Journal of Clinical Pathology最新文献

Background: 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.

Objective: To summarise evidence on the diagnostic accuracy of FS and TI in the NST context.

Methods: A systematic search of PubMed, Embase, Scopus and Web of Science was conducted through April 2024 for studies evaluating FS and/or TI in SLNs of breast cancer patients treated with NST. Meta-analysis was performed using the logit function, and Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 and Grading of Recommendation, Assessment, Development and Evaluation were employed to assess risk of bias and evidence certainty.

Results: 20 studies were included. At the lymph node level, TI demonstrated pooled sensitivity and specificity of 0.54 and 1.00, respectively, while FS achieved 0.85 and 0.99. At the patient level, TI showed sensitivity and specificity of 0.72 and 1.00, while FS reached 0.82 and 0.98. Combined, FS and TI presented pooled sensitivity and specificity of 0.59 and 1.00 at the patient level. Risk of bias was frequently unclear, and the certainty of evidence for both techniques ranged from low to very low.

Conclusion: FS exhibits higher sensitivity and specificity than TI at both lymph node and patient levels, but evidence certainty remains limited. Further prospective, blinded studies are needed to validate these findings and optimise IOE methods for NST-treated patients.

Prospero registration number: CRD42023483079.

Aims: Colorectal cancer (CRC) is increasingly detected at an early stage through national screening programmes, including tumours confined to the submucosa (pT1). Many pT1 CRC are managed by local endoscopic excision, and histological risk assessment is central to determining the need for further treatment.

Methods: Clinical and pathology data were analysed for screen-detected pT1 CRC removed by local excision within the English Bowel Cancer Screening Programme (BCSP) between 2021 and 2022. The completeness of data recorded in the Bowel Cancer Screening System (BCSS) was audited against national pathology guidance. Clinicopathological features and subsequent management were described.

Results: 1267 pT1 CRC from 1260 patients were identified. BCSS data were available for all cases, although some histological fields were incomplete or coded as 'not assessable'. Most tumours were adenocarcinoma, not otherwise specified (NOS) (95.7%) and well-moderately differentiated (90.4%). Venous, lymphatic and perineural invasion were recorded in 8.9%, 9.2% and 1.0% of cases, respectively. Complete local resection (R0) was documented in 643 tumours. Following local excision, 342 pT1 CRC (27.0%) received further treatment, most commonly colorectal resection (287 cases) or repeat local excision (23 cases). Lymph node metastases were reported histologically in 33 patients.

Conclusions: This large, contemporary cohort demonstrates that the English BCSP holds rich clinical and histological data suitable for audit and research. The audit highlights parameters where assessment is constrained by specimen-related factors and where data entry could be improved. These data characterise the histological features of locally excised pT1 CRC and their subsequent management and provide a foundation for future outcome-focused studies.

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: 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: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition of unknown aetiology. It is a diagnosis of exclusion with a wide differential diagnosis. To date, no diagnostic guidelines exist for IGM in the UK. This scoping review aims to evaluate histopathological and microbiological approaches for the diagnosis of IGM.

Methods: A scoping review was performed by conducting a search of MEDLINE, Embase and Cochrane databases from 2003 to 2023. Studies involving human participants with histopathologically confirmed IGM were included. Data on histopathological and microbiological investigations were extracted and analysed.

Results: Out of 3208 search results, 225 studies involving 13 062 participants were included. Histological assessment was performed in 72.5% of participants, predominantly via core or excision biopsy. Microbiological investigations were inconsistently applied; only 47% of studies reporting the use of microscopy and culture. Only 24.9% of studies tested for tuberculosis using methods beyond histochemical Ziehl-Neelsen staining, and just 14 studies including 5% of participants described performing mycobacterial culture, despite this being the gold standard for diagnosis. Corynebacterium kroppenstedtii was identified in several studies using advanced molecular techniques, suggesting possible misclassification of cystic neutrophilic granulomatous mastitis as IGM.

Conclusions: Substantial heterogeneity exists in the diagnostic workup for IGM, particularly in excluding infectious and systemic causes. Histopathology alone is insufficient for definitive diagnosis. A comprehensive, standardised diagnostic framework that incorporates clinical, microbiological and epidemiological factors is needed to improve diagnostic accuracy and ensure appropriate management, particularly in the context of possible immunosuppressive therapy.

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.