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Peripheral neuroblastic tumours are the most common extracranial solid neoplasms occurring in children. Proper classification is critical for directing therapy and predicting prognosis. Nonetheless, their relative rarity makes accurate pathological assessment challenging, even for experienced pathologists. Here we report on a new international data set for the pathology reporting of biopsy and resection specimens with peripheral neuroblastic tumours. The data set was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. According to the ICCR's process for data set development, an international expert panel consisting of paediatric pathologists and oncologists produced a set of core and non-core data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were neuroblastic tumour experts affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the data sets, including a synoptic reporting guide, were published on the ICCR website. This first international data set for paediatric peripheral neuroblastic tumours is intended to promote high-quality, standardised pathology reporting. Its widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve management of children with peripheral neuroblastic tumours., (© 2025 John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest: The authors declare they have no conflicts of interest.

Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.

Background: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy and minor trauma-induced skin blisters., Objectives: To identify genetic variants in patients with EB in India and to examine the relationship between genotypic and phenotypic manifestations., Methods: Patients with EB seen consecutively over a period of 5 years at an outpatient department of dermatology (Postgraduate Institute of Medical Education and Research, Chandigarh, India) were included in the study. Baseline demographic data, birth history, family history, skin manifestations at birth, medical history, current cutaneous manifestations and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing for 23 EB-related genes and a genetic-phenotype analysis was performed., Results: Our study included 65 patients with EB. Among these 65 patients with EB, 38 had dystrophic EB (DEB, 58%), 12 had junctional EB (JEB, 18%), 12 had EB simplex (EBS, 18%) and 3 had Kindler EB (KEB, 5%). Dominant and recessive forms of dystrophic EB accounted for 17% (n = 11) and 42% (n = 27), respectively, of the 65 individuals with EB. We identified 75 genetic variants, 59% (n = 44) newly discovered and 41% (n = 31) previously reported. Compound heterozygous variants were more frequent (56%; 15/27) than homozygous ones (44%; 12/27) in individuals with recessive DEB. Patients with JEB harboured LAMB3 mutations more frequently, whereas patients with EBS harboured KRT5 and KRT14 missense heterozygous mutations. Patients with KEB had homozygous mutations in FERTM1., Conclusions: Our study has unveiled several novel genetic variants and severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.

Introduction: The diagnosis and management of abdominal tuberculosis, i.e Gastrointestinal Tuberculosis (GITB) and tuberculous peritonitis (TBP) is challenging. Abdominal tuberculosis, presenting usually with abdominal pain, intestinal obstruction, and constitutional symptoms, is typically a paucibacillary condition. The diagnosis hinges on a correct interpretation of clinical, radiological, histological, biochemical, and microbiological findings as also appropriately assessing response to therapy., Areas Covered: The authors review potential missteps that could occur in managing GITB and TBP sourced from published literature and clinical experience. These include avoiding excess use of tests with limited accuracy, understanding limitations of ascitic adenosine deaminase (ADA) and granulomas, avoiding empirical antitubercular therapy (ATT) where possible but also understanding that microbiological tests may not always be positive, and finally not to bank solely on subjective clinical responses but to use objective markers in assessing response to therapy. In addition, diagnosis of predisposing immunosuppressed states, attention to nutrition, appropriate management of sequelae with endoscopic dilatation/surgery, and early surgery when indicated are some of the additional issues discussed., Expert Opinion: In future, a more secure diagnosis banking on the use of better microbiological tools, multiparameter-based models, artificial intelligence-based approaches, and use of advances in -omics-based approaches can improve diagnosis and avoid some missteps.

