Retrospective application of WHO reporting system for lung cytopathology with assessment of risk of malignancy.

INTRODUCTION: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category. MATERIALS AND METHODS: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually. RESULTS: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%. CONCLUSIONS: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy.

Large-scale validation study of an improved semiautonomous urine cytology assessment tool: AutoParis-X.

BACKGROUND: Adopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy, and reliability of bladder cancer screening, which has heretofore relied on semisubjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices (e.g., The Paris System for Reporting Urinary Cytology), algorithms to emulate semiautonomous diagnostic decision-making have lagged behind, in part because of the complex and nuanced nature of urine cytology reporting. METHODS: In this study, the authors report on the development and large-scale validation of a deep-learning tool, AutoParis-X, which can facilitate rapid, semiautonomous examination of urine cytology specimens. RESULTS: The results of this large-scale, retrospective validation study indicate that AutoParis-X can accurately determine urothelial cell atypia and aggregate a wide variety of cell-related and cluster-related information across a slide to yield an atypia burden score, which correlates closely with overall specimen atypia and is predictive of Paris system diagnostic categories. Importantly, this approach accounts for challenges associated with the assessment of overlapping cell cluster borders, which improve the ability to predict specimen atypia and accurately estimate the nuclear-to-cytoplasm ratio for cells in these clusters. CONCLUSIONS: The authors developed a publicly available, open-source, interactive web application that features a simple, easy-to-use display for examining urine cytology whole-slide images and determining the level of atypia in specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis-X (and other semiautomated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms in head-to-head clinical trials.

Oral brush biopsy using liquid-based cytology is a reliable tool for oral cancer screening: A cost-utility analysis: Oral brush biopsy for oral cancer screening.

BACKGROUND: This study aimed to assess the diagnostic utility and associated cost of oral liquid-based brush cytology (OLBC) in the diagnosis of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: A total of 284 patients with oral mucosal lesions were included. OLBC samples were collected from all patients immediately before undergoing surgical biopsies. A liquid-based cytology slide was prepared from each OLBC sample for cytological evaluation using the modified 2014 Bethesda cytology system. The results and the cost were compared with the histopathological outcomes. RESULTS: The level of agreement between the two approaches was very good (weighted kappa = 0.824). The accuracy of OLBC in differentiating between the different diagnostic groups was 91.69%, whereas the associated sensitivity and specificity were 79.23% and 94.81%, respectively. The estimated cost of each OLBC sample was at least 26% less than the cost of a single biopsy and more than 42% less in cases of multiple biopsied lesions. CONCLUSIONS: The proposed modifications of the Bethesda system can be adopted as a standardized system for oral cytological assessment. Our findings support OLBC as a reliable adjunct to surgical biopsy in the diagnosis of OPMDs. This tool has potential for oral cancer-finding and surveillance programs.

Diagnostic accuracy of Thinprep® in cervical lymph node aspiration: Assessment according to the Sydney system.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable technique that has been used for many years in lymphadenopathy diagnosis. Although conventional smear is the standard approach in FNAC, liquid-based cytology (LBC) is accepted as an alternative method. Reporting standardization is a significant gap in fine-needle aspiration cytology, leading to failure in pathologist-clinician dialog and interobserver variability. In 2020, an expert panel proposed the Sydney system for classifying and reporting lymph node aspiration cytology. This study aimed to evaluate the diagnostic accuracy of LBC in lymph node aspiration cytology under the guidance of the Sydney system. METHODS: Five hundred-four LBC samples were reevaluated and classified according to the Sydney system. Of these, n = 24 were categorized as L1-inadequate/non-diagnostic, n = 283 as L2-benign, n = 36 as L3- atypical cells of undetermined significance/atypical lymphoid cells of uncertain significance (AUS/ALUS), n = 48 as L4-suspicious, and n = 113 as L5-malignant. Four hundred-one samples were histopathologically confirmed. The diagnostic accuracy of LBC and the risk of malignancy for each Sydney category were calculated. RESULTS: The results were as follows: sensitivity 98.97%; specificity 98.60%; positive predictive value 94.80%; negative predictive value 99.29%; and overall diagnostic accuracy 98.75%. The ROM was 16.6% for L1, 0.7% for L2, 88.8% for L3, and 100% for L4 and L5. CONCLUSION: LBC is suitable for use in lymph node aspiration under the guidance of the Sydney system and has high diagnostic accuracy. Future comprehensive studies will increase the applicability of the Sydney system and minimize interobserver variability.

