JOURNAL OF CLINICAL PATHOLOGY

Rapid evaluation of muscularis propria in transurethral resection of bladder tumour specimens using non-linear microscopy (NLM)
Weber TD, Gershman B, Wang L, Rosen S, Fujimoto JG and Sun Y
Transurethral resection of bladder tumour (TURBT) is the standard approach for diagnosing and staging non-muscle invasive bladder cancer. Accurate staging depends on the presence of muscularis propria (MP) in resected tumour specimens, and inadequate MP sampling may necessitate repeat procedures. Non-linear microscopy (NLM), a laser-scanning, non-destructive imaging technique, enables real-time evaluation of fresh tissue and has the potential to improve staging accuracy intraoperatively.
Accelerated chronic lymphocytic leukaemia shows distinctive lymphocyte morphology in peripheral blood smears
Aldinger J, Wolniak K, Gao J, Chen YH, Chen QC and Tariq H
Accelerated chronic lymphocytic leukaemia (A-CLL) is an aggressive variant of chronic lymphocytic leukaemia (CLL) characterised by distinct histologic features and a higher risk pathogenetic profile compared with conventional CLL (C-CLL). Although well recognised histologically, peripheral blood (PB) morphology of A-CLL is not well studied. In this study, we compared the PB lymphocyte morphology between 22 cases of biopsy-confirmed A-CLL and 60 cases of biopsy-confirmed C-CLL. PBs in A-CLL had a significantly lower percentage of typical CLL cells (mean: 51.28% vs 86.73%; p<0.001) and a higher percentage of classical prolymphocytes (12.11% vs 3.69%; p=0.021), non-classical prolymphocytes (17.48% vs 5.59%; p<0.001) and other atypical forms (cleaved, Downey-like and flower-shaped cells). Our data ties this distinct PB lymphocyte morphology in A-CLL with aggressive histology and a high-risk pathogenetic profile. Recognising the morphologic spectrum of PB lymphocytosis in A-CLL can facilitate earlier identification of this aggressive variant and help avoid misdiagnosis as other types of lymphoma/leukaemias.
Patient safety in AI-powered diagnostic pathology
Rugge M, Fraschini M, Orvieto E, Didaci L, Sandona' L, D'Amuri A, Saba L and Faa G
Artificial intelligence (AI)-powered diagnostic pathology involves combining traditional histological techniques with computer-assisted AI technology. This process comprises several key steps: generating whole slide digital images; annotating and training algorithms; constructing robust datasets; testing and monitoring consistency with clinical expectations; validating results externally and overseeing the output of algorithms. All of these steps must adhere to quality standards and ensure patient safety.Current scientific evidence suggests that, while AI can enhance the accuracy of human diagnostics, it cannot replace humans as autonomous classifiers. Generative intelligence offers new, promising technological advancements. When applying these technologies in clinical practice, international healthcare institutions recommend clearly defining the application domains and implementing and monitoring safety measures.This critical review of current AI applications in diagnostic pathology underscores the paramount significance of patient-centred safety considerations. It also highlights the necessity of collaborative efforts among governments, academic institutions, international healthcare agencies, scientific societies, patient associations and algorithm developers to implement safety-oriented regulatory measures for AI-powered pathology.
Clinical performance assessment of the Papilloplex HR-HPV assay on self-taken urine and vaginal swab samples: findings from a multicentre European study
Cuschieri K, Latsuzbaia A, McMahon H, Giubbi C, Martinelli M, Iacobone AD, Bottari F, Piana AF, Pietri R, Salinaro F, Odicino F, Cocuzza C, Arbyn M and
Given the increasing adoption of self-sampling in cervical cancer screening, it is essential to evaluate the performance of human papillomavirus (HPV) tests in this context. The aim of the present work was to assess the accuracy of the Papilloplex high-risk (HR)-HPV test on self-taken samples.
Gastrointestinal stromal tumour with rearrangement: a report of two cases and including a novel and intergenic region fusion
Zhang Y, He X, Chen M and Zhang H
Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer treated with systemic neoadjuvant therapy: a systematic review and meta-analysis of diagnostic studies
Huerta-Rosario M, Quispe-Vicuña C, Julca-Marín D, Zumaran-Nuñez CJ, Baltazar-Ñahui H, Acuña-Chávez LM, Medina-Navia F, Nieto-Gutierrez W, Alva-Diaz C and Sahoo S
Frozen section (FS) and touch imprint (TI) are common intraoperative evaluation (IOE) techniques for sentinel lymph nodes (SLNs) in breast cancer surgery. Their accuracy in patients receiving neoadjuvant systemic therapy (NST) remains variable.
