Liquid biopsy testing in urological cancers: Focus on urine.

Liquid biopsy has significantly transformed the management of patients with urological cancers. In particular, alternative sources of tumor nucleic acids and analytes beyond blood have taken on a crucial role in these malignancies. In this context, urine represents a valuable alternative to blood and should be considered within an expanded concept of liquid biopsy.

Smaller, cheaper, faster: where next for liquid biopsies?

Introduction: Liquid biopsy (LB) has shifted the paradigm in cancer diagnosis and management, offering a minimally invasive and dynamic approach to understanding tumor biology. Advanced next-generation sequencing (NGS) technologies have significantly improved the accuracy of LB results, enhancing both its analytical and clinical validity. However, tissue biopsy (TB) remains the gold standard for molecular analysis, often negatively impacting the molecular profiling of tumor patients owing to inadequate tissue samples, or lack thereof.

The routine use of a digital tool for the tumor cell fraction quantification in molecular pathology: an international validation of QuANTUM.

Objective: The absolute and relative quantification of tumor cell fraction (TCF) in tissue samples for molecular pathology testing is time-consuming and poorly reproducible.

Methods: Here we report the results of an international survey on non-small cell lung cancer (NSCLC), validating the Qupath Analysis of Nuclei from Tumor to Uniform Molecular tests (QuANTUM) automated computational pipeline for TCF quantification.

Results: The TCF obtained with QuANTUM is reliable, as demonstrated by the comparison with the manual counting of cells (ground truth, GT) in cell blocks, small biopsies and surgical specimens (overall correlation of 0.

Cancer in a drop: Advances in liquid biopsy in 2024.

Over the past decade, liquid biopsy (LB) has emerged as a key tool in oncology. Its utility in non-invasive sampling and real-time monitoring has made it a cornerstone in precision medicine. Since 2020, publications on LB in solid tumors have doubled, underscoring its pivotal role in advancing cancer care.

Biologics for novel driver altered non-small cell lung cancer: potential and pitfalls.

Precision medicine has revolutionized clinical paradigm of lung cancer (LC) patients optimizing therapeutical options on the basis of molecular fingerprinting of tumor cells. The advent of the genomic era contributed to the widespread diffusion of sequencing technologies laying the basis for the approval of an increasing number of clinically relevant predictive biomarkers in clinical settings. In the rapidly evolving scenario of predictive biomarkers, mandatory testing genes demonstrated a statistically significant clinical benefit in LC patients elected to molecular tests, but emerging biomarkers are under investigation to raise the bar in the clinical management of LC patients.

Liquid Biopsy in Solid Tumours: An Overview.

The advent of personalised and precision medicine has radically modified the management and the clinical outcome of cancer patients. However, the expanding number of predictive, prognostic, and diagnostic biomarkers has raised the need for simple, noninvasive, quicker, but equally efficient tests for molecular profiling. In this complex scenario, the adoption of liquid biopsy, particularly circulating tumour DNA (ctDNA), has been a real godsend for many cancer patients who would otherwise have been denied the benefits of targeted treatments.

A challenging case of enteric-type lung adenocarcinoma metastatic to the thyroid harboring RET-fusion diagnosed on fine-needle aspiration.

Enteric-type lung adenocarcinoma is a histological entity where the enteric component exceeds 50% and must show the expression of at least one immunohistochemical marker of enteric differentiation. The most common differential diagnosis is colorectal carcinoma. Molecular alterations less commonly observed in colorectal adenocarcinoma but more frequently associated with enteric-type lung adenocarcinoma can be helpful in differential diagnosis.

Liquid biopsy through non-blood fluids: The show must go on.

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Rare epithelial gastric cancers: a review of the current treatment knowledge.

Gastric cancer (GC), one of the tumours with the highest mortality worldwide, is not a homogeneous disease, showing different features according to location, macroscopic aspect, histotype and molecular alterations. Adenocarcinoma is the most frequent epithelial GC (95%), the remaining 5% comprising rare epithelial tumours with their peculiarities, behaviour and incidence <6 cases/100,000/year. Due to the low number of cases, many aspects must be elucidated in this context.

On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study.

Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index.

Interventional cytopathologist perspective on the Milan System Classification: a study on 929 consecutive salivary gland fine-needle aspirations with a focus on challenging diagnostic categories.

Background: Although the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has improved the diagnosis and management of salivary gland lesions, determining the risk of malignancy (ROM) for AUS and SUMP categories remains challenging. We investigated the role of interventional cytopathologists in refining the differential diagnosis of these categories.

Methods: We searched for salivary gland fine-needle aspirations (FNAs) performed at our Institution since the publication of the first edition of MSRSGC.

RNA-Based Next-Generation Sequencing in Non-Small Cell Lung Cancer patients: data from Campania, Italy.