Assessment of Risk of Malignancy of Fine-needle Aspiration Cytology in Salivary Gland Lesions Using the Milan System for Reporting Salivary Gland Cytopathology Categorization: A Systematic Review and Meta-analysis.

BACKGROUND: Fine-needle aspiration cytology (FNAC) of the salivary gland is crucial in the identification of salivary gland lesions, but the variation in morphological pattern and the overlap of morphological traits can result in erroneous interpretation and affect treatment, making FNAC of the salivary gland problematic. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was created to address these problems. OBJECTIVES: To ascertain whether the FNAC method using MSRSGC was reliable in predicting the risk of malignancy (ROM) in each category of salivary gland lesions. MATERIALS AND METHODS: The databases PubMed-MEDLINE, Web of Science, Cochrane, Scopus, and Google Scholar were all searched using pertinent keywords, reference searches, and citation searches. A fixed effect model was used to determine the pooled proportion with a 95% confidence interval (CI). All statistical analyses were performed using Meta Disc and R version 4.0.2 (R Foundation for Statistical Computing). RESULTS: After reviewing the submissions' abstracts and titles, 58 documents that satisfied the necessary inclusion and exclusion criteria were ultimately selected. A total of 19,652 samples from 19,408 individuals was analyzed, out of which 9,958 samples were available for histopathological follow-up. The pooled ROM for category I was 10%, category II was 5%, category III was 28%, category IV A was 2%, Category IV B was 34%, category V was 91%, and category VI was 99%. CONCLUSION: Milan System for Reporting Salivary Gland Cytopathology is useful for risk stratification and quality control, confirming its validity and diagnostic utility. Widespread use of MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care and improved treatment strategies. The results of this study are in consonance with reported values as per MSRSGC except for category V. CLINICAL SIGNIFICANCE: The MSRSGC which was first reported in 2018 is a very useful tool for proper stratification of ROM in salivary gland FNAC. This study allowed us to validate the ROM values in different categories as reported in MSRSGC.

Cervical cytopathological changes in pregnancy: An experience from a low resource setting.

Background: Cervical cancer is the leading cause of death among women in developing countries. It is preventable through effective cervical cancer screening program. However, in Nigeria, screening programs are opportunistic and coverage is insufficient to make an impact. Aim: This study assessed the cervical cytopathological changes among pregnant women at booking using liquid-based cytology (LBC) in Aminu Kano Teaching Hospital (AKTH). Methodology: This was a cross-sectional study that was carried out at the antenatal Clinic of AKTH, Kano, Nigeria. A total of 161 pregnant women who fulfilled the criteria and gave their consent were recruited into the study using systematic sampling technique at booking for antenatal care. LBC was employed using standard procedure and samples sent to histopathology department for analysis. Pro forma developed for the study was used to obtain the socio-demographic and reproductive characteristics of the women and the risk factors for abnormal cervical cytology. Results: Out of the 161 pregnant women that had cervical cytology screening using LBC on their first prenatal visit during the study, 22 had abnormal cervical cytology, giving a prevalence rate of 13.7%. Out of this, six (27.3%) were atypical squamous cells of undetermined significance, 3 (13.6%) were Atypical Squamous Cells, Cannot Rule Out HSIL (ASC-H), 11 (50.0%) were low-grade Squamous Intraepithelial Lesions while 2 (9.1%) were high grade squamous intraepithelial lesions. Negative smears were seen in 104 women (64.6%). Inflammatory and other conditions of the cervix which are technically negative smears made up the remaining 21.7%. There was a statistically significant association between cervical cytology results and advanced age (P < 0.01), increasing number of lifetime sexual partners since coitarche (P < 0.01), high parity (P < 0.01), absent previous Pap test (P < 0.027), previous history of sexually transmitted infections (P < 0.040), and positive HIV status (P < 0.001). Following binary logistic regression, advanced maternal age, increasing number of sexual partners, high parity, and positive HIV status stood out to be independent predictors of premalignant lesions of the cervix in pregnancy in this study. Conclusion: Advanced maternal age, increasing number of sexual partners, high parity, and positive HIV status stood out to be independent predictors of premalignant lesions of the cervix in the study. Routine cervical cytology screening using LBC should be offered to all antenatal clients in our setting to increase coverage and detection rate of preinvasive lesions of the cervix, and/or pregnant women with increased risk of abnormal cervical cytology from this study.