Introduction: The armamentarium of 'Endo-hepatology' is proliferating with the advancements in techniques and availability of new devices in the field of endoscopic ultrasound (EUS). This has resulted in the merger of multitude of diagnostic and therapeutic interventions, such as EUS-liver biopsy (LB), EUS-angioembolization of gastric varices, EUS-portal pressure gradient (PPG) measurement, and others into a 'one-stop-shop' for efficient patient management. Lack of standardization of these techniques form a major hinderance in their widespread adoption., Areas Covered: A comprehensive literature search was undertaken across various databases on EUS-LB and EUS-PPG till November 2024 for reviews, observational studies, and randomized trials on EUS-LB and EUS-PPG, describing its indications, technique, and data of safety and efficacy, detailing its role in day-to-day clinical practice., Expert Opinion: EUS-LB and EUS-PPG have shown promise in the ever-growing field of endo-hepatology. EUS-LB has exhibited excellent safety profile and comparable tissue yield compared to its percutaneous counterpart. On the other hand, EUS-PPG seems to be a viable alternative although it needs to be standardized further. From a patient and hospital perspective, they might prove to be convenient and cost effective. Nevertheless, more evidence is warranted before they can be labeled as the new standard of care.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer-related mortality worldwide 1,2 . HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulate progressive driver mutations 3 , with hepatocytes the most likely cell of origin 2 . However, the landscape of driver mutations in HCC is broadly independent of the underlying aetiologies 4 . Despite an increasing range of systemic treatment options for advanced HCC, outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations 5,6 . Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC 7 . Here we generated a suite of genetically driven immunocompetent in vivo and matched in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance and metastasis. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with the human histopathology. In a proof-of-principle analysis, we verified response to standard-of-care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not previously been linked to HCC treatment. Cladribine acts in a highly effective subtype-specific manner in combination with standard-of-care therapy., Competing Interests: Competing interests: Material for the lenvatinib day 15 and day 30 timepoint experiments (Fig. 4h–j) was provided by Eisai. AZD2171 was provided by AstraZeneca. D.A.M. is a director, shareholder and employee of FibroFind. L.M.C. has consulted for Ono Pharmaceuticals UK on unrelated work. J.M.L. is receiving research support from Eisai Inc and Bayer Pharmaceuticals; is consulting and performing sponsored lectures for Eisai Inc., Merck, Roche, Genentech, AstraZeneca, Bayer Pharmaceuticals, AbbVie, Sanofi, Moderna, Glycotest and Exelixis; and participates in the Data Safety Monitoring Board for Bristol Myers Squibb. The other authors declare no competing interests., (© 2025. The Author(s).)

Background: Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB (tuberculosis) and autoimmune granulomatous liver diseases. Antitubercular (ATT) and other drugs' metabolism in the presence of a specific type of liver injury is not well understood. The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG (Bacillus Calmette-Guérin) vaccine, further studying it in the presence of ATT dosing, and analyze the pharmacokinetics of isoniazid, rifampicin, and their respective primary metabolites., Methods: We used 56 rats in seven equal groups. Group I functioned as a normal control (NC) receiving normal saline only. Groups II-IV received intravenous injections of low-, medium-, and high-dose BCG vaccine daily for 21 days. Groups V, VI, and VII received isoniazid (H) alone, rifampicin (R) alone, and isoniazid + rifampicin(HR) for a subsequent 15 days in addition to high dose BCG for the first 21 days, respectively. Liver function tests (LFT) were monitored on days 0, 21, 28, and 36. Rats were sacrificed later for oxidative stress and histopathological examination., Results: The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21 (p < 0.05). Isoniazid, rifampicin, and combination intervention groups demonstrated normalization of the BCG-led LFT changes. Histology and oxidative stress parameters confirmed model development and biochemical changes. Isoniazid area under the curve (AUC) showed a reduction of 16.9% in BCG + HR group in comparison to the BCG + H group (p = 0.01). Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG + HR group in comparison to the BCG + R group (p = 0.001)., Conclusion: A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response., (© 2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Catecholamine-producing tumors of childhood include neuroblastic tumors, phaeochromocytoma, and paraganglioma (PPGL). PPGL and neuroblastic tumors can arise in similar anatomical locations and clinical presentations can overlap, resulting in diagnostic challenges. Distinguishing between these tumor types is critical as management and long-term surveillance strategies differ depending on the diagnosis. Herein we describe 2 clinical cases and illustrate key considerations in the diagnostic workup of a neuroblastoma vs PPGL for patients presenting with adrenal, pelvic, and retroperitoneal masses in childhood., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Aims: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait., Methods: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations., Results: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs., Conclusion: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest concerning this article.

