Pub Date : 2025-10-16DOI: 10.1016/j.anndiagpath.2025.152577
Yasemin Akca, Elif Busra Gokce
The primary aim of this study was to evaluate the FDA-cleared Ventana® Digital Progesterone (PR) scoring algorithm, originally designed for breast carcinoma, in meningiomas. This work was conducted retrospectively and included 129 meningioma cases diagnosed between 2018 and 2024, with only patients who underwent progesterone receptor immunohistochemical staining at initial diagnosis being eligible. Archived PR-stained slides were digitized with the VENTANA® DP200 scanner and analyzed using the uPath PR (1E2) algorithm. Three independent scoring rounds were performed, and digital results were compared with manual assessments using the H-score method. Correlations between digital and manual scores were evaluated by Spearman's rank correlation coefficient, Pearson's correlation coefficient, and the Intraclass Correlation Coefficient (ICC). Spearman's coefficients exceeded 0.75 across all scoring rounds (p < 0.001), indicating strong monotonic relationships. Pearson's coefficients showed strong linear associations in two rounds (r = 0.701 and r = 0.800) and weaker alignment in one (r = 0.188). ICC values indicated near-perfect agreement in one round (0.968), good agreement in another (0.755), and moderate agreement in the third (0.633). These findings demonstrate that the Ventana® Digital PR algorithm provides a reliable and feasible alternative to manual scoring in meningiomas, offering objectivity, reproducibility, and diagnostic applicability in neuro-oncology.
{"title":"Evaluation of a breast cancer–trained digital progesterone receptor scoring algorithm in meningiomas: A comparative study with manual assessment","authors":"Yasemin Akca, Elif Busra Gokce","doi":"10.1016/j.anndiagpath.2025.152577","DOIUrl":"10.1016/j.anndiagpath.2025.152577","url":null,"abstract":"<div><div>The primary aim of this study was to evaluate the FDA-cleared Ventana® Digital Progesterone (PR) scoring algorithm, originally designed for breast carcinoma, in meningiomas. This work was conducted retrospectively and included 129 meningioma cases diagnosed between 2018 and 2024, with only patients who underwent progesterone receptor immunohistochemical staining at initial diagnosis being eligible. Archived PR-stained slides were digitized with the VENTANA® DP200 scanner and analyzed using the uPath PR (1E2) algorithm. Three independent scoring rounds were performed, and digital results were compared with manual assessments using the H-score method. Correlations between digital and manual scores were evaluated by Spearman's rank correlation coefficient, Pearson's correlation coefficient, and the Intraclass Correlation Coefficient (ICC). Spearman's coefficients exceeded 0.75 across all scoring rounds (<em>p</em> < 0.001), indicating strong monotonic relationships. Pearson's coefficients showed strong linear associations in two rounds (<em>r</em> = 0.701 and <em>r</em> = 0.800) and weaker alignment in one (<em>r</em> = 0.188). ICC values indicated near-perfect agreement in one round (0.968), good agreement in another (0.755), and moderate agreement in the third (0.633). These findings demonstrate that the Ventana® Digital PR algorithm provides a reliable and feasible alternative to manual scoring in meningiomas, offering objectivity, reproducibility, and diagnostic applicability in neuro-oncology.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152577"},"PeriodicalIF":1.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.anndiagpath.2025.152574
Byoung Uk Park , Fowsiyo Ahmed , Christopher P. Hartley , Maria Carolina Olave , Roger K. Moreira , Chady Meroueh , Rondell P. Graham , Catherine E. Hagen
Background
Graft-versus-host disease (GVHD) is a common and serious complication of allogeneic hematopoietic stem cell transplantation, with the gastrointestinal (GI) tract being a major target. Histologic diagnosis of GI GVHD remains challenging due to overlapping features with other conditions and variability in guideline adoption.
Objective
To assess current diagnostic practices, histologic thresholds, and guideline utilization among practicing pathologists evaluating GI GVHD.
Methods
A 30-question, anonymous, web-based survey was distributed to GI pathologists worldwide. The survey explored diagnostic strategies, threshold criteria for apoptosis, use of grading systems, ancillary testing practices, and satisfaction with existing guidelines.
