is a well-established cause of gastritis and gastric malignancy, but other species-collectively termed non- (NHPH)-also contribute to gastric disease. This study retrospectively analysed the prevalence of NHPH in 1115 r...is a well-established cause of gastritis and gastric malignancy, but other species-collectively termed non- (NHPH)-also contribute to gastric disease. This study retrospectively analysed the prevalence of NHPH in 1115 routine gastric biopsies from a large academic medical centre submitted for drug susceptibility genotyping using a next-generation sequencing (NGS) assay targeting and rRNA genes. NGS results of identified pathogens were compared against those identified on histology. NHPH species were detected in 15 of 1115 cases (1.3%), including 7 NHPH-only infections and 8 mixed infections with Detected NHPH species included , and No mutations associated with antimicrobial resistance were identified in NHPH. Broader molecular testing may improve recognition of mixed infections and guide more accurate diagnosis and treatment for gastric disease.
AIMS: Despite continually improving guidelines, human epidermal growth factor receptor 2 (HER2) testing for breast and gastro-oesophageal carcinoma continues to be a technical challenge in clinical laboratories. Manual H...AIMS: Despite continually improving guidelines, human epidermal growth factor receptor 2 (HER2) testing for breast and gastro-oesophageal carcinoma continues to be a technical challenge in clinical laboratories. Manual HER2 fluorescence in situ hybridisation (FISH) testing is labour-intensive and prone to inter-run and interoperator variability. We aimed to adopt and validate a Leica BOND-III automated staining platform for HER2 FISH testing. METHODS: We recently validated the Leica BOND-III automated staining platform for HER2 FISH testing and compared it to our previous manual FISH (Agilent HER2 IQFISH pharmDx) methodology using 77 breast cancer cases and 8 gastric cancer cases. RESULTS: Using the automated Leica BOND-III automated staining platform, we achieved 0.95 sensitivity and 0.97 specificity in HER2 FISH testing for breast cancer cases and 1.0 sensitivity and specificity for gastric carcinoma cases. There was a 98% concordance rate between results of automated testing versus our previous manual method. The automated staining platform decreased technical hands-on time significantly while also reducing overall supply costs for the laboratory. CONCLUSIONS: We were able to implement and validate the automated Leica BOND-III staining platform seamlessly into a complex laboratory for HER2 FISH testing that has overall significantly decreased hands-on time by technologists and supply costs. Automated Leica BOND-III HER2 FISH staining results were highly concordant with our previous manual FISH method in both breast cancer and gastric cancer cases.
AIMS: gene is amplified in 15%-20% of invasive breast cancers (IBCs), serving as critical prognostic and predictive marker. -targeted therapies have improved outcomes for -positive patients, highlighting the importance...AIMS: gene is amplified in 15%-20% of invasive breast cancers (IBCs), serving as critical prognostic and predictive marker. -targeted therapies have improved outcomes for -positive patients, highlighting the importance of accurate assessment. Immunohistochemistry is commonly used for screening overexpression, with equivocal cases reflex tested using in situ hybridisation (ISH) methods like fluorescence (FISH) or dual-colour dual ISH (D-DISH). While FISH displays quantitative accuracy, it is expensive, time-consuming and technically demanding. D-DISH offers a faster, automated alternative using bright-field microscopy for easier interpretation and better archiving. Advances in digital pathology, such as whole slide imaging and automated image analysis (IA), promise to improve evaluation. The CE-IVD marked uPath HER2 Dual ISH IA algorithm by Ventana Medical Systems (Tucson, Arizona, USA) is designed to assist in this process, providing computer-assisted evaluation of . Thus, we undertook this study to standardise and validate uPath Dual ISH IA algorithm and assess interobserver reproducibility in interpreting D-DISH assay. METHODS: This study retrospectively analysed 106 IBC cases, evaluating the concordance between manual and algorithm-assisted D-DISH evaluations. RESULTS: A consensus concordance rate of 91.5% and a Cohen's kappa value of 0.83 was observed between the manual and on-site IA evaluations, indicating near-perfect agreement. Remote IA evaluations also demonstrated substantial concordance, with a concordance rate of 88.89% and kappa value of 0.70. CONCLUSIONS: We successfully validated the uPath IA algorithm as a time-efficient, screening modality as well as viable alternative to manual interpretation for both on-site and remote interpretation of D-DISH in a high-volume centre.
