Journal of Clinical Pathology最新文献

Aims: 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.

Methods: Women provided a clinician-taken cervical sample (CS), a urine sample and a vaginal swab according to the VALidation of HUman papillomavirus assays and collection Devices for Self-samples and urine samples protocol. Relative sensitivity and specificity for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of the Papilloplex HR-HPV assay on self-taken samples versus CS were assessed. Additionally, type-specific concordance and viral load signals (expressed in Ct (crossing thershold) values) between the two self-taken sample types and the CS were evaluated.

Results: At the manufacturers' cut-off, the assay showed a relative clinical sensitivity and specificity for CIN2+of 0.95 (95% CI 0.88 to 1.03) and 0.95 (95% CI 0.88 to 1.03) for urine versus CS. Corresponding values for vaginal samples versus CS were 1.05 (95% CI 1.01 to 1.09) and 0.81 (95% CI 0.74 to 0.89). Cut-off optimisation led to relative sensitivity and specificity that included unity for vaginal swabs. Median Ct values were lower in vaginal swabs versus CS, although higher in urine versus CS samples. No relationship between mean Ct values and disease outcome was observed.

Conclusions: The clinical sensitivity of the Papilloplex HR-HPV test was similar on self-collected vaginal swabs and urine compared with CS; clinical specificity on urine was similar to CS yet lower on vaginal samples. Cut-off optimisation resulted in a similar assay specificity on vaginal swabs and CS with no significant detriment to sensitivity.

Aims: To provide a practical, pathology-centred overview of Claudin 18.2 as a biomarker and therapeutic target, covering biology, assay methods and interpretation, pre-analytical factors, clinicopathological associations and implications for treatment selection.

Methods: We performed a narrative review of the biomedical and pathology literature on CLDN18/Claudin 18.2, including basic science, translational studies, immunohistochemistry (IHC) and in situ assays, and clinical trials of Claudin 18.2-directed therapies. Reference lists were hand-searched to capture additional relevant reports. Emphasis was placed on data informing routine diagnostic practice (expression patterns, scoring, fixation variables, pitfalls).

Results: Claudin 18.2 localises to tight junctions of differentiated gastric epithelium and is aberrantly expressed in gastric and gastro-oesophageal junction adenocarcinomas, with variable expression reported in pancreatic, biliary and other tumours. Loss or dysregulation of Claudin 18.2 contributes to tumour progression via disruption of epithelial integrity and activation of oncogenic pathways; infection-related and inflammation-related downregulation is described in gastric mucosa. For IHC, clone selection, tissue handling, fixation time and membrane-dominant scoring critically affect results; common pitfalls include cytoplasmic staining and heterogeneity. Claudin 18.2 expression shows predictive value for targeted agents under clinical use/evaluation, supporting its role as a companion biomarker. Reporting recommendations include membrane intensity/percentage thresholds and clear documentation of pre-analytical conditions.

Conclusions: Claudin 18.2 is a biologically plausible and clinically actionable biomarker. Robust pre-analytical handling, validated IHC protocols and standardised scoring are essential for reliable patient selection. Wider adoption of harmonised methods and further disease-specific studies will refine cut-offs, clarify prognostic value and optimise integration of Claudin 18.2-directed therapies into routine care.

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.

Aim: 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.

Methods and results: We retrospectively reviewed 94 TURBT pathology reports with high-grade urothelial carcinoma to assess MP sampling rates by tumour stage. MP was present in 55% (52/94) of cases, with variability across stages: 55% (23/42) in high-grade pTa, 39% (9/23) in pTis, 55% (11/20) in pT1 and 100% (9/9) in pT2. NLM was used to evaluate six fresh and 25 archived formalin-fixed, paraffin-embedded (FFPE) TURBT specimens. Fresh tissues were stained and imaged in real time, while thick sections from FFPE specimens were deparaffinised, imaged using NLM and converted to a digital format analogous to whole-slide images. NLM provided high-resolution imaging of MP as distinct, thick smooth muscle bundles in fresh specimens. Furthermore, NLM images of deparaffinised sections closely resembled conventional H&E histology, and a blinded reader achieved a sensitivity of 95% and specificity of 100% for MP detection.

Conclusion: This proof-of-concept study supports the feasibility of NLM for intraoperative MP assessment during TURBT. By providing rapid, high-resolution and non-destructive tissue evaluation, NLM has the potential to improve staging accuracy, optimise intraoperative surgical decision-making and reduce the need for repeat TURBT.

Aims: The diagnosis and therapeutic decision-making in chronic myeloid leukaemia (CML) depend on the detection and quantification of BCR::ABL1. Currently, no clinical assay is used in routine practice to simultaneously quantify multiple BCR::ABL1 isoforms, requiring separate tests for each isoform. To address this challenge, we have developed and optimised an assay (BloodHound) that leverages quantitative reverse transcription PCR (RT-qPCR) and high-resolution melting (HRM) technologies to simultaneously detect and quantify four BCR::ABL1 isoforms (p190, p210, p230 and p203), with a limit of detection of 0.001%.

