AIMS: Current diagnostic criteria for pancreatic serous cystadenocarcinoma (SCC) create a grey zone for tumours that are locally invasive but not yet metastatic. We sought to resolve this ambiguity by defining the clinic...AIMS: Current diagnostic criteria for pancreatic serous cystadenocarcinoma (SCC) create a grey zone for tumours that are locally invasive but not yet metastatic. We sought to resolve this ambiguity by defining the clinicopathological features and searching for the malignant potential of this aggressive subset of serous neoplasms. METHODS: A combined cohort of 25 patients was compiled from a systematic literature review and augmented with two institutional cases. RESULTS: Infiltrative growth was a near-universal finding (23/25), often in tumours with a prominent solid architecture. This growth pattern was reflected by frequent local invasion into adjacent organs (40%). The malignant potential of these neoplasms was confirmed by the development of metachronous distant metastases in 28% of patients (median time: 40.5 months) despite their absence at presentation. Our institutional cases highlight the diagnostic value of Ki-67 immunohistochemistry, revealing markedly elevated proliferation indices (5% and 10% in hotspots) that starkly contrast with those of conventional serous cystadenomas (<2%). CONCLUSION: Local invasion in serous neoplasms, especially when combined with a solid architecture and high Ki-67 index, defines a high-risk subset highly suspicious for serous cystadenocarcinoma. This interpretation must be balanced against the generally indolent behaviour of most serous neoplasms, and such cases warrant closer clinical surveillance.
AIMS: Distinguishing epithelioid malignant mesothelioma (EMM) from poorly differentiated lung adenocarcinoma (PD-LUAD) remains challenging, particularly when 21.7% of PD-LUADs lack lineage-specific markers (thyroid trans...AIMS: Distinguishing epithelioid malignant mesothelioma (EMM) from poorly differentiated lung adenocarcinoma (PD-LUAD) remains challenging, particularly when 21.7% of PD-LUADs lack lineage-specific markers (thyroid transcription factor-1 (TTF-1)/Napsin A), creating a diagnostic blind spot. While GATA-binding protein 3 (GATA3) is established in sarcomatoid mesothelioma, its complementary diagnostic value and prognostic relevance in EMM are not well defined. METHODS: This retrospective study analysed 115 tissue specimens (55 EMMs; 60 PD-LUADs). Immunohistochemistry for GATA3, calretinin, Wilms' tumour gene 1 (WT-1), TTF-1, Napsin A and pan-cytokeratin was performed. Results were correlated with clinicopathological parameters and overall survival (OS) using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: GATA3 was expressed in 78.2% of EMM but only 6.7% of PD-LUAD cases (p<0.001). Although not specific enough for standalone diagnosis, GATA3 provided meaningful complementary value: in TTF-1/Napsin A-negative PD-LUAD, GATA3 remained negative in 92.3%, helping to exclude EMM when used within a broader panel. Incorporating GATA3 with calretinin and WT-1 improved panel sensitivity to 96.4% while maintaining 100% specificity.High GATA3 expression in EMM correlated significantly with advanced T stage, higher International Mesothelioma Interest Group stage and poor functional status (Karnofsky performance status/Eastern Cooperative Oncology Group). Multivariate analysis identified GATA3 expression (p=0.037), smoking (p=0.041) and clinical T stage (p<0.001) as independent predictors of shorter OS. A qualitative inverse relationship between tumorous GATA3 and GATA3-positive tumour-infiltrating lymphocytes was also noted. CONCLUSIONS: GATA3 serves as a useful adjunct within established immunohistochemical panels, particularly in resolving ambiguity in double-negative PD-LUAD. Beyond its supportive diagnostic role, GATA3 demonstrates independent prognostic significance and may reflect underlying immune-microenvironmental features, meriting further exploration in biomarker-guided therapeutic stratification.
BackgroundMucinous breast carcinoma (MBC) is a well-recognised special type of invasive breast carcinoma (BC) characterised by abundant extracellular mucin and, in its classical form, a favourable clinical behaviour. How...BackgroundMucinous breast carcinoma (MBC) is a well-recognised special type of invasive breast carcinoma (BC) characterised by abundant extracellular mucin and, in its classical form, a favourable clinical behaviour. However, extracellular mucin production is not unique to classical MBC and extracellular mucin is associated with a spectrum of benign and malignant entities with varying and overlapping morphological patterns but with very different clinical outcomes. Failure to recognise this diversity risks diagnostic imprecision and inappropriate management decisions.This review adopts a clinicopathological and pathogenetic framework centred on BCs associated with extracellular mucin, using classical low-grade MBC as the prototype lesion. The review integrates available molecular data, clinical outcome studies, observations on associated in situ and precursor lesions and accumulated diagnostic experience to generate conceptual models linking morphology, biology and clinical behaviour. Emphasis is placed on reproducible features relevant to routine diagnostic practice to enable pathologists to resolve a differential diagnosis of breast lesions in core biopsies and resections.