RésuméContexte: Le cancer du col de l'utérus est la principale cause de décès chez les femmes des pays en développement. Il est évitable grâce à un programme efficace de dépistage du cancer du col utérin. Cependant, au Nigéria, les programmes de dépistage sont opportunistes et la couverture est insuffisante pour avoir un impact. Objectif: Cette étude a évalué les changements cyto-pathologiques cervicaux chez les femmes enceintes lors de la réservation en utilisant la cytologie en phase liquide (LBC) à l'hôpital universitaire Aminu Kano (AKTH). Méthodologie: Il s'agissait d'une étude transversale qui a été réalisée à la clinique prénatale de 'AKTH, Kano, Nigéria. Un total de 161 femmes enceintes qui remplissaient les critères et ont donné leur consentement ont été recrutées dans l'étude en utilisant une technique d'échantillonnage systématique lors de la réservation pour les soins prénatals. LBC a été utilisé en utilisant la procédure standard et des échantillons envoyés au service d'histopathologie pour analyse. Le pro forma développé pour l'étude a été utilisé pour obtenir les caractéristiques sociodémographiques et reproductives des femmes et les facteurs de risque d'une cytologie cervicale anormale. Résultats: Sur les 161 femmes enceintes qui ont subi un dépistage cytologique cervical utilisant le LBC lors de leur première visite prénatale au cours de l'étude, 22 avaient une cytologie cervicale anormale, ce qui donne un taux de prévalence de 13,7%; six (27,3%) étaient des cellules squameuses atypiques de signification indéterminée, 3 (13,6%) étaient des cellules squameuses atypiques, ne peut exclure HSIL (ASC-H), 11 (50,0%) étaient des lésions intraépithéliales squameuses de bas grade tandis que 2 (9,1%) étaient des lésions intraépithéliales squameuses de haut grade. Des frottis négatifs ont été observés chez 104 femmes (64,6%). Les conditions inflammatoires et autres du col de l'utérus qui sont des frottis techniquement négatifs constituaient les 21,7% restants. Il y avait une association statistiquement significative entre l'âge avancé (P <0,01), un nombre croissant departenaires sexuels à vie depuis la coïtarche (P <0,01), parité élevée (P <0,01), absence de test Pap précédent (P <0,027), antécédents d'infections sexuellement transmissibles (P <0,040) et statut VIH positif (P <0,001). Suite à la régression logistique binaire, l'âge maternel avancé, le nombre croissant de partenaires sexuels, une parité élevée et un statut VIH positif se sont révélés être des prédicteurs indépendants des lésions prémalignes du col de l'utérus pendant la grossesse dans cette étude. Conclusion: L'âge maternel avancé, le nombre croissant de partenaires sexuels, la parité élevée et le statut VIH positif se sont révélés être des prédicteurs indépendants des lésions prémalignes du col de l'utérus dans l'étude. Un dépistage cytologique cervical de routine utilisant le LBC doit être proposé à tous les clients prénatals dans notre environnement pour augmenter la couverture et le taux de détection des lésions pré-invasives du col de l'utérus et / ou aux femmes enceintes présentant un risque accru de cytologie cervicale anormale de cette étude.

HPV-specific risk assessment of cervical cytological abnormalities.

BACKGROUND: Cytology and HPV genotype screening play an important role in cervical cancer detection. Whether multiple HPV genotyping can predict cytological lesions remains to be further studied. METHODS: Two thousand two hundred twenty-four females were analyzed for cytology and HPV genotypes test. The possibility of predicting cytological lesions by HPV genotypes test was evaluated by multivariate logistic regression and area under the receiver operator characteristic curve (AUC). RESULT: Abnormal cytological results were found in 479 participants. A total of 688 patients were detected with HPV infection, 619 with HR-HPV infection and 112 with LR-HRV infection. HPV-52 was found to be the most common type among these patients, and a relatively higher risk of cervical lesions was found in HPV positive females. HPV-16, 31, 33 and 58 were found to have significantly higher infection rates in patients with HSIL and higher lesions. The prediction model was developed based on age and HPV-specific genotypes, with the AUC of 0.73 for cytological abnormalities and 0.82 for HSIL and higher lesions. CONCLUSION: HPV-16, 31, 33 and 58 infection are significant risk factors for cervical lesions. Combined HPV genotypes test can effectively predict cytological abnormalities.