AIMS: Papillary carcinoma diagnosed in core needle biopsy (CNB) refers to carcinoma with papillary features but no definitive invasion, including papillary ductal carcinoma in situ (DCIS), papilloma with DCIS, encapsulat...AIMS: Papillary carcinoma diagnosed in core needle biopsy (CNB) refers to carcinoma with papillary features but no definitive invasion, including papillary ductal carcinoma in situ (DCIS), papilloma with DCIS, encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC). This study assesses the upgrade rate of papillary carcinoma in CNB and supports the use of 'papillary carcinoma' as an umbrella term. METHODS: A retrospective review identified 41 CNB cases of non-invasive papillary carcinoma with subsequent excision (2011-2018). H&E and immunohistochemistry slides from CNBs were reviewed, and excisional diagnoses were retrieved. RESULTS: All 41 CNB cases were either DCIS or upgraded to invasive carcinoma upon excision, with an overall upgrade rate to invasive carcinoma of 39% (16/41). Subtypes showed varying upgrade rates: 16.7% (1/6) for papillary DCIS, 25% (1/4) for papilloma with DCIS, 83.3% (5/6) for SPC, 100% (1/1) for EPC and 33.3% (8/24) for unclassifiable papillary carcinoma. No lymph node metastases, recurrences or breast cancer-related mortality were observed during the follow-up period. CONCLUSIONS: Given the high upgrade rate, subclassification of papillary carcinoma in CNB lacks clinical significance. The term 'papillary carcinoma' should be used in CNB, and lymph node removal warrants further investigation.
p53 immunohistochemistry (IHC) is widely used as a rapid surrogate for detecting mutations, with mutations being a key biomarker for poor outcomes in lymphomas. We developed two algorithms using digital quantification...p53 immunohistochemistry (IHC) is widely used as a rapid surrogate for detecting mutations, with mutations being a key biomarker for poor outcomes in lymphomas. We developed two algorithms using digital quantification tools to assess p53 expression from whole slide images of 77 lymphoma samples. An experienced pathologist visually evaluated the p53 slides, classifying cases as likely wild-type or mutated genotype. We correlated the results of the algorithms and visual inspection with the actual genotype. For cases with p53 overexpression (likely missense mutations), the algorithms achieved 86.7% sensitivity and 98.2% specificity (visual inspection: 80% and 95.2%). For cases with reduced p53 expression (likely 'other' mutations), the algorithms showed 92.7% sensitivity and 100% specificity (visual inspection: 40% and 95.8%). This study demonstrates that combining digital pathology with digital quantification tools-based algorithms can reliably predict genotype from p53 IHC patterns, with comparable or slightly superior performance to an experienced pathologist.