Objectives: Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined., Methods: Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS. Data simulation was repeated for different MSG numbers (range, 2-7)., Results: Higher reproducibility was noted for every unit increase in MSG number, with the median absolute difference between 2 within-patient FS measurements decreasing from 1.05 (SD = 0.25) with 2 glands to 0.52 (SD = 0.12) with 7 glands. MSG number influenced the probability of a simulated patient receiving a FS ≥1, increasing from a median of 0.67 with 2 glands to 0.77 with ≥5 glands. MSG number influenced clinical trial sample sizes. For example, 80% statistical power to detect a 40% FS reduction required a sample size per group of 62 with 2 glands and 25 with 7 glands., Conclusions: For a diagnostic threshold of FS ≥1, a minimum of 5 glands should ideally be targeted. For continuous FS values, a larger number of MSGs (eg, 6) will increase reproducibility further and reduce clinical trial sample size requirements., Competing Interests: Competing interests BAF has undertaken consultancy for Novartis, BMS, Servier, Galapagos, Roche, UCB, Sanofi, Janssen, AstraZeneca, Otsuka, Amgen, and Kiniksa and received research funding from Janssen, Servier, Galapagos, and Celgene. SJB has undertaken consultancy on SjD in the past 3 years for: AbbVie, Amgen, Argenx, Aurinia, Bain, BMS, EcoR1, Iqvia, J&J/Janssen, Kiniksa, and Novartis. FB is a current employee of Candel Therapeutics. KT, SN, VP, CGS, RMB, TB, AS, MP, and JD have nothing to declare., (Copyright © 2025. Published by Elsevier B.V.)

Persistent selective T-lymphocytopaenia is found both in SCID and congenital athymia. Without molecular diagnosis, it is challenging to determine whether HCT or thymus transplantation ought to be performed. Ex vivo T-lymphopoiesis assays have been proposed to assist clinical decision-making for genetically undefined patients. We investigated 20 T-lymphocytopaenic patients, including 13 patients awaiting first-line treatment and 7 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst developmental blocks in ex vivo T-lymphopoiesis indicated haematopoietic cell-intrinsic defects, successful T-lymphocyte differentiation required careful interpretation, in conjunction with clinical status, immunophenotyping, and genetic investigations. Of the 20 patients, 13 proceeded to treatment, with successful immune reconstitution observed in 4 of the 6 patients post-HCT and 4 of the 7 patients after thymus transplantation, the latter including two patients who had previously undergone HCT. Whilst further validation and standardization are required, we conclude that assessing ex vivo T-lymphopoiesis during the diagnostic pathway for genetically undefined T-lymphocytopaenia improves patient outcomes by facilitating corrective treatment choice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore undertook an exploratory study of the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11 and 15 weeks post conception (n = 78). Although most pseudoautosomal region 1 (PAR1) genes are lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g., KDM5C and KDM6A), several ancestral X-Y gene pairs, and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast, higher expression of an autosomal, long non-coding RNA (OVCH1-AS1) is seen in all 45,X tissues. In the placenta, lower expression of CSF2RA is demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes., Methods: A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors., Results: Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes., Discussion: Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Ltd.)

