthree groups, the difference was statistically significant (χ(2)=78.516, P<0.05); cervical exfoliated cells p16/Ki-67 expression rate was 13.0%(28/215) in cervical low-grade lesions [cervical intraepithelial neoplasia (CIN) Ⅰ], which was 69.4%(25/36) in high level lesions (CIN Ⅱ-Ⅲ), the difference was statistically significant (χ(2)=7.932, P<0.05). (2) The specificity of p16/Ki-67 detection and diagnosis were higher than those of HC-Ⅱ in ASCUS, LSIL, and ASC-H (89.8% vs 71.4%, 83.3% vs 15.6%, 88.9% vs 40.7%; all P<0.05), meanwhile, the positive predictive value of p16/Ki-67 detection and diagnosis exceed those of HC-Ⅱ in ASCUS, LSIL, and ASC-H (33.3% vs 26.3%, 31.8% vs 12.6%, 81.3% vs 38.5%; all P<0.05). Moreover, the ROC curve of p16/Ki-67 were bigger than those of HC-Ⅱ in ASCUS, LSIL, and ASC-H (0.799 vs 0.696, 0.708 vs 0.531, 0.909 vs 0.561; all P<0.05). Conclusion: For patients with cytological diagnosis of ASCUS, LSIL, and ASC-H, p16/Ki-67 double staining method could be used as an effective method to assist in the diagnosis of high-grade cervical lesions, and the screening efficiency is superior to that of high-rist HPV.

The utility of molecular markers in pre-operative assessment of thyroid nodules.

The pre-operative diagnosis of thyroid tumors is determined by gold standard fine needle aspiration (FNA) biopsy. This has been widely accepted and offers the most cost-effective approach for evaluation of thyroid nodules. However, its diagnostic accuracy can pose a challenging scenario to surgeons. These diagnostic difficulties may subject patients to unnecessary thyroidectomies for benign thyroid nodules. Thus, additional molecular tests are needed to improve the sensitivity and specificity of FNA. The role of molecular markers is being proposed to predict the type and risk of malignancy to abate the need for diagnostic thyroidectomies. This review discusses their utility and validity in pre-operative diagnosis of thyroid nodules and how these markers can enhance the accuracy of FNA cytology.

A systematic approach to assess the strengths and limitations of cytomorphology in the diagnosis of the follicular variant of papillary thyroid carcinoma.

OBJECTIVE: To identify the most useful cytomorphological features of follicular variant of papillary thyroid carcinoma (FVPTC). METHODS: Fine needle aspiration cytological features of seven histologically proven FVPTCs were systematically evaluated in a blinded manner for various architectural, nuclear, cytoplasmic and background features with special reference to nuclear morphology. RESULTS: Most smears were moderate to highly cellular with clustered and/or repetitive microfollicles, rare macrofollicles and minimal thick gummy colloid. Six of seven cases showed significant nuclear crowding/overlapping. Fairly uniform nucleomegaly (mostly three to five times the size of a mature lymphocyte) of intact neoplastic cells and enlarged naked nuclei were prominent features in all seven cases, whereas enlarged ovoid nuclei were seen in two cases. Chromatin was fine to coarsely granular and evenly distributed. Occasional nuclear grooves (NGs) and intranuclear cytoplasmic inclusions (INCIs) were seen in five and three cases, respectively. This refined approach led to a precise diagnosis of FVPTC in six cases, which were earlier interpreted as various follicular lesions. Follicular hyperplasia was excluded by the absence of significant amounts of colloid and atretic naked nuclei, whilst the possibility of follicular adenoma or follicular carcinoma was excluded by the presence of one or more features suggestive of papillary thyroid carcinoma. CONCLUSIONS: Our study showed a high cell yield, microfollicular pattern, nuclear overcrowding/overlapping, scanty gummy colloid and enlarged naked nuclei as the most consistent features of FVPTC. Although inconsistent, features such as enlarged ovoid nuclei and syncytial clusters were complementary to the diagnosis in the absence of NGs and INCIs.

The efficacy of bile liquid biopsy in the diagnosis and treatment of biliary tract cancer.

BACKGROUND: Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures. METHODS: A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy. RESULTS: The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p < .001). Among the 43 patients with malignant biliary strictures, mutations with FDA-approved drugs were detected in 11 (26%). CONCLUSIONS: Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets.

Fractal Dimension, Circularity, and Solidity of Cell Clusters in Liquid-Based Endometrial Cytology Are Potentially Useful for Endometrial Cancer Detection and Prognosis Prediction.

Endometrial cancer (EC) in women is increasing globally, necessitating improved diagnostic methods and prognosis prediction. While endometrial histology is the conventional approach, liquid-based endometrial cytology may benefit from novel analytical techniques for cell clusters. A clinical study was conducted at the University of Fukui Hospital from 2012 to 2018, involving 210 patients with endometrial cytology. The liquid-based cytology images were analyzed using cell cluster analysis with Image J software. Logistic regression, ROC analysis, and survival analysis were employed to assess the diagnostic accuracy and prognosis between cell cluster analysis and EC/atypical endometrial hyperplasia (AEH). Circularity and fractal dimension demonstrated significant associations with EC and AEH, regardless of age and cytology results. The ROC analysis revealed improved diagnostic accuracy when combining fractal dimension with cytology, particularly in menopausal age groups. Lower circularity and solidity were independently associated with poor overall survival, while higher fractal dimension values correlated with poorer overall survival in Grades 2 and 3 endometrial cancers. The combination of circularity and fractal dimension with cytology improved diagnostic accuracy for both EC and AEH. Moreover, circularity, solidity, and fractal dimension may serve as prognostic indicators for endometrial cancer, contributing to the development of more refined screening and diagnostic strategies.

Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.