The Nancy histological index (NHI) is a measure of disease activity within colorectal biopsies and a predictor of clinical outcome in ulcerative colitis (UC). We measured interobserver agreement (IOA) during NHI scoring...The Nancy histological index (NHI) is a measure of disease activity within colorectal biopsies and a predictor of clinical outcome in ulcerative colitis (UC). We measured interobserver agreement (IOA) during NHI scoring of 20 colorectal biopsies in UC by 13 pathologists of varying grade and experience. The level of IOA was measured using Fleiss' kappa statistic. The degree of IOA was moderate, with kappa scores of 0.53 (SE 0.01) for the whole group (n=13), 0.50 (SE 0.05) for the consultants (n=4) and 0.54 (SE 0.019) for the trainees (n=9). Normal biopsies or those showing a mild increase in lamina propria chronic inflammation were graded most reproducibly. Subjectivity existed at NHI grade boundaries, particularly identification of mild acute inflammation (AI), assessment of AI severity and identification of ulceration. An education programme for pathologists or an artificial intelligence tool may improve IOA in the future.
Scarmozzino F, Pizzi M, Gianesello I
… +10 more, Bonaldi L, Martines A, Danesin N, Zoletto S, Pravato S, Cassani B, Gianelli U, Trentin L, Binotto G, Dei Tos AP
Moalla M, Ellouze N, Fendri H
… +11 more, Keskes I, Abdelmoula A, Smaoui H, Kchaou M, Charfi S, Fendri S, Sellami T, Mnif Z, Boujelbene S, Gdoura H, Tahri N
Liao H, Weber TD, Tan RY
… +4 more, Liu J, Fujimoto JG, Rosen S, Sun Y
J Clin Pathol
· 2025 May · PMID 40127917
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AIM: Over the past several decades, optical sectioning technologies have emerged as valuable tools for evaluating tissue histology. Unlike conventional tissue sectioning, these technologies allow for real-time intraopera...AIM: Over the past several decades, optical sectioning technologies have emerged as valuable tools for evaluating tissue histology. Unlike conventional tissue sectioning, these technologies allow for real-time intraoperative assessments and more efficient tissue triage. In the era of digital pathology, the demand for high-quality, high-throughput optical sectioning platforms is increasing, as they eliminate the need for traditional slide preparation and scanning, potentially transforming anatomical pathology workflows. While non-linear microscopy (NLM) has demonstrated promise in histological evaluation across various tissue types, its application in gastrointestinal tissue assessment remains unexplored. METHODS: This study extends the use of NLM to gastrointestinal histology and develops an image atlas to highlight its potential as an automated digital pathology platform. RESULTS: Our results indicate that NLM generates diagnostic-quality images comparable to traditional H&E slides. Moreover, NLM provides valuable three-dimensional (3D) spatial information, improving clinical evaluations of key histological features such as depth of invasion, lymphovascular and perineural invasion, tumour budding and margin assessment. Time-lapse videos further demonstrate NLM's capability to capture 3D histological structures up to a depth of approximately 100 µm. CONCLUSION: Our findings demonstrate that NLM can serve as an optical sectioning platform for gastrointestinal histology, providing both diagnostic-quality imaging and advanced 3D visualisation. The introduction of an NLM-based atlas has the potential to redefine anatomical pathology workflows and advance digital pathology image analysis.
Reporting of prostate cancer grade has drifted to higher reported grades over the past decades. In prostate cancers diagnosed on needle biopsy of 1 72 112 men reported to The National Prostate Cancer Register of Sweden 2...Reporting of prostate cancer grade has drifted to higher reported grades over the past decades. In prostate cancers diagnosed on needle biopsy of 1 72 112 men reported to The National Prostate Cancer Register of Sweden 2000-2020, we also noted a grade shift among high-grade cancers. We applied multinomial logistic regression to assess time trends. Among International Society of Urological Pathology (ISUP) grade 4 cancers, Gleason score 3+5 increased from 8% in 2000 to 22% in 2020, while Gleason score 4+4 decreased from 88% to 77%. Among ISUP grade 5, Gleason score 4+5 and 5+4 cancers increased from 85% to 93%, while Gleason score 5+5 decreased from 15% to 7%. This may be explained by a reluctance to assign Gleason scores composed of a uniform grade following recommendations to include minimal components of higher grade in the scores. These changes are obscured by merging Gleason scores into ISUP grades.