Results
Of the 200 pathologists contacted, 80 responded (40 % response rate), with 69 actively evaluating GI GVHD. Most respondents (92.8 %) practiced in academic settings, and 81.2 % had completed GI pathology fellowships. A majority (73.9 %) reported no standardized diagnostic criteria within their practice groups. Among those using guidelines, the NIH criteria were most commonly applied. There was substantial variability in the threshold for apoptosis, ranging from the presence of any apoptotic body to higher thresholds. Only 42 % of respondents routinely graded GI GVHD, primarily using the Lerner system. CMV immunostaining was frequently employed, and mycophenolate toxicity was commonly considered in the differential diagnosis.
Conclusions
The survey highlights marked heterogeneity in the histologic evaluation of GI GVHD among pathologists. These findings underscore the need for more standardized, evidence-based diagnostic criteria and enhanced consensus on grading practices.
{"title":"Histopathologic evaluation of gastrointestinal graft-versus-host disease: Opportunities for improvement based on a survey of practicing pathologists","authors":"Byoung Uk Park , Fowsiyo Ahmed , Christopher P. Hartley , Maria Carolina Olave , Roger K. Moreira , Chady Meroueh , Rondell P. Graham , Catherine E. Hagen","doi":"10.1016/j.anndiagpath.2025.152574","DOIUrl":"10.1016/j.anndiagpath.2025.152574","url":null,"abstract":"<div><h3>Background</h3><div>Graft-versus-host disease (GVHD) is a common and serious complication of allogeneic hematopoietic stem cell transplantation, with the gastrointestinal (GI) tract being a major target. Histologic diagnosis of GI GVHD remains challenging due to overlapping features with other conditions and variability in guideline adoption.</div></div><div><h3>Objective</h3><div>To assess current diagnostic practices, histologic thresholds, and guideline utilization among practicing pathologists evaluating GI GVHD.</div></div><div><h3>Methods</h3><div>A 30-question, anonymous, web-based survey was distributed to GI pathologists worldwide. The survey explored diagnostic strategies, threshold criteria for apoptosis, use of grading systems, ancillary testing practices, and satisfaction with existing guidelines.</div></div><div><h3>Results</h3><div>Of the 200 pathologists contacted, 80 responded (40 % response rate), with 69 actively evaluating GI GVHD. Most respondents (92.8 %) practiced in academic settings, and 81.2 % had completed GI pathology fellowships. A majority (73.9 %) reported no standardized diagnostic criteria within their practice groups. Among those using guidelines, the NIH criteria were most commonly applied. There was substantial variability in the threshold for apoptosis, ranging from the presence of any apoptotic body to higher thresholds. Only 42 % of respondents routinely graded GI GVHD, primarily using the Lerner system. CMV immunostaining was frequently employed, and mycophenolate toxicity was commonly considered in the differential diagnosis.</div></div><div><h3>Conclusions</h3><div>The survey highlights marked heterogeneity in the histologic evaluation of GI GVHD among pathologists. These findings underscore the need for more standardized, evidence-based diagnostic criteria and enhanced consensus on grading practices.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152574"},"PeriodicalIF":1.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endoscopic submucosal dissection (ESD) enables en-bloc resection of superficial gastrointestinal lesions, offering curative treatment while preserving organ function. This study aimed to characterize the clinico-pathological spectrum of gastrointestinal ESD specimens at a tertiary care centre over five years and identify factors influencing patient management. All ESD specimens received from January 2020 to December 2024 were retrospectively reviewed, with grossing performed according to International Collaboration on Cancer Reporting (ICCR) guidelines. Histological evaluation included lesion type, depth of invasion, margin status, lymphovascular and perineural invasion, and tumour budding, with follow-up obtained from electronic medical records. Seventy-two specimens were analyzed (mean age 68 years; M:F = 1.5:1), with lesion sites comprising stomach (32 %), esophagus (21 %), rectum (21 %), sigmoid colon (18 %), and duodenum (8 %). Epithelial lesions constituted 69 % (50/72), of which malignant epithelial tumours formed 24 % (17/72), including esophageal squamous cell carcinomas (n = 4), esophageal adenocarcinoma (n = 1), gastric adenocarcinomas (n = 4), and colorectal adenocarcinomas (n = 8). En-bloc resection was achieved in 93 % overall and 88 % of malignant specimens. After excluding two indeterminate cases, R0 resection was achieved in 60 % (9/15) of malignant tumours, enabling accurate margin assessment and staging. Additional surgical intervention was required in 29.4 % (5/17) malignant cases due to margin positivity, with one specimen showing further high-risk features. No patients received neoadjuvant therapy. Residual tumour and lymph node metastasis were identified in three and one malignant specimens, respectively. The use of standardized grossing and reporting protocols facilitated accurate pathological risk stratification and guided subsequent clinical decision-making.