The Milan System for Reporting Salivary Gland Cytopathology: Assessment of Cytohistological Concordance and Risk of Malignancy.

INTRODUCTION: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was proposed by the American Society of Cytopathology and the International Academy of Cytology to bring uniformity in the reporting system and the treatment protocol. A wide range of risk of malignancy for each category has been reported by various authors by applying the system. AIM: We intend to study the cytohistological concordance and the ROM for each of the diagnostic categories of the Milan system. MATERIALS AND METHODS: The study included 292 cases of fine-needle aspiration cytology (FNAC) of salivary gland lesions over a period of 3 years. The diagnosis of these cases was reclassified into the 6 categories of the Milan system. The cytohistological concordance and ROM for each category of the Milan system were calculated based on the clinical and histopathological follow-up. RESULTS: The patients' age ranged from 3 to 81 years with the mean of 42.65 ± 16.3 years. The cases included 189 (64.7%) parotid, 82 (28.1%) submandibular, and 21 (7.2%) cases of minor salivary gland swellings. Follow-up histopathological diagnosis for 102 cases was available. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to be 64.28, 97.01, 90, 86.67, and 87.37%, respectively. After reclassification, the number of cases in each category was as follows: category I: 31 (10.62%), category II: 80 (27.4%), category III: 2 (0.68%), category IVA: 143 (48.97%), category IVB: 1 (0.34%), category V: 13 (4.45%), and category VI: 22 (7.53%). The calculated ROM was as follows: category I: 42.86%, category II: 26.67%, category III: 100% category IVA: 10.17%, category IVB: 0%, category V: 71.42%, category VI: 100%. CONCLUSION: FNAC is an excellent procedure to differentiate benign from malignant tumors, and MSRSGC is a useful system for risk assessment and deciding the further treatment protocol. Our findings also suggest that in addition to the surgical follow-up, inclusion of the clinical and radiological follow-up may be a better strategy for calculation of ROM, especially for categories I and II.

Quantitative assessment of p16 expression in FNA specimens from head and neck squamous cell carcinoma and correlation with HPV status.

BACKGROUND: This study investigated p16 by immunohistochemistry (IHC) on cellblocks (CBs) and human papillomavirus (HPV) by polymerase chain reaction (PCR) in fine-needle aspiration (FNA) of head and neck squamous cell carcinoma (HNSCC). METHODS: Receiver operating characteristic (ROC) curve analysis was used to assess test performance in CBs compared with p16 IHC in 42 surgical specimens from patients with HNSCC and in correlation with HPV by PCR in cytology specimens. The study assessed HPV by PCR in FNA specimens as a substitute for p16 IHC in surgical specimens. RESULTS: Of 42 cases, 38 CBs showed malignant cells as cohesive clusters of viable cells with or without single tumor cells, whereas 4 specimens were composed exclusively of single tumor cells and degenerated cells. All p16-negative surgical specimens showed an absence of p16 staining in the corresponding CBs (n = 16). In the p16-positive surgical cases (n = 26), corresponding CBs with tumor clusters (n = 23) showed heterogeneous p16 expression ranging from 40% to 100%; however, scoring single cells was challenging and unreliable because of cellular degradation. ROC curve inspection showed the optimal threshold to be at least 40% p16 staining in tumor clusters with 100% sensitivity and specificity. In cases with inadequate CBs, HPV by PCR on needle rinse showed 88% sensitivity and 100% specificity for p16 expression in surgical specimens. CONCLUSIONS: A cutoff of at least 40% p16 expression in tumor clusters may be appropriate for p16 positivity in cytology CB specimens. A positive HPV finding by PCR on needle rinse can be used as a substitute for p16 expression in surgical specimens.

Results from the 2019 American Society of Cytopathology survey on rapid onsite evaluation (ROSE)-part 2: subjective views among the cytopathology community.

