HistopathologyPub Date : 2026-09-24DOI: 10.1111/his.70280
Angela J Jiang, Erika Koh, Cynthia Truong, Adam I Rubin
{"title":"Histopathology of nail unit tumours: diagnostic features and emerging advances.","authors":"Angela J Jiang, Erika Koh, Cynthia Truong, Adam I Rubin","doi":"10.1111/his.70280","DOIUrl":"10.1111/his.70280","url":null,"abstract":"<p><p>Nail unit tumours are unusual and frequently underrecognized neoplasms that may pose diagnostic challenges to both clinicians and dermatopathologists. This review focuses on nail unit tumours that most frequently present diagnostic difficulty, owing to significant clinical or histopathological overlap with one another, and provides a comprehensive update on their histopathology. Entities covered include melanocytic tumours, onychopapilloma, onychomatricoma, superficial acral fibromyxoma, onychocytic matricoma, onychocytic carcinoma, subungual keratoacanthoma, squamous cell carcinoma and onycholemmal carcinoma. For each entity, we summarize the clinical presentation, histopathological features, immunohistochemical profile and relevant updates in classification and molecular pathogenesis. Familiarity with this diverse group of neoplasms is essential for timely and accurate diagnosis, given the significant diagnostic delay that commonly affects patients with nail unit tumours.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-24DOI: 10.1111/his.70285
Jiwon Koh, Koung Jin Suh, Hye Yeon Park, Hyun Jung Kwon, Hyun-Jung Sung, Han Suk Ryu, Jung Ho Kim, Jaemoon Koh, Kyung-Hun Lee, Dae-Won Lee, Changhee Park, Jeongmin Seo, Heejung Chae, Woochan Hwang, Ye Yoon Suh, Chang Ho Ahn, Seock-Ah Im, Jee Hyun Kim, So Yeon Park
{"title":"Heterogeneity of breast and nodal response to neoadjuvant pembrolizumab-based chemoimmunotherapy in early triple-negative breast cancer and its clinical significance.","authors":"Jiwon Koh, Koung Jin Suh, Hye Yeon Park, Hyun Jung Kwon, Hyun-Jung Sung, Han Suk Ryu, Jung Ho Kim, Jaemoon Koh, Kyung-Hun Lee, Dae-Won Lee, Changhee Park, Jeongmin Seo, Heejung Chae, Woochan Hwang, Ye Yoon Suh, Chang Ho Ahn, Seock-Ah Im, Jee Hyun Kim, So Yeon Park","doi":"10.1111/his.70285","DOIUrl":"https://doi.org/10.1111/his.70285","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the heterogeneity of pathological responses in the breast and regional lymph nodes after neoadjuvant pembrolizumab-based chemoimmunotherapy in early-stage triple-negative breast cancer (TNBC) and to explore their clinical implications.</p><p><strong>Methods and results: </strong>A total of 203 patients with TNBC treated with neoadjuvant chemotherapy combined with pembrolizumab followed by surgery were included. Histopathological features of baseline biopsy and post-treatment specimens, including residual carcinoma patterns and tumour-bed features, were systematically reviewed and correlated with treatment response and clinical outcomes. Pathological complete response (pCR) was achieved in 63.1% of patients. Higher histological grade, increased tumour-infiltrating lymphocytes (TILs), and higher Ki-67 labelling index were independently associated with pCR. Residual carcinoma patterns and tumour-bed changes were heterogeneous, with residual disease most commonly presenting as a solitary, confined focus (51.4%). Fibrotic tumour beds were more frequently observed in non-pCR cases, whereas stromal elastosis was enriched among pCR cases. Nodal responses were also heterogeneous, including complete nodal response (23.6%), non-response (8.4%), and mixed nodal response (7.4%). Disease recurrence was more frequent among patients without pCR, and among those with multifocal baseline tumours, higher cT stage, rare histological subtypes, low TILs and residual nodal disease.</p><p><strong>Conclusions: </strong>This real-world study provides a comprehensive pathological characterization of breast and nodal responses after neoadjuvant chemoimmunotherapy in early TNBC, highlighting heterogeneity beyond pCR and ypN staging and offering a more detailed characterization of treatment-response patterns.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-24DOI: 10.1111/his.70286
Elisa Scandiuzzi Maciel, Anna E Kersh, Emily Y Chu