Objective: ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations represent fundamental predictive biomarkers for advanced non-small cell lung cancer (NSCLC) patients to ensure the best treatment choice. In this scenario, RNA-based NGS approach has emerged as an extremely useful tool for detecting these alterations. In this study, we report our NGS molecular records on ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations detected by using a narrow RNA-based NGS panel, namely SiRe fusion.

The relevance of the reference range for EGFR testing in non-small cell lung cancer patients.

Introduction: Identifying mutations in the epidermal growth factor receptor (EGFR) gene is crucial for individualized treatment of non-small cell lung cancer (NSCLC) patients. Accordingly, several methodologies and instruments are now commercially available to detect these alterations. The aim of this study was to examine the performance of next generation sequencing (NGS) in detecting both common and uncommon EGFR gene mutations in advanced NSCLC patients.

The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

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.

Computer-assisted urine cytology: Faster, cheaper, better?

Recent advancements in computer-assisted diagnosis (CAD) have catalysed significant progress in pathology, particularly in the realm of urine cytopathology. This review synthesizes the latest developments and challenges in CAD for diagnosing urothelial carcinomas, addressing the limitations of traditional urinary cytology. Through a literature review, we identify and analyse CAD models and algorithms developed for urine cytopathology, highlighting their methodologies and performance metrics.

Current role of cytopathology in the molecular and computational era: The perspective of young pathologists.

Cytopathology represents a well established diagnostic approach because of its limited cost, reliability, and minimal invasiveness with respect to other methodologies. The evolving complexity of the different classifications systems and the implementation of ancillary techniques to refine the diagnosis is progressively helping in the risk of malignancy stratification, and the adoption of next-generation sequencing techniques contributes to enrich this valuable tool with predictive information, which is always more essential in the tailored medicine era. The recent introduction of digital and computational pathology is further boosting the potentialities of cytopathology, aiding in the interpretation of samples to improve the cost effectiveness of large screening programs and the diagnostic efficiency within intermediate/atypical categories.

Economic assessment of NGS testing workflow for NSCLC in a healthcare setting.

Background: The molecular diagnostic and therapeutic pathway of Non-Small Cell Lung Cancer (NSCLC) stands as a successful example of precision medicine. The scarcity of material and the increasing number of biomarkers to be tested have prompted the routine application of next-generation-sequencing (NGS) techniques. Despite its undeniable advantages, NGS involves high costs that may impede its broad adoption in laboratories.

A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers.

Despite recent advances, biliary tract cancer (BTC) remains one of the most lethal tumor worldwide due to late diagnosis, limited therapeutic strategies and resistance to conventional therapies. In recent years, high-throughput technologies have enabled extensive genome, and transcriptome sequencing unveiling, among others, the regulatory potential of microRNAs (miRNAs). Compelling evidence shown that miRNA are attractive therapeutic targets and promising candidates as biomarkers for various therapy-resistant tumors.

The biomarkers ATLAS: An audit on 1100 non-small cell lung cancer from an Italian knowledge-based database.

Aims: To date, precision medicine has revolutionized the clinical management of Non-Small Cell Lung Cancer (NSCLC). International societies approved a rapidly improved mandatory testing biomarkers panel for the clinical stratification of NSCLC patients, but harmonized procedures are required to optimize the diagnostic workflow. In this context a knowledge-based database (Biomarkers ATLAS, https://biomarkersatlas.

Interobserver variability in cytopathology: How much do we agree?

Interobserver variability remains a major challenge for cytopathologists despite the development of standardized reporting and classification systems. Indeed, whereas moderate-to-good interobserver agreement is generally achievable when the differential diagnosis between benign and malignant entities is straightforward, high levels of variability make the diagnostic interpretation of atypical and suspicious samples not consistent. This review explores the landscape of interobserver agreement in cytopathology across different anatomical sites.

testing in hormone receptor-positive/HER2-negative metastatic breast cancer: real-world data from Italian molecular pathology laboratories.

gene mutations occur in approximately 40% of hormone receptor-positive/HER2-negative (HR/HER2) metastatic breast cancers (MBCs), electing them to targeted therapy. Testing status is complex due to selection of biological specimen and testing method. This work investigates real-life experience on testing in HR/HER2 MBC.

Molecular testing in salivary gland cytopathology: A practical overview in conjunction with the Milan system.

Recently, significant advances in the molecular characterization of salivary gland neoplasms have facilitated the classification and diagnosis of specific diagnostic entities. In the highly challenging diagnostic scenario of salivary malignancies, molecular testing is increasingly being adopted in routine practice to refine the cytological diagnosis of salivary lesions. Here, we reviewed the most recent evidence in the field of salivary glands molecular cytopathology.