Atypia Of Undetermined Significance Research Articles

The indeterminate categories of the Milan system for reporting salivary gland cytopathology (MRSGC): A minireview

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), first published in 2018, attempted to develop a standardized and objective system of reporting salivary gland fine needle aspiration smears. It was widely accepted by the cytopathologists who started using it in their day-to-day practice. With the publication of new literature, the Milan system was updated and the 2 edition was released in 2023. The 5 WHO classification of salivary neoplasms, ancillary tests, and imaging characteristics of various salivary neoplasms have also been highlighted in the new edition. The 3 indeterminate categories of the Milan system of reporting are the atypia of undetermined significance (AUS), salivary gland tumor of undetermined malignant potential (SUMP), and suspicious for malignancy (SM) that create major dilemmas for the reporting cytopathologists. The present minireview highlights the criteria of diagnosis and further workup of the various lesions in these categories.

A systematic review on performance characteristics of FNA of renal lesions: It is time for a standardized classification system.

The incidence of renal tumors has steadily increased over the past decade. In this study, the authors performed a systematic review and analysis of the literature on renal fine-needle aspiration (FNA) to determine its performance and explore whether a standardized classification system can be used for reporting renal FNA cytology. A systematic search of published articles on renal FNA was conducted. The data on FNA and histologic diagnosis were extracted and categorized, and the risk of malignancy was calculated. Different scenarios were used to estimate FNA performance statistics. Of the 3766 potentially relevant studies, 23 met the inclusion criteria of the study. The 2231 FNA cases included were re-categorized according to the classification system, rendering 142 (6.36%) nondiagnostic, 270 (12.1%) nonneoplastic, 271 (12.14%) benign neoplasm, 65 (2.91%) renal neoplasm with unknown malignant potential, oncocytic type, 25 (1.12%) atypia of undetermined significance, 60 (2.68%) suspicious for malignancy, and 1398 (62.66%) malignant FNA diagnoses. The risk of malignancy in these cases was 65.4%, 18.1%, 16.6%, 16.9%, 60%, 73.3%, and 96.9%, respectively. According to the classification system, the study indicated that the accuracy of renal FNA was between 91% and 95%, the sensitivity was 90.9%-96.7%, and the specificity was 82%-92% in different scenarios. There is a need for a standardized reporting in renal cytology that will improve the sensitivity and accuracy of renal cytology, reduce the rate of indeterminate diagnoses, and alter the management strategies of renal lesions. Based on the available literature, a new reporting system is proposed, including categories with an associated risk of malignancy.

Atypia of Undetermined Significance in Thyroid Fine Needle Aspiration Cytology Revisited

Atypia of Undetermined Significance in Thyroid Fine Needle Aspiration Cytology Revisited

A case of hyalinizing trabecular tumor of the thyroid: diagnostic significance of PAX8-GLIS3 fusion

BackgroundHyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT.Case presentationA 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination. Contrast-enhanced computed tomography scan revealed a solid mass exhibiting slight homogeneous enhancement in the lower pole of the thyroid gland. The mass was diagnosed as atypia of undetermined significance by fine-needle aspiration cytology. The patient underwent left hemithyroidectomy with routine central compartment dissection. Histologic findings revealed tumor cells with elongated nuclei and intranuclear pseudoinclusions arranged with trabeculae architecture or small nests in hyalinized stroma. Weak membranous and cytoplasmic staining was found by MIB1 (Ki-67) immunostaining. The final diagnosis was HTT of the thyroid gland. Next-generation sequencing genetic analysis of a surgical specimen revealed no pathologic mutations, including BRAF, H/K/NRAS, or RET-PTC fusions. The PAX8-GLIS3 fusion was detected by RT-PCR.ConclusionsA rare case of HTT was demonstrated through imaging, cytologic, histologic and molecular investigations. PAX8-GLIS3 fusion detected by RT-PCR and Sanger sequencing was confirmed to be a genetic hallmark of HTT.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey’s test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

The International System for Reporting Serous Fluid Cytopathology: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