{"title":"Cutaneous reactions to modern systemic oncologic therapies: a histopathological and clinical review.","authors":"Elisa Scandiuzzi Maciel, Anna E Kersh, Emily Y Chu","doi":"10.1111/his.70286","DOIUrl":"https://doi.org/10.1111/his.70286","url":null,"abstract":"<p><p>Modern oncologic treatments such as antibody-drug conjugates, targeted therapies, CAR-T-cell therapies and immune checkpoint inhibitors show improved efficacy through novel mechanisms of action when compared to conventional chemotherapy. However, these agents are often associated with cutaneous adverse events, many of them with distinctive clinical and histopathological patterns. Such events may be severe, impairing quality of life and sometimes leading to interruption of critical cancer treatment. As the use of these therapies continues to expand, dermatologists and dermatopathologists will increasingly encounter their associated toxicities. Recognition of histopathological patterns enables an accurate diagnosis and guides clinical management. Herein, we review the main cutaneous adverse events associated with antibody-drug conjugates, targeted therapies, CAR-T cell therapies and immune checkpoint inhibitors, summarizing clinical features and emphasizing histopathological findings.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-21DOI: 10.1111/his.70276
Andrea Quaranta, Donato Mancini, Concetta Caporusso, Andrea Marzullo, Luigi Vimercati, Cecilia Salzillo, Federica Pezzuto, Fiorella Calabrese, Gabriella Serio
{"title":"Low frequency of MTAP co-deletion with CDKN2A in peritoneal mesothelioma suggests an independent diagnostic role for MTAP.","authors":"Andrea Quaranta, Donato Mancini, Concetta Caporusso, Andrea Marzullo, Luigi Vimercati, Cecilia Salzillo, Federica Pezzuto, Fiorella Calabrese, Gabriella Serio","doi":"10.1111/his.70276","DOIUrl":"https://doi.org/10.1111/his.70276","url":null,"abstract":"<p><strong>Aims: </strong>Loss of MTAP expression by immunohistochemistry (IHC) is widely used as a surrogate for CDKN2A homozygous deletion (HD) in pleural mesothelioma (PM), but its diagnostic value in peritoneal mesothelioma (PeM) is less well defined. We investigated whether the observed limited reliability of MTAP IHC in PeM reflects a lower frequency of MTAP/CDKN2A co-deletion.</p><p><strong>Methods and results: </strong>Twenty-four PeMs selected from a previously characterized cohort according to CDKN2A and MTAP status underwent MTAP fluorescence in situ hybridization (FISH) using a custom-made probe. Twenty-five PMs and 10 reactive mesothelial proliferations (RMPs) were included as external controls. MTAP IHC, CDKN2A FISH and MTAP FISH were evaluated, and concordance was assessed using Cohen's kappa. In PM, MTAP IHC showed perfect concordance with MTAP FISH (kappa = 1.00; p < 0.001) and good concordance with CDKN2A FISH, as did MTAP FISH (kappa = 0.613; p = 0.002). MTAP IHC and FISH showed 100% specificity and 68.8% sensitivity for CDKN2A HD by FISH. In PeM, MTAP IHC remained highly concordant with MTAP FISH (kappa = 0.83; p = 0.001), whereas concordance with CDKN2A FISH was poor and not significant for both MTAP IHC (kappa = 0.21; p = 0.36) and MTAP FISH (kappa = 0.33; p = 0.17). In PeM, MTAP FISH showed 75% specificity and 62.5% sensitivity, MTAP IHC showed 75% specificity and 50% sensitivity for CDKN2A HD by FISH. All RMPs showed complete agreement and full specificity and sensitivity across all assays.</p><p><strong>Conclusions: </strong>Our findings indicate that in PeM, MTAP, although a less reliable surrogate for CDKN2A status, may serve as an independent adjunct diagnostic marker. The low concordance between MTAP and CDKN2A alterations suggests a lower rate of co-deletion and points to potential site-specific molecular differences.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-18DOI: 10.1111/his.70282
Timothy Law, Won-Tak Choi, Sarah E Umetsu, Kwun Wah Wen
{"title":"Orcein is a more sensitive stain than EVG for detecting large vessel (venous) invasion in colorectal cancer.","authors":"Timothy Law, Won-Tak Choi, Sarah E Umetsu, Kwun Wah Wen","doi":"10.1111/his.70282","DOIUrl":"10.1111/his.70282","url":null,"abstract":"<p><strong>Background: </strong>Large vessel invasion (VI) is a well-established adverse prognostic factor in colorectal cancer (CRC). Assessment based solely on haematoxylin-eosin (H&E)-stained sections is relatively insensitive, prompting professional medical societies to recommend elastin stains. However, comparative data between elastin stains, such as orcein or elastic Verhoeff-Van Gieson (EVG), remain limited.