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Objectives: The high incidence of prostate cancer causes prostatic samples to significantly affect pathology laboratories workflow and turnaround times (TATs). Whole-slide imaging (WSI) and artificial intelligence (AI) have both gained approval for primary diagnosis in prostate pathology, providing physicians with novel tools for their daily routine. Methods: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was carried out in electronic databases to gather the available evidence on the application of AI-based algorithms to prostate cancer. Results: Of 6290 articles, 80 were included, mostly (59%) dealing with biopsy specimens. Glass slides were digitized to WSI in most studies (89%), roughly two-thirds of which (66%) exploited convolutional neural networks for computational analysis. The algorithms achieved good to excellent results about cancer detection and grading, along with significantly reduced TATs. Furthermore, several studies showed a relevant correlation between AI-identified histologic features and prognostic predictive variables such as biochemical recurrence, extraprostatic extension, perineural invasion, and disease-free survival. Conclusions: The published evidence suggests that AI can be reliably used for prostate cancer detection and grading, assisting pathologists in the time-consuming screening of slides. Further technologic improvement would help widening AI's adoption in prostate pathology, as well as expanding its prognostic predictive potential.

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis (N=361) from 23 centers in North America, Europe and Asia were independently scored by 3 pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients (N=309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using Latent Class Mixed Models (LCMM) to identify classes of eGFR trajectories over a median follow-up of 2.7 years (IQR 1.2, 5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. Results: M, E, T and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by LCMM, one with initial improvement in eGFR followed by a late decline (Class 1, N=91) and another with stable eGFR (Class 2, N=218). Class 1 was associated with a higher risk of an established kidney outcome (time to >30% decline in eGFR or kidney failure, HR 5.84, 95%CI 2.37, 14.4). Among MEST-C scores, only E1 was associated with Class 1 by multivariable analysis. Other factors associated with Class 1 were age <18 years, male sex, lower eGFR at biopsy, and extrarenal non-cutaneous disease. Fibrous crescents without active changes were associated with Class 2. Conclusions: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors, and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the ISKDC classification..

Transplantation of an organ from a donor carries an unavoidable risk of tumor transmission. The need to extend the donor pool increases the use of organs from donors with malignancies and potential disease transmission is a constant tension influencing donor suitability decisions. Current classification systems for the assessment of donor malignancy transmission risk have evolved from reports of potential transmission events in recipients to national donation and transplant surveillance agencies. Although the risk of malignancy transmission is very low in the general transplant setting it must constantly be balanced with the transplant benefits. Guidelines are mainly based on large registries and sparse case reports of transmission, so they cannot cover all the possible situations. For this reason, in 2004 in Italy, the National Transplant Center gave rise to the Second Opinion Service, charged by the Ministry of Health, by structuring expertise in diagnostic oncology and risk transmission and making it available to the Italian Transplant Centers. In this paper the registry of the Italian Oncological Second Opinion was reviewed, from 2016 to 2018, to detail the most frequent and problematic neoplastic topics addressed, those are separately reported and discussed. Furthermore, a review of the most recent strategies and risk stratification is provided, according to the most recent literature evidence and to the European Guidelines.

Background: Immunotherapy represented a turning point for treating extensive small-cell lung cancer (ES-SCLC). Although, many issues remain debated. Methods: A group of Italian medical and radiation oncologists with expertise in managing patients with ES-SCLC developed a list of statements divided in six areas of interest. The Delphi method was used to assess the consensus on the defined list of statements. Results: 32 statements were included in the final list to be voted by the Delphi panel, and 26 reached a consensus on the agreement. A prompt involvement of a multidisciplinary team is a priority to provide an integrated treatment strategy. First-line recommended treatment is immunotherapy in combination with platinum-based chemotherapy and etoposide for four cycles followed by maintenance immunotherapy. Conclusions: While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool to guide the management of ES-SCLC patients in daily practice.

Molecular biomarker testing is increasingly becoming standard of care for advanced non-small cell lung cancer (NSCLC). Tissue and liquid biopsy-based next-generation sequencing (NGS) is now highly recommended and has become an integral part of the routine management of advanced NSCLC patients. This highly sensitive approach can simultaneously and efficiently detect multiple biomarkers even in scant samples. However full optimization of NGS in clinical practice requires accurate reporting and interpretation of NGS findings. Indeed, as the number of NSCLC biomarkers continues to grow, clinical reporting of NGS data is becoming increasingly complex. In this scenario, achieving standardization, simplification, and improved readability of NGS reports is key to ensuring timely and appropriate treatment decisions. In an effort to address the complexity and lengthy reporting of NGS mutation results, an Italian group of 14 healthcare professionals involved in NSCLC management convened in 2023 to address the content, structure, and ease-of-use of NGS reporting practices and proposed a standard report template for clinical use This article presents the key discussion points addressed by the Italian working group and describes the essential elements of the report template.