AIMS: Seminal vesicle invasion (SVI) in prostatic adenocarcinoma (PCa) is a high-risk feature associated with lymph node (LN) metastasis and adverse outcomes. However, the impact of SVI laterality on LN metastasis patter...AIMS: Seminal vesicle invasion (SVI) in prostatic adenocarcinoma (PCa) is a high-risk feature associated with lymph node (LN) metastasis and adverse outcomes. However, the impact of SVI laterality on LN metastasis patterns, nodal burden, metastatic focus size and extranodal extension (ENE) remains underexplored. METHODS: We retrospectively analysed 225 PCa patients with SVI who underwent radical prostatectomy with LN dissection. Associations between SVI laterality, tumour grade, volume and nodal parameters were assessed using univariable and multivariable models. RESULTS: LN metastases were identified in 97 of 225 (43.1%) patients. Bilateral SVI was significantly associated with higher odds of LN metastasis (OR=2.01; p=0.040), nodal burden (IRR=1.89; p=0.004) and ENE (OR=3.76; p=0.013), independent of tumour volume, grade, age and race. Tumour volume and grade independently predicted LN metastasis (p=0.004 and p=0.048, respectively) and were associated with metastatic focus size (p=0.003 and p<0.001, respectively) and nodal burden (p=0.061 and p=0.045, respectively). LN spread mirrored SVI extent: unilateral SVI primarily led to ipsilateral involvement (22/36; 61.1%; p<0.001), while bilateral SVI increased the risk of bilateral spread (OR=3.81; p=0.003). White patients had significantly higher LN metastasis rates than black patients (p=0.010). CONCLUSIONS: Bilateral SVI is a strong, independent predictor of LN metastasis, nodal burden and ENE. SVI laterality also correlates with LN spread patterns and could inform future risk stratification, though further validation is needed.
Jorns JM, Smith RS, Strenk D
… +7 more, Stauble G, Khelifa S, Seltzer R, Manuel J, Rosenbaum MW, Almas J, Li Z
J Clin Pathol
· 2026 Jan · PMID 40850743
·
Full text
AIMS: Adequate lymph node examination is key to accurate cancer staging. This study investigates the effectiveness of shortwave infrared imaging in increasing the overall and positive lymph node numbers. METHODS: Specime...AIMS: Adequate lymph node examination is key to accurate cancer staging. This study investigates the effectiveness of shortwave infrared imaging in increasing the overall and positive lymph node numbers. METHODS: Specimens from various anatomic sites, including colorectal, pancreatic, breast, gastric, skin and small bowel resections, were evaluated. 104 specimens were first grossed with manual palpation and then grossed with the assistance of shortwave infrared imaging. The overall and positive lymph node numbers were documented. RESULTS: In 90 of the 104 cases (86.5%), shortwave infrared imaging helped identify additional lymph nodes. On average, 4.81 additional lymph nodes were found. In 11 of the 104 cases (10.6%), additional positive lymph nodes were found. In 4 of the 104 cases (3.8%), cancer stages were changed. CONCLUSIONS: Shortwave infrared imaging may increase the number of lymph nodes identified and has the potential to improve cancer staging accuracy. Further validation in larger, randomised or prospective studies is warranted.
AIMS: To investigate immunohistochemical expression of the E26 transformation-specific factors (ETS)-related gene () in a large number of soft tissue neoplasms using a tissue microarray technique. METHODS: 489 cases of s...AIMS: To investigate immunohistochemical expression of the E26 transformation-specific factors (ETS)-related gene () in a large number of soft tissue neoplasms using a tissue microarray technique. METHODS: 489 cases of soft tissue neoplasms, including benign and malignant entities, were collected from the files of the respective institutions and constructed into tissue microarrays. Tissue microarrays were stained for ERG immunohistochemistry using two antibodies, EP111 and EPR3864. RESULTS: A total of 25 cases (5.1%) were identified that were positive for ERG using the monoclonal antibody EP111 and 15 cases (3%) using the monoclonal antibody EPR3864, including rhabdomyosarcoma, peripheral nerve sheath tumours, synovial sarcoma, myxofibrosarcoma, epithelioid sarcoma, dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, nodular fasciitis and dedifferentiated liposarcoma. The most consistently stained tumours included synovial sarcoma, rhabdomyosarcoma and benign and malignant peripheral nerve sheath tumours. Various other fibroblastic proliferations, including dermatofibrosarcoma protuberans, myxofibrosarcoma, low-grade fibromyxoid sarcoma and nodular fasciitis, also showed positive staining in a small fraction of cases. One case of dedifferentiated liposarcoma showed nuclear positivity for ERG, and one case of epithelioid sarcoma was also positive. CONCLUSIONS: This study supports the value of ERG as a highly sensitive and specific marker for the diagnosis of vascular neoplasms but also demonstrates rare cases of aberrant staining and underscores the need to assess soft tissue tumours using a panel of stains and interpret the results of immunohistochemistry in the appropriate histological and clinical context.