Low molecular weight heparin (LMWH) is a common agent given in pregnancy; however, cutaneous drug reactions with its use in pregnancy are rarely reported. The case describes a 30-year-old woman with stable Crohn's disease on ustekinumab presenting with a rash at prophylactic LMWH injection sites 30 weeks into her third pregnancy. Skin biopsy reported appearance consistent with an urticarial drug hypersensitivity reaction. A combination of steroid treatment, topical emollient and cessation of LMWH resulted in resolution of symptoms over 2 weeks. Postnatal venous thromboembolism prophylaxis with fondaparinux was uncomplicated. Overall, this case highlights the importance of reporting drug reactions in pregnancy. It additionally exposes a gap in research surrounding immunomodulators and heparins in the development of cutaneous reactions in pregnancy., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Pilocytic astrocytoma (PA) is the commonest low-grade tumour affecting children and is frequently experienced as a chronic disease associated with extended treatment, periods of regrowth, and long-term disability. This contrasts with the view of PA as a benign tumour with positive clinical outcomes and raises the fundamental question of biologically driven change over time within these tumours, which will impact diagnosis, stratification, and management. To investigate the molecular, cellular, and pathological stability of PA we performed RNA sequencing, methylation array profiling, immunohistochemistry, and targeted panel DNA sequencing on a cohort of 15 PA patients with matched primary/longitudinal samples at a mean sampling interval of 2.7 years. Through pairwise analysis of primary versus longitudinal tumour samples we identified changes to immune-related pathways within the expression and methylation profiles of longitudinal PA. Further interrogation of these changes revealed an enrichment over time for microglial cell populations, which was validated by immunohistochemistry against common monocyte/microglial markers. Moreover, immunohistochemical characterisation revealed concurrent increases in the expression of M2-like and anti-inflammatory markers. Microglial enrichments were consistent across the cohort and were not adequately explained by a range of potential confounders, including receipt of adjuvant therapy. Taken together, these data challenge the idea of pilocytic astrocytoma as a static entity and indicate that they consistently accumulate microglia over time, potentially co-opting the immune microenvironment towards an anti-inflammatory phenotype that may affect the natural course and treatment response of the tumours., Competing Interests: Declarations. Ethical approval: Institutional approval for this project was granted by the joint UCL Great Ormond Street Institute of Child Health/Great Ormond Street Hospital R&D department with approval from the local research ethics committee and BRAIN UK (ref: 17/007). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Our study's aim was to evaluate the clinicopathological profile of colorectal cancer (CRC) patients from North-East Romania in relation to the Kirsten rat sarcoma viral oncogene homolog ( KRAS ). We designed a retrospective study on 108 CRC patients using the fully automated real-time PCR-based molecular testing system, Idylla TM Mutation Test (Biocartis, Mechelen, Belgium). Of the patients, 64 (59.3%) were men and 62 (57.4%) were older than the group average, with left bowel location in 38 cases (35.2%), adenocarcinoma NOS in 102 cases (94.4%), mixed histological pattern in 65 cases (60.2%), T3 in 60 patients (55.6%), N2 in 46 patients (42.6%), and 7-12 tumour buds registered in 58 tumours (53.7%). A total of 54 tumour samples (50%) showed KRAS Mutation Test (Biocartis, Mechelen, Belgium). Of the patients, 64 (59.3%) were men and 62 (57.4%) were older than the group average, with left bowel location in 38 cases (35.2%), adenocarcinoma NOS in 102 cases (94.4%), mixed histological pattern in 65 cases (60.2%), T3 in 60 patients (55.6%), N2 in 46 patients (42.6%), and 7-12 tumour buds registered in 58 tumours (53.7%). A total of 54 tumour samples (50%) showed KRAS mutation. Statistical comparative analyses associated KRAS mutations with the histopathological pattern ( p = 0.030), depth of invasion (pT) ( p = 0.030), depth of invasion (pT) ( p < 0.001), lymph node involvement (pN) ( p < 0.001), venous vascular invasion ( p = 0.048), and tumour buds' number ( p = 0.007). Our results demonstrate the relationship between KRAS mutation and clinicopathological features, with possible impact in clinical tumour stratification and therapeutic management.

Aims: There is no consensus on whether oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status should be assessed after neoadjuvant chemotherapy. This study assessed the frequency of changes in ER, PR and HER2 status after neoadjuvant chemotherapy., Methods and Results: Of 353 patients who had neoadjuvant chemotherapy and anti-HER2 treatment, receptors were assessed in 185 residual carcinomas. Eight per cent of carcinomas that were ER-negative in the core biopsy were ER-positive in the excision compared with 1.5% of controls. All were HER2-positive in the core biopsy and 23% were HER2-negative in the excision compared with 0% of controls. Controls were cases tested in the core biopsy and subsequent surgical resection with no neoadjuvant treatment. Of 589 patients who had neoadjuvant chemotherapy alone, receptors were assessed in 495 residual carcinomas. Six per cent of carcinomas that were ER-negative in the core biopsy were ER-positive in the excision (mainly ER-low positive) compared with 1.5% of controls. All were HER2-negative in the core biopsy and 6% were HER2-positive in the excision (mainly immunohistochemistry score 2+ and HER2 gene amplified) compared with 2% of controls., Conclusions: Negative to positive changes in receptor status after neoadjuvant chemotherapy are infrequent and the positive result in the excision is often weakly positive. These results imply that repeat assessment after neoadjuvant chemotherapy and surgery could influence the subsequent treatment in a small proportion of patients., (© 2025 John Wiley & Sons Ltd.)

The surgical repair of hernias, a prevalent condition affecting millions worldwide, has traditionally relied on polypropylene (PP) mesh due to its favorable mechanical properties and biocompatibility. However, postoperative infections remain a significant complication, underscoring the need for the development of infection-resistant hernia meshes. This study provides a comprehensive analysis of current advancements and innovative strategies aimed at enhancing the infection resistance of PP mesh. It presents an overview of various research efforts focused on the integration of antimicrobial agents, surface modifications, and the development of bioactive coatings to prevent bacterial colonization and biofilm formation. Additionally, the synergistic effects of novel material designs and the role of nanotechnology in optimizing the anti-infective properties of PP mesh are explored. Recent clinical outcomes and in vitro studies are critically examined, highlighting challenges and potential future directions in the development of next-generation hernia meshes. Emphasis is placed on the importance of interdisciplinary approaches in advancing surgical materials with the ultimate goal of improving patient outcomes in hernia repair.

