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Endometrial cancer (EC) represents one of the most newly diagnosed cancers across gynecological malignancies. In particular, a plethora of risk factors (both biological and lifestyle-related) drastically impact the incidence rate of novel diagnosis accounting for 8300 cases/year. In the recent era of precision medicine EC molecular classification, integrating ESGO/ESTRO/ESP guidelines, four distinct diagnostic groups have been established including POLE-mutant (POLE-pos); High-instability MSI (H-MSI)–MMR-deficient (MMR-d); p53-abnormal (p53abn); and non-specific molecular profile (NSMP), also known as p53-wild-type EC patients on the basis of clinically relevant emerging biomarkers. In addition, molecular testing also plays a pivotal role in defining the best therapeutical option. In this scenario, the European Society for Medical Oncology (ESMO) recommended d-MMR/MSI-H status evaluation in the diagnostic workflow of Lynch syndrome or selecting EC patients that could benefit from immune checkpoint inhibitors (ICIs). Although immunohistochemistry (IHC) is considered the gold standard approach for d-MMR profiling, a series of molecular PCR-based techniques have rapidly developed to integrate H-MSI status in routine practice. Here, we technically overviewed the most relevant commercially available diagnostic assays for the determination of the H-MSI/dMMR status in EC patients. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (cHL) consists of a heterogeneous group of haematological disorders that covers undifferentiated B cell neoplasms originating from germinal centre B cells. The HL molecular characterization still represents an ongoing challenge due to the low fraction of tumour Hodgkin and Reed–Sternberg cells mixed with a plethora of non‐tumour haematological cells. In this scenario, next generation sequencing of liquid biopsy samples is emerging as a useful tool in HL patients' management. In this review, we aimed to overview the clinical and methodological topics regarding the implementation of molecular analysis in cHL, focusing on the role of liquid biopsy in diagnosis, follow‐up, and response prediction. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the use of liposomal-encapsulated doxorubicin in the treatment of primary mediastinal large B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma (MGZL). The study examined the efficacy and safety of a new treatment regimen called R-COMP-DIx6, which included a higher dose of the medication. The study found that the treatment resulted in a high rate of complete metabolic response and was well-tolerated with minimal side effects. However, the study had limitations, including a small sample size and a long duration of data collection. Further research is needed to validate these findings in a larger clinical trial. [Extracted from the article]

Fine‐needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US‐guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade‐long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next‐generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports. [ABSTRACT FROM AUTHOR]

Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays., Methods: A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen's (dual) and Fleiss (triple) κ coefficients., Results: In-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%., Conclusions: In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays., Competing Interests: Competing interests: EG-R has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants and non-financial support) with AstraZeneca, Exact Sciences, GlaxoSmithKline (GSK), Novartis, Roche, Thermo Fisher Scientific unrelated to the current work. MF reports research funding (to Institution) from QED, Macrophage pharma, Astellas, Diaceutics; personal honoraria as invited speaker from Roche, Astellas, AstraZeneca, Incyte, Bristol Myers Squibb (BMS), Merck Serono, Pierre Fabre, GSK, Novartis, Amgen; participation in advisory board for Amgen, Astellas, Roche, Merck Serono, GSK, Novartis, Janssen unrelated to the current work. NF reports honoraria from Merck Sharp and Dohme (MSD), Boehringer Ingelheim, Novartis, AstraZeneca and Daiichi Sankyo unrelated to the current work. CDA Consulting/Advisor: Roche, AstraZeneca, Lilly, GSK, Novartis, Pfizer, Seagen Honoraria: Novartis, Pfizer, Lilly. Research funding to the institution: Novartis, Daiichi Sankyo. Travel, accommodation, expenses: Roche, AstraZeneca, Lilly, GSK, Novartis, Celgene, Pfizer unrelated to the current work. GV reports speaking honoraria from PharmaMar, AstraZeneca, Roche, Clovis and GSK-Tesaro and travel grants from GSK-Tesaro and PharmaMar and has been part of the advisory boards of Tesaro, Amgen and PharmaMar outside of the submitted work. UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. GT reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. MB has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD Oncology, Roche/Genetech, AstraZeneca, Thermo Fisher Scientific, GSK and Illumina unrelated to the current work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cell-free DNA (cfDNA) has long been established as a useful diagnostic and prognostic tool in a variety of clinical settings, ranging from infectious to cardiovascular and neoplastic diseases. However, non-neoplastic diseases can act as confounders impacting on the amount of cfDNA shed in bloodstream and on technical feasibility of tumour derived free circulating nucleic acids selecting patients with cancer. Here, we investigated the potential impact of other pathological processes in the clinical stratification of 637 FIT+ patients. A single and multiple logistic regression yielded similar results. Crude sensitivity was 75.9% versus adjusted sensitivity of 74.1%, relative risk 0.9761 (0.8516 to 1.1188), risk difference 0.0181 (-0.0835 to 0.1199) and OR 0.9079 (0.5264 to 1.5658). Potential confounding effect from other source of cfDNA plays a pivotal role in the clinical stratification of FIT+ patients., Competing Interests: Competing interests: MSc, SSc, RC, HT, MSh, DC and SSh have a collaboration contract with the sponsor. FP has received personal fees (as consultant and/or speaker bureau) from Menarini unrelated to the current work. UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. GT reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)