INTRODUCTION: This study aims to improve understanding of the cytopathology community's perspective regarding the value of rapid onsite evaluation (ROSE) in clinical practice. MATERIALS AND METHODS: The American Society of Cytopathology membership was surveyed in 2019 to obtain subjective data on the cytopathology community's perceptions regarding ROSE. Comments were categorized by major themes and attitudes and analyzed by respondent's role in laboratory, practice size, and practice setting (Fisher's exact and χ2 tests). RESULTS: A total of 541 responses were received from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 trainees, and 6 others (as previously reported). Reasons for which cytopathology personnel provide this service aligned with their perceptions of why clinicians request ROSE. A minority of respondents, disproportionally from high volume centers, felt ROSE is unnecessary. Overall attitude regarding ROSE was generally positive. There were no significant differences in attitude regarding ROSE according to role in laboratory or practice size, but respondents from academic centers provided a significantly higher percentage of positive comments than those in private or community practice. Although survey respondents generally felt that ROSE is valuable to patient care, they also highlighted several challenges, including staffing, time commitment, and inadequate reimbursement. Implementation of telecytology was felt to potentially alleviate some of these challenges. CONCLUSIONS: Survey results show that the cytology community views ROSE favorably, practices vary considerably, and there is a perceived need for improved reimbursement. Data from this study may be used to identify areas that warrant additional research to clarify the clinical value of ROSE.

Risk of malignancy assessment for the Paris System for reporting urinary cytology.

BACKGROUND: The Paris System for reporting urinary cytology was introduced in 2013 and has a global impact. In our study, we assess the risk of malignancy (ROM) for each diagnostic category and our diagnostic accuracy in urinary cytology. METHODS: We have conducted a prospective study during 2019, including only new cases of urothelial neoplasms, all of them with subsequent histology. The risk of malignancy for each category was calculated and the diagnostic accuracy parameters were estimated in correlation with histology. RESULTS: The estimated risk of malignancy (ROM) for high-grade neoplasms was 0% for TPS1, 6.5% (2/31) for TPS2, 36% (9/25) for TPS3, 65% (13/20) for TPS4, 100% (18/18) for TPS5 and 16% (2/13) for TPS6. Accuracy parameters for high-grade urothelial carcinoma (HGUC) were evaluated in two ways, in the first considering TPS3 as a negative and in the second as a positive result and the values were: sensitivity 70% vs 90.9%, specificity 89.3% vs 65.2%, PPV 81.5% vs 63.5%, NPV 82% vs 91.5% and diagnostic accuracy 81.8% vs 75.4%. For low-grade urothelial neoplasm (LGUN) diagnosis, sensitivity was 42%, specificity 76%, PPV 71%, NPV 48.6% and diagnostic accuracy 56%. CONCLUSION: The risk of malignancy for the TPS categories has a clinically meaningful gradation and the effectiveness of urinary cytology is improved by the application of the Paris System.

Visual histological assessment of morphological features reflects the underlying molecular profile in invasive breast cancer: a morphomolecular study.

AIMS: Tumour genotype and phenotype are related and can predict outcome. In this study, we hypothesised that the visual assessment of breast cancer (BC) morphological features can provide valuable insight into underlying molecular profiles. METHODS AND RESULTS: The Cancer Genome Atlas (TCGA) BC cohort was used (n = 743) and morphological features, including Nottingham grade and its components and nucleolar prominence, were assessed utilising whole-slide images (WSIs). Two independent scores were assigned, and discordant cases were utilised to represent cases with intermediate morphological features. Differentially expressed genes (DEGs) were identified for each feature, compared among concordant/discordant cases and tested for specific pathways. Concordant grading was observed in 467 of 743 (63%) of cases. Among concordant case groups, eight common DEGs (UGT8, DDC, RGR, RLBP1, SPRR1B, CXorf49B, PSAPL1 and SPRR2G) were associated with overall tumour grade and its components. These genes are related mainly to cellular proliferation, differentiation and metabolism. The number of DEGs in cases with discordant grading was larger than those identified in concordant cases. The largest number of DEGs was observed in discordant grade 1:3 cases (n = 1185). DEGs were identified for each discordant component. Some DEGs were uniquely associated with well-defined specific morphological features, whereas expression/co-expression of other genes was identified across multiple features and underlined intermediate morphological features. CONCLUSION: Morphological features are probably related to distinct underlying molecular profiles that drive both morphology and behaviour. This study provides further evidence to support the use of image-based analysis of WSIs, including artificial intelligence algorithms, to predict tumour molecular profiles and outcome.

Use of cytology centrifuged supernatants improves cost and turnaround time for targeted next generation sequencing.