AI is quicker and more accurate than pathologists at SNOMED coding pathology reports
Mayall C, Mayall H, Mayall FG, Perring L, Truman D and Bodger I
Laboratory requirements for assessment of alcohol misuse
Ford L
The primary aims of this best practice article are to provide a laboratory perspective of the merits and pitfalls of different markers currently in use in UK National Health Service (NHS) hospital laboratories, and how best these tests can be used for the detection of heavy (harmful) alcohol consumption. Included are suggested testing algorithms for carbohydrate-deficient transferrin (CDT), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth16:0/18:1), for the purpose of creating suitable bench-to-bedside alcohol services in support of the delivery of hospital alcohol strategy, and the NHS long-term health plan.
AI portal tract detection and characterisation for a regional analysis of steatosis and inflammation in MASLD, MASH and AIH
Windell D, Magness A, Beyer C, Brears HT, Larkin S, Hobson K, Aljabar P, Fleming K, Fryer E, Kendall TJ, Kainth R, Wakefield P, Langford CR, Bedossa P and Goldin R
Annotation of liver biopsies for disease staging is increasingly aided by digital pathology; however, existing systems do not quantify inflammation and steatosis within an anatomical framework. We hypothesise that an artificial intelligence (AI) system that quantifies portal tracts (PT) and the anatomical distribution of steatotic vesicles and inflammatory cells will align with manual pathologist scoring and stratify liver diseases.
Stability of plasma and erythrocyte porphyrins: implications for diagnosis and monitoring of erythropoietic protoporphyria
Schulenburg-Brand D, Maw K, Bentley LA, Challenger R, Jones M and Gallagher CJ
Diagnosing and identifying the type of porphyria in a patient requires specialist analysis of porphyrins and/or precursors in blood, urine and faeces. Correct sample storage and handling prior to analysis is essential to minimise preanalytical error.We evaluated the impact of light exposure, time and temperature on erythrocyte and plasma porphyrins in samples from patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) stored as whole blood for up to 96 hours, and in addition, the effect of freeze-thaw on plasma porphyrins in EPP, PCT and hereditary coproporphyria patient samples.Plasma porphyrins in the EPP patient samples decreased on average by 19% after 6 hours despite light protection and fridge storage, 36% by 24 hours stored light protected at room temperature, 67% within 1 hour when light exposed and 33% after one freeze-thaw cycle. In contrast, plasma porphyrin in PCT samples demonstrated greater stability compared to the EPP samples when stored light protected or exposed at room temperature and during freeze-thaw. Erythrocyte porphyrins in EPP samples were stable for 96 hours under all three storage conditions examined.Erythrocyte protoporphyrin analysis should be undertaken as an additional first-line investigation alongside plasma porphyrin analysis whenever protoporphyria needs to be excluded, due to the significant instability of plasma protoporphyrin.
-mutant renal cell carcinoma: practical diagnostic features and differential considerations
Lin M, Chen C, Guo S, Wu Y, Lin F and Ding X
()-mutant renal cell carcinoma (RCC) is a recently recognised entity in the 2022 WHO classification. Due to overlapping features, it is frequently misdiagnosed as clear cell RCC (CCRCC). This study characterises the clinicopathological, immunohistochemical and molecular features of six -mutant RCCs to aid in their diagnostic distinction.
Fixative faux pas: glutaraldehyde's limitation in imaging mass cytometry studies of kidney biopsies
Alexander MP, Pavelko K, Strausbauch M, Murugesan VD, Kourelis T, Mckee T and Taner T
Adding interpretative comments to results of thyroid function tests from patients on thyroxine replacement does not improve management
Mallorie A, James T, deFonseka S, Weerasinghe G, Green D and Shine B
To assess the impact of adding clinical comments to reports of thyroid function testing in patients treated for hypothyroidism.
High upgrade rate to invasive carcinoma makes subclassification of papillary carcinoma of the breast in core needle biopsy unnecessary
Ai D, Ewaz AM, Van Smaalen K and Li X
Papillary carcinoma diagnosed in core needle biopsy (CNB) refers to carcinoma with papillary features but no definitive invasion, including papillary ductal carcinoma in situ (DCIS), papilloma with DCIS, encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC). This study assesses the upgrade rate of papillary carcinoma in CNB and supports the use of 'papillary carcinoma' as an umbrella term.