This is the first systematic review and meta-analysis of The International System (TIS) for reporting serous fluid cytopathology. Our aims were to present the pooled malignancy rate of each TIS reporting category and the diagnostic accuracy of cytology using this system. Database search using a predefined strategy was followed by study selection, data extraction, study quality assessment, and statistical analysis. Data derived from 16 eligible studies were pooled. The pooled rates of malignancy were as follows: 27% (95% CI; 16%-41%) for "nondiagnostic" (ND), 11% (95% CI; 7%-18%) for negative for malignancy" (NFM), 49% (95% CI; 37%-61%) for "atypia of undetermined significance" (AUS), 90% (95% CI; 81%-95%) for "suspicious for malignancy" (SFM), and 100% (95% CI; 98%-100%) for "positive for malignancy" (MAL). Studies performed exclusively in cancer hospitals showed higher pooled malignancy rates, compared with academic and community hospitals serving the general population, in the ND [40% (95% CI; 21%-62%) vs. 22% (95% CI; 11%-39%)], NFM [20% (95% CI; 13%-30%) vs. 9% (95% CI; 5%-17%)], and AUS categories [55% (95% CI; 47%-63%) vs. 46% (95% CI; 31%-62%)]. Notably, the difference was significant in the NFM category (P=0.04). When both SFM and MAL cytology interpretations were considered as malignant outcomes, the pooled sensitivity and specificity were 68.74% (95% CI; 59.90%-76.39%) and 98.81% (95% CI; 98.18%-99.22%), respectively. In addition, the diagnostic odds ratio (DOR) was found to be 170.7 (95% CI; 96.2-303.3). Despite its strengths, our study also had some limitations. Therefore, future large-scale longitudinal studies could strengthen the findings of this review.

Comparison of ultrasonography findings and fine needle aspiration biopsy results in benign-malign differentiation of thyroid nodules

Aims: The aim of this study was to compare the ultrasonography findings and cytology-histopathology findings of thyroid nodules undergoing a fine needle aspiration biopsy. Methods: The records of patients with thyroid nodules who underwent a fine needle aspiration biopsy between January 2023 and February 2024 in the Radiology Clinic were retrospectively analyzed. Patients with malign, benign, and atypia of undetermined significance on pathology were evaluated. The correlation and concordance between ultrasonography, cytology, and histopathology findings were investigated. Results: A total of 114 patients with biopsy pathology results of 75 (65.7%) benign, 21 (18.4%) malign, and 18 (15.7%) atypia of uncertain significance were evaluated. The study included 87 (76%) female and 27 (24%) male patients. The mean age of all patients was 53.04 years. There was no significant correlation between age, gender, nodule location, and pathology result. The presence of contour irregularity and microcalcification in the nodule was significant for malignancy (p&lt;0.001). Conclusion: Ultrasonography is an effective diagnostic method to differentiate between benign-malign thyroid neoplasms. Ultrasound-guided fine needle aspiration biopsy has a high diagnostic rate. It is helpful in determining the subsequent clinical management option for most patients.

Optimal Volume Assessment for Serous Fluid Cytology.

This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.

Exploring the atypia of undetermined significance: Malignant ratio, ThyroSeq v3 positive call rate, molecular-derived risk of malignancy, and risk of malignancy as possible quality metric tools in thyroid cytology.

The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular-derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback.

Atypia of undetermined significance and ThyroSeq v3-positive call rates as quality control metrics for cytology laboratory performance.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated. A retrospective analysis of all thyroid cytology cases in a 4.5-year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report. A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%-35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%-42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases. The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology.

How the Milan System for Reporting Salivary Gland Cytopathology works in cytopathology practice: Meta-analysis of prospective studies and comparison with retrospective studies.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice. A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program. Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1). This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.

Consistency in the Distribution of Bethesda System for Reporting Thyroid Cytology Categories Over 9 Years: A Single Institute, Retrospective Study

BackgroundThe Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has evolved since it was first introduced in 2009 to become a worldwide accepted cytologic analysis reference, due to its simplicity and reproducibility. To date, the consistency of BSRTC throughout time has yet to be investigated. MethodsRetrospective single institution case series with chart review of all patients who underwent fine-needle aspirations for a thyroid nodule in our institution between the years 2010 and 2018 with a documented BSRTC classification. Data collection included demographics, risk factors, sonographic evaluation, nodule size, and final pathology when feasible. The main outcome is the difference in the rates of BSRTC categories benign, atypia of undetermined significance (AUS), follicular neoplasm, suspicious for malignancy, and malignant (BSRTC II-VI, respectively) between the study years. ResultsA total of 2830 thyroid nodules were included. BSRTC II-VI distribution was 83.9% (2373), 8.2%, (232), 2.7% (75), 3.3% (93), and 2.0% (57), respectively. There was no significant change in the overall trend of each BSRTC category distribution throughout the study. There was a significant increase in the benign cytology rate (BSRTC II) in 2011 compared to 2015 and 2018 (76.4% compared to 88.7% and 87.6%, respectively. P < .005) alongside a significant decline in the AUS category rate (BSRTC III) between the same years (13.0% compared to 4.8% and 5.5%, respectively. P < .005). ConclusionBSRTC showed consistency throughout the study across all observed categories. An overlap between AUS and benign may exist, possibly due to the heterogenic definition of AUS as reflected in the 2023 BSRTC subclassification for AUS.