BACKGROUND: Molecular testing is an essential step in providing patients with advanced non-small-cell lung cancer (NSCLC), the most appropriate front-line targeted therapies. We recently implemented targeted NGS on previously discarded cytology centrifuged supernatant (CCS). METHODS: In this study, we reviewed our implementation process to evaluate its performance. Performance and turnaround time (TAT) of molecular testing on all cytology NSCLC cases submitted for targeted NGS from June 2018 to September 2019 were evaluated, which included 46 and 62 cytology cases before and after implementation of CCS, respectively. Associated cost savings using CCS was also analyzed. RESULTS: The mean TAT defined as the time of collection to time of reporting was 8.5 ± 1.8 days in CCS cohort (range 5-13) as compared with 12.2 ± 5.3 days in the (FFPE) cell block (CB) cohort (range: 6-27). The success rate of sequencing was similar for both cohorts (100% in CCS and 96% in FFPE CB). CONCLUSION: Our results demonstrate that NGS using CCS improves TAT, preserves FFPE CB for other testing, and results in cost savings of $50 per case.

The texture analysis as a predictive method in the assessment of the cytological specimen of CT-guided FNAC of the lung cancer.

The lung cancer is the principle cause of the worldwide deaths and its prognosis is poor with a 5-year overall survival rate. Computed tomography (CT) gives many information about the prognosis, but the problem is the subject interpretation of the findings. Thanks to the computer-aided diagnosis/detection (CAD), it is possible to reduce the second opinion. "Radiomics" is an extension of CAD and overlaps the quantitative imaging data of the CT texture analysis (CTTA) with the clinical information, increasing the power and precision of the decision going through the personalized medicine. The aim of this study is to describe the role of the radiomics in the characterization of the pulmonary nodule. For this study, we retrospectively analyzed the images of the 87 NSCLC patients with a waiver of informed consent from the Institutional Review Board (IRB) at the Campania University "Luigi Vanvitelli" of Naples. All tumors were semiautomatically segmented by a radiologist with 10 years of experience using three diameters (AW Server 3.2). The examinations were acquired using 128 MDCT (GSI CT, GE) with a peak tube voltage of 120 kVp, tube current of 100 or 200 mA, and rotation times of 0.5 or 0.8 s. To confirm the imaging results, the FNAC was performed and for every nodule the following parameters were extracted: the presence of the solid component (named = 1), papillary component (named = 2), and mixed component (named = 3). Feature calculation was performed using the HealthMyne software and Integrated Platform That Enables Better Patient Management Decisions For Oncology. The radiologist uses the Rapid Precise Metrics (RPM)™ functionality to identify a lesion with the algorithm and these methods are put to work. The correlation between each feature and the tumor volume was calculated using a two-step cluster statistical analysis. In this retrospective study, in one year from 2018 to 2019 20 patients with lung adenocarcinoma confirmed with FNAC were enrolled. The pathologic results were subdivided into three categories: the solid architecture (group 1), papillary architecture (group 2), and mixed architecture (group 3). Nine lesions resulted with component 1, seven patients with component 2, and 3 patients with component 3. Eight females and 12 males with a median age 61 and 15 years (mean ± SD = 67.4 ± 9.7 years, range 39-73 years) were enrolled. The two results suggest, with p < 0.05, that the GGO variable is a good discriminating estimator of the kurtosis variable: GGO = "no" implies a high kurtosis value, while GGO = "yes" implies a low value. The numerous data obtained from the automatic analysis allow to have a fertile ground on which to develop a new concept of medicine which is precision medicine. The limit of this study is the poor sample. In the future, in order to have a more mature and consolidated discipline, it is necessary to increase the large scale of observations with further studies to establish the rigorous evaluation criteria. In order for radiomics to mature as a discipline in the future, it will be necessary to develop studies that consolidate its role to standardize the collected data.

ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule.