Digital pathology and image analysis of p53 biomarker in lymphomas using two algorithms: correlation with genotype and visual inspection
Naik A, Kanzaria A, Chen X, Kaur N, Ho CJ, Smith SD, Gopal AK, Shadman M and Naresh KN
p53 immunohistochemistry (IHC) is widely used as a rapid surrogate for detecting mutations, with mutations being a key biomarker for poor outcomes in lymphomas. We developed two algorithms using digital quantification tools to assess p53 expression from whole slide images of 77 lymphoma samples. An experienced pathologist visually evaluated the p53 slides, classifying cases as likely wild-type or mutated genotype. We correlated the results of the algorithms and visual inspection with the actual genotype. For cases with p53 overexpression (likely missense mutations), the algorithms achieved 86.7% sensitivity and 98.2% specificity (visual inspection: 80% and 95.2%). For cases with reduced p53 expression (likely 'other' mutations), the algorithms showed 92.7% sensitivity and 100% specificity (visual inspection: 40% and 95.8%). This study demonstrates that combining digital pathology with digital quantification tools-based algorithms can reliably predict genotype from p53 IHC patterns, with comparable or slightly superior performance to an experienced pathologist.
Validation of uPath HER2 dual-colour dual in-situ hybridisation image analysis tool for HER2/neu testing in breast cancer
Rathi A, Arora A, Sahay A, Shet TM, Pai T, Patil A and Desai SB
gene is amplified in 15%-20% of invasive breast cancers (IBCs), serving as critical prognostic and predictive marker. -targeted therapies have improved outcomes for -positive patients, highlighting the importance of accurate assessment. Immunohistochemistry is commonly used for screening overexpression, with equivocal cases reflex tested using in situ hybridisation (ISH) methods like fluorescence (FISH) or dual-colour dual ISH (D-DISH). While FISH displays quantitative accuracy, it is expensive, time-consuming and technically demanding. D-DISH offers a faster, automated alternative using bright-field microscopy for easier interpretation and better archiving. Advances in digital pathology, such as whole slide imaging and automated image analysis (IA), promise to improve evaluation. The CE-IVD marked uPath HER2 Dual ISH IA algorithm by Ventana Medical Systems (Tucson, Arizona, USA) is designed to assist in this process, providing computer-assisted evaluation of . Thus, we undertook this study to standardise and validate uPath Dual ISH IA algorithm and assess interobserver reproducibility in interpreting D-DISH assay.
Proposals to make diagnostic criteria truly usable and useful to pathologists worldwide
Stephenson PB, Folaranmi O, Jiménez Heffernan J and Mukhopadhyay S
Automation of fluorescent in situ hybridization (FISH) leading to cost savings and consistent high-quality results
Kwon GJ, Blackley A, Perkinson K, Bentley RC, Pavlisko EN and Cardona DM
Despite continually improving guidelines, human epidermal growth factor receptor 2 (HER2) testing for breast and gastro-oesophageal carcinoma continues to be a technical challenge in clinical laboratories. Manual HER2 fluorescence in situ hybridisation (FISH) testing is labour-intensive and prone to inter-run and interoperator variability. We aimed to adopt and validate a Leica BOND-III automated staining platform for HER2 FISH testing.
EBV-positive Burkitt lymphoma arising in a patient with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a case report
Chang C, Huang BY, Chen YP, Medeiros LJ and Chang KC
Prevalence of non- (NHPH) species in -associated gastritis
Chen YF, Tayal A, Friedman K and Sadri N
is a well-established cause of gastritis and gastric malignancy, but other species-collectively termed non- (NHPH)-also contribute to gastric disease. This study retrospectively analysed the prevalence of NHPH in 1115 routine gastric biopsies from a large academic medical centre submitted for drug susceptibility genotyping using a next-generation sequencing (NGS) assay targeting and rRNA genes. NGS results of identified pathogens were compared against those identified on histology. NHPH species were detected in 15 of 1115 cases (1.3%), including 7 NHPH-only infections and 8 mixed infections with Detected NHPH species included , and No mutations associated with antimicrobial resistance were identified in NHPH. Broader molecular testing may improve recognition of mixed infections and guide more accurate diagnosis and treatment for gastric disease.
Lymph node metastases characteristics and spread patterns in prostatic adenocarcinoma with seminal vesicle invasion: a comprehensive analysis
Saeed F and Osunkoya AO
Seminal vesicle invasion (SVI) in prostatic adenocarcinoma (PCa) is a high-risk feature associated with lymph node (LN) metastasis and adverse outcomes. However, the impact of SVI laterality on LN metastasis patterns, nodal burden, metastatic focus size and extranodal extension (ENE) remains underexplored.