Background Cytopathological examination of pleural effusions is a fast and minimally invasive method for verification of the presence of neoplastic cells. We report our 2‐year experience using a categorised diagnostic system and reporting risks of malignancy (ROMs) for each defined category. Methods Cytological reports of patients between November 2016 and October 2018 were collected, with results primarily classified into a five‐tiered classification scheme. Immunohistochemistry markers used in cytology and their results were also recorded. Final agreement to histology and overall test performance was calculated for cases with available concomitant (up to 3 months) pleural biopsies. Results A total of 519 samples from 385 patients were collected, being 29 (5.6%) classified as non‐diagnostic, 291 (56%) as negative, 28 (5.4%) as atypical, 30 (5.8%) as suspicious and 141 (27.2%) as positive. Most requested markers were calretinin, TTF1, Ber‐EP4 and Gata‐3, being conclusive in 45 (76.3%) cases. Total cyto‐histological agreement was achieved in 49 (80.3%) specimens, with an overall sensitivity and specificity of 69.4% and 93.3%, respectively. Positive predictive value was 96.2% and negative predictive value was of 56%. ROM for each diagnostic category was 50% for non‐diagnostic, 44% for negative, 50% for atypical, 83.3% for suspicious and 96.2% for positive. Conclusions Our 2‐year retrospective study has shown a high specificity and positive predictive value for pleural cytology. The use of a five‐tiered system has also shown to be highly effective, with a concordantly progressive higher ROM for the assigned diagnostic categories.

IntroductionThe Paris system for reporting urinary cytology (TPS) was published in order to provide clear cytomorphological criteria for urine cytology specimens, focusing on high‐grade urothelial lesions. The aim of this study was to evaluate the impact of implementing TPS and to correlate with available concomitant histological samples, accessing overall sensitivity and specificity.MethodsA retrospective analysis of urine cytology reports from 2017 to 2018 using TPS was carried out, with histological correlation to concomitant samples (up to 3 months). Statistical analysis was performed with calculation of sensitivity and specificity, positive and negative predictive values and risk of malignancy (ROM) for all TPS categories.ResultsA total of 1660 specimens were evaluated. Histological specimens were available for 611 (36.8%) cases. Urine cytology categorised by TPS had 2.4% non‐diagnostic cases, 87.1% negative for high‐grade urothelial carcinoma (HGUC), 4.6% atypical urothelial cells, 2.7% suspicious for HGUC, 2.7% HGUC and 0.5% cases of other malignancies. Sensitivity, specificity, negative predictive value and positive predictive value were 40.0%, 99.3%, 88.2% and 92.3%, respectively. ROM of each category was 0% for non‐diagnostic, 11.1% for negative for HGUC, 32.4% for atypical, 64.9% for suspicious for HGUC and 87.9% for HGUC and other malignancies.ConclusionOur findings indicated that implementation of TPS provided a high specificity and predictive positive value for the detection of high‐grade urothelial lesions, with proportionally increasing ROMs as categories progress from negative to positive.

ObjectiveTo better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity.DesignWe characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial.ResultsWe found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expandedCXCL13+tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens.ConclusionWe provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

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