Background: Novel molecular tests (MTs), such as ThyroSeq, may improve the management of thyroid nodules with indeterminate cytologic diagnoses; however, the impact of these tests on cost and outcome of management is unknown. Here, we evaluated the impact of ThyroSeq testing on the cytopathologic diagnosis, management, and cost of care in patients with thyroid nodules. Methods: In a retrospective study, using actual patient cohorts, the outcome and cost of management of patients with thyroid nodules seen before the introduction of ThyroSeq v2 at our institution (standard of care [StC] cohort) were compared with those seen after the introduction of this test (MT cohort). Results: A total of 773 consecutive patients entered the study (393 StC, 380 MT). The incidence of cytologically benign nodules decreased from 71.0% (StC) to 53.2% (MT) and those of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) increased from 8.9% (StC) to 21.3% (MT) and from 3.1% (StC) to 6.3% (MT), respectively. The overall rate of surgery did not change significantly (23.4% in StC vs. 23.2% in MT). Among patients who underwent surgery, the rate of overtreatment (surgeries performed on histologic benign nodules without clinical indication: compressive symptoms, hyperthyroidism resistant to medication, and nodule size >4 cm) slightly decreased from 18.8% (StC) to 16.7% (MT). The rate of malignancy decreased from 45.5% (StC) to 37.9% (MT) in AUS/FLUS and increased from 40.0% to 53.8% in FN/SFN. However, the overall rate of malignancy remained equal (47.8% in StC vs. 47.7% in MT). The average cost of care per patient in the AUS/FLUS and FN/SFN categories increased from $6,566 (StC) to $8,444 (MT) and from $9,313 (StC) to $10,253 (MT), respectively. Similarly, the overall average cost of care of a patient who underwent thyroid fine-needle aspiration increased from $3,088 (StC) to $4,282 (MT). Finally, the average cost per thyroid cancer detected increased from $26,312 (StC) to $38,746 (MT). Conclusions: Introduction of ThyroSeq v2 resulted in a shift toward indeterminate cytology results. The institutional rate of surgery, overtreatment, and malignancy did not change significantly. Lack of decrease in the rate of surgery along with the additional cost of ThyroSeq v2 increased the overall cost of care of patients including those with indeterminate cytology results.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours.

Fine needle aspiration cytology (FNAC) is a widely accepted safe, simple and rapid diagnostic procedure used in the examination of neoplastic and non-neoplastic lesions of various locations. Since its introduction, FNAC has developed into an effective diagnostic tool practiced in a large majority of medical centres evaluating and treating oncological patients. The role of FNAC has been limited in the examination of primary soft tissue lesions, however, as many physicians working in this area recommended against using FNAC. An increasing use of minimally invasive diagnostic procedures in the last decade has resulted in a better acceptance of FNAC as a first-line approach or as a complementary tool to core needle biopsy in the diagnosis of musculoskeletal lesions. This review discusses the role and value of FNAC in the evaluation and treatment of soft tissue tumours based on the experience gathered over the course of 48 years at the Sarcoma Center in Lund, Sweden. FNAC reports most often provide diagnostic information allowing the initiation of treatment or, when definitive diagnosis cannot be rendered from a cytological examination, guiding the continued diagnostic investigation. The main advantages of soft tissue FNAC are good sensitivity and specificity, low morbidity, speed of diagnosis, and low cost/benefit ratio. The most important disadvantages stem from limited experience in cytological diagnosis of soft tissue tumours and a lack of standardised and uniform reporting system for soft tissue FNAC.

Preoperative bronchial cytology for the assessment of tumor spread through air spaces in lung adenocarcinoma resection specimens.

BACKGROUND: Tumor spread through air spaces (STAS), a significant prognostic indicator, has been described recently as a pattern of invasion in pulmonary carcinomas. However, questions remain regarding preoperative identification of STAS and whether it represents an in vivo phenomenon versus an ex vivo artifact. METHODS: We retrospectively reviewed 67 paired preoperative bronchoalveolar lavage (BAL) or bronchial washing (BW) cytology specimens with the subsequent lung adenocarcinoma surgical resection specimen to determine whether preoperative cytology could predict STAS. Other clinical, radiologic, and pathologic features of the resected lesions were also correlated with preoperative bronchial cytology results. RESULTS: Positive bronchial cytology was observed in 28 cases (41.8%), 24 of which had STAS (85.7%); however, negative BAL/BW cytology was observed in 39 cases (58.2%), 29 of which had STAS (74.4%) (x2  = 1.27, P = .26, not significant). High-STAS burden was observed in 44 cases (83.0%), 21 (47.7%) with negative BAL/BW and 23 (52.3%) with positive BAL/BW. Low-STAS burden was observed in 9 cases (17.0%), 8 (88.9%) with negative BAL/BW and only 1 (11.1%) with positive BAL/BW (x2  = 5.11, P = .024, significant). For tumors with STAS, a statistically significant difference was identified in the maximal STAS distance from the main tumor edge between BAL/BW-positive and BAL/BW-negative groups (P = .007). Of the remaining clinicopathologic and radiologic features, only visceral pleural invasion was significantly associated with BAL/BW positivity. CONCLUSION: Presurgical bronchial cytology alone cannot adequately predict tumor STAS; however, it may provide useful information regarding the extent and overall burden of STAS on the subsequent resection specimen.