Methods: To evaluate the clinical utility of this assay, we analysed 895 peripheral blood and bone marrow samples from patients with suspected, established or relapsed CML. Sanger sequencing was used as an orthogonal method to confirm fusion junction identity, and the Qiagen ipsogen BCR::ABL1 RT-qPCR assay was used for quantitative comparison.

Results: BCR::ABL1 was detected in 20.9% of samples, with p210 alone being the most prevalent (86.1% (161/187), 95 CI 80.3% to 90.7%), followed by coexpression of p190 and p210 (12.3% (23/187), 95% CI 7.6% to 17.0%), while p190 alone (1.1% (2/187), 95% CI 0.1% to 3.8%) and p230 alone (0.5% (1/187), 95% CI 0% to 2.9%) were rare and p203 was not detected. The assay demonstrated high sensitivity and specificity, with 100% concordance with Sanger sequencing and showed excellent agreement with the Qiagen BCR::ABL1 RT-qPCR assay (r=0.998).

Conclusions: The present multiplex RT-qPCR/HRM assay may help streamline clinical workflows, enhance diagnostic precision and offer a practical platform for studying CML clonal dynamics. It also holds promise for facilitating interlaboratory standardisation of non-p210 quantification.

Aims: 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.

Methods: In this observational, cross-sectional study, digitised images of haematoxylin and eosin-stained specimens were pooled from four independent cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH) or autoimmune hepatitis (AIH) (n=390: 89 MASLD, 238 MASH, 63 AIH). PT, steatosis, and inflammation were quantified using a proprietary AI system and scored by expert pathologists.

Results: The percentage of steatosis was higher in MASH (7.5%) than in MASLD (3.2%). Lobular regions had larger steatotic vesicles (260 vs 190 μm²). AI-derived steatosis quantification correlated with manual grading (r_s=0.72). The inflammatory cell number (ICN) was twofold higher in AIH than MASLD/MASH in interface (390 vs 140), portal (4600 vs 1500) and lobular (1500 vs 650) regions. Portal inflammation from manual grading correlated with ICN count at PT (r_s=0.71) but not lobular regions (r_s≤0.29). For equivalent grades of portal inflammation, the ICN was up to threefold higher in AIH than in MASLD/MASH (r_s=0.71).

Conclusion: A new AI system for anatomical quantification of liver biopsy features measured variation in fat and inflammation across the lobule. It showed that inflammation burden was higher in AIH than MASLD/MASH, despite equivalent portal grades, providing objective support for histological scoring.

The classification and clinical implications of colorectal intramucosal adenocarcinoma remain controversial. Given the increasing frequency of diagnosis through colorectal cancer screening programmes, a reassessment of terminology and its impacts is necessary. This paper critically examines the diagnostic criteria, biological behaviour and clinical consequences of labelling these lesions as colorectal intramucosal carcinoma. While intramucosal adenocarcinoma exhibits cytological and architectural atypia beyond high-grade dysplasia, it remains confined to the mucosa and has minimal metastatic potential, with rare documented exceptions. Conversely, the use of carcinoma terminology has been associated with potential overtreatment, including unnecessary surgical resection, increased patient anxiety and financial burdens such as insurance complications. We explore geographic variations in classification and analyse the impact of terminology shifts. We propose a standardised framework that restricts the term intramucosal adenocarcinoma to intramucosal lesions exhibiting tumour budding or poorly differentiated clusters, signet ring cells, desmoplasia, vascular invasion, mucinous differentiation or features of neuroendocrine carcinoma, while reclassifying adenomas with cribriform architecture and complex glands as high-grade dysplasia. This nomenclature shift aims to reduce overtreatment, align with current oncologic understanding and ensure optimal patient care and communication.

Aims: Malignant transformation of fibrous dysplasia (FD) in long bones is very rare. This study aimed to explore its clinicopathological and molecular characteristics to reveal the diagnostic features and pathogenesis.

Methods: We conducted a clinicopathological analysis of 19 FD-associated sarcomas. Sanger and next-generation sequencing were used to detect molecular alterations, and clinical, radiological and histopathological features were reviewed in detail.

Results: The cohort consisted of 10 female and nine male patients (mean age, 48.4 years). Eleven patients had a previous diagnosis of FD, and eight patients presented de novo with acute symptoms like pain, swelling or dysfunction. Radiologically, in the monostotic cases (n=13), osteolytic lesions were observed with ill-defined margins, cortical destruction and soft tissue masses. Polyostotic cases (n=6) had both malignant masses and classic FD features of other skeletal sites. Histopathologically, osteosarcoma was the most common (57.9%), followed by undifferentiated pleomorphic sarcoma (26.3%), grade 2 spindle cell sarcoma (not otherwise specified, 5.3%) and low-grade central osteosarcoma (10.5%). Molecular analysis revealed identical GNAS mutations in paired FD and malignant components. Next-generation sequencing identified universal CDKN2A/B alterations (100%), along with concurrent TP53 (28.6%), TERT (28.6%) and KDM6A (28.6%) mutations, indicating a potential collaborative role in the FD malignant transformation process.

Conclusions: Our analysis revealed unique clinicopathological characteristics and genetic markers in FD-associated sarcomas, deepening our knowledge of the mechanisms behind malignant transformation in FD and offering diagnostic tools for enhanced pathological assessment.