AIMS: To study the clinicopathological, immunohistochemical and molecular features of carcinoma arising in microglandular adenosis (MGACA) of the breast. METHODS: Clinicopathological features of 13 cases of MGACA were an...AIMS: To study the clinicopathological, immunohistochemical and molecular features of carcinoma arising in microglandular adenosis (MGACA) of the breast. METHODS: Clinicopathological features of 13 cases of MGACA were analysed. All tumours were molecular subtype by immunohistochemistry (IHC) of AR, CD8, FOXC1 and DCLK1 expression. Next-generation sequencing including 511 genes was analysed. RESULTS: All tumours showed a histological spectrum ranging from microglandular adenosis (MGA) to atypical MGA (AMGA), ductal carcinoma in situ (DCIS) and MGACA. Invasive components in 10 of 13 tumours were invasive carcinoma of no special type (NST), 3 were metaplastic carcinoma with mesenchymal differentiation (including two cases of matrix-producing carcinoma) mixed with NST. All lesion-associated epithelial cells were triple negative (TNBC) and positive for S-100. Reticulin staining showed the presence of basement membrane in MGA, AMGA and DCIS, and its absence in invasive carcinoma. According to IHC-based TNBC molecular subtyping, 10 tumours were basal-like immune-suppressed (BLIS), 2 were luminal androgen receptor and 1 was immunomodulatory. 10 patients had gene mutations. Pathogenic germline mutations of the and genes were detected in four tumours (30.7%) and one tumour (7.7%). Somatic mutation rate of the gene was 69.2%. Amplification rates of , , and genes in our cohort were 46.2%, 15.4%, 15.4% and 7.7%, respectively. CONCLUSION: MGACA is a rare breast carcinoma, with distinct morphological, immunohistochemical and molecular features. Most MGACA were BLIS molecular subtype of TNBC. and gene mutation and gene amplification were the most common genetic changes in MGACA.
Pineda CM, O'Loughlin L, Benjamin HL
… +10 more, Rangachari D, Viray H, Widick PC, Guan Z, Beattie JA, Swenson KE, Parikh MS, Majid A, Costa DB, VanderLaan PA
J Clin Pathol
· 2025 Dec · PMID 40081882
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AIMS: Fam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved for advanced stage or metastatic solid tumours with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) 3+ staining. Data on HER2...AIMS: Fam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved for advanced stage or metastatic solid tumours with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) 3+ staining. Data on HER2 IHC testing and knowledge of genomic correlates in lung cancer are scarce. This study analyses genomic characteristics of HER2-expressing tumours and addresses issues with preanalytical variables for lung cancer specimens. METHODS: HER2 IHC staining was performed on selected archival cytology and surgical pathology lung cancer specimens for patients eligible for T-DXd therapy. Patient and tumour characteristics and next-generation sequencing (NGS) data were correlated with HER2 IHC results. RESULTS: 166 patients with thoracic tumour samples had HER2 expression assessed: 46% were IHC 0, 28% IHC 1+, 13% IHC 2+ and 13% IHC 3+. HER2 IHC scores were overall lower for cytology cell blocks as compared with surgical pathology specimens; 79% of cases with paired specimens had a decrease in their HER2 IHC score from their surgical specimen to their paired cytology specimen. Of specimens with HER2 IHC 3+ and NGS available, only 14% (3/21) had concomitant ERBB2 alterations. Among all specimens, ERBB2 point mutations were noted in 4% (4/110) and ERBB2 amplification in 3% (3/110). The majority of HER2 3+ cases with paired NGS (17/21, 81%) had non- genomic alterations, including: , and mutations. CONCLUSIONS: HER2 IHC 3+ is seen in a small but clinically significant proportion of samples and is associated with a variety of co-occurring non-ERBB2 genomic alterations. Preanalytical variables including specimen fixation can significantly impact the assessment of HER2 expression via immunohistochemistry.