Thyroid nodules with DICER1 mutation or PTEN alteration: A comparative cytologic, clinical, and molecular study of 117 FNA cases.

DICER1 mutations and PTEN alterations are increasingly detected by thyroid fine-needle aspiration (FNA). Both are associated with nodular thyroid disease and cancer. The authors analyzed a large comparative thyroid FNA cohort with DICER1 mutation or PTEN alteration. A total of 117 thyroid FNAs with DICER1 or PTEN alterations were retrieved from the databases of two academic medical institutions. Demographic, clinical, and radiologic data were collected; FNA slides were analyzed for 29 cytomorphologic features. Of 117 thyroid FNAs, 36 (30.8%) had DICER1 mutation and 81 (69.2%) showed PTEN alteration. The DICER1 cohort had 33 (91.7%) females and three (8.3%) males (mean, 40.9 years); 61.8% had multinodular disease. FNAs were classified as atypia of undetermined significance (AUS), 23 (63.9%); follicular neoplasm (FN), 12 (33.3%); and malignant, 1 (2.8%). The PTEN subgroup had 66 (81.5%) females and 15 (18.5%) males (mean, 55.2 years) with increased multinodular disease (93.8%, p=.0016). PTEN FNAs had greater cytologic diversity: non-diagnostic, 2 (2.5%); benign, 5 (6.2%); AUS, 44 (54.3%); FN, 24 (29.6%); and malignant, 6 (7.4%). Both DICER1 and PTEN cases showed a range of resected tumor subtypes. The DICER1 cohort included thyroblastoma, and the PTEN group included anaplastic carcinoma. The cytomorphology of DICER1 and PTEN cases showed overlapping features, especially microfollicular patterns. Minor cytomorphologic differences included papillary patterns in DICER1 (p=.039), and oncocytic changes (p<.0001) in PTEN. DICER1 and PTEN FNAs reveal many cytologic similarities. DICER1 patients are younger, and PTEN patients had multinodular disease. Awareness of these genetic cohorts can identify patients at risk for thyroid cancer.

Role of Ancillary Techniques in Reporting Serous Fluid Cytology – “Redefining Categories, Refining Diagnosis”

Background: The “International System of Reporting Serous Fluid Cytology (TIS)” together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology. Objective: To classify serous effusion fluid samples received at our department in line with “TIS”, indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing. Materials and Methods: Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to ‘TIS’. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn’t require further assessment. Results: A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%. Conclusion: Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.

Concordance between conventional cytology and cell block of suspected malignant pleural effusion: A record-based study in a tertiary care center of eastern India

Background: Cytological study of pleural fluid helps establishing the underlying cause of pleural effusion. It is considered the most important tool in diagnosing malignancy in effusions. However, accurate identification of cellular morphology can be a problem in conventional cytology. Cell block preparation from pleural effusion aids in this diagnosis due to the preservation of tissue architecture, and multiple sections can be obtained for further studies. Aims and Objectives: The objectives of this study were to compare the diagnostic results of conventional cytology and cell block studies of suspected malignant pleural effusions and find out the diagnostic agreement or concordance between the two methods. Materials and Methods: A record-based study was conducted at the Department of Pathology on conventional cytology and cell block study reports of 150 suspected malignant pleural effusion cases over 35 months. The diagnoses were expressed in five categories – non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. χ2 test was used to identify the percentage of malignancy reported. Agreement of both methods was assessed through Kappa statistics. Results: About 4.67% of cases were reported as malignant by conventional cytology, whereas cell block study diagnosed malignancy in 19.33% of cases. Relative diagnostic agreement between the two methods was 0.73 and concordance by Cohen’s Kappa was 0.34, which signifies fair concordance. Conclusion: Cell block study, though having a fair concordance, is much superior to conventional cytology smears in detecting malignant cells and diagnosing a pleural effusion as malignant.