The 2017 guideline-recommended gating strategy (RGS) for antineutrophil cytoplasmic antibody (ANCA) testing for ANCA-associated vasculitis (AAV) diagnosis has not been evaluated in Australia, and the optimal gating strat...The 2017 guideline-recommended gating strategy (RGS) for antineutrophil cytoplasmic antibody (ANCA) testing for ANCA-associated vasculitis (AAV) diagnosis has not been evaluated in Australia, and the optimal gating strategy remains unclear. We aimed to determine the performance characteristics of the RGS, a novel classification criteria-based gating strategy (CCGS) and the non-gated strategy (NGS) and estimated local cost-savings. We performed a retrospective analysis of ANCA tests at a tertiary referral laboratory (n=516, 19 AAV cases). NGS had 89.5% sensitivity, 98.2% specificity, 65.4% positive predictive value (PPV), 99.6% negative predictive value (NPV), likelihood ratios (LR+ and LR-) LR+49.4 and LR- 0.11. RGS had improved PPV (94.4%) and LR+ (444.7) and would have avoided 79.8% of ANCA tests. CCGS performed the same but would have avoided 85.9% of ANCA tests. No AAV cases were missed. CCGS would have yielded annual healthcare cost-savings of $A86 574. Implementing gating strategies may improve ANCA diagnostic performance for AAV, reduce testing volume and lead to significant healthcare cost-savings.
Transitioning from total to active vitamin B12 testing may influence diagnostic categorisation and costs. In this retrospective population study, a total of 181 794 vitamin B12 results from primary care requests in a UK...Transitioning from total to active vitamin B12 testing may influence diagnostic categorisation and costs. In this retrospective population study, a total of 181 794 vitamin B12 results from primary care requests in a UK laboratory were analysed -90 036 using total B12 assay before transitioning, and 91 758 using active B12 assay after transitioning- according to the National Institute for Health and Care Excellence (NICE)-defined thresholds. Compared with total B12, active B12 testing identified proportionately fewer patients as deficient (2.1% vs 6.5%) or indeterminate (37.0% vs 46.2%), and more as deficiency-unlikely (60.9% vs 47.3%). Although active B12 improved classification and may reduce the need for confirmatory testing by classifying fewer individuals as indeterminate, it incurred substantially higher cost, with an estimated 26-fold increase in expenditure to identify one deficient patient based on unit test cost in the NICE guidance. While active B12 may enhance diagnostic precision, its financial impact could limit broader adoption for routine testing unless test costs decrease.
BACKGROUND: Although histological criteria underpin current classification, accurate risk stratification, particularly for borderline and malignant tumours, remains challenging. METHODS: We analysed a 20-year institution...BACKGROUND: Although histological criteria underpin current classification, accurate risk stratification, particularly for borderline and malignant tumours, remains challenging. METHODS: We analysed a 20-year institutional series of phyllodes tumours (PTs), integrating clinicopathological data with long-term clinical outcomes. Histological features were extracted from original pathology reports, with slide re-review where archival material was available. RESULTS: Among 111 PTs, 80% were benign, 11% borderline and 9% malignant. The follow-up ranged from 0 to 20 years, with 11.3, 10.3 and 7.6 years for benign, borderline and malignant PT, respectively. Most patients underwent local excision; mastectomy was performed in 22% of malignant PT. Final positive margins were identified in 18% of benign, 8% of borderline and none of the malignant tumours. Adjuvant radiotherapy was administered in 18% of borderline and 67% of malignant PT. Local recurrence occurred in 3%, 11% and 22% of benign, borderline and malignant tumours, respectively. Distant metastases were observed exclusively in malignant PTs (33%, 3/9 cases), two of which were preceded by local recurrence. Notably, two of the three metastatic malignant PTs showed either ≤10 mitoses/10 high-power field or <marked stromal atypia and lack of stromal overgrowth, which are required for diagnosis of malignant PT per WHO 5 edition recommendation. The low event rate precluded robust multivariable analysis. CONCLUSION: Our results highlight the biological heterogeneity of malignant PTs and the limitations of rigid histological thresholds. These findings underscore the need for collaborative, multi-institutional prospective studies with standardised tumour sampling and reporting and molecular correlation to refine clinically meaningful risk stratification in PT.
