Journal of Clinical Pathology最新文献

Aims: Gallbladder carcinoma (GBC) is frequently diagnosed and treated in advanced stages and has a poor prognosis. Recent studies have identified claudin18.2 (CLDN18.2) as a promising target in digestive system cancer. In this study, we aimed to determine the expression of CLDN18.2 and its correlation with clinicopathological characteristics in patients with GBC.

Methods: The expression of CLDN18.2 of 228 patients with GBC was studied via immunohistochemistry. Immunostained samples were evaluated according to the H-score. The samples were divided into low/negative (H-score=0-49) and high/positive (H-score=50-300) expression groups. The correlations between CLDN18.2 and various clinicopathological characteristics, including survival, were assessed. Multiplex immunofluorescence and image acquisition were used to analyse the relationship between CLDN18.2 expression and the immune microenvironment.

Results: The overall positive CLDN18.2 staining rate was 39.91% (91/228); 137 (60.08%) were given 0 points, 30 (13.15%) were given 1 point, 28 (12.28%) were given 2 points and 33 (14.47%) were given 3 points. Low CLDN18.2 expression was correlated with adverse prognostic factors, including poor differentiation, deep infiltration depth, lymph node metastasis and distant metastasis. High CLDN18.2 expression was associated with better survival. Furthermore, the distribution of immune cell subsets significantly differed between the high and low CLDN18.2 expression groups.

Conclusions: The correlations between the expression of CLDN18.2 and clinicopathological characteristics and prognosis suggest that early-stage patients could benefit more from future anti-CLDN18.2 treatment and that CLDN18.2 may function as a pivotal regulatory molecule in patients with GBC. The underlying mechanism may be related to immune activation caused by high CLDN18.2 expression.

Aim: Over the past several decades, optical sectioning technologies have emerged as valuable tools for evaluating tissue histology. Unlike conventional tissue sectioning, these technologies allow for real-time intraoperative assessments and more efficient tissue triage. In the era of digital pathology, the demand for high-quality, high-throughput optical sectioning platforms is increasing, as they eliminate the need for traditional slide preparation and scanning, potentially transforming anatomical pathology workflows. While non-linear microscopy (NLM) has demonstrated promise in histological evaluation across various tissue types, its application in gastrointestinal tissue assessment remains unexplored.

Methods: This study extends the use of NLM to gastrointestinal histology and develops an image atlas to highlight its potential as an automated digital pathology platform.

Results: Our results indicate that NLM generates diagnostic-quality images comparable to traditional H&E slides. Moreover, NLM provides valuable three-dimensional (3D) spatial information, improving clinical evaluations of key histological features such as depth of invasion, lymphovascular and perineural invasion, tumour budding and margin assessment. Time-lapse videos further demonstrate NLM's capability to capture 3D histological structures up to a depth of approximately 100 µm.

Conclusion: Our findings demonstrate that NLM can serve as an optical sectioning platform for gastrointestinal histology, providing both diagnostic-quality imaging and advanced 3D visualisation. The introduction of an NLM-based atlas has the potential to redefine anatomical pathology workflows and advance digital pathology image analysis.

Aims: Despite the 1988 'Dundee Initiative', which maximised the use of view and grant examinations to reduce the invasive forensic autopsy rate in Tayside, the view and grant itself remains controversial. This is the first study to measure attitudes towards view and grants, applying the Theory of Planned Behaviour to investigate what attitudes are held, the reasons behind them and their association with deciding the scope of postmortem examinations.

Methods: A mixed-methods cross-sectional study examined 62 UK pathologists, coroners and procurators fiscal using an online questionnaire. Participants were asked their demographics and attitudes towards view and grants before allocating five fictitious reportable deaths to either view and grant or invasive forensic autopsy (both in ideal and real world conditions), explaining their decisions using free-text.

Results: Participants held both positive and negative attitudes towards view and grants, and most were relatively strong and ambivalent. Attitudes predicted respondents' decisions to favour view and grant or invasive forensic autopsy in all ideal world scenarios, but no real world scenarios. There were significant differences in attitudes and decisions when comparing pathologists and judicial officers, and respondents working in Coroner and Fiscal systems. Thematic analysis was conducted on free-text responses.

