Journal of Clinical Pathology最新文献

Aim: This systematic review aims to comprehensively evaluate the clinicopathological and molecular features of superficial CD34-positive fibroblastic tumour (SCD34FT), a recently described intermediate-grade soft-tissue neoplasm recognised in the 5th edition of the WHO classification of soft tissue tumours.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched for English-language studies in PubMed, Scopus, Google Scholar and Web of Science. Retrospective or original case series with ≥3 histologically confirmed cases were selected for review, whereas review articles, single case reports and conference abstracts were excluded. Risk of bias was assessed using the Joanna Briggs Institute checklist.

Results: A total of 190 patients across 14 selected studies met the inclusion criteria. SCD34FT mainly affected middle-aged adults, with the most common site being the lower extremity. Diffuse CD34 expression was universal across all studies. A high number of cases displayed SynCAM/CADM3 positivity, while WT1 and Pan-CK (focal) were frequent. PRDM10 fusion was detected in 73% of cases, and the most common fusions were PRDM10::MED12 (66%) and PRDM10::CITED2 (28%). Only 9/169 (5.3%) had local recurrences, whereas 4/190 (2.1%) cases had lymph node metastasis, with no distant metastasis or disease-related death.

Conclusion: SCD34FT is a novel entity with consistent CD34 expression and recurrent PRDM10 rearrangements and shows indolent behaviour. A high index of suspicion for SCD34FT should be warranted in a superficially located tumour with striking nuclear pleomorphism but an unexpectedly low mitotic index. Molecular studies demonstrating PRDM10 rearrangement may be helpful in atypical cases.

A 49-year-old woman was admitted with gastrointestinal symptoms and imaging consistent with duodeno-ileitis. Her clinical course was complicated by mesenteric ischaemia, requiring resection of a 45-cm ileal segment. A pre-adult Anisakis spp. larva was identified within a mesenteric nodule through an innovative diagnostic approach combining histopathological analysis with shotgun metagenomic analysis.

Aims: To characterise histological patterns and heterogeneity in testicular biopsies from azoospermic men, assess bilateral concordance, evaluate morphometric parameters for a structured reporting template and place findings in context with the existing literature on testicular biopsy evaluation.

Methods: Retrospective cross-sectional study of 112 men with non-obstructive azoospermia who underwent open testicular biopsy at a single centre between 2006 and 2019. Archived H&E-stained slides were digitised and re-evaluated. Morphological changes were classified into predefined categories at whole-biopsy and individual tubule level, enabling detailed characterisation of hypospermatogenesis and mixed atrophy. Mean seminiferous tubule diameter, lamina propria thickness and interstitial Leydig cell quantity were measured and compared between histological groups.

Results: Bilateral biopsies were obtained in 104/112 patients (92.9%), and 26.9% showed discordant histological patterns. Mature spermatozoa were present bilaterally in 43.8% and unilaterally in 7.7% of bilaterally biopsied patients. Hypospermatogenesis was the predominant pattern (42.9%), followed by normal spermatogenesis (19.6%), Sertoli cell-only syndrome (23.2%), maturation arrest (12.5%) and tubular hyalinisation (1.8%). Two-thirds of hypospermatogenesis biopsies had heterogeneous mixed patterns. Mixed atrophy, a non-spermatozoa-producing heterogeneous pattern, was subdivided into 10 clusters based on the relative proportions of tubular types. Greater spermatogenic impairment was associated with reduced tubule diameter, increased lamina propria thickness and Leydig cell hyperplasia.

Conclusions: Testicular biopsies in azoospermic men show marked intratesticular and intertesticular heterogeneity, and bilateral sampling reveals clinically relevant discordance in many patients. Simple quantitative morphometry complements qualitative assessment. A structured reporting template may standardise terminology, improve interobserver agreement and support evidence-based decisions in daily male infertility care.

Aims: To determine if the frequency of CD103+ T cells among background lymphocytes is associated with non-haematopoietic metastasis in samples of clinically concerning unexplained lymphadenopathy.

Methods: We retrospectively reviewed clinical flow cytometry data from 126 lymph node (LN) samples including 36 involved by metastatic non-haematopoietic malignancy and 90 control LNs (54 benign/reactive and 36 lymphomas). We evaluated the frequency of CD103+ cells among CD3+, CD3+CD4+ and CD3+CD8+ T cell subsets. Immunohistochemistry was used to visualise CD103 expression in a limited number of cases.