Comprehensive evaluation of cytomorphologic, histologic, and molecular features of DICER1-altered thyroid lesions on FNA: A multipractice experience.

DICER1 mutations, though infrequent, are encountered on preoperative molecular testing of indeterminate adult and pediatric thyroid fine-needle aspiration (FNA) specimens. Yet, published cytomorphologic features of DICER1-altered thyroid lesions are limited. Cytomorphological features of DICER1-altered thyroid lesions were examined in a multipractice FNA cohort with clinical, radiological, and histologic data. The cohort comprised 18 DICER1-altered thyroid FNAs, with 14 having slides available and eight having corresponding surgical resections. Smears, ThinPrep, and formalin-fixed cell block slides were reviewed and correlated with histology, when available. Clinical and radiologic data were obtained from the medical record. Most DICER1-altered FNAs were classified as atypia of undetermined significance (94.4%). DICER1 mutations occurred in codons 1709 (50%), 1810 (27.8%), and 1813 (22.2%). One patient had an additional DICER1 p.D1822N variant in both of their FNAs. Lesions were often hypoechoic (35.3%) and solid (47.1%) on ultrasound. Notable cytomorphologic features include mixed but prominent microfollicular or crowded component, variable colloid, and insignificant nuclear atypia. On resection (n=10), histologic diagnoses ranged from benign follicular adenoma and low-risk follicular thyroid carcinoma to high-grade follicular-derived nonanaplastic thyroid carcinoma. Subcapsular infarct-type change was the most common histologic change. There was no evidence of recurrence or metastasis in eight patients on limited follow-up. DICER1-altered thyroid lesions occurred frequently in young females and FNAs show RAS-like cytomorphology including crowded, mixed macro-/microfollicular pattern, and bland nuclear features. On resection, DICER1-altered thyroid lesions include benign (50%), low-risk lesions (30%), or high-risk malignancies (20%).

Application of the International System for Reporting Serous Fluid Cytopathology: An Experience at a Tertiary Care Centre in India

Abstract Background: The cytological analysis of body fluids is the preliminary investigation performed for the diagnostic evaluation of body fluids, helping the physician make the diagnosis and plan proper treatment. The International System for Reporting Serous Fluid Cytology (ISFRSFC) was created using best international practises, current literature and expert consensus to make a uniform reporting system for serous fluids. Aims: The present study was conducted with the aim of recategorising the effusion fluids as per the guidelines prescribed by ISRFRC, knowing the distribution of cases into various categories and assessing their feasibility in day-to-day reporting. Patients and Methods: This study was performed on serous fluids (ascitic, pleural, peritoneal and pericardial) received over a period of 5 years, from January 2017 to April 2022, in the cytology unit of the Department of Pathology, ABVIMS, Dr. Ram Manohar Lohia Hospital, New Delhi. Wherever possible, clinicoradiological and histopathological data were obtained and correlated with cytological findings. Serous fluids were categorised into reporting formats as prescribed by ISRFRC and its feasibility was assessed in day-to-day reporting. Results: A total of 1115 cases of serous effusion fluid were examined. The male-to-female ratio was 1:1.12. Pleural fluid constituted the majority of the sample (436, 39.10%). Overall, 56 (5.02%) cases were non-diagnostic (ND), 1013 (90.85%) cases were negative for malignancy, 8 (0.72%) were atypia of undetermined significance, 11 (0.99%) were suspicious of malignancy and 27 (2.42%) were malignant (MAL). Conclusion: The current study emphasises the significance of cytological analysis of serous fluid as a comprehensive diagnostic investigation that also aids in determining the cause and monitoring the disease process. With the introduction of ISFRSFC, serous fluid reporting is now uniform and more comprehensive, both for cytopathologists and clinicians.

Unveiling Variations: A Comprehensive Comparison of Five Globally Used Thyroid Cytology Reporting Systems With Histopathological Correlation.