Kaistha A, Situ JJ, Evans S
… +3 more, Ashton-Key M, Ogg G, Soilleux E
J Clin Pathol
· 2026 Jun · PMID 42062047
·
Full text
AIM: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates. Clonality testing is frequently required for diagnosis. It lacks the spatial context and is slow and expensive, relying on...AIM: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates. Clonality testing is frequently required for diagnosis. It lacks the spatial context and is slow and expensive, relying on complex multiplexed PCR reactions, interpreted by scientists or pathologists with specialist molecular training. We set out to make monoclonal antibodies to develop a novel immunohistochemical test for T-cell lymphoma, analogous to the kappa/lambda assay for B-cell and plasma cell neoplasms. METHODS: We developed a pair of highly specific monoclonal antibodies against the two alternatively used but very similar T-cell receptor β constant regions, TCRβ1 and TCRβ2 (encoded by the TRBC1 and TRBC2 gene segments). We demonstrate the feasibility of immunohistochemical detection of TCRβ1 and TCRβ2 in formalin-fixed, paraffin-embedded tissue as a novel diagnostic strategy for T-cell lymphomas. RESULTS: Single immunostaining results are presented for 13 T-cell lymphomas and 8 benign T-cell populations, together with illustrative examples of TCRβ1/2 double immunostaining. Finally, we show that this single immunostaining is amenable to automated cell counting, permitting accurate calculation of the TCRβ2:TCRβ1 ratio. CONCLUSION: This novel assay can be used in a similar way to the kappa/lambda assay for B-cell and plasma cell neoplasms.
AIMS: To develop, deploy and evaluate artificial intelligence (AI) for triaging duodenal biopsies within a National Health Service (NHS) histopathology laboratory, with the aim of improving reporting turnaround times for...AIMS: To develop, deploy and evaluate artificial intelligence (AI) for triaging duodenal biopsies within a National Health Service (NHS) histopathology laboratory, with the aim of improving reporting turnaround times for clinically significant diagnoses. METHODS: The pathway was developed in the UK in an NHS laboratory. Rule-based automation software was used to find all newly scanned duodenal biopsy slides. Those with case numbers ending in an odd number were exported for AI triage and if they had significant AI predicted abnormalities they were prioritised for reporting. The cases with even numbers followed the routine reporting pathway. RESULTS: 313 cases (517 duodenal slides) were processed by the routine pathway, and 329 cases (533 duodenal slides) were processed by the AI triage pathway. AI processing took about 70 s per slide. The AI classifier had a sensitivity and positive predictive value (PPV) as follows: normal small bowel: 99.6%, 95.7%; coeliac disease: 86.7%, 100%; gastric heterotopia: 84.6%, 95.7%; adenoma: 88.9%, 88.9%; adenocarcinoma: 50.0%, 100%. In the AI triage workstream coeliac disease, and non-neoplastic abnormalities as a group, were reported quicker than in the standard workstream (6 days vs 10 days and 7 days vs 10 days, respectively, both p<0.005), but neoplastic lesions were not reported quicker. The cost of deployment and operation was reasonable. CONCLUSIONS: An NHS histopathology laboratory successfully developed and implemented an AI-based triage system for duodenal biopsies, achieving high diagnostic accuracy and significantly improving turnaround times for coeliac disease and non-neoplastic abnormalities as a group. This study demonstrates the feasibility and clinical value of locally developed AI tools within routine diagnostic practice.
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...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. fusion was detected in 73% of cases, and the most common fusions were (66%) and (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 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 rearrangement may be helpful in atypical cases.
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 find...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.
Kariya E, Tirard-Collet P, Boulagnon-Rombi C
… +11 more, Destras G, Wallon M, Menotti J, Lapendry A, Kaidi N, Rabodonirina M, Lievre L, Depaquit J, Villena I, Trecourt A, Huguenin A
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 pr...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 spp. larva was identified within a mesenteric nodule through an innovative diagnostic approach combining histopathological analysis with shotgun metagenomic analysis.
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 retrospecti...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-L...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.
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 represents a rec...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 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 in LPL and in DLBCL-define distinct molecular subtypes with prognostic and therapeutic implications. 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, L265P predicts response to BTK inhibitors in WM, although concurrent 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 mutations in lymphoid malignancies.
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...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.
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 worldwi...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.