AIMS: For phyllodes tumours (PT), local and distant recurrence rates increase with higher grades and are difficult to predict. The Singapore nomogram has been used to predict recurrence events for PT. We aimed to test th...AIMS: For phyllodes tumours (PT), local and distant recurrence rates increase with higher grades and are difficult to predict. The Singapore nomogram has been used to predict recurrence events for PT. We aimed to test this nomogram for accuracy in a US cohort and to compare with a histological score. METHODS: Patients with PT were selected from a prospective institutional database. Histological parameters and margin status were used to estimate the nomogram score and the histological score, as previously defined. Multivariable analyses were used to estimate the association of recurrence-free survival (RFS) with individual factors, nomogram score and histological score. Harrel's C-index was estimated. RESULTS: Of 81 PT cases, 25.9% were benign, 40.7% borderline and 33.3% malignant. Recurrences occurred in 33.3% (n=27). The adjusted RFS analysis including the four factors used in the Singapore nomogram performed well (C-index of 0.78). However, despite a higher nomogram score being associated with increased risk of recurrence (HR 1.03, 1.01-1.05, p=0.007), the individual numeric scale defined in the nomogram only moderately fit our data (C-index of 0.66). Patients with higher histological scores also had an increased risk of recurrence (HR 1.25, 1.07-1.47, p=0.005; C-index of 0.70). CONCLUSION: Histological score more accurately predicted PT recurrence in our cohort, which includes a higher proportion of higher-grade PT. Refining the nomogram to include factors specific to malignant PT and factors with more variance, as well as refining the assigned weights, may result in improved performance. This study identifies an opportunity for international collaboration to refine the predictive model.
Lin LH, Huang CJ, Lo CY
… +2 more, Lee YH, Chen YC
J Clin Pathol
· 2025 Sep · PMID 40829872
·
Full text
AIMS: Although some cases of intussusception in older children are associated with pathological changes such as lymphoma or polyps, the cause of most cases in infants is unknown. Several reports have identified an associ...AIMS: Although some cases of intussusception in older children are associated with pathological changes such as lymphoma or polyps, the cause of most cases in infants is unknown. Several reports have identified an association between adenovirus infection and intussusception in children. However, much of the evidence is indirect, such as stool samples or throat swab data. Our study analysed intestinal tissue, which may be more direct evidence of the relationship between adenovirus infection and intussusception. METHODS: We retrospectively reviewed children<6 years of age with intussusception who underwent surgery for failed reduction. The pathological tissue was processed into formalin-fixed paraffin-embedded (FFPE) sections. Adenovirus immunohistochemistry (IHC) and PCR testing were performed to obtain direct evidence of the relationship between adenovirus infection and intussusception. RESULTS: Our study included 29 patients, 27 appendiceal and 8 intestinal tissues. Only eight appendix specimens were successfully processed into FFPE tissue. IHC testing was positive in three cases (37.5%), and PCR testing was positive for adenovirus type C in four cases (50%). The control group consisted of eight children <6 years who underwent incidental appendectomies, and all control subjects had negative IHC and PCR analyses. PCR is as useful and reliable as IHC in diagnosing adenovirus in intussusception and has greater sensitivity than IHC. CONCLUSION: We directly confirmed the relationship between adenovirus infection and intussusception through IHC analysis and PCR detection of pathological evidence. PCR is more sensitive than IHC for diagnosing adenovirus in intussusception.
