Molecular Pathology of Soft-tissue Neoplasms.

Clinically Relevant Molecular Pathology of Endometrial Cancer.

Molecular Pathology of Lung Cancer.

Molecular Pathology of Mature Lymphoid Neoplasms.

Molecular Pathology of Myeloid Neoplasms.

Molecular Pathology of Primary Central Nervous System Tumors: When and How Immunohistochemical Surrogates Inform Diagnosis.

Integrated biomarker and treatment correlates of prognosis in infant non-WNT/non-SHH medulloblastoma: a multinational retrospective cohort study.

Endometrial cancer incidence and mortality are rising globally, disproportionately affecting health systems facing diagnostic, therapeutic, and survivorship constraints. Rapid innovations-including the International Federation of Gynecology and Obstetrics (FIGO) 2023 staging, molecular classification, sentinel lymph node (SLN) mapping, evolving adjuvant strategies, immunotherapy, and digital tools-risk exacerbating inequities if implementation mismatches system readiness. This narrative review synthesizes key trials, international guidelines, and high-impact implementation studies published between 2010 and September 2025. We summarize contemporary evidence across staging, molecular pathology, imaging, surgery, radiotherapy, systemic therapy, survivorship, equity, and artificial intelligence (AI), translating this into a pragmatic, resource-stratified framework. A previously published principal-component-based structural-readiness clustering model encompassing 68 countries is applied-but not re-derived-to illustrate how health-system capacity shapes access to diagnostics, treatment, and innovation. Persistent gaps include limited availability of universal mismatch repair (MMR) and p53 immunohistochemistry, variable adoption of standardized SLN mapping, uneven radiotherapy access, restricted use of immunotherapy for mismatch-repair deficient (dMMR)/microsatellite instability high (MSI-H) tumors, and fragmented survivorship care. A minimum-core-optimal implementation ladder is proposed to guide diagnostic, surgical, radiotherapeutic, systemic-therapy, and survivorship priorities across varying resource levels. AI-supported quality assurance is discussed alongside essential requirements of local validation, bias mitigation, and robust governance. Rather than generating new empirical data, this review employs a cluster-informed, equity-oriented lens, applying previously validated system-level typologies to contextualize implementation gaps and support context-sensitive guideline adaptation.

Endometrial cancer: A Society of Gynecologic Oncology evidence-based review and recommendations, part II.

Multi-omics analysis reveals organ-specific oxidative stress, apoptosis, and ferroptosis-related signatures in Macrobrachium rosenbergii under ammonia-hypoxia co-stress.

Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers' genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.

Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of AD may help identify new ways to reduce neuronal damage. In the past decades, Drosophila has become a powerful tool in modelling mechanisms underlying human diseases. Here, we investigate how the expression of the human 42-residue β-amyloid (Aβ) carrying the E22G pathogenic 'Arctic' mutation (Aβ42Arc) affects axonal health and behaviour in Drosophila. We find that Aβ42Arc flies present aberrant neurons, with altered axonal transport of mitochondria and aberrant terminal boutons at neuromuscular junctions. We demonstrate that the motor proteins kinesin-1 and kinesin-3 are essential for the correct development of neurons in Drosophila larvae and in human induced pluripotent stem cell-derived cortical neurons. We then show that the overexpression of kinesin-1 or kinesin-3 restores the correct number and morphology of boutons in Aβ42Arc-expressing neurons and rescues neuronal function measured by negative geotaxis locomotor behavioural assay. We therefore provide new evidence towards understanding the mechanisms of axonal transport defects in AD, and our results support the idea that kinesins should be considered as potential drug targets to help reduce dementia-associated disorders.

Proteotoxicity and tubular epithelial cell fate in acute kidney injury: Molecular insights and treatment strategies.

Concordance between intraoperative frozen section (FS) diagnosis and permanent section diagnosis is essential for quality assurance in pathology. However, in cases involving small lesions (≤ 1cm), tissue dehydration following FS processing often reduces visibility and hinders localization, leading to diagnostic discrepancies between FS and permanent sections. This study introduces nano-titanium dioxide (nano-TiO2) and Direct Black (DB) for intraoperative tissue marking to enhance tumor identification. Surgical specimens from lung, thyroid, and breast cancers (January 2024-March 2025) with tumors ≤ 1cm were included. Following FS diagnosis, tissues were marked using methylene blue, carbon nanoparticle suspension, nano-TiO2, and DB. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and reverse transcription polymerase chain reaction were applied to evaluate visibility, stability, and diagnostic impact. Nano-TiO2 and DB exhibited excellent visibility and tissue adherence across all three tumor types without interfering with H&E, immunomarkers (PD-L1, TTF-1, and HER2), or molecular pathology assays (EGFR and BRAF). Compared with unmarked specimens, marked tissues demonstrated higher concordance between FS and permanent diagnosis: Lung cancer (95% versus 84.38%), thyroid cancer (100% versus 81.25%), and breast cancer (100% versus 85.71%) (all p < 0.05). These findings indicate that nano-TiO2 and DB are safe, effective, and significantly improve intraoperative localization and diagnostic accuracy of small lesions. The method offers potential for workflow standardization and broader use in pathological practice.