</p><p><strong>Design: </strong>Seventy-eight random CRC resections (≥ pT1) from 2023 to 2025 were analysed. H&E slides were evaluated for VI to facilitate ordering additional studies to complete two sets of orcein, EVG, and H&E recut on average for each case. Sets lacking the lesion on deeper sections were excluded, yielding 155 sets. All H&E slides were evaluated for VI followed by elastin stains. VI status and elastin stain quality (partial: 50%-99% vs. circumferential: 100% of the vessel wall) were assessed by at least two pathologists.</p><p><strong>Results: </strong>Elastin stain confirmed VI was identified in 30% of slide sets (46% of resections). Using orcein with H&E as the reference comparator (sensitivity 100%, specificity 100%), H&E alone demonstrated 70% sensitivity and 80% specificity. EVG failed to detect 21% of cases identified by orcein (EVG sensitivity 79%, specificity 100%; p = 0.002). Orcein demonstrated a significantly higher circumferential staining rate than EVG (78% vs. 43%; p < 0.001).</p><p><strong>Conclusion: </strong>H&E assessment alone is less accurate than evaluation supplemented with elastin stains for detecting VI. While EVG is highly specific, it is less sensitive than orcein, in part due to diminished staining and lower background contrast. These findings support the use of orcein to optimize VI detection in CRC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-16DOI: 10.1111/his.70284
Nazario P Tenace, Maurizio Colecchia, Arndt Hartmann, Maurilio Ponzoni, Claudio Doglioni, Sebastian Rauch, Marco Moschini, Andrea Necchi, Alberto Briganti, Francesco Montorsi, Markus Eckstein
{"title":"Immunohistochemical stratification of bladder small cell carcinoma reveals two major phenotypes with distinct therapeutic biomarker profiles.","authors":"Nazario P Tenace, Maurizio Colecchia, Arndt Hartmann, Maurilio Ponzoni, Claudio Doglioni, Sebastian Rauch, Marco Moschini, Andrea Necchi, Alberto Briganti, Francesco Montorsi, Markus Eckstein","doi":"10.1111/his.70284","DOIUrl":"https://doi.org/10.1111/his.70284","url":null,"abstract":"<p><strong>Aims: </strong>Small cell carcinoma of the bladder (SmCCB) is a rare and aggressive malignancy that remains poorly defined. Using the transcriptional taxonomy established for small cell lung carcinoma (SCLC), we aimed to stratify SmCCB by dominant transcription factors and assess associations between IHC-defined phenotype, neuroendocrine differentiation and therapeutic biomarker expression.</p><p><strong>Methods and results: </strong>A retrospective multi-institutional cohort of 88 SmCCBs was assembled. Of these, 79 cases underwent immunohistochemical characterization for ASCL1, NEUROD1, POU2F3, YAP1 and HNF4α, along with classical neuroendocrine markers, therapeutic biomarkers and antibody-drug conjugate targets. NECTIN4 amplification was also assessed by fluorescence in situ hybridization (FISH). Six IHC-defined subgroups were identified: ASCL1-driven (41.8%), NEUROD1-driven (25.3%), POU2F3-driven (20.3%), YAP1-driven (6.3%), mixed (5.1%) and full-negative (1.3%). ASCL1-driven, NEUROD1-driven and mixed tumours were classified as High-NE, with diffuse NE marker expression, whereas POU2F3-driven, YAP1-driven and full-negative tumours were classified as Low-NE, with weak or absent expression. Overall membranous Nectin-4 expression was low or absent but significantly higher in Low-NE tumours (P < 0.001). NECTIN4 amplification occurred in 21.9% (16/73), comparable to that reported in non-neuroendocrine urothelial carcinoma. Conversely, DLL3 and SLFN11 were significantly overexpressed in High-NE tumours, while expression of the remaining targets was almost entirely absent.</p><p><strong>Conclusions: </strong>SmCCB may be stratified into two IHC-defined phenotypic groups with distinctive neuroendocrine differentiation and therapeutic biomarker profiles. Taken together, low membranous Nectin-4 expression and preferential DLL3 and SLFN11 expression in High-NE tumours support further investigation of alternative therapeutic strategies.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-15DOI: 10.1111/his.70279
Monika Vyas, Wei Chen, Raul S Gonzalez