Zhang Y, Liang R, Purnell GC
… +12 more, Yan L, Nazarullah A, Hackman S, Thomas C, Abarbanell AM, Sugalski A, Foster JL, Thomas LP, Ong P, DeArmond D, David MP, Li F
J Clin Pathol
· 2026 Jan · PMID 40829871
·
Full text
Primary lung tumours are rare in paediatric patients. Mucoepidermoid carcinoma (MEC), typically low-grade and diagnostically straightforward, is the second most common tumour of the bronchus after carcinoid tumours. Howe...Primary lung tumours are rare in paediatric patients. Mucoepidermoid carcinoma (MEC), typically low-grade and diagnostically straightforward, is the second most common tumour of the bronchus after carcinoid tumours. However, rare MEC may show divergent differentiation, be misdiagnosed as low-grade adenocarcinoma, not otherwise classified, and pose clinical challenges, especially when mastermind-like protein 2 (MAML2) gene arrangement is negative by fluorescence in situ hybridisation (FISH). Here, we report an MAML2 FISH-negative low-grade bronchial tumour in a juvenile patient that demonstrates both mucoepidermoid and acinar differentiation based on morphology and immunophenotype. Next-generation sequencing identified a CREB regulated transcription coactivator 3 () fusion gene, located upstream of traditional translocation points and potentially undetectable by currently available FISH probes. This tumour appears to be a novel presentation of a bronchial tumour with dual mucoepidermoid and acinar differentiation, first described as mucoacinar carcinoma-a newly proposed subtype of MEC, originally described in the major salivary gland.
Elhalaby RE, Zeina WO, Nessim L
… +6 more, Ahmed ME, Kamel NN, Anis SE, Dong H, Cheville JC, Kwon ED
J Clin Pathol
· 2026 Jan · PMID 40812994
·
Full text
AIMS: Schistosomiasis remains endemic in various parts of the world, and insights into pathogen immunobiology are mainly based on experimental models, while studies on human tissues are limited. METHODS: We explored the...AIMS: Schistosomiasis remains endemic in various parts of the world, and insights into pathogen immunobiology are mainly based on experimental models, while studies on human tissues are limited. METHODS: We explored the role of immune checkpoint pathway by evaluating the immunohistochemical expression of programmed death-ligand 1 (PD-L1) in a retrospective cohort of patients with bilharzial cystitis. Inflammation severity by conventional histology and staining intensity by immunohistochemistry were assigned three-tier scores (0/1+/2+), and a cut-off for staining percentage was set at 5%. RESULTS: 38 biopsies from 31 patients were considered adequate for evaluation, and positive staining was detected in 80.6% of patients (34 biopsies). High expressors (22.6%) showed strong positive membranous staining (score 2+) with high staining density (more than 5% of inflammatory cells). Low expressors (58.1%) showed mild/moderate staining (score 1+) predominantly in less than 5% of the cells (91.6%) or expressed restricted cytoplasmic staining (6/31). All high expressors showed severe inflammation (score 2+) (p<0.001), and viable ova were only observed in these cases. Calcified ova were associated with mild/moderate inflammation or absent/minimal inflammation, correlating with low expressors or non-expressors (19.4%), respectively. CONCLUSION: Schistosomal granuloma exhibits upregulated PD-L1 expression proportional to inflammation severity and pathogen viability, highlighting a critical immune checkpoint engagement in disease pathology.
We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genom...We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into 'essential' and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings.
In December 2024, the Chinese expert panel released the updated Chinese Guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer (2024 edition), building on the 2019 version and incorporati...In December 2024, the Chinese expert panel released the updated Chinese Guidelines for human epidermal growth factor receptor 2 (HER2) testing in breast cancer (2024 edition), building on the 2019 version and incorporating recent advancements. These guidelines, referred to as the 2024 guidelines, feature significant format changes, enhance clinical applicability and provide more robust evidence-based recommendations. Identifying patients who may benefit from emerging anti-HER2 antibody-drug conjugates (ADCs) therapies has become increasingly important. The 2024 guidelines provide comprehensive guidance on the interpretation and reporting of relevant HER2 statuses. Recent advances in HER2 testing methods, along with the potential role of artificial intelligence in enhancing testing precision, are introduced. The 2024 guidelines reinforce quality control standards across multiple aspects of the testing process, including optimised specimen handling protocols, refined decalcification procedures, improved unstained slide preservation conditions and enhanced gradient external controls. These comprehensive updates are designed to improve the accuracy and clinical relevance of HER2 testing, ultimately contributing to better patient outcomes in breast cancer management.
