A Retrospective Analysis of Serous Effusions Based on the Newly Proposed International System for Reporting Serous Fluid Cytopathology: A Report of 3633 Cases in an Oncological Center

Background: The International System for Reporting Serous Fluid Cytopathology (TIS) was recently proposed. We retrospectively applied TIS recommendations for reporting the cytological diagnosis of serous effusions and reported our experience.Methods: All the serous effusions from January 2018 to September 2021 were retrieved from the database. Recategorization was performed using the TIS classification, the risk of malignancy (ROM) was calculated for each TIS category, and the performance evaluation was carried out among different samples (pleural, peritoneal and pericardial effusions) and preparation methods (conventional smears, liquid-based preparations and cell-blocks). Results: A total of 3633 cases were studied, 17 (0.5%) were diagnosed as ND, 1100 (30.3%) as NFM, 101 (2.8%) as AUS, 677 (18.6%) as SFM, and 1738 (47.8%) as MAL. The ROM for the categories were found to be 38.5%, 28.6%, 52.1%, 99.4% and 100%, respectively. The ROM for SFM was significantly higher than that for AUS (P < 0.001), while the difference between the ROMs for the IVa and IVb was insignificant. The sensitivity, negative predictive value(NPV) and diagnostic accuracy of liquid-based preparations were all superior to conventional smears and cell-blocks in detecting abnormalities. Using three preparation methods simultaneously had the highest sensitivity, NPV and diagnostic accuracy.Conclusion: Serous effusion cytology has a high specificity and positive predictive value(PPV), and the TIS is a user-friendly reporting system. Liquid-based preparations could improve the sensitivity of diagnosis, and it is best to use three different preparation methods simultaneously for serous effusion cytologic examination.

Performance of the Bethesda System for Reporting Thyroid Cytology in Multi-Institutional Large Cohort of Pediatric Thyroid Nodules: A Detailed Analysis

Background: To evaluate the performance of TBSRTC through multi-institutional experience in the paediatric population and questioning the management recommendation of ATA Guidelines Task Force on Paediatric Thyroid Cancer; Methods: A retrospective search was conducted in 4 institutions to identify consecutive thyroid FNAC cases in paediatric population between 2000 and 2018. Following the 2nd TBSRTC, the risk of malignancy ratios (ROMs) was given in ranges and calculated by 2 different ways. Sensitivity, specificity, PPV, NPV and DA ratios were calculated using histologic diagnosis as the gold standard; Results: Among a total of 405 specimens, the distribution of cases for each category was, 44 (11%) for ND, 204 (50%) for B category, 40 (10%) for AUS/FLUS, 36 (9%) for FN/SFN, 24 (6%) for SFM and 57 (14%) for M categories. 153 cases have a histological diagnosis. The ratio of surgery was 23% in ND, 16% in the B, 45% for AUS/FLUS, 75% for SFN/FN and 92% for SFM and 75% in M categories; Conclusions: The data underlines the high ROM values in paediatric population which might be clinically meaningful. The high rate of malignancy of the cohort of operated patients (50%) also underlines the need of better preoperative indicators for stratification. Considering that more than half of the nodules in AUS/FLUS category were benign, direct surgery recommendation could be questionable as proposed in ATA 2015 guidelines.

Percepta Genomic Sequencing Classifier and decision-making in patients with high-risk lung nodules: a decision impact study