The concept of extensive intraductal component (EIC), currently defined by the presence of a prominent ductal carcinoma in situ (DCIS) component within an invasive tumor and extending beyond its margins, was introduced i...The concept of extensive intraductal component (EIC), currently defined by the presence of a prominent ductal carcinoma in situ (DCIS) component within an invasive tumor and extending beyond its margins, was introduced in the 1980s as a predictor of local recurrence following breast-conserving therapy for invasive breast carcinoma. At the time, surgical excision to negative margins was not the standard of care, making EIC a valuable tool for identifying patients at risk of recurrence. However, with modern oncologic and surgical advancements, its clinical relevance has diminished. Despite its continued inclusion as a mandatory entry in the CAP synoptic checklist, studies have shown that EIC does not independently predict local recurrence when margins are negative. Instead, objective parameters such as DCIS size and nuclear grade more accurately correlate with margin status and recurrence risk. While EIC may still be useful in preoperative biopsy assessments for evaluating disease extent among other things, its routine reporting in resection specimens appears less informative. Given its vague definition and limited prognostic value, we propose that EIC reporting should be discretionary rather than mandatory, with emphasis placed on more objective and clinically relevant metrics.
Nelan R, Mijuskovic M, Hughes M
… +12 more, Becq J, Kingsbury Z, Tsogka E, He M, Vucenovic D, Craig C, Elgar G, Levey P, Suaris T, Walsh E, Ross M, Jones JL
J Clin Pathol
· 2025 Dec · PMID 40032506
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AIMS: Whole-genome sequencing (WGS) is beginning to be applied to cancer samples in the clinical setting. This ideally requires high-quality, minimally degraded DNA of high tumour cell content, while retaining sufficient...AIMS: Whole-genome sequencing (WGS) is beginning to be applied to cancer samples in the clinical setting. This ideally requires high-quality, minimally degraded DNA of high tumour cell content, while retaining sufficient tissue with excellent morphology for histopathological diagnosis and immunohistochemistry. The aim of this study was to investigate alternative ways of handling cancer samples to fulfil both diagnostic and molecular requirements. METHODS: Ex vivo biopsies were taken to investigate the feasibility of using cancer cells 'shaken' from the surface of a biopsy for WGS, while maintaining the tissue biopsy for histological diagnosis. WGS from the shaken cells was compared with the gold standard of a fresh-frozen (FF) biopsy. The procedure was piloted in the real-world setting for breast cancer samples. RESULTS: Cells shaken from ex vivo biopsies can yield DNA of sufficient quantity and quality for WGS, while having no discernible impact on quality of tissue morphology. WGS data showed good coverage, comparable variant calls and generally higher tumour content in shaken cell samples compared with the control FF samples. For real-world biopsies, DNA yields were lower, but WGS data were of excellent quality for the cases analysed. CONCLUSIONS: Shaken biopsy sampling allows genomic sequencing from patients with cancer who may otherwise not receive a genome sequence due to limited sample availability. It represents a way of overcoming the logistics of obtaining and storing FF tissue making it a suitable technique for wider scale implementation in the clinical setting.