{"title":"Ki67 proliferation indices in advanced jejunoileal well-differentiated neuroendocrine tumours are most prognostic when evaluated in mesenteric tumour deposits.","authors":"Monika Vyas, Wei Chen, Raul S Gonzalez","doi":"10.1111/his.70279","DOIUrl":"https://doi.org/10.1111/his.70279","url":null,"abstract":"<p><strong>Background: </strong>Ki67 proliferation indices are used for grading well-differentiated neuroendocrine tumours (NETs). Selection of tissue for staining can be challenging, especially in jejunoileal NETs (JI-NETs), which can be multifocal and produce multiple metastases. This study aimed to determine parameters for selecting the most prognostically appropriate tissue for Ki67 staining in JI-NETs.</p><p><strong>Materials and methods: </strong>We identified JI-NETs with at least one nodal metastasis and/or mesenteric tumour deposit. For each, we recorded patient age and sex; size of largest primary tumour, nodal metastasis and/or deposit; AJCC staging; and patient outcome (recurrence and disease-specific death). We stained the largest primary, node and deposit in each case for Ki67 (clone SP6, Biocare Medical CRM325, 1:50) and also assessed mitotic rates. We photographed hotspot areas on each Ki67 slide. Ki67 index was calculated for each photo using QuPath digital image analysis software after training using a random forest supervised classifier. Twenty cases underwent manual Ki67 counting to validate QuPath results. All variables were compared to patient outcomes using standard univariate and multivariate Cox proportional hazard regression (α = 0.05).</p><p><strong>Results: </strong>Among 75 JI-NETs from 42 female and 33 male patients (mean age 61 years), 71 had positive nodes and 47 had deposits. Mean sizes of the largest primary tumours, nodal metastases and deposits were 1.97, 1.28 and 2.0 cm. Mean Ki67 was 1.82 (largest primaries), 2.24 (largest nodes) and 2.08 (largest deposits). In 51 cases (68%), the Ki67 of a node or deposit was higher than the primary tumour. Twenty-one tumours (28%) recurred, with median projected time to recurrence time of 108 months. Over a median overall follow-up of 72 months, six patients (8%) died of disease. Tumour deposit Ki67 was the only factor associated with increased risk of progression on multivariate analysis (hazard ratio [HR] 1.22 for each 1.0% increase, 95% confidence interval [CI] 1.02-1.46, P = 0.032); primary and nodal Ki67 were not, nor was the highest Ki67 or the Ki67 of the largest focus within each case. No Ki67 indices were significantly relevant to overall survival on multivariate analysis, though largest tumour deposit size was (HR 1.51 for each 1.0 cm increase, 95% CI 1.08-2.11, P = 0.015).</p><p><strong>Conclusions: </strong>Tumour deposits appear to play a key role in the outcome of patients with JI-NETs. For meaningful Ki67 evaluation of JI-NETs, the largest tumour deposit should be stained, if available.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-13DOI: 10.1111/his.70277
Olivia J Leung, Esther Baranov, Isairis Peralta Valerio, Robin Collingwood, Natalie Respond, Don Siegel, Pooja Devi, Kristen M Stashek
{"title":"Comparison of intestinal histopathological changes following teclistamab, BCMA-directed CAR T, CD19-directed CAR T and rituximab therapies.","authors":"Olivia J Leung, Esther Baranov, Isairis Peralta Valerio, Robin Collingwood, Natalie Respond, Don Siegel, Pooja Devi, Kristen M Stashek","doi":"10.1111/his.70277","DOIUrl":"https://doi.org/10.1111/his.70277","url":null,"abstract":"<p><strong>Aims: </strong>Immunotherapy-associated intestinal tract injury is increasingly recognized; however, histological patterns associated with specific agents remain incompletely defined. Data directly comparing CD19- and BCMA-directed CAR T therapies with other B-cell-targeted treatments are limited, and histological findings associated with teclistamab in the gastrointestinal tract have not been well described.</p><p><strong>Methods and results: </strong>We retrospectively reviewed intestinal biopsies from patients treated with BCMA-directed CAR T (n = 23), teclistamab (n = 8), CD19-directed CAR T (n = 31) and rituximab (n = 11), identifying distinct but overlapping histological patterns. Lamina propria plasma cell depletion was the most prominent finding in BCMA-targeted therapies (74% BCMA CAR T, 88% teclistamab), occurring at significantly lower rates in CD19 CAR T (32%) and rituximab (27%) cohorts (P < 0.001). Crypt apoptotic bodies (65% BCMA CAR T, 88% teclistamab, 48% CD19 CAR T, 45% rituximab) and active inflammation (48% BCMA CAR T, 38% teclistamab, 35% CD19 CAR T, 9% rituximab) were also observed. Intraepithelial lymphocytosis, villous blunting, goblet cell depletion and erosion were infrequent. No significant histopathological differences were identified between agents sharing a similar target.