{"title":"Clinico-pathological findings in a series of gastrointestinal endoscopic submucosal dissection specimens: A retrospective 5-year study","authors":"Sunayana Misra , Sonia Badwal , Seema Rao , Shivam Khare , Shrihari Anikhindi , Anil Arora , Shashi Dhawan","doi":"10.1016/j.anndiagpath.2025.152575","DOIUrl":"10.1016/j.anndiagpath.2025.152575","url":null,"abstract":"<div><div>Endoscopic submucosal dissection (ESD) enables en-bloc resection of superficial gastrointestinal lesions, offering curative treatment while preserving organ function. This study aimed to characterize the clinico-pathological spectrum of gastrointestinal ESD specimens at a tertiary care centre over five years and identify factors influencing patient management. All ESD specimens received from January 2020 to December 2024 were retrospectively reviewed, with grossing performed according to International Collaboration on Cancer Reporting (ICCR) guidelines. Histological evaluation included lesion type, depth of invasion, margin status, lymphovascular and perineural invasion, and tumour budding, with follow-up obtained from electronic medical records. Seventy-two specimens were analyzed (mean age 68 years; M:F = 1.5:1), with lesion sites comprising stomach (32 %), esophagus (21 %), rectum (21 %), sigmoid colon (18 %), and duodenum (8 %). Epithelial lesions constituted 69 % (50/72), of which malignant epithelial tumours formed 24 % (17/72), including esophageal squamous cell carcinomas (<em>n</em> = 4), esophageal adenocarcinoma (<em>n</em> = 1), gastric adenocarcinomas (n = 4), and colorectal adenocarcinomas (<em>n</em> = 8). En-bloc resection was achieved in 93 % overall and 88 % of malignant specimens. After excluding two indeterminate cases, R0 resection was achieved in 60 % (9/15) of malignant tumours, enabling accurate margin assessment and staging. Additional surgical intervention was required in 29.4 % (5/17) malignant cases due to margin positivity, with one specimen showing further high-risk features. No patients received neoadjuvant therapy. Residual tumour and lymph node metastasis were identified in three and one malignant specimens, respectively. The use of standardized grossing and reporting protocols facilitated accurate pathological risk stratification and guided subsequent clinical decision-making.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152575"},"PeriodicalIF":1.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1016/j.anndiagpath.2025.152576
Ayushi Sahay , Asawari Patil , Trupti Pai , Poonam Panjwani , Shalaka Joshi , Palak Popat Thakkar , Sangeeta B. Desai , Tanuja M. Shet
Invasive breast carcinoma (IBC) arising within microglandular adenosis (MGA-CA), a rarity, is usually triple-negative (TNBC). TNBC burden is high in the South-Asian region, but little is known about MGA-CA. Herein, we analyze the clinicopathological spectrum of MGA-CA diagnosed at our tertiary care oncology center. Twenty-three cases of MGA-CA from 2005 to 2024 were collected. Clinicopathological parameters, including immunohistochemistry and available follow-up, were noted. Median age was 47.5 years (range 33–60 years). Interestingly, 7/14 cases (50 %) either had a family history of malignancy or a germline BRCA1 mutation. Diagnostic core biopsies (n = 12) showed IBC in 5, MGA-CA in 3, and only atypical MGA (AMGA) in 4. Nearly all MGA-CA were grade 3 (22/23), no special type (15/23), and TNBC (22/23). Typical and/or AMGA showed a transition to AMGA-like in-situ carcinoma to IBC (12/23) or merged directly with IBC (9/23). Both MGA and IBC showed mutant-type p53 expression in the majority (11/14). The median follow-up duration (n = 16) was 46 months (range 4–128 months). Patients receiving neoadjuvant chemotherapy showed a good response (4/5 cases). Local/metastatic tumor progression was noted in 7/16 cases (43.75 %), higher in those with family history/BRCA+ status than without (57.1 % vs 33.3 %). Our study represents the second-largest single institutional MGA-CA series to date. Mutant-type p53 overexpression is noted in both MGA and associated CA, reinforcing MGA as a likely precursor to high-grade TNBC-type IBC. Diagnosis is possible even on core biopsies. Family history/germline BRCA mutations are frequent and herald higher chances of progression, suggesting the need for genetic testing in MGA-CA.