Results: CD103 expression in ≥3% of total CD3+ T cells and ≥7% of CD3+CD8+ T cells correlated with the presence of metastatic non-haematopoietic malignancy in LNs, and differentiated LNs with metastasis from control LNs with sensitivities of 75% (95% CI 59% to 86%) and 78% (95% CI 62% to 88%) and specificities of 100% (95% CI 96% to 100%) and 99% (95% CI 94% to 100%), respectively.

Conclusion: Increased frequency of CD103+ T cells is associated with metastatic non-haematopoietic malignancies in excisional and core needle biopsies of clinically concerning lymphadenopathy.

Aims: Malignant effusion is a common manifestation of metastatic gastric cancer. This study compared the expression of key biomarkers (human epidermal growth factor receptor 2 (HER2), programmed cell death ligand 1 (PD-L1), claudin 18.2 (CLDN18.2) and fibroblast growth factor receptor 2b (FGFR2b)) between malignant effusion-derived cell blocks (CBs) and matched primary or metastatic tumour tissues and evaluated the longitudinal concordance of biomarker expression in serially collected CBs.

Methods: Biomarker status was retrospectively assessed by immunohistochemistry in CBs from malignant effusions and paired primary/metastatic gastric adenocarcinomas. HER2+ cases underwent fluorescence in situ hybridisation to confirm amplification.

Results: CLDN18.2 showed the highest positivity rate (34.0%). PD-L1 expression was positive in 8.6% of tumours and 13.9% of stroma. Lower rates were observed for FGFR2b (3.8%) and HER2 (3.3%). FGFR2b positivity was more frequent in CBs than in primary tumours (p=0.044) with higher expression levels (p=0.02). Conversely, CLDN18.2 positivity was lower in CBs versus primary tumours (p=0.004). Metastatic lesions showed higher CLDN18.2 positivity (p=0.04) and expression levels (p=0.002) compared with CBs. Serial CB analysis revealed high concordance rates: FGFR2b (99.1%), HER2 (98.1%), tumour PD-L1 (94.8%) and CLDN18.2 (92.2%).

Conclusions: Malignant effusion CBs show favourable intra-patient biomarker consistency over time, supporting their feasibility for longitudinal monitoring. Effusion-based testing shows potential value for potentially identifying candidates for FGFR2b-targeted therapies, pending further clinical validation.

Background: Cell division cycle 25A (CDC25A) is a key regulator of cell cycle progression, DNA replication and apoptosis in cancer cells. This study employed multiple well-characterised breast cancer cohorts to evaluate the prognostic significance of CDC25A and to characterise the molecular association linked to its expression in early-stage breast cancer.

Methods: CDC25A transcriptomic expression was systematically assessed for statistical associations with key genes and pathways implicated in cell cycle regulation, DNA damage repair, cyclin-dependent signalling, tumour microenvironment and epithelial-mesenchymal transition. Its prognostic relevance was further evaluated through survival analyses. These investigations were conducted across the Molecular Taxonomy of Breast Cancer International Consortium (n=1980), the Cancer Genome Atlas (n=854) and Kaplan-Meier Plotter (n=4929) breast cancer cohorts. Subsequently, this study explored the associations between CDC25A protein expression and established clinicopathological parameters, molecular characteristics and patient outcomes using immunohistochemistry in a large, well-characterised Nottingham breast cancer cohort (n=1045).

Results: High CDC25A expression was associated with altered expression of key breast cancer-related genes involved in cell cycle control, DNA damage repair, cyclin-dependent signalling, matrix remodelling and epithelial-mesenchymal transition-related biology. Elevated CDC25A expression at both transcriptomic and proteomic levels was significantly associated with aggressive clinicopathological features, including higher tumour grade, larger tumour size, hormone receptor negativity and lymphovascular invasion. High CDC25A protein expression independently predicted poorer survival outcomes (p=0.027; HR 1.28, 95% CI 1.18 to 1.98).

Conclusion: CDC25A is an independent prognostic biomarker of clinical outcome in breast cancer. Further functional studies are warranted to validate CDC25A as a potential prognostic and therapeutic biomarker in breast cancer.