</p><p><strong>Conclusion: </strong>Intestinal biopsies from patients treated with plasma cell and B-cell-targeted immunotherapies showed distinct but overlapping histological patterns. Lamina propria plasma cell depletion was most prominent in BCMA-directed therapies, while crypt apoptotic bodies and active inflammation were identified across all treatment groups.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-08Epub Date: 2026-06-09DOI: 10.1111/his.70198
Zikun Ma, Xinyan Zhao
{"title":"Response to the Letter to the Editor: further clarifications on the new histological criteria for autoimmune hepatitis","authors":"Zikun Ma, Xinyan Zhao","doi":"10.1111/his.70198","DOIUrl":"10.1111/his.70198","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 4","pages":"719-720"},"PeriodicalIF":3.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2026-09-08Epub Date: 2026-06-19DOI: 10.1111/his.70193
Ylva A. Weeda, Sarah M. Issa, Hans Halfwerk, Michel Botros, Onno J. de Boer, Lodewijk A. Brosens, Michail Doukas, Gursah Kats-Ugurlu, Fiebo ten Kate, Jaap van der Laan, Ineke van Lijnschoten, Ariadne H. A. G. Ooms, Lindsey Oudijk, Rachel S. van der Post, Mihaela G. Raicu, Bert Timmer, Myrtle J. van der Wel, Sybren L. Meijer
{"title":"Diagnostic impact and reproducibility of p53 immunohistochemistry in Barrett's oesophagus: results of the Dutch Esophageal Pathology Panel (DEPP)","authors":"Ylva A. Weeda, Sarah M. Issa, Hans Halfwerk, Michel Botros, Onno J. de Boer, Lodewijk A. Brosens, Michail Doukas, Gursah Kats-Ugurlu, Fiebo ten Kate, Jaap van der Laan, Ineke van Lijnschoten, Ariadne H. A. G. Ooms, Lindsey Oudijk, Rachel S. van der Post, Mihaela G. Raicu, Bert Timmer, Myrtle J. van der Wel, Sybren L. Meijer","doi":"10.1111/his.70193","DOIUrl":"10.1111/his.70193","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Evidence supporting the use of p53 immunohistochemistry (p53-IHC) in Barrett's oesophagus (BE) is largely based on selected series, limiting generalizability. This study evaluates p53-IHC in a nationwide, real-world BE-cohort within a universal healthcare system, assessing concordance with referring hospitals, interobserver agreement (IOA) and its impact on routine diagnostic decisions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Revision cases submitted to the Dutch Esophageal Pathology Panel (DEPP) were assessed by trained and experienced pathologists for haematoxylin and eosin (H&E)-based classification (Vienna classification), p53-IHC patterns (wild-type, overexpression, double clone, null mutation and equivocal) and combined H&E/p53-IHC review. Concordance between referring hospitals and the expert panel (Cohen's kappa) and IOA among panel pathologists (Fleiss' kappa) were assessed, along with the impact of p53-IHC on diagnostic reclassification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1,146 consecutive patient consultation cases (1,704 biopsy levels) were included, with a median of 12 DEPP pathologist assessments per biopsy. Overall concordance of p53 assessment between referring hospitals and the expert panel was moderate-to-substantial (<i>κ</i> = 0.61, 95% CI 0.58–0.64), with 24.2% of p53-IHC assessments reclassified. IOA among 13 pathologists assessing 316 endoscopic biopsies was substantial (<i>κ</i> = 0.65, 95% CI 0.61–0.69). Ancillary p53-IHC influenced pathologists' decisions across biopsy levels. For non-dysplastic (NDBE) biopsies, aberrant p53-IHC prompted reclassification to indefinite for dysplasia (IND, 9.2%) or low-grade dysplasia (LGD, 4.8%). For IND biopsies, p53-IHC shifted diagnoses toward NDBE (17.0%) or LGD (37.1%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion/discussion</h3>\u0000 \u0000 <p>p53-IHC interpretation is reliable, reproducible and clinically meaningful in BE diagnostics when standardized criteria are applied. These findings support broader use of p53-IHC in routine practice and incorporation of assessment criteria into guidelines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 4","pages":"614-623"},"PeriodicalIF":3.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}