{"title":"Microglandular adenosis associated with invasive breast carcinoma: Tertiary care oncology centre experience of an under-recognized entity","authors":"Ayushi Sahay , Asawari Patil , Trupti Pai , Poonam Panjwani , Shalaka Joshi , Palak Popat Thakkar , Sangeeta B. Desai , Tanuja M. Shet","doi":"10.1016/j.anndiagpath.2025.152576","DOIUrl":"10.1016/j.anndiagpath.2025.152576","url":null,"abstract":"<div><div>Invasive breast carcinoma (IBC) arising within microglandular adenosis (MGA-CA), a rarity, is usually triple-negative (TNBC). TNBC burden is high in the South-Asian region, but little is known about MGA-CA. Herein, we analyze the clinicopathological spectrum of MGA-CA diagnosed at our tertiary care oncology center. Twenty-three cases of MGA-CA from 2005 to 2024 were collected. Clinicopathological parameters, including immunohistochemistry and available follow-up, were noted. Median age was 47.5 years (range 33–60 years). Interestingly, 7/14 cases (50 %) either had a family history of malignancy or a germline <em>BRCA1</em> mutation. Diagnostic core biopsies (<em>n</em> = 12) showed IBC in 5, MGA-CA in 3, and only atypical MGA (AMGA) in 4. Nearly all MGA-CA were grade 3 (22/23), no special type (15/23), and TNBC (22/23). Typical and/or AMGA showed a transition to AMGA-like in-situ carcinoma to IBC (12/23) or merged directly with IBC (9/23). Both MGA and IBC showed mutant-type p53 expression in the majority (11/14). The median follow-up duration (<em>n</em> = 16) was 46 months (range 4–128 months). Patients receiving neoadjuvant chemotherapy showed a good response (4/5 cases). Local/metastatic tumor progression was noted in 7/16 cases (43.75 %), higher in those with family history/<em>BRCA</em>+ status than without (57.1 % vs 33.3 %). Our study represents the second-largest single institutional MGA-CA series to date. Mutant-type p53 overexpression is noted in both MGA and associated CA, reinforcing MGA as a likely precursor to high-grade TNBC-type IBC. Diagnosis is possible even on core biopsies. Family history/germline <em>BRCA</em> mutations are frequent and herald higher chances of progression, suggesting the need for genetic testing in MGA-CA.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152576"},"PeriodicalIF":1.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145395021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-05DOI: 10.1016/j.anndiagpath.2025.152572
Mehmet Özen , Ender Özden , Mehmet Necmettin Mercimek , Murat Gülşen , Sultan Çalışkan , Oğuz Aydın
Partial nephrectomy (PN) is the preferred treatment for cT1 and cT2 renal tumors, with the goal of preserving renal function while maintaining oncological outcomes. Achieving negative surgical margins is crucial for minimizing recurrence risk. This prospective study included 113 patients with 117 renal tumors who underwent PN. IC samples were collected by pressing glass slides onto the specimen surface (Sample A) and from Tru-cut biopsies (Sample B). All slides were processed with hematoxylin-eosin staining and evaluated by a senior pathologist. Cytological findings were classified as positive, negative, or indeterminate. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed relative to the final pathological results. Positive surgical margins (PSM) were observed in five patients. In one case, the surgical margin could not be evaluated and was therefore excluded from the IC evaluation. Of the 116 cytology A samples, 101 were negative, 7 were positive and 8 were indeterminate. The sensitivity was 100 %, specificity was 98 %, PPV was 71.4 %, and NPV was 100 %. No recurrence was observed in patients with PSM during a median follow-up of 16.9 months. The present study demonstrated that IC is a simple, rapid, and cost-effective method for predicting surgical margins and can be a useful as a rule-out test during intraoperative decision-making.