MYD88 is a signal-transducing adaptor protein that plays a central role in Toll-like receptor and interleukin 1 receptor signalling through activation of the NF-κB pathway. The somatic L265P mutation in MYD88 represents a recurrent gain-of-function alteration in mature B-cell neoplasms, most notably lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinaemia (WM) (>90%), IgM monoclonal gammopathy of undetermined significance (27%-87%) and activated B-cell-type diffuse large B-cell lymphoma (DLBCL), particularly those arising in immune-privileged sites such as the central nervous system (CNS) and testis. The L265P substitution promotes constitutive myddosome assembly, IRAK1/4 recruitment and aberrant Bruton tyrosine kinase (BTK) activation, resulting in sustained NF-κB signalling independent of receptor engagement. Concurrent mutations-including CXCR4 in LPL and CD79B in DLBCL-define distinct molecular subtypes with prognostic and therapeutic implications. MYD88 mutation status serves as a valuable diagnostic biomarker, aiding differentiation of LPL from morphological mimics and enabling liquid biopsy approaches in primary CNS lymphoma. The prognostic significance of L265P is context-dependent: it confers favourable outcomes in WM but portends inferior survival in DLBCL. Therapeutically, MYD88 L265P predicts response to BTK inhibitors in WM, although concurrent CXCR4 mutations attenuate treatment efficacy. Detection methodologies include allele-specific PCR for targeted L265P detection and next-generation sequencing for comprehensive mutational profiling. This review summarises the molecular biology, disease associations, clinical utility and therapeutic implications of MYD88 mutations in lymphoid malignancies.

Aims: Metabolic-associated steatotic liver disease (MASLD), which encompasses metabolic associated steatotic liver (MASL) and metabolic-associated steatohepatitis (MASH), is the most common chronic liver disorder worldwide. Fibrosis stage remains the most dependable histological predictor of prognosis; however, routine stains do not fully capture regenerative and injury-related processes. Keratin 7 (K7) immunohistochemistry highlights bile ducts (BDs), ductular reaction (DR), hepatic progenitor cells (PCs) and intermediate hepatocytes (IHs), all of which are involved in regeneration and fibrogenesis. This study aims to quantify K7-positive cell populations across histological stages of MASLD to enhance disease characterisation and evaluate the diagnostic value of K7 immunohistochemistry in this setting.

Methods: Archived liver biopsies from a clinically well-characterised cohort of 36 patients (17 MASH, 19 MASL) were stained for K7, digitised and analysed using QuPath with manual expert review. K7-positive structures were classified into BD, DR, PC or IH, with over 10 000 objects quantified. Profile densities and portal tract normalised ratios were calculated and correlated with clinical, biochemical and histological grading and staging by the Steatosis Activity and Fibrosis score.

Results: PC showed the strongest association with necro-inflammatory activity, peaking at grade 3. DR density increased significantly with fibrosis, supporting its role as an early marker of disease progression. IH was notably higher in MASH than in MASL, resulting in higher IH/DR ratios.

Conclusion: Specific quantitation of K7-positive cell populations can refine the diagnosis of MASLD and complement routine scoring in clinical trials to improve patient stratification.

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.

Aim: The clinical significance of histologic margin involvement by basal cell carcinoma (BCC)-associated stroma remains uncertain. This study aimed to determine the incidence of residual BCC in immediate re-excision specimens or clinical recurrence in cases managed without re-excision.

Methods: Fifty-eight cases of BCC with stromal margin involvement diagnosed between 2016 and 2020 were retrospectively reviewed. Fifty cases underwent immediate surgical re-excision, and eight were managed with clinical observation for at least two years. Tumors were classified by histologic subtype, and stromal margin involvement was categorized as peripheral, deep, or both. Residual carcinoma on re-excision or clinical recurrence within two years was recorded.

Results: Residual carcinoma was identified in 8% of re-excised cases (4/50) and occurred exclusively in tumors with a superficial component, including three pure superficial BCCs and one mixed superficial-nodular BCC; all residual tumors were of superficial subtype. No residual carcinoma was observed among 23 nodular or infiltrative BCCs that underwent re-excision. None of the eight cases managed with observation (1 superficial, 2 mixed superficial-nodular, 5 nodular) demonstrated clinical recurrence within two years. Overall, residual or recurrent disease occurred in 7% of cases (4/58). The distribution of adverse outcomes differed significantly by histologic subtype.

Conclusions: Stromal margin involvement in non-superficial BCCs is rarely associated with residual or recurrent carcinoma. Adverse outcomes were confined to tumors containing a superficial component, highlighting biologic heterogeneity among BCC subtypes. These findings suggest that routine re-excision may be unnecessary for stromal-margin-positive BCCs lacking a superficial component and support more selective, subtype-informed management.