Label-free optical absorption microscopy techniques continue to evolve as promising tools for label-free histopathological imaging of cells and tissues. However, critical challenges relating to specificity and contrast, as compared to current gold-standard methods continue to hamper adoption. This work introduces Photon Absorption Remote Sensing (PARS), a new absorption microscope modality, which simultaneously captures the dominant de-excitation processes following an absorption event. In PARS, radiative (auto-fluorescence) and non-radiative (photothermal and photoacoustic) relaxation processes are collected simultaneously, providing enhanced specificity to a range of biomolecules. As an example, a multiwavelength PARS system featuring UV (266nm) and visible (532nm) excitation is applied to imaging human skin, and murine brain tissue samples. It is shown that PARS can directly characterize, differentiate, and unmix, clinically relevant biomolecules inside complex tissues samples using established statistical processing methods. Gaussian mixture models (GMM) are used to characterize clinically relevant biomolecules (e.g., white, and gray matter) based on their PARS signals, while non-negative least squares (NNLS) is applied to map the biomolecule abundance in murine brain tissues, without stained ground truth images or deep-learning methods. PARS unmixing and abundance estimates are directly validated and compared against chemically stained ground truth images, and deep learning based-image transforms. Overall, it is found that the PARS unique and rich contrast may provide comprehensive, and otherwise inaccessible, label-free characterization of molecular pathology, representing a new source of data to develop AI and machine learning methods for diagnostics and visualization.

Molecular pathology has become acentral component of modern pathological diagnostics. With the increasing importance of therapeutically predictive biomarkers and complex molecular procedures, the technical and organizational demands on diagnostic practice are also growing. Natural scientists play an essential role within interdisciplinary teams, but until now their qualifications have not been systematically reflected in structured, standardized continuing education programs.Against this background, the Molecular Pathology Curriculum (CuMo) was developed. It is astructured, part-time continuing education program for scientists in molecular pathological diagnostics that builds on the existing skills of the participants and is closely linked to routine diagnostics. The curriculum combines theoretical training components with documented proof of practical experience and afinal professional examination.In addition to individual qualification, the curriculum promotes professional exchange and networking across institutional boundaries. CuMo sees itself as acomplementary building block for strengthening molecular pathology diagnostics and ensuring quality-assured expertise within pathology and neuropathology.

The increase in incidence of early-onset pancreatic cancer (EOPC) is of concern and poorly understood. The aim of this study was to investigate the clinical outcomes of surgically resected patients with EOPC and the potential molecular heterogeneity between EOPC and late age-onset disease. A retrospective cohort study was conducted, with clinical, pathological, and survival outcome data obtained from two large independent prospective cohorts curated by the Australian Pancreatic Genome Initiative (APGI) and the West of Scotland Pancreatic Unit (Glasgow Royal Infirmary) between 1997 and 2022. Patients were categorized into two age groups (<50 and ≥50 years) at time of diagnosis. Clinicopathological features and survival outcomes, in addition to gene expression and tumour microenvironment data, were compared between groups. In total, 851 patients were identified, of whom 68 (8%) were aged <50 years. EOPC was associated with significantly earlier recurrence after surgery (median disease-free survival (DFS) 10.9 versus 14.2 months; P = 0.011) and there was no statistically significant difference in disease-specific survival (median 19.9 versus 23.8 months; P = 0.117). There were no differences in validated clinicopathological variables to account for the shorter DFS in the EOPC group. Despite an increased proportion of patients with EOPC receiving adjuvant chemotherapy (P = 0.032), DFS was significantly worse (DFS 12.6 versus 16.0 months; P = 0.022). EOPC demonstrated enrichment of genes associated with more aggressive molecular pathology and the squamous (basal-like) molecular subtype of pancreatic ductal adenocarcinoma, including S100A2 (P < 0.001) and TP63 (P = 0.044), and down-regulation of GATA6 (P = 0.016). EOPC is associated with a shorter time to recurrence and more aggressive, adverse molecular pathology.

Dr. Dilek Colak is an Associate Professor of Neuroscience at the Feil Family Brain and Mind Research Institute and Associate Professor of Pediatrics at the Gale and Ira Drukier Institute for Children's Health, both at Weill Cornell Medicine in New York City. Her scientific training began in Germany, where she pursued doctoral work at the Max Planck Institute of Neurobiology and the Helmholtz Center's Stem Cell Institute in Munich under the mentorship of Dr. Magdalena Götz, laying the foundation for her enduring interest in the cellular logic of brain development. She relocated to New York in 2009 for postdoctoral research in the laboratory of Dr. Samie Jaffrey in the Department of Pharmacology at Weill Cornell Medicine, where she uncovered an RNA-directed silencing mechanism implicated in Fragile X Syndrome, a discovery that reshaped her thinking about translational opportunities in neuropsychiatric disease and prompted her transition to an independent faculty position in 2015. Now promoted to Associate Professor, she leads a research program that integrates genetically engineered mouse models and human stem cell-derived brain organoids to investigate how glial cell dysfunction and RNA regulation shape the cellular and molecular pathology of neurodevelopmental and neuropsychiatric disorders, with particular attention to autism and schizophrenia. Her dual appointment positions her at the interface of molecular neuroscience and pediatric medicine, where she champions rigorous methodology, collaborative integrity, and the scrutiny of long-standing dogmas. In this Genomic Press Interview, Dr. Colak is happy to share reflections on her life and career with our readers.

XVIIth Banff Conference on Allograft Pathology: The Banff Workshop Heart Report on Microvascular Inflammatory Burden in Heart Transplantation and the Impact of Molecular and Non-Invasive Diagnostic Tools.

Bridging the gap between tumor evolution and clonality diagnostics in multiple lung carcinomas.