Fibroepithelial lesions (FELs) of the breast constitute a heterogeneous group of biphasic tumours with variable morphology and behaviour. The classification of FELs is mainly based on a constellation of diagnostic criteria and intralesional heterogeneity is not uncommon. Therefore, reporting of FELs in a core needle biopsy (CNB) with limited tissue material can be challenging as not all the features may be represented for assessment. Distinction between classic fibroadenoma and representatively sampled phyllodes tumour is generally straightforward. However, cellular fibroadenoma, morphologically heterogeneous benign phyllodes tumour and myoid hamartoma can overlap histologically. Accurate grading of phyllodes tumour is also challenging on CNB and carries significant management implications. In this article, we provide an overview and propose a pragmatic approach to reporting FELs on CNB, particularly for lesions with overlapping features. Guidance using the UK/European 'B' classification of FELs, as well as free text descriptions of the various lesions, is also presented to help further management decision making., (Copyright © 2025. Published by Elsevier Inc.)

Background: Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality of life impact), long-term compliance can be poor, with many men undergoing radical treatment after starting AS., Methods and Analysis: Finasteride in Active Surveillance for men with low and intermediate-risk prostate cancer (FINESSE) is a prospective, open-label, two-arm, phase 3 trial, in which men with low or intermediate PCa are randomised (1:1) to receive AS with or without finasteride (5 mg once a day for 2 years). Randomisation is stratified by age and PCa risk. AS includes regular prostate-specific antigen testing, MRI scans and the offer of repeat biopsy (at 3 years, or if imaging suggests progression). Additional MRI scans and/or biopsies will be performed for biochemical or clinical indications. We aim to recruit 550 men (aged 50 to 75 years) from up to eight sites. Active outpatient follow-up will be for 3-5 years (depending on date recruited), followed by passive registry-based follow-up for up to 10 years. Primary outcome is adherence to AS. Secondary outcomes include rates and type of disease progression, treatments received (for PCa and benign prostatic enlargement), overall and PCa-specific mortality, an understanding of patients/professionals views of this approach and health-related quality of life. An external panel of experts blinded to allocation will review all AS cessation and progression events. Trial pathologist's and radiologist's, blinded to allocation, will review representative cases. Analysis is Intention to Treat., Ethics and Dissemination: The study received Health Research Authority and South-Central Oxford Research Ethics Committee (14/12/2021: 21/SC/0349) and CTA/MHRA (29/12/2021: 21304/0274/001-0001) approvals. Results will be made available to providers and researchers via publicly accessible scientific journals., Trial Registration Number: ISRCTN16867955., Competing Interests: Competing interests: MC has received speaker fees from Ipsen and Pfizer. JC has received reimbursement for consultancy from Astra Zeneca, BMS, Ipsen, Janssen and Roche, speaker fees from BMS, Ipsen, MSD, Nucleix and Roche, honoraria for membership of advisory boards from Astra Zeneca, Ferring, Roche and Janssen, and research funding from Roche. PS is a paid member of the Scientific Advisory Board of GRAIL and the medical advisory board of NSV. The remaining authors declare no potential conflicts of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Purpose of Review: Paediatric thyroid cancer management traditionally relied on extrapolation from adult data and, despite good survival outcomes, often involved extensive surgical approaches and radioactive iodine (RAI) therapy with potentially life-long complications. Increasing understanding of paediatric diagnostic techniques, molecular tumour drivers and targeted therapies will allow a more nuanced, disease-specific comprehensive model of care. This review summarises recent developments in paediatric thyroid cancer biology, diagnosis and models of care., Methods: Review of relevant literature from the last 5 years to inform a narrative summary by a multidisciplinary team of clinician experts in paediatric thyroid cancer management., Findings: Standardised risk scoring systems will likely improve the objectivity and accuracy of paediatric thyroid nodule risk stratification on ultrasound, but further studies are needed to validate these. Identification of somatic and germline gene variants is playing a rapidly increasing role in paediatric thyroid cancer diagnosis and planning of surgical approaches and neoadjuvant and adjuvant therapies. There is growing recognition that lobectomy may achieve comparable outcomes, with reduced risk of complications, to total thyroidectomy in patients with low-risk disease. Molecularly targeted therapies are now available for the management of advanced disease as an adjuvant, and likely neo-adjuvant, therapy for medical debulking of large tumours and resensitisation of RAI-resistant disease., Conclusions: The management pathways for paediatric thyroid cancer are rapidly evolving due to the increasing availability of paediatric-specific data. As management options become more complex, interdisciplinary collaboration and shared decision-making are ever more important., (© 2025 The Author(s). Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