Background Incidental and screening-identified lung nodules are common, and a bronchoscopic evaluation is frequently nondiagnostic. The Percepta Genomic Sequencing Classifier (GSC) is a genomic classifier developed in current and former smokers which can be used for further risk stratification in these patients. Percepta GSC has the capability of up-classifying patients with a pre-bronchoscopy risk that is high (> 60%) to “very high risk” with a positive predictive value of 91.5%. This prospective, randomized decision impact survey was designed to test the hypothesis that an up-classification of risk of malignancy from high to very high will increase the rate of referral for surgical or ablative therapy without additional intervening procedures while increasing physician confidence. Methods Data were collected from 37 cases from the Percepta GSC validation cohort in which the pre-bronchoscopy risk of malignancy was high (> 60%), the bronchoscopy was nondiagnostic, and the patient was up-classified to very high risk by Percepta GSC. The cases were randomly presented to U.S pulmonologists in three formats: a pre-post cohort where each case is presented initially without and then with a GSG result, and two independent cohorts where each case is presented either with or without with a GSC result. Physicians were surveyed with respect to subsequent management steps and confidence in that decision. Results One hundred and one survey takers provided a total of 1341 evaluations of the 37 patient cases across the three different cohorts. The rate of recommendation for surgical resection was significantly higher in the independent cohort with a GSC result compared to the independent cohort without a GSC result (45% vs. 17%, p < 0.001) In the pre-post cross-over cohort, the rate increased from 17 to 56% (p < 0.001) following the review of the GSC result. A GSC up-classification from high to very high risk of malignancy increased Pulmonologists’ confidence in decision-making following a nondiagnostic bronchoscopy. Conclusions Use of the Percepta GSC classifier will allow more patients with early lung cancer to proceed more rapidly to potentially curative therapy while decreasing unnecessary intervening diagnostic procedures following a nondiagnostic bronchoscopy.

The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis

Background The relationship between IgG4-related disease (IgG4-RD) and the risk of malignancy is still controversial. This article focused on assessing the risk of cancer in patients with IgG4-RD by meta-analysis. Methods We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (pancreas, lung, gastric and lymphoma) in patients with IgG4-RD. A search from 2003 to 2020 was performed using specified terms from PubMed, Embase, Web of Science and SinoMed. Random-effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to clarify the heterogeneity of the included studies. Begg’s funnel plot and Egger’s linear regression test were used to evaluate the bias of the meta-analysis. A P value < 0.05 indicated the existence of publication bias. Results A total of 10 studies were included in the article. The overall SIR estimates suggested an increased risk of overall cancer in IgG4-RD patients (SIR 2.57 95% CI 1.72–3.84) compared with the general population. The specific SIRs for pancreas and lymphoma were higher than those of the general population in IgG4-RD patients (SIR 4.07 95% CI 1.04–15.92, SIR 69.17 95% CI 3.91–1223.04, respectively). No significant associations were revealed in respiratory and gastric cancer (SIR 2.14 95% CI 0.97–4.75, SIR 0.95 95% CI 0.24–3.95, respectively). Four studies were found to be the major sources of heterogeneity by sensitivity analysis. There was no evidence of publication bias via Egger’s test. Conclusion Compared with the general population, patients with IgG4-RD appear to have a higher risk of overall cancer, especially pancreatic and lymphoma. The risk of lung and gastric cancer was not different between IgG4-RD patients and the general population.

DIAGNOSTIC ROLE OF COMPRESSION SONOELASTOGRAPHY IN MULTIPARAMETRIC ULTRASOUND INVESTIGATION IN THE DETECTION OF BENIGN OVARIAN FORMATION