{"title":"Diagnostic utility of imprint cytology in assessing surgical margins during laparoscopic partial nephrectomy","authors":"Mehmet Özen , Ender Özden , Mehmet Necmettin Mercimek , Murat Gülşen , Sultan Çalışkan , Oğuz Aydın","doi":"10.1016/j.anndiagpath.2025.152572","DOIUrl":"10.1016/j.anndiagpath.2025.152572","url":null,"abstract":"<div><div>Partial nephrectomy (PN) is the preferred treatment for cT1 and cT2 renal tumors, with the goal of preserving renal function while maintaining oncological outcomes. Achieving negative surgical margins is crucial for minimizing recurrence risk. This prospective study included 113 patients with 117 renal tumors who underwent PN. IC samples were collected by pressing glass slides onto the specimen surface (Sample A) and from Tru-cut biopsies (Sample B). All slides were processed with hematoxylin-eosin staining and evaluated by a senior pathologist. Cytological findings were classified as positive, negative, or indeterminate. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed relative to the final pathological results. Positive surgical margins (PSM) were observed in five patients. In one case, the surgical margin could not be evaluated and was therefore excluded from the IC evaluation. Of the 116 cytology A samples, 101 were negative, 7 were positive and 8 were indeterminate. The sensitivity was 100 %, specificity was 98 %, PPV was 71.4 %, and NPV was 100 %. No recurrence was observed in patients with PSM during a median follow-up of 16.9 months. The present study demonstrated that IC is a simple, rapid, and cost-effective method for predicting surgical margins and can be a useful as a rule-out test during intraoperative decision-making.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152572"},"PeriodicalIF":1.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-05DOI: 10.1016/j.anndiagpath.2025.152573
Omar Al-Rusan , David E. Ward , Chung-Che Chang , Qi Shen , L. Jeffrey Medeiros
Castleman disease (CD) is a complex group of at least four lymphoproliferative diseases of which unicentric CD is most common. Morphologically, unicentric CD can be subdivided into hyaline-vascular and mixed/plasmacytic variants. Indolent T-lymphoblastic proliferation (iT-LBP) is a benign, extrathymic expansion of T-lymphoblasts that sometimes can be associated with CD. Cases of iT-LBP do not exhibit morphologic atypia or a destructive growth pattern, lack evidence of monoclonality or recurrent genetic abnormalities and are regarded as reactive processes. We describe a 49-year-old woman who developed a pelvic mass. Needle biopsy showed stroma-rich hyaline-vascular unicentric CD. Two years later, the mass enlarged, and an incisional biopsy revealed a diffuse proliferation of immature lymphoblasts positive for TdT, CD4 and CD8 without immunophenotypic evidence an aberrant T-cell or B-cell population. There was no morphologic evidence of CD, however, a spindle cell proliferation was present in the background. Next generation sequencing showed a PDGFRB N666S mutation suggesting the presence of residual CD. We present this case because it highlights the known association between CD and iT-LBP and the detection of PDGFRB mutation supports the interpretation that the iT-LBP likely arose from hyaline-vascular CD.
{"title":"From the archives of MD Anderson Cancer Center: Stroma-rich hyaline vascular Castleman disease followed by indolent T-lymphoblastic proliferation and detection of PDGFRB mutation","authors":"Omar Al-Rusan , David E. Ward , Chung-Che Chang , Qi Shen , L. Jeffrey Medeiros","doi":"10.1016/j.anndiagpath.2025.152573","DOIUrl":"10.1016/j.anndiagpath.2025.152573","url":null,"abstract":"<div><div>Castleman disease (CD) is a complex group of at least four lymphoproliferative diseases of which unicentric CD is most common. Morphologically, unicentric CD can be subdivided into hyaline-vascular and mixed/plasmacytic variants. Indolent T-lymphoblastic proliferation (iT-LBP) is a benign, extrathymic expansion of T-lymphoblasts that sometimes can be associated with CD. Cases of iT-LBP do not exhibit morphologic atypia or a destructive growth pattern, lack evidence of monoclonality or recurrent genetic abnormalities and are regarded as reactive processes. We describe a 49-year-old woman who developed a pelvic mass. Needle biopsy showed stroma-rich hyaline-vascular unicentric CD. Two years later, the mass enlarged, and an incisional biopsy revealed a diffuse proliferation of immature lymphoblasts positive for TdT, CD4 and CD8 without immunophenotypic evidence an aberrant T-cell or B-cell population. There was no morphologic evidence of CD, however, a spindle cell proliferation was present in the background. Next generation sequencing showed a <em>PDGFRB</em> N666S mutation suggesting the presence of residual CD. We present this case because it highlights the known association between CD and iT-LBP and the detection of <em>PDGFRB</em> mutation supports the interpretation that the iT-LBP likely arose from hyaline-vascular CD.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152573"},"PeriodicalIF":1.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-02DOI: 10.1016/j.anndiagpath.2025.152571