The study examines the utility of AMACR, ERG, and AR immunostains in diagnosing prostatic adenocarcinoma (PCa) and assessing prognosis in comparison to the Gleason score and new WHO grading groups. Seventeen PCa biopsies and five benign prostatic hyperplasia (BPH) biopsies were analyzed. Immunoreactivity, scored from 1 to 3 based on percentage of positive cells and intensity of expression, was assessed, revealing 76.47% positivity for AMACR, 35.29% for ERG, and 94.12% for AR in PCa cases, with variable scores and intensity among markers and grade groups. AMACR sensitivity and ERG specificity were noted. Higher-grade PCa exhibited increased positivity for both markers, indicating prognostic significance. In BPH cases, AMACR showed positivity in 2 cases, ERG in 1, and AR in all cases, albeit with lower expression. Differential expression was observed among immunomarkers and grade groups of malignancy. AMACR and ERG stains serve as sensitive and specific markers for PCa diagnosis and prognosis. Their increasing positivity with higher-grade groups underscores prognostic value. These findings highlight the importance of immunostains in refining PCa diagnosis and prognostication.

Background: Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) polymorphisms predispose to thiopurine-related leukopenia., Methods: Retrospective evaluation of inflammatory bowel disease (IBD) patients harboring NUDT15 polymorphisms and exposed to thiopurines. We report the frequency of NUDT15 polymorphism, frequency of leukopenia, the tolerated dose of azathioprine, and the clinical efficacy of thiopurines., Results: Of 1440 patients, 118 (8.2%) had NUDT15 polymorphism. Among 51 with complete details, 46 were heterozygous (90.2%), and 5 homozygous (9.2%) for NUDT15. Twenty (43.5%) heterozygous and all homozygous patients developed leukopenia. Leukopenia was significantly more in NUDT15 heterozygous group compared to controls (43.45% vs 7.8%, Odds ratio: 9, 95% CI 3.57-22.9). The maximum tolerated dose of azathioprine was lower in NUDT15 heterozygous group (1.1 ± 0.4 mg per kg vs 1.7 ± 0.7 mg per kg, p  = 0.002). The mean time to leukopenia was earlier in the heterozygous group vs controls (19 ± 56 weeks vs 70 ± 53 weeks, p-value 0.002). Seven (35%) of 20 heterozygous patients who developed leukopenia, could be maintained at a lower dose of thiopurine. Twenty-five maintained clinical remission while on thiopurines., Conclusion: Thiopurines should be avoided in NUDT15 homozygous but can be used cautiously at lower dosages with frequent monitoring among heterozygous patients.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response. This immunophenotype is not exclusive to dMMR CRCs but comprises a subset of MMR proficient (pMMR) CRCs. Single-cell spatial analysis and in vitro cell co-cultures indicate that interferon-producing cytotoxic T cells induce overexpression of antigen presentation in adjacent macrophages and tumor cells, including MHC class II invariant chain CD74. dMMR CRCs expressing high levels of CD74 respond to ICI and a subset of CD74 high pMMR CRC patients show better progression free survival when treated with ICI. Therefore, CD74 abundance can identify the constitutive interferon-high immunophenotype determining clinical benefit in CRC, independently of tumor mutational burden or MMR status., Competing Interests: Declaration of interests A.A.S., P.A., K.C., and F.C. hold a pending patent (patent no 2401121.5). C.A. is on the advisory board of or has a consultant role with Takeda; and is invited speaker with compensation for Merck. F.B. is on the advisory board of Servier, AAA Novartis and is invited speaker with compensation from Eli-Lilly, MSD, EISAI, Bristol Myers Squibb, AstraZeneca, and Pierre Fabre. R.I. is on the advisory board of or has a consultant role with Bayer. E.C.S. is on the advisory board of, has a consultant role with or has received travel support from: Amal Therapeutics, Aptitude Health, Amgen, Astellas, Astra Zeneca, Beigene, BMS, Celgene, Daiichi Sankyo, Elsevier, Everest