Properly diagnosed benign ovarian tumors are a condition for optimal treatment tactics. Qualitative assessment of signs detected by multiparametric ultrasound, including compression elastography, is highly effective in the differential diagnosis of benign ovarian tumors. Our study became especially relevant for women in the reproductive period, because the correct diagnosis influenced the choice of surgical treatment in order to preserve the ovarian reserve. A comprehensive radiological study of 51 women with benign ovarian tumors was performed. The age of patients averaged 37.3 ± 8.7 years. In the structure of benign ovarian tumors, the frequency of serous cystadenoma was 31.38%, serous superficial papillomas - 25.49%, mucinous cystadenoma - 17.65%, mature teratomas - 15.68%, fibroma - 9.8%. Ultrasound was performed on a HITACHI ALOCA ARIETTA 70 using a cavitary multifrequency sensor with a frequency of 7.5-10 mHz and a sector sensor with a frequency of 2-5 mHz. The article analyzes the detailed sonographic picture of these formations in B-mode, Doppler mode and compression sonoelastography mode. Color and energy Doppler mapping techniques, as well as pulsed Doppler mode, which gave a quantitative characterization of blood flow, were used to study blood vessels. Vessel localization was determined using color Doppler mapping, and detailed qualitative assessment of blood flow loci was determined using energy Doppler. For all types of benign ovarian formations, a qualitative feature was determined - elastotype on the Ueno scale and stiffness index - Strain Ratio (coefficient of deformation) - a quantitative indicator. It was found that serous and mucinous cystadenomas belong to 0 and I elastotype on the Ueno scale, the papillary component of serous superficial papillomas was mapped with I and II elastotype, fibroids mainly belonged to II and III elastotype, and mature teratomas - to IV end V elastotype. Quantitative deformation rate for all benign ovarian tumors ranged from 0,63 to 24,9. Thus, the cardiac index of stiffness in serous cystadenomas was 0.92 ± 0.46, and in mature teratomas - 16.7 ± 8.4. The increased density of the latter in comparison with other representatives of benign formations can be explained by the presence in their structure of such elements as fibroblasts, bundles of spindle-shaped cells and bundles of collagen fibers (fibroids), bone and cartilage (mature teratoma). In addition to all the above research methods, the mobile application IOTA ADNEX 2014 was used, which helped to calculate the risk of malignancy. This is a simple calculator, which loads the data of the ultrasound examination, the patient's age, the level of CA-125. Our results showed that ultrasound examination of ovarian tumors is an accurate and highly informative method for stratification of risks according to the O-RADS classification. For stratification and the ultrasound risk management system, the O-RADS system was guided by consensus guidance from the American College of Radiology, which reduces or eliminates ambiguity in the interpretation of data in ultrasound protocols and provides a more accurate definition of ovarian malignancy. The O-RADS working group includes 5 categories: O-RADS 0 - incomplete examination score, O-RADS 1 - normal unchanged premenopausal ovary, O-RADS 2 - almost always benign (risk of malignancy - <1%), O-RADS 3 - the presence of education with a low level of malignancy - from 1 to 10%, O-RADS 4 - medium risk of malignancy - from 10 to 50% and O-RADS 5 - education with a high level of malignancy -> 50%.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in thyroid cytology: Data from Singapore

Introduction: The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. Methods: We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. Results: The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. Conclusion: Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies Keywords: Bethesda, cytology, NIFTP, risk of malignancy, TBSRTC, thyroid nodule

A Study of Reproducibility of Papanicolaou Society of Cytopathology System of Reporting Respiratory Cytology-A Single Institutional Experience on Image Guided Aspiration Cytology

Background: Cytologic examination of specimens obtained from the respiratory tract is a primary and frequently the initial diagnostic technique performed in patients with pulmonary abnormalities. Fine needle aspiration (FNA) is extensively used for diagnosis of pulmonary lesions. The Papanicolaou Society of Cytopathology (PSC) issued a new classification for respiratory cytology and criteria, risk of malignancy, post-cytologic diagnosis management and follow-up. Methods: Respiratory FNA specimens obtained between January 2015 to March 2021 were reviewed and reclassified according to PSC guidelines. Cytologic category as per PSC system was assigned after reviewing by two pathologists. Risk of malignancy for each category was calculated for cases where biopsy was available for correlation. Results: Three eighty-four samples were classified as non-diagnostic (30.5%), negative for malignancy (13.3%), atypical (0.5%), neoplastic (benign/ low malignant potential) (0%), suspicious for malignancy (5.7%%) and malignancy (50%). Risk of malignancy for malignant category (Category V and Category VI) was 64.1% and for non-malignant (Category I to Category IV) cases was 35.9%. Overall, there was lesser incidence of atypical category and more specific diagnoses were possible on cytology in non-malignant category. Sensitivity and specificity for malignant cases was 99.33% and 100% respectively. Conclusion: Our study substantiates that use of PSC guidelines improves the overall reporting of respiratory cytology due to the use of standardized terminology.