AIMS: Patients of The Ottawa Hospital (TOH) are given immediate access to their pathology reports via an online patient portal. The purpose of this study was to determine how often patients accessed their reports, the so...AIMS: Patients of The Ottawa Hospital (TOH) are given immediate access to their pathology reports via an online patient portal. The purpose of this study was to determine how often patients accessed their reports, the sociodemographic and pathologic variables associated with access and the latency between sign out and access. METHODS: This retrospective cross-sectional observational study was conducted on the first 250 consecutive pathology reports published in 2023 from 10 different subspecialties in anatomical pathology at TOH. Data regarding date/time of report publication and access, as well as demographic data, and variables related to the individual report contents were extracted from the hospital's electronic health records. RESULTS: Of the 2500 patients included in this study, 1315 (52.6%) accessed their report online. Patients under 65 years of age, female patients and those residing within Ottawa were more likely to access their reports. Biopsies and reports with malignant diagnoses were accessed at higher rates than resections and benign cases, respectively. 463 (36.0%) patients accessed their reports within 24 hours; 822 (68.5%) accessed them within the first week. In 53% of cases, the patient accessed their report before the treating physician. CONCLUSIONS: These findings highlight that while over half of patients accessed their pathology reports online, significant differences in access rates were observed based on age, gender, location and report type. The high proportion of patients reviewing their reports before their treating physician underscores the need for patient-centred strategies to enhance understanding and support timely communication of results.
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 inc...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'.
Kiraz U, Rewcastle E, Pettersen KB
… +5 more, Abono DM, Raghe SH, Gudlaugsson EG, Baak JPA, Janssen EAM
J Clin Pathol
· 2025 Aug · PMID 39965885
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AIMS: Triple-negative breast cancer (TNBC) is prognostically and therapeutically heterogeneous. The mitotic activity index (MAI) and fibrotic focus (FF) have been established as predictors in non-TNBC but not in TNBC. La...AIMS: Triple-negative breast cancer (TNBC) is prognostically and therapeutically heterogeneous. The mitotic activity index (MAI) and fibrotic focus (FF) have been established as predictors in non-TNBC but not in TNBC. Late distant metastases occur in TNBC, but previous studies had short follow-up. High stromal tumour-infiltrating lymphocytes (sTILs) are prognostically favourable, but prognostic sTILs-thresholds are not well assessed. We evaluated prognostic/predictive characteristics in an observational population-based cohort of 231 consecutive TNBC patients with long follow-up. METHODS: MAI, FF, sTILs and other characteristics were analysed with standard receiver operating characteristic curve analysis, percentile-derived prognostic thresholds, univariate and multivariate survival methods. A TNBC index and decision tree were assessed for distant metastasis-free survival. RESULTS: Long follow-up was decisive: 7% of patients developed late distant metastases. In agreement with the aggressive nature of TNBC, the strongest prognostic MAI-threshold was 5 (p=0.001), lower than that for non-TNBC phenotypes. Lymph-node (LN) status (p=0.0003), FF (p=0.002), MAI5 (p=0.009) and sTILs (threshold 40%, p=0.003) were multivariable based significant and independent prognosticators, but no other characteristics (age, tumour size and grade). LN status was the strongest prognosticator, followed by FF, MAI5 and sTILs40. Subgroup analyses of patients undergoing adjuvant chemotherapy (ACT) showed that only FF and sTILs had significant prognostic value, while LN-positivity and the combination of LN-positivity and MAI≥5 could be a predictive factor for ACT outcome. CONCLUSIONS: LN status, MAI5, FF and sTILs40 are prognostic factors in TNBC patients. In TNBC patients who have undergone ACT, the combination of LN-positivity and MAI5 is predictive for response to treatment.