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. This study aims to assess the detailed costs linked to the integration of NGS diagnostics in NSCLC to comprehend their financial impact. Materials and methods: The retrospective analysis encompasses 210 cases of early and advanced stages NSCLC, analyzed with NGS and collected at the IRCCS San Gerardo dei Tintori Foundation (Monza, Italy). Molecular analyses were conducted on FFPE samples, with an hotspot panel capable of detecting DNA and RNA variants in 50 clinically relevant genes. The economic analysis employed a full-cost approach, encompassing direct and indirect costs, overheads, VAT (Value Added Tax). Results: We estimate a comprehensive cost for each sample of €1048.32. This cost represents a crucial investment in terms of NSCLC patients survival, despite constituting only around 1% of the expenses incurred in their molecular diagnostic and therapeutic pathway. Conclusions: The cost comparison between NGS test and the notably higher therapeutic costs highlights that the diagnostic phase is not the limiting economic factor. Developing NGS facilities structured in pathology networks may ensure appropriate technical expertise and efficient workflows.

In the molecular era, proper archival conditions within pathology laboratories are crucial, especially for formalin-fixed paraffin-embedded (FFPE) tissue specimens retrieved years after the original diagnosis. Indeed, improper preservation can impact the integrity of nucleic acids and protein antigens. This study evaluates the quality status of stored FFPE blocks using multilevel omics approaches. FFPE blocks from 45 Non-Small Cell Lung Carcinoma (NSCLC) cases were analyzed. The blocks were collected from six different pathology archives across Italy with distinct environmental characteristics. Nucleic acids' quantity and quality, as well as protein antigens, were assessed using various techniques, including MALDI-MSI. RNA was quantitatively higher, but more fragmented, compared to DNA. DNA quantity and quality were suitable for molecular analyses in 94.4% and 62.3% of samples, respectively. RNA quantity was adequate across all samples, but it was optimal only in 22.3% of cases. DNA quality started to deteriorate after 6-8 years, whereas RNA quality diminished only after 10 years of storage. These data might suggest a particular DNA susceptibility to FFPE blocks conservation. Immunohistochemical intensity decreased significantly after 6-8 years of storage, and MALDI-MSI analysis revealed that younger tissue blocks contained more unique proteomic signals than the older ones. This study emphasizes the importance of proper FFPE archiving conditions for molecular analyses. Governance should prioritize attention to pathology archives to ensure quality preservation and optimize predictive testing. By elucidating the nuances of FFPE block storage, this research paves the way for enhanced molecular diagnostics and therapeutic insights regarding oncology and beyond.

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.com/) was developed by a supervising group of expert pathologists and thoracic oncologists collecting updated clinical and molecular records from about 80 referral Italian institutions. Here, we audit molecular and clinical data from n = 1100 NSCLC patients collected from January 2019 to December 2020. Methods: Clinical and molecular records from NSCLC patients were retrospectively collected from the two coordinating institutions (University of Turin and University of Naples). Molecular biomarkers (KRAS, EGFR, BRAF, ROS1, ALK, RET, NTRK, MET) and clinical data (sex, age, histological type, smoker status, PD-L1 expression, therapy) were collected and harmonized. Results: Clinical and molecular data from 1100 (n = 552 mutated and n = 548 wild-type) NSCLC patients were systematized and annotated in the ATLAS knowledge-database. Molecular records from biomarkers testing were matched with main patients’ clinical variables. Conclusions: Biomarkers ATLAS (https://biomarkersatlas.com/) represents a unique, easily managing, and reliable diagnostic tool aiming to integrate clinical records with molecular alterations of NSCLC patients in the real-word Italian scenario.

The estimation of tumor cellular fraction (TCF) is a crucial step in predictive molecular pathology, representing an entry adequacy criterion also in the next-generation sequencing (NGS) era. However, heterogeneity of quantification practices and inter-pathologist variability hamper the robustness of its evaluation, stressing the need for more reliable results. Here, 121 routine histological samples from non-small cell lung cancer (NSCLC) cases with complete NGS profiling were used to evaluate TCF interobserver variability among three different pathologists (pTCF), developing a computational tool (cTCF) and assessing its reliability vs ground truth (GT) tumor cellularity and potential impact on the final molecular results. Inter-pathologist reproducibility was fair to good, with overall Wk ranging between 0.46 and 0.83 (avg. 0.59). The obtained cTCF was comparable to the GT (p = 0.129, 0.502, and 0.130 for surgical, biopsies, and cell block, respectively) and demonstrated good reliability if elaborated by different pathologists (Wk = 0.9). Overall cTCF was lower as compared to pTCF (30 ± 10 vs 52 ± 19, p < 0.001), with more cases < 20% (17, 14%, p = 0.690), but none containing < 100 cells for the algorithm. Similarities were noted between tumor area estimation and pTCF (36 ± 29, p < 0.001), partly explaining variability in the human assessment of tumor cellularity. Finally, the cTCF allowed a reduction of the copy number variations (CNVs) called (27 vs 29, − 6.9%) with an increase of effective CNVs detection (13 vs 7, + 85.7%), some with potential clinical impact previously undetected with pTCF. An automated computational pipeline (Qupath Analysis of Nuclei from Tumor to Uniform Molecular tests, QuANTUM) has been created and is freely available as a QuPath extension. The computational method used in this study has the potential to improve efficacy and reliability of TCF estimation in NSCLC, with demonstrated impact on the final molecular results.