Deep learning helps discriminate between autoimmune hepatitis and primary biliary cholangitis.

Background & Aims: Biliary abnormalities in autoimmune hepatitis (AIH) and interface hepatitis in primary biliary cholangitis (PBC) occur frequently, and misinterpretation may lead to therapeutic mistakes with a negative impact on patients. This study investigates the use of a deep learning (DL)-based pipeline for the diagnosis of AIH and PBC to aid differential diagnosis.

Methods: We conducted a multicenter study across six European referral centers, and built a library of digitized liver biopsy slides dating from 1997 to 2023.

6-Aza-2-Thiothymine as an Alternative Matrix for Spatial Proteomics with MALDI-MSI.

Matrix Assisted Laser Desorption/Ionisation-Mass Spectrometry Imaging (MALDI-MSI) is a well-established spatial omic technique which enables the untargeted mapping of various classes of biomolecules, including tryptic peptides, directly on tissue. This method relies on the use of matrices for the ionisation and volatilisation of analytes, and α-Cyano-4-hydroxycinnamic acid (CHCA) represents the most widespread matrix for tryptic peptides analysis. However, CHCA also presents certain limitations that foster the quest for novel matrix compounds.

Sequential MALDI-HiPLEX-IHC and Untargeted Spatial Proteomics Mass Spectrometry Imaging to Detect Proteomic Alterations Associated with Tumour Infiltrating Lymphocytes.

MALDI-HiPLEX-IHC mass spectrometry imaging (MSI) represents a newly established workflow to map tens of antibodies linked to photocleavable mass tags (PC-MTs), which report the distribution of antigens in formalin-fixed paraffin-embedded (FFPE) tissue sections. While this highly multiplexed approach has previously been integrated with untargeted methods, the possibility of mapping target cell antigens and performing bottom-up spatial proteomics on the same tissue section has yet to be explored. This proof-of-concept study presents a novel workflow combining MALDI-HiPLEX-IHC with untargeted spatial proteomics to analyze a single FFPE tissue section, using clinical clear cell renal cell carcinoma (ccRCC) tissue as a model.

Automate the process of formalin-fixed paraffin-embedded blocks storage in the pathology laboratory: A proof of concept study.

Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals' working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena.

Spatially Resolved Molecular Characterization of Noninvasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features (NIFTPs) Identifies a Distinct Proteomic Signature Associated with RAS-Mutant Lesions.

Follicular-patterned thyroid neoplasms comprise a diverse group of lesions that pose significant challenges in terms of differential diagnosis based solely on morphologic and genetic features. Thus, the identification of easily testable biomarkers complementing microscopic and genetic analyses is a highly anticipated advancement that could improve diagnostic accuracy, particularly for noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). These tumors exhibit considerable morphological and molecular heterogeneity, which may complicate their distinction from structurally similar neoplasms, especially when genetic analyses reveal shared genomic alterations (e.

Detecting BRAF mutations in colorectal cancer in clinical practice: An Italian experts' position paper.

BRAF p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated BRAF p.

Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.

Background: Anaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians.

Digital transition in pathology lab: a survey from the Lombardy region.

Objective: Digital pathology is an opportunity to revise the routine and old artisanal workflow, moving to standard operating procedures, quality control and reproducibility. Here the results of a survey promoted by the Coordinamento della Medicina di Laboratorio (CRC Med Lab) of the Lombardy region in Italy are reported to shed light on the current situation of digital adoption in the country.

Methods: The survey composed of 58 questions was sent to 60 pathology laboratories.

A Transcriptomic Analysis of Laryngeal Dysplasia.

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery.

Machine Learning Streamlines the Morphometric Characterization and Multiclass Segmentation of Nuclei in Different Follicular Thyroid Lesions: Everything in a NUTSHELL.

The diagnostic assessment of thyroid nodules is hampered by the persistence of uncertainty in borderline cases and further complicated by the inclusion of noninvasive follicular tumor with papillary-like nuclear features (NIFTP) as a less aggressive alternative to papillary thyroid carcinoma (PTC). In this setting, computational methods might facilitate the diagnostic process by unmasking key nuclear characteristics of NIFTP. The main aims of this work were to (1) identify morphometric features of NIFTP and PTC that are interpretable for the human eye and (2) develop a deep learning model for multiclass segmentation as a support tool to reduce diagnostic variability.

Improving the Annotation Process in Computational Pathology: A Pilot Study with Manual and Semi-automated Approaches on Consumer and Medical Grade Devices.

