Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.

Background: Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule.

Methods: To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients' sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets.

Immunohistochemical Expression of PAX8 in Central Nervous System Hemangioblastomas: A Potential Diagnostic Pitfall for Neuropathologists.

The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak.

A Diagnostic Approach in Large B-Cell Lymphomas According to the Fifth World Health Organization and International Consensus Classifications and a Practical Algorithm in Routine Practice.

In this article, we provide a review of large B-cell lymphomas (LBCLs), comparing the recently published fifth edition of the WHO classification and the International Consensus Classification (ICC) on hematolymphoid tumors. We focus on updates in the classification of LBCL, an heterogeneous group of malignancies with varying clinical behaviors and different pathological and molecular features, providing a comparison between the two classifications. Besides the well-recognized diagnostic role of clinical, morphological and immunohistochemical data, both classifications recognize the ever-growing impact of molecular data in the diagnostic work-up of some entities.

Primary and Metastatic Pancreatic Ewing Sarcomas: A Case Report and Review of the Literature.

Ewing sarcomas are rare tumors arising mainly in the bones and the surrounding soft tissues. Primary extraosseous Ewing sarcomas have also been described in several other organs and locations other than bones, including the pancreas. These tumors have well-defined histological, immunohistochemical, and molecular characteristics.

Clinico-Pathological Features of Diffuse Midline Glioma, H3 K27-Altered in Adults: A Comprehensive Review of the Literature with an Additional Single-Institution Case Series.

Diffuse midline glioma (DMG), H3 K27-altered, is a WHO grade 4 malignant glioma located at midline structures, including the thalamus, brainstem and spinal cord. While H3 K27-altered DMG is more common in pediatric age in which it shows a uniformly aggressive clinical behavior, its occurrence is relatively unusual among adults, and its clinico-pathological and prognostic features are not fully characterized in this age group. In this present paper, a review of the literature, including all cases of adult H3 K27-altered DMG published from January 2010 to December 2023 was performed, and the following clinical parameters were evaluated: sex, age (median and range), anatomic site, median follow-up, leptomeningeal dissemination, local recurrence and treatment.

Application of Additive Manufacturing in Assisted Reproductive Techniques: What Is the Evidence? A Clinical and Technical Systematic Review of the Literature.

This article investigates the transformative impact of 3D and bio 3D printing technologies in assisted reproductive technology (ART), offering a comprehensive review of their applications in improving reproductive outcomes. Following PRISMA guidelines, we conducted a thorough literature search focusing on the intersection of ART and additive manufacturing, resulting in the inclusion of 48 research papers. The study highlights bio 3D printing's potential in revolutionizing female infertility treatments, especially in follicle complex culture and ovary printing.

Artificial Intelligence in Head and Neck Cancer Diagnosis: A Comprehensive Review with Emphasis on Radiomics, Histopathological, and Molecular Applications.

The present review discusses the transformative role of AI in the diagnosis and management of head and neck cancers (HNCs). It explores how AI technologies, including ML, DL, and CNNs, are applied in various diagnostic tasks, such as medical imaging, molecular profiling, and predictive modeling. This review highlights AI's ability to improve diagnostic accuracy and efficiency, particularly in analyzing medical images like CT, MRI, and PET scans, where AI sometimes outperforms human radiologists.

The emerging role of artificial intelligence in neuropathology: Where are we and where do we want to go?

The field of neuropathology, a subspecialty of pathology which studies the diseases affecting the nervous system, is experiencing significant changes due to advancements in artificial intelligence (AI). Traditionally reliant on histological methods and clinical correlations, neuropathology is now experiencing a revolution due to the development of AI technologies like machine learning (ML) and deep learning (DL). These technologies enhance diagnostic accuracy, optimize workflows, and enable personalized treatment strategies.

Line-Field Confocal Optical Coherence Tomography Imaging of Psoriasis With Histopathology Correlation.

