Journal of Clinical Pathology最新文献

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.

Aims: Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs.

Methods: MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes.

Results: Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCA ^{A1219GfsTer59} variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes.

Conclusions: Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.

The fifth edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) introduces significant advancements in the understanding and diagnosis of mature T cell and NK cell, and stroma-derived neoplasms, and incorporates molecular and genetic data/findings accrued over the past years. The classification has been reorganised using a hierarchical system, employed across the fifth edition of the WHO classification of tumours of all organ systems. This review highlights recent developments, evolving concepts, and key updates since the revised fourth edition (WHO-HAEM4R). It enumerates the minimal/essential criteria necessary for diagnosis and classification, constituting not only the importance of clonality analysis in the workup of certain T cell neoplasms and the detection of infectious agents and specific genetic alterations in a subset of entities but also the applicability of these criteria in resource-constrained settings. 'Stroma-derived neoplasms of lymphoid tissues discussed in this review is a new category introduced in HAEM5 that encompasses mesenchymal tumours occurring exclusively in lymph nodes and spleen and mesenchymal dendritic cell neoplasms previously classified as 'histiocytic/dendritic cell neoplasms'.