Introduction Accurate cytological assessment is pivotal for managing thyroid lesions and various global reporting systems are in use, such as the globally acclaimed The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), alongside other reporting systems namely, the Japanese Reporting System for Thyroid Aspiration Cytology (JRSTAC), Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC), the UK Royal College of Pathologists System for Reporting Thyroid Cytopathology (UK RCPath), the Royal College of Pathologists of Australasia and Australian Society of Cytology Classification System (RCPA/ASC). Notably, variations exist among these systems which are influenced by country-specific statistics. Given the lack of large-scale data in India and the difference in prevalence of diagnostic entities compared to the western population, this study aimed to identify reporting systems suitable for the Indian population focusing on distinguishing neoplastic from non-neoplastic lesions. Materials and methods A cross-sectional analysis of 40 thyroid cytology cases with histopathological correlation was conducted. Pathologists independently assessed cytology slides using JRSTAC, ICCRTC, RCPA/ASC, UK RCPath and TBSRTC. Five performance indicators, sensitivity, specificity, positive predictive value (PPV) of neoplastic conditions, negative predictive value (NPV) of non-neoplastic conditions, diagnostic accuracy and two quality indicators, percentage of Atypia of undetermined significance (AUS) and AUS/Malignant ratio were analyzed and compared. Results Among 40 cases, 22 cases were neoplastic (16 papillary thyroid carcinoma, six follicular adenoma) and 18 non-neoplastic (14 multinodular goiter, four lymphocytic thyroiditis). Specific patterns emerged in cases labeled "Non-diagnostic", prompted questions about categorizing inadequately cellular cases as "benign" in light of the presence of specific findings. All reporting systems showed 100% specificity in detecting non-neoplastic and neoplastic conditions in Category 1 and Category 6 respectively. Performance and quality indicators varied among reporting systems with TBSRTC (PPV of neoplastic cases 85.71%, NPV of non-neoplastic cases 70.58%, specificity 85.7%, sensitivity 70.58%, diagnostic accuracy 60%, AUS percentage 22.5% and AUS/Malignant ratio 3%) and RCPA/ASC (PPV of neoplastic cases 76.47%, NPV of non-neoplastic cases 70.58%, specificity 75%, sensitivity 72.2%, diagnostic accuracy 62.5%, AUS percentage 15% and AUS/Malignant ratio 3%) showing better results. Conclusion Among the five thyroid cytology reporting systems studied, TBSRTC and RCPA/ASC showed better overall performance results and quality indicators were close to benchmark. Better performance by TBSRTC 2023 could be due to the detailed criterion mentioned per category with subcategorization of AUS and suspicious for malignancy by features of cytological and architectural atypia. Similarly, RCPA/ASC has subcategorized AUS with defined criteria and certain background features were included as an isolated criterion for the suspicious for malignancy category. These defined criteriaoutlined in TBSRTC and RCPA/ASC played a crucial role in minimizing and reclassifying cases from the indeterminate categories (AUS and suspicious for malignancy) into well-defined categories with established management protocols.

A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More

Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS “nuclear” and AUS “other” is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely “high-risk group” than the group including other subcategories, namely “low-risk group” (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.

Diagnostic models for predicting malignancy in thyroid nodules classified as Bethesda Category III in an endemic region.

This study aims to develop a diagnostic model to help physicians determine whether thyroid nodules categorized as atypia of undetermined significance (AUS) in category III of the Bethesda system are benign or malignant preoperatively. To create a diagnostic model for predicting thyroid nodules' benign or malignant with AUS cytology based on clinical, ultrasonographic, and cytopathological findings. This is a retrospective cohort study involving patients (>19) at risk of thyroid cancer who had thyroidectomy after an AUS cytology. The dataset consists of 53 variables 204 nodules from 183 patients. Binary logistic regression and factor analysis methods were used to identify risk factors for malignancy. Finally, four prediction models were developed using different approaches, based on clinical, pathological clinical + pathological, and the factors. A total of 88 (48.1%) of 183 patients diagnosed with AUS were benign and 95 (51.9%) the malignant. After determining risk factors, four prediction models were developed based on different approaches to assist physicians in deciding to detect AUS nodules early. It was seen that bilaterality was found to be a risk factor for malignancy in the clinical model (pbilaterality  = .03) and it was also seen that the pathological variables pale chromatin and irregular contours in the oncocyte variables were risk factors for malignancy (ppalechromatin  = .02, pirregularcontoursintheoncocyte  = .04). The best model obtained sensitivity and specificity values are 73% and 87% based on clinical and pathological variables. This comprehensive study may provide a more in-depth understanding of AUS and make a notable contribution to healthcare professionals before surgery.