Line-field confocal optical coherence tomography (LC-OCT) is a novel imaging technique for in vivo examination of the skin that has recently been introduced in the dermatologic armamentarium of non-invasive diagnostic tools. Its usefulness in the diagnosis and treatment monitoring of some neoplastic, inflammatory, and infectious skin conditions has been demonstrated. The aim of this study was to evaluate the LC-OCT features of psoriasis in a large number of psoriatic plaques along with their histopathologic correlation.

H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications.

Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.

Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma.

Background: Cancer onset and progression are driven by genetic and epigenetic alterations leading to oncogene activation and the silencing of tumor suppressor genes. Among epigenetic mechanisms, DNA methylation (methDNA) is gaining growing interest in cancer. Promoter hypomethylation is associated with oncogene activation while intragenic methDNA can be involved in transcriptional elongation, alternative spicing, and the activation of cryptic start sites.

Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court.

Purpose: Ponticulus posticus (PP) is a bony protrusion located between the posterior portion of the superior articular process and the posterolateral portion of a posterior arch of the atlas vertebrae in the cervical spine. The aim of this study is to verify the presence of different types of PP in a Southern Italian pre-orthodontic cohort to understand its correlation with skeletal class and maturity.

Methods: A case-control retrospective study was conducted, utilizing 212 latero-lateral telecranium radiographs to analyze skeletal maturity according to the cervical vertebral maturation method, the Angle's classification of malocclusion (I, II, or III), and the presence or absence of the PP, whether complete (c-PP) or partial (p-PP).

Programmed Death Ligand 1 (PD-L1) Expression in Lymphomas: State of the Art.

The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis.

Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas.

CYP7B1 as a Biomarker for Prostate Cancer Risk and Progression: Metabolic and Oncogenic Signatures (Diagnostic Immunohistochemistry Analysis by Tissue Microarray in Prostate Cancer Patients-Diamond Study).

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression.

Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers.

Pharmacological enhancement of cholinergic neurotransmission alleviates neuroinflammation and improves functional outcomes in a triple transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Due to the multifactorial nature of the disease, involving impairment of cholinergic neurotransmission and immune system, previous attempts to find effective treatments have faced challenges. In such scenario, we attempted to investigate the effects of alpha-glyceryl-phosphoryl-choline (α-GPC), a cholinomimetic molecule, on neuroinflammation and memory outcome in the triple transgenic mouse model of AD (3xTg-AD).

Methylation‑sensitive restriction enzyme‑droplet digital PCR assay for the one‑step highly sensitive analysis of DNA methylation hotspots.

DNA methylation is an epigenetic modification that plays a key role in several cellular processes mediating the fine regulation of gene expression. Aberrant DNA methylation is observed in a wide range of pathologies, including cancer. Since these DNA modifications are transferred to the cell progenies and are stable over the time, the analysis of DNA methylation status has been proposed for diagnostic and prognostic purposes in cancer.

Analysis of a Combination Therapy Protocol for the Treatment of Oral Mucous Membrane Pemphigoid: A Retrospective Case Series Study.

Mucous membrane pemphigoid (MMP) is an autoimmune-based bullous disease affecting the mucous membranes, mainly oral and ocular. One of the most common clinical manifestations is desquamative gingivitis (DG), characterized by intense symptoms and functional limitations. The dentist is among the first specialists to observe DG and, therefore, must be able to diagnose it.

Co-occurrence of mutation and translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination.

Myeloproliferative neoplasms (MPNs) are classified into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. translocation is the key genetic event of CML, whereas mutations are molecular aberrations of Ph-negative MPNs. Despite initially considered mutually exclusive genetic aberrations, the co-occurrence of and has been reported in a limited number of cases.

Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists.

Although novel knowledge has been acquired on the molecular landscape of glioblastoma (GBM), a relatively few steps forward have been made regarding its therapy. With the increasing use of novel immunotherapeutic drugs capable of stimulating the antitumor inflammatory response, in the last decades numerous studies aimed to characterize the tumor-associated microenvironment (TME) and its relationship with the immunogenicity of GBM. In this regard, although the tumor-associated microglia and macrophages (TAMs) and PD-L1/PD-1 axis have been emerged as one of the most relevant components of the GBM TME and one of the potential molecular pathways targetable with immunotherapy, respectively.