CP is defined as an amalgam of Pathology with computer science, AI and data analysis with the goal of improving diagnostic accuracy, providing better prognostics, predictive value and pharmacotherapeutics in a quicker, leaner and cost-effective manner. It is important to point out that AI is a part, although pivotal, in the bigger picture and should not always be viewed as a stand-alone entity.
In broad terms, CP therefore embraces whole slide imaging, task automation, AI-assisted diagnostics and prognostic/predictive and therapeutic modelling.
A mundane but important role of CP...]]>
A woman in her 60s had a 10-day history of a dry cough and thoracic back pain associated with a chest X-ray demonstrating an acute T9 compression fracture and a minor band of atelectasis in the right lower zone. She had been started on amoxicillin and tapentadol analgesia. Over the 24 hours prior to presentation, she had developed episodic visual changes and dizziness. On examination, there was mild confusion, normal oxygen saturations and a moderate sized left retinal haemorrhage The white cell count (WCC) at presentation was 351x109/L (reference interval 4.0–11.0) compared with a routine test performed 1 week prior to this presentation showing a WCC of 5.1x109/L indicating the highly proliferative nature of her disease at presentation.
This patient had dual diagnoses of high-risk myelodysplastic syndrome and smouldering myeloma, both identified 12 months prior. She had previously been treated with four cycles of azacitidine 75 mg/m2 followed...]]>
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Specific quantitation of K7-positive cell populations can refine the diagnosis of MASLD and complement routine scoring in clinical trials to improve patient stratification.
To objectively evaluate the prevalence of histological border irregularities in fibroadenomas (FAs) and characterise their association with specimen type, histological subtypes, prior procedures and associated pathologies.
A retrospective review of 912 FA specimens (549 core needle biopsies (CNBs), 45 vacuum-assisted biopsies (VABs), 242 excisions and 76 mastectomies) from 816 lesions was conducted. An irregular border was defined as an interface between the FA and adjacent parenchyma that was not smooth or circumscribed. Statistical analyses were performed to identify factors associated with irregularities in the FA contours.
Border irregularity was present in 20.6% (188/912) of specimens. Prevalence was significantly lower in CNB (8.4%) compared with VAB (31.1%), mastectomy (34.2%) and excision (42.1%). By subtype, irregularity was most frequent in myxoid (41.7%), cellular (35.8%) and hyalinised (28.9%) FAs, compared with complex (20.4%), usual (16.2%) and juvenile (13.3%) forms. Calcifications, carcinoma in situ and invasive carcinoma, occurring within FAs, were associated with increased frequency of irregular borders. In multivariable analysis, a history of prior procedure was the strongest independent predictor of irregularity (OR 3.69, p<0.001). We found 1.6%, 2.5% and 0.2% of FAs to be accompanied by atypical hyperplasia, carcinoma in situ and invasive carcinoma, respectively.
While FAs are conventionally described as possessing circumscribed contours, our study found irregular borders in approximately one in five specimens. This feature is significantly associated with prior clinical procedures, specific histological subtypes and certain concurrent pathologies. It is essential to recognise that an irregular border in fibroepithelial lesions can be encountered in FAs and is not exclusive to phyllodes tumours.
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.
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.
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.
Increased frequency of CD103+ T cells is associated with metastatic non-haematopoietic malignancies in excisional and core needle biopsies of clinically concerning lymphadenopathy.
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.
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.
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%).
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.
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.
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.
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.
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.
In this letter, we discuss some of the problems arising from such guidelines and make proposals that could...]]>