The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant advancements in the understanding and diagnosis of myeloid neoplasms, emphasising molecular and genetic insights. T...The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant advancements in the understanding and diagnosis of myeloid neoplasms, emphasising molecular and genetic insights. This review highlights key updates from the revised fourth edition (WHO-HEM4R), particularly the integration of genetic criteria for disease classification. Many entities are now defined by specific genetic abnormalities, enhancing diagnostic precision and prognostic assessment. Notably, the elimination of the 20% blast threshold for acute myeloid leukaemia (AML) with specific defining genetic alterations reflects a shift towards genomic-driven diagnostics. Additional updates include the refined subclassification of myelodysplastic neoplasms (MDS) and MDS/myeloproliferative neoplasms, as well as the recognition of novel entities such as clonal haematopoiesis and MDS with biallelic TP53 inactivation, further expanding the spectrum of myeloid neoplasms. WHO-HEM5 illustrates the diagnostic utility of morphology, flow cytometry, immunohistochemistry and next-generation sequencing in resource-rich settings. However, its implementation in low-income and middle-income countries (LMICs) remains challenging due to limited access to advanced diagnostic tools. This review explores strategies to optimise diagnosis in resource-constrained environments, where morphology and immunophenotyping remain fundamental. By integrating molecular diagnostics with traditional methods, WHO-HEM5 aims to refine classification and facilitate risk stratification in the era of personalised medicine, providing haematopathologists and clinicians with an essential framework to navigate the complexities of myeloid neoplasms. The emphasis on advancing haematopathology practices worldwide, including in LMICs, demonstrates the ongoing commitment to improving global outcomes in haematological malignancies.
AIMS: Gallbladder carcinoma (GBC) is frequently diagnosed and treated in advanced stages and has a poor prognosis. Recent studies have identified claudin18.2 (CLDN18.2) as a promising target in digestive system cancer. I...AIMS: Gallbladder carcinoma (GBC) is frequently diagnosed and treated in advanced stages and has a poor prognosis. Recent studies have identified claudin18.2 (CLDN18.2) as a promising target in digestive system cancer. In this study, we aimed to determine the expression of CLDN18.2 and its correlation with clinicopathological characteristics in patients with GBC. METHODS: The expression of CLDN18.2 of 228 patients with GBC was studied via immunohistochemistry. Immunostained samples were evaluated according to the H-score. The samples were divided into low/negative (H-score=0-49) and high/positive (H-score=50-300) expression groups. The correlations between CLDN18.2 and various clinicopathological characteristics, including survival, were assessed. Multiplex immunofluorescence and image acquisition were used to analyse the relationship between CLDN18.2 expression and the immune microenvironment. RESULTS: The overall positive CLDN18.2 staining rate was 39.91% (91/228); 137 (60.08%) were given 0 points, 30 (13.15%) were given 1 point, 28 (12.28%) were given 2 points and 33 (14.47%) were given 3 points. Low CLDN18.2 expression was correlated with adverse prognostic factors, including poor differentiation, deep infiltration depth, lymph node metastasis and distant metastasis. High CLDN18.2 expression was associated with better survival. Furthermore, the distribution of immune cell subsets significantly differed between the high and low CLDN18.2 expression groups. CONCLUSIONS: The correlations between the expression of CLDN18.2 and clinicopathological characteristics and prognosis suggest that early-stage patients could benefit more from future anti-CLDN18.2 treatment and that CLDN18.2 may function as a pivotal regulatory molecule in patients with GBC. The underlying mechanism may be related to immune activation caused by high CLDN18.2 expression.
Several types of tumours and tumour-like lesions are recognised. Their classification is based mainly on the cell or tissue differentiation pathway found within the lesion. Not all tumour cells in a bone tumour different...Several types of tumours and tumour-like lesions are recognised. Their classification is based mainly on the cell or tissue differentiation pathway found within the lesion. Not all tumour cells in a bone tumour differentiate towards a single cell type. For instance, cartilage-producing cells and cartilaginous matrix are often found within osteosarcoma, and on rare occasions, cartilage can be found in fibrous dysplasia. Here, we discuss the presence of cartilaginous differentiation with fibrous dysplasia, its differential diagnosis and the use of molecular techniques to show that cartilaginous differentiation is an integral part of the lesion in that case, also known as fibrocartilaginous variant of fibrous dysplasia.