The development of reliable artificial intelligence (AI) algorithms in pathology often depends on ground truth provided by annotation of whole slide images (WSI), a time-consuming and operator-dependent process. A comparative analysis of different annotation approaches is performed to streamline this process. Two pathologists annotated renal tissue using semi-automated (Segment Anything Model, SAM)) and manual devices (touchpad vs mouse).

Concurrent presence of primary hemangioma and breast cancer metastasis within a lymph node: a case report inspired by the legacy of Professor Juan Rosai.

Secondary neoplastic lesions in lymph nodes are predominantly metastases from solid tumors, whereas primary lymph node hemangiomas are exceptionally uncommon, with only 24 well-documented cases in the literature. Histologically, they are characterized by endothelial cells that may appear flattened or enlarged, with variable vascular density, and the presence of stromal elements. Notably, the concurrent presence of a primary hemangioma and a metastasis from breast cancer - the latter being the most prevalent secondary lesion in axillary lymph nodes - represents an unprecedented observation.

The value of the current histological scores and classifications of ANCA glomerulonephritis in predicting long-term outcome.

Background: Three different histological scores-histopathologic classification (Berden), Renal Risk Score (RRS) and the Mayo Clinic Chronicity Score (MCCS)-for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) were compared to evaluate their association with patient and kidney prognosis of ANCA-GN.

Methods: Patients aged >18 years with at least 1 year of follow-up and biopsy-proven ANCA-GN entered this retrospective study. Renal biopsies were classified according to Berden's classification, RRS and MCCS.

The phenotypic landscape of primary biliary cholangitis and autoimmune hepatitis variants.

Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) stand as distinct diseases, yet occasionally intertwine with overlapping features, posing diagnostic and management challenges. This recognition traces back to the 1970s, with initial case reports highlighting this complexity. Diagnostic scoring systems like IAIHG and simplified criteria for AIH were introduced but are inherently limited in diagnosing variant syndromes.

Feasibility of MALDI-MSI-Based Proteomics Using Bouin-Fixed Pathology Samples: Untapping the Goldmine of Nephropathology Archives.

The application of innovative spatial proteomics techniques, such as those based upon matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology, has the potential to impact research in the field of nephropathology. Notwithstanding, the possibility to apply this technology in more routine diagnostic contexts remains limited by the alternative fixatives employed by this ultraspecialized diagnostic field, where most nephropathology laboratories worldwide use bouin-fixed paraffin-embedded (BFPE) samples. Here, the feasibility of performing MALDI-MSI on BFPE renal tissue is explored, evaluating variability within the trypsin-digested proteome as a result of different preanalytical conditions and comparing them with the more standardized formalin-fixed paraffin-embedded (FFPE) counterparts.

Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms.

Introduction: Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs.

Pathology Laboratory Archives: Conservation Quality of Nucleic Acids and Proteins for NSCLC Molecular Testing.

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.

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.

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.

Digital Pathology Applications for PD-L1 Scoring in Head and Neck Squamous Cell Carcinoma: A Challenging Series.

The assessment of programmed death-ligand 1 (PD-L1) combined positive scoring (CPS) in head and neck squamous cell carcinoma (HNSCC) is challenged by pre-analytical and inter-observer variabilities. An educational program to compare the diagnostic performances between local pathologists and a board of pathologists on 11 challenging cases from different Italian pathology centers stained with PD-L1 immunohistochemistry on a digital pathology platform is reported. A laboratory-developed test (LDT) using both 22C3 (Dako) and SP263 (Ventana) clones on Dako or Ventana platforms was compared with the companion diagnostic (CDx) Dako 22C3 pharm Dx assay.

Benchmarking digital displays (monitors) for histological diagnoses: the nephropathology use case.

Aim: The digital transformation of the pathology laboratory is being continuously sustained by the introduction of innovative technologies promoting whole slide image (WSI)-based primary diagnosis. Here, we proposed a real-life benchmark of a pathology-dedicated medical monitor for the primary diagnosis of renal biopsies, evaluating the concordance between the 'traditional' microscope and commercial monitors using WSI from different scanners.

Methods: The College of American Pathologists WSI validation guidelines were used on 60 consecutive renal biopsies from three scanners (Aperio, 3DHISTECH and Hamamatsu) using pathology-dedicated medical grade (MG), professional grade (PG) and consumer-off-the-shelf (COTS) monitors, comparing results with the microscope diagnosis after a 2-week washout period.