Conclusions: Discrepancies between attitudes, and ideal and real world choices suggest that what respondents wanted to do did not necessarily translate to what they would actually do in the scenarios tested. Applying concepts of attitudes, norms and perceived control can help to understand decision-making by death investigators, and why some jurisdictions favour more invasive procedures.

The healthcare sector significantly contributes to global greenhouse gas emissions, with surgical pathology (SP) playing a notable role. This review explores the ecological transformation of SP, offering a global overview of existing challenges and sustainable initiatives worldwide.While some countries, such as the UK and France, have developed national strategies to reduce the carbon footprint of healthcare, including SP, many regions remain at an early stage of implementing green practices. Several studies have assessed the carbon footprint of SP, focusing on key aspects such as laboratory operations, pathology procedures and functional units, highlighting materials and transportation as major contributors to emissions. The integration of digital pathology and artificial intelligence (AI) presents opportunities to enhance efficiency and address medical deserts but also poses challenges due to the associated energy consumption.Local initiatives such as the 'Transformation Ecologique en Anatomie et Cytologie Pathologiques' (Ecological transformation in SP) or TEAP collective in France, Belgium's 'Green Team' and sustainable practices in Tunisia and New Zealand demonstrate the global effort to reduce the environmental impact of SP. Key strategies discussed include ecodesign of care, circular economy practices, green AI and partnerships with industry. However, achieving meaningful reductions in SP's environmental impact requires international cooperation and support from national health policies. This review emphasises the importance of collaborative efforts to implement sustainable solutions without compromising the quality and safety of healthcare services.

Aims: Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could provide deeper insights into its prognostic implications and treatment determination.

Methods: We conducted a search of articles in PubMed, EMBASE and the Cochrane Library from inception to January 2024. A domestic cohort consisting of 52 LUAD samples was subjected to whole-exome sequencing as internal validation. Data from The Cancer Genomic Atlas and the Gene Expression Omnibus datasets were obtained to characterise the genomic and immune profiles of LP+A. Pooled HRs and rates were calculated.

Results: The pooled results indicated that lepidic growth pattern was either predominant (0.35, 95% CI 0.22 to 0.56, p<0.01) or minor (HR 0.50, 95% CI 0.36 to 0.70, p<0.01) histological subtype was associated with favourable disease-free survival. Pooled gene mutation rates suggested higher EGFR mutation (0.55, 95% CI 0.46 to 0.64, p<0.01) and lower KRAS mutation (0.14, 95% CI 0.02 to 0.25, p=0.02) in lepidic-predominant LUAD. Lepidic-predominant LUAD had lower tumour mutation burden and pooled positive rate of PD-L1 expression compared with other subtypes. LP+A was characterised by abundance in resting CD4+memory T cells, monocytes and γδ T cells, as well as scarcity of cancer-associated fibroblasts.

Conclusions: LP+A was a unique histological subtype with a higher EGFR mutation rate, lower tumour mutation burden and immune checkpoint expression levels. Our findings suggested potential benefits from targeted therapy over immunotherapy in LP+A.

Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

Methods: A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period.

Results: 40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03).

Conclusions: Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.

Pseudoangiomatous stromal hyperplasia (PASH) is commonly present in gynaecomastia, can be seen in some mammary fibroepithelial lesions and in fibrocystic change, and rarely forms a mass. Spindle cell carcinoma of the breast can have a wide range of appearances. This case series describes five spindle cell carcinomas of the breast resembling PASH, a pattern that does not appear to have been reported before. All had bland nuclei like those in fibromatosis-like spindle cell carcinoma. All cases had more close-packed areas, but this was only a very minor component in the index case. Two had associated ductal carcinoma in situ. All were cytokeratin positive with immunohistochemistry. The similarity of the carcinomas in this series to PASH is a diagnostic pitfall particularly in core biopsies as more cellular areas may be only focal.