BACKGROUND: Current guidelines emphasise examining at least 12 lymph nodes (LN) in colorectal cancer resections. This study surveyed surgeon perspectives on suboptimal LN yield (<12) to assess interpretive variability an...BACKGROUND: Current guidelines emphasise examining at least 12 lymph nodes (LN) in colorectal cancer resections. This study surveyed surgeon perspectives on suboptimal LN yield (<12) to assess interpretive variability and beliefs regarding its clinical impact. METHODS: A voluntary 19-question electronic survey was distributed to colorectal and general surgeons, exploring clinical, pathological and molecular considerations in cases with low LN yield. RESULTS: Among 168 respondents (58% colorectal surgeons; 32% general surgeons), most practised in academic or mixed settings, and 73% had over 10 years of experience. While 71% reported suboptimal LN yields as infrequent, 29% encountered them more regularly. A majority (92%) contacted pathology when LN yield was low; however, opinions diverged on next steps-particularly when maximum N-stage was already achieved or when considering total fat submission. Nearly half (49%) believed that low LN yield rarely alters treatment decisions, yet many acknowledged its association with poorer outcomes. Regarding potential contributing factors, 56% cited neoadjuvant therapy, 47% noted specimen length or sidedness, but most did not consider mismatch repair status, age or body mass index to significantly impact LN yield. CONCLUSION: Despite the '12-node rule', surgeon perspectives vary regarding the significance, aetiology and clinical consequences of suboptimal LN yield. The overarching message for pathology is that thoughtful communication among surgeons and pathologists is critical to understand the idiosyncrasies around individualised care and nuances around factors that may influence LN yield, with the ultimate hope to best manage resources and optimise patient care.
J Clin Pathol
· 2025 Sep · PMID 40701796
·
Full text
AIMS: The aim of this research is to diagnose polycythaemia vera (PV) disease using different machine learning (ML) algorithms with complete blood count (CBC) parameters before further investigations such as Janus kinase...AIMS: The aim of this research is to diagnose polycythaemia vera (PV) disease using different machine learning (ML) algorithms with complete blood count (CBC) parameters before further investigations such as Janus kinase 2 (), erythropoietin (EPO) and bone marrow biopsy (BMB). METHODS: The study included 1484 patients who presented to the adult haematology clinic with elevated haemoglobin. Participants were retrospectively screened for , EPO and BMB results, and patients were categorised as PV group (n=82) and non-PV (other) (n=1402). First, the synthetic minority oversampling technique (SMOTE) method was used to avoid data imbalance. Then, classification predictions were made using Random Forest, Support Vector Machine Technique, Extreme Gradient Boosting (XGBoost) and K-Nearest Neighbours algorithms according to the participants' CBC parameters of white cell count (WBC), haematocrit (HCT), haemoglobin (HGB) and platelet (PLT). RESULTS: The XGBoost algorithm was found to be the most effective ML algorithm in predicting the model (area under the curve=0.99, accuracy=0.94, F1-Score=0.94). In addition, the most effective parameter in the prediction of the model was PLT with 42.4%. As a result of the t-test, there was a highly significant difference between the WBC, PLT, HGB, HCT, EPO, and bone marrow density results of PV and other groups (p<0.001). CONCLUSION: ML algorithms can diagnose PV with CBC parameters with high accuracy, thus emphasising the potential to reduce the dependence on costly diagnostic methods such as , EPO and BMB.