Hristo Milev , Desislava Dimitrova , Ivan Ivanov
Ki-67 is a nuclear protein linked to cellular proliferation and is used as a prognostic and predictive biomarker in breast carcinoma. However, variability in its assessment limits its clinical utility. This study evaluated interobserver reproducibility in Ki-67 scoring and compared proliferative indices between core needle biopsy (CNB) and corresponding resection specimens in invasive breast carcinoma. Sixty-three cases with matched CNB and resection specimens were retrospectively analyzed. Ki-67 immunohistochemistry was independently evaluated by two pathologists using manual image-based counting. Interobserver agreement and CNB–resection concordance were assessed using the intraclass correlation coefficient (ICC), Cohen's kappa, Bland–Altman analysis, and Spearman's correlation. Tumor characteristics were analyzed for their association with variability. Interobserver agreement was excellent, with ICCs of 0.89 for CNB and 0.91 for resection specimens. Cohen's kappa for binary classification (<20 % vs. ≥20 %) showed moderate agreement for CNB (κ = 0.54) and substantial agreement for resections (κ = 0.78). Bland–Altman analysis revealed small but consistent bias, with CNB values slightly higher (+2.89 % and + 2.25 % for raters 1 and 2, respectively). However, discrepancies >10 % were observed in some cases. Tumor characteristics had minimal to no association with scoring variability. Despite excellent statistical agreement, clinically significant variability in Ki-67 scoring may occur. These findings support interpreting Ki-67 as a continuous variable rather than relying on fixed cutoffs. Pathologists should consider specimen type and scoring limitations when reporting Ki-67, and may recommend which value is more reliable or suggest retesting when appropriate.
{"title":"Assessment of Ki-67 in breast carcinoma: Interobserver variability and comparison between core needle biopsy and resection specimens","authors":"Hristo Milev , Desislava Dimitrova , Ivan Ivanov","doi":"10.1016/j.anndiagpath.2025.152571","DOIUrl":"10.1016/j.anndiagpath.2025.152571","url":null,"abstract":"<div><div>Ki-67 is a nuclear protein linked to cellular proliferation and is used as a prognostic and predictive biomarker in breast carcinoma. However, variability in its assessment limits its clinical utility. This study evaluated interobserver reproducibility in Ki-67 scoring and compared proliferative indices between core needle biopsy (CNB) and corresponding resection specimens in invasive breast carcinoma. Sixty-three cases with matched CNB and resection specimens were retrospectively analyzed. Ki-67 immunohistochemistry was independently evaluated by two pathologists using manual image-based counting. Interobserver agreement and CNB–resection concordance were assessed using the intraclass correlation coefficient (ICC), Cohen's kappa, Bland–Altman analysis, and Spearman's correlation. Tumor characteristics were analyzed for their association with variability. Interobserver agreement was excellent, with ICCs of 0.89 for CNB and 0.91 for resection specimens. Cohen's kappa for binary classification (<20 % vs. ≥20 %) showed moderate agreement for CNB (κ = 0.54) and substantial agreement for resections (κ = 0.78). Bland–Altman analysis revealed small but consistent bias, with CNB values slightly higher (+2.89 % and + 2.25 % for raters 1 and 2, respectively). However, discrepancies >10 % were observed in some cases. Tumor characteristics had minimal to no association with scoring variability. Despite excellent statistical agreement, clinically significant variability in Ki-67 scoring may occur. These findings support interpreting Ki-67 as a continuous variable rather than relying on fixed cutoffs. Pathologists should consider specimen type and scoring limitations when reporting Ki-67, and may recommend which value is more reliable or suggest retesting when appropriate.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152571"},"PeriodicalIF":1.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.anndiagpath.2025.152568
Taylor Barr, Erik Washburn, Guoli Chen, Xiaobang Hu
Gallbladder metastases are rare and the clinical presentations are often nonspecific. Intra-operative gross and frozen section diagnosis can be particularly challenging. Here we present three cases and reviewed the patients' clinical, gross, frozen, and final pathology findings. Patient one is a 59-year-old male with a history of clear cell renal cell carcinoma status post partial nephrectomy seven years ago. Surveillance imaging showed two small gallbladder polyps. Intra-operative gross examination showed gallbladder with a firm, polypoid area and two detached nodules. Frozen sections of the polypoid area showed histiocytic appearing inflammation and was interpreted as chronic cholecystitis. Permanent sections showed similