The space of Retzius is a clinically important but often overlooked extraperitoneal compartment that serves as a common site of disease involvement and a key pathway for the spread of pelvic and retroperitoneal pathology. Its complex anatomical relationship with other extraperitoneal/retroperitoneal spaces renders it prone to involvement in different pathologic processes. Most cases represent secondary involvement rather than primary pathology. CT and MRI play a pivotal role in depicting the anatomy of the space of Retzius, characterizing lesions, and identifying routes of disease extension. This review provides a comprehensive imaging-based overview of the anatomy of the space of Retzius and illustrates the imaging findings of a broad spectrum of diseases involving this region. We highlighted the anatomical pathways of disease spread, characteristic imaging features, and surgical considerations relevant to radiologists. Familiarity with these imaging patterns and anatomical relationships can improve diagnostic confidence, facilitate identification of the underlying disease process, and guide appropriate clinical management. KEY POINTS: Question Accurate recognition of diseases involving the space of Retzius is challenging because of its complex anatomy and diverse patterns of disease spread. Findings Most pathologies involving the space of Retzius represent secondary extension from adjacent compartments rather than primary disease. Critical relevance statement By integrating imaging anatomy, patterns of disease spread, and surgical relevance, this review provides a practical framework for evaluating abnormalities involving the space of Retzius, improves diagnostic confidence, facilitates identification of the disease process, and guides clinical and surgical management.

Transsphenoidal surgery is the first-line treatment for most pituitary adenomas (PA), also known as pituitary neuroendocrine tumors (PitNET), and a precise intraoperative histopathological evaluation of tissue samples is essential to optimize tumor resection and clinical outcome. However, it still remains a challenge for pathologists to distinguish between PA and pituitary gland. In this study, we evaluated the effect of an additional Cason collagen fiber stain on the accuracy of intraoperative histopathological diagnostics of PAs by visualizing either physiologically retained or pathologically lost lobulation.

A total of 252 cases were included in this study. In the control group (n = 93) cytological smear preparations and H&E-stained frozen sections were evaluated. In the experimental group (n = 159), both H&E- and Cason-stained frozen sections as well as smear preparations were examined. The concordance rate of the intraoperative diagnoses with the final diagnoses made on the paraffin material was determined.

When compared with the HE only group, the HE+Cason approach markedly increased the diagnostic accuracy from 87% to 98% (p < 0.001), sensitivity from 90% to 98% (p < 0.05) and specificity from 40% to 100% (p = 0.06), whereas the rate of inconclusive cases was significantly reduced from 11% to 0% (p < 0.001).

This study introduces the Cason stain on frozen sections as a rapid, simple and inexpensive diagnostic tool essentially improving certainty in intraoperative histopathological diagnostics of PAs, thus facilitating surgical decision-making and optimizing clinical outcomes.

Small-cell lung cancer (SCLC) responds poorly to immune checkpoint blockade, but how tumor-cell states shape the myeloid microenvironment remains unclear. Here we identify downstream neighbor of SON (DONSON) as a prognostic factor associated with macrophage-related programmes in SCLC. Across bulk transcriptomic cohorts, clinical specimens, and mouse and human single-cell atlases, DONSON is preferentially expressed in malignant epithelial cells and is associated with neuroendocrine features and an immunosuppressive phenotype. Genetic perturbation of DONSON alters SCLC-cell proliferation, apoptosis and tumor growth, as well as macrophage migration and M2-like polarization. DONSON abundance also tracks with p38 MAPK activity and macrophage migration inhibitory factor (MIF) expression and secretion. Pharmacological inhibition, constitutively active MKK6 rescue, and MIF gain- and loss-of-function experiments support functional contributions of p38 and MIF to these phenotypes. Regorafenib alters the thermal stability of endogenous DONSON and enhances anti-PD-1 activity in syngeneic SCLC models, accompanied by increased proportions of CD86-positive macrophages and IFN-γ-positive CD8⁺ T cells. These findings implicate a DONSON-associated p38-MIF programme in neuroendocrine SCLC and tumor-macrophage crosstalk, nominating this pathway for further therapeutic investigation.

The ubiquitin-specific peptidase 42 (USP42) is a cysteine-dependent deubiquitinase with pro-tumorigenic roles in several cancers. In lung adenocarcinoma (LUAD), elevated USP42 expression correlates with advanced stage and poor survival, mirroring the prognostic impact of prostaglandin-endoperoxide synthase 2 (PTGS2) overexpression. However, the substrate repertoire and mechanisms by which USP42 drives malignant progression and immune evasion in LUAD remain largely undefined. Using TCGA datasets and functional experiments in LUAD cell lines, we found that USP42 is significantly overexpressed in LUAD, and its high expression is associates with advanced stages and reduced overall survival. Besides, USP42 knockdown suppressed proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, USP42 physically interacted with PTGS2, thereby stabilizing PTGS2 from proteasomal degradation. Mouse Lewis lung carcinoma (LLC) cells with USP42 knockdown were subcutaneously injected into C57BL/6 mice. Our results demonstrated that USP42 depletion attenuated tumor growth, reduced PTGS2 and PD-L1 expression, alleviated CD8⁺ T cell exhaustion, and increased intratumoral CD8⁺ T cell infiltration. Importantly, forced PTGS2 expression largely rescued the tumor-suppressive phenotypes induced by USP42 knockdown, confirming PTGS2 as a critical downstream effector of USP2. In conclusion, our findings identify USP42 as a novel oncogenic deubiquitinase in LUAD that promotes tumor progression and immune escape by deubiquitinating and stabilizing PTGS2, and targeting USP42 is a promising strategy against LUAD.

Mitochondrial metabolic reprogramming is a hallmark of tumor progression, yet its gene-level determinants in oral squamous cell carcinoma (OSCC) remain poorly defined. Here, we integrated multi-omics analyses, machine learning, and experimental validation to elucidate the mitochondrial energy metabolism landscape in OSCC. A six-gene prognostic signature (CTSG, HPRT1, SLC20A1, TRIB3, MTFP1, and ADA) was constructed using Cox regression, CoxBoost, and random survival forest algorithms, which accurately predicted patient survival and delineated distinct immune microenvironment patterns in OSCC. Among these genes, HPRT1 emerged as a pivotal mitochondrial metabolic driver. Single-cell transcriptomics revealed that HPRT1 was predominantly expressed in malignant epithelial clusters and correlated with proliferative and immunosuppressive phenotypes. Validation in patient tissues and xenograft models confirmed that HPRT1 overexpression promoted tumor growth. Multiplex immunofluorescence on tissue microarrays demonstrated that high HPRT1 expression was associated with increased M2 macrophage infiltration and reduced densities of CD8⁺ T cells and M1 macrophages, indicating its role in establishing an immunosuppressive tumor microenvironment. Structure-based virtual screening, molecular dynamics simulations, and in vivo xenograft experiments identified troxerutin as a potential HPRT1-binding compound with favorable binding stability and free energy. Collectively, our study identifies HPRT1 as a key regulator linking mitochondrial metabolism and immune evasion in OSCC, providing a promising therapeutic target and supporting drug repurposing strategies for precision oncology.

The cGAS-STING pathway acts as a central and highly potent innate immune sensing system in the human body. It can efficiently recognize cytoplasmic double-stranded DNA originating from invading exogenous pathogens and damaged endogenous host cells. This unique molecular recognition feature lays a solid foundation for its multiple vital physiological functions, including host defense against infections, tumor immune surveillance, and the maintenance of normal cellular homeostasis. This review systematically investigates the distinct functional states and biological behaviors of the cGAS-STING pathway under a variety of disease conditions. When the pathway is activated properly at the right time and with appropriate intensity, it can effectively eliminate invasive pathogens and exert potent anti-tumor effects to restrain malignant progression. On the contrary, aberrant, excessive or long-term persistent activation of this signaling cascade will trigger severe inflammatory reactions, which further drive the onset and deterioration of autoimmune disorders, neurodegenerative diseases and multiple aging-related illnesses. Moreover, this article also summarizes the latest research progress of targeted agonists and inhibitors developed for this pathway. We elaborate on their application scenarios, core advantages and existing bottlenecks, aiming to provide comprehensive theoretical references and research directions for follow-up basic mechanistic studies and clinical transformation of cGAS-STING targeted therapeutic strategies.

Recently identified as a variant of cemento-osseous dysplasia, familial florid cemento-osseous dysplasia (FFCOD) differs from the sporadic florid variant in both clinical and radiographic behaviour and has an autosomal dominant inheritance pattern. The aim of this study is to describe the clinical, imaging, and histopathological findings of two white young sisters who were diagnosed with FFCOD, as well as the difficulties in diagnosing and treating this condition. Multifocal fibro-osseous lesions of the jaws with early onset and maturation, and association with multiple unerupted teeth were found in both patients. Other fibro-osseous lesions and systemic disorders, such as fibrous dysplasia, familial gigantiform cementoma, gnathodiaphyseal dysplasia, Paget's disease of bone, and hyperparathyroidism-jaw tumour syndrome, were taken into consideration and ruled out during the diagnostic procedure. Even though conservative management is the preferred course of treatment for FFCOD, the frequent association with unerupted teeth presents an additional challenge for the management of lesions and oral rehabilitation of these patients. Therefore, more research is needed to better understand this variant and develop safer therapeutic and rehabilitative strategies.

Brucea javanica oil oral emulsion (BJOE) serves as an adjunctive therapeutic agent for glioblastoma multiforme (GBM); however, the inhibitory effects of its serum metabolites remain unexplored. In this study, ultrahigh performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze serum metabolites in rats following BJOE administration. The inhibitory effects of the serum on GBM were assessed using U251 cell bioassays, and the relationship between serum metabolites and cellular inhibitory activity was examined. Six prototype components and six metabolites were identified in the serum, including linoleic acid, linoleic acid-M1, linoleic acid-M2, linoleic acid-M3, oleic acid, oleic acid-M1, oleic acid-M2, oleic acid-M3, sphingosine, palmitoleic acid, oleamide, and 1-stearoyl-rac-glycerol. Rat serum collected 2 h postdosing significantly inhibited U251 cell proliferation. Gray relationship analysis indicated that oleic acid, oleic acid-M1, linoleic acid, linoleic acid-M1, linoleic acid-M2, sphingosine, palmitoleic acid, oleamide, and 1-stearoyl-rac-glycerol were highly correlated with the inhibition rate of U251 cell proliferation, with oleic acid-M1 showing the highest correlation coefficient (0.9806). These findings suggest that BJOE and its metabolites may possess therapeutic potential against GBM, particularly in inhibiting glioma cell proliferation, with oleic acid and its metabolites likely playing a significant role.

Over recent decades, advances in cancer diagnosis and treatment have improved survival and quality of life, leading to a growing number of cancer patients being admitted to Intensive Care Units (ICUs). In this setting, clinical decision-making is challenged by prognostic uncertainty, intensive technology use, and therapeutic interventions whose proportionality may be uncertain, generating relevant ethical conflicts in clinical practice. The application of bioethics to critical oncology provides a deliberative framework based on the principles of autonomy, beneficence, nonmaleficence, and justice, aimed at ensuring value-based, dignity-centered care. This review addresses three key decisions in managing critically ill oncology patients: ICU admission criteria, integration of palliative care, and definition of terminal illness, offering ethical tools to support prudent, proportionate, and humane decision-making.

Paediatric tumour pathology poses diagnostic challenges due to morphological variation, overlap and the rarity and diversity of neoplasms, for which the WHO provides a comprehensive diagnostic framework. In clinical practice, however, diagnostic reasoning starts with an unknown tumour and a broad differential diagnosis which may conflict with theoretical requirements. This study evaluates the contribution of ancillary techniques to the diagnostic process of non-central nervous system (CNS) solid paediatric tumours.

Clinicopathological data were retrospectively obtained from all patients diagnosed between January 2019 and December 2021 in a national single paediatric centre. Contribution of ancillary techniques was categorised into four groups: (1) morphology only, (2) morphology and immunohistochemistry (IHC), (3) morphology and molecular diagnostics or (4) morphology, IHC and molecular diagnostics.

In total, 309 patients were included. Morphology alone was sufficient in 58.9% of cases, additional IHC was required in 15.2%, additional molecular techniques in 1.3% and all three modalities in 24.6%. Morphology alone was sufficient for most neuroblastic, renal, bone and digestive system tumours. IHC was required for undifferentiated neuroblastomas and frequently for germ cell and ovarian tumours. The combined use of morphology, IHC and molecular techniques was necessary to diagnose soft tissue tumours and undifferentiated small round cell sarcomas.

The majority of paediatric, solid, non-CNS, tumours can be diagnosed based on morphology alone, whereas ancillary techniques are required to resolve remaining cases. These findings highlight that current tumour classification does not always match daily clinical practice.