Clinical Research, First Word Group, Five Prime Therapeutics, Gritstone Oncology, Imedex, Merck, MSD, My Personal Therapeutics, Novartis, Pfizer, Roche, Sai-Med, Servier, Viracta, and Zymeworks; holds research funding (to Institution) from BMS and Astra Zeneca; and holds leadership roles in: EORTC GI Clinical Trials Group, ESMO Guidelines Committee and ESMO GI Faculty. S.L. is on the advisory board of or has a consultant role with: Amgen, Astellas, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm, Beigene, Fosum, Nimbus Therapeutics; holds research funding (to Institution) from: Amgen, Astellas, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, Servier; and has received personal honoraria as invited speaker from Amgen, Astra Zeneca, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche, Servier. C.C. is on the advisory board of or has a consultant role with: Astra Zeneca, Bicara Therapeutics, BMS, Lilly, Merck, Mirati, MSD, Nordic Pharma, Roche, Pierre Fabre, Rottapharm, Takeda, and Tempus; is an invited speaker with compensation for Amgen, Bayer, Merck Serono, MSD, Pierre Fabre, Servier, and Takeda; and holds research grants by Amgen, Merck, Pierre Fabre, Roche, Seagen (Pfizer), Servier, and Tempus. M.R.-J. has attended advisory boards, chaired educational meetings, consulted for, or been reimbursed travel, accommodation and registration at national/international meetings by Bristol Myers Squibb/BMS, Merk Sharp & Dohme/MSD, Roche Diagnostics, Servier, Jazzpharma, Astellas and Agilent; and holds a research grant from Pfizer. E.F. holds an advisory or consulting role with Astellas Pharma, Pfizer, Bicycle Therapeutics, and BMS; holds research funding (to Institution) from Repair Therapeutics, Bicycle Therapeutics, Artios Pharma, Seagen, Amgen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Tahio Pharmaceutical, Pfizer, Roche, Daiichi Sankyo, Gilead Sciences, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, HUTCHMED, Merus, Crescendo Biologics, GSK plc, BeiGene, Turning Point Therapeutics, Sapience Pharma, Acerta Pharma, ADC Therapeutics, Arcus Biosciences, Astella Pharma, Astra Zeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Calithera Biosciences, Carrick Therapeutics, CASI Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, Deciphera, Lilly, Ellipses Pharma, Exelixis, Fore Biotherapeutics, GI Therapeutics, Genentech, H3 Biomedicine, Ignyta/Genentech/Roche, Immunocore, Immunomedics, Incyte, Instil Bio, Iovance Biotherapeutics, Janssen, Kronos Bio, Lupin Pharmaceuticals, Macrogenics, Menarini, Merck KGaA, Millenium Pharmaceuticals, Nerviano Medical Sciences, Oxford VacMedix, Plexxicon, QED Therapeutics, Ribon Therapeutics, SERVIER, Stemline Therapeutics, Synthon, Tesaro, PMV Pharma and Takeda; has had travel, accommodation or expenses reimbursed by: Repair Therapeutics, CARIS life Science, Seagen, Sapience Pharma, Bicycle Therapeutics, and Erasca Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Plasmablastic lymphoma (PBL) is an aggressive lymphoma with the proliferation of plasmablastic cells with a plasma cell immunophenotype and immunonegativity for B-cell markers. Here we present a case of jejunal PBL in an 82-year-old human immunodeficiency virus (HIV) negative and Epstein-Barr (EBV) negative male who presented with subacute intestinal obstruction and histopathological examination showed a large cell lymphoma with plasmablastic differentiation diffusely infiltrating full thickness of the jejunal wall. Neoplastic cells were immunopositive for CD138, MUM-1, EMA, and CD56, along with aberrant expression of pan T-cell marker CD3. No restrictions for kappa and lambda light chains were noted. Ki67 index was >90%. Tumor cells were immunonegative for CD20, CD5, CD7, CD30, and PAX 5. Suspicion of this rare and high-grade lymphoma in immunocompetent patients and at extra-nodal locations along with awareness of diagnostic pitfalls in its immunoprofile will aid in accurate diagnosis and prognostication., (Copyright © 2025 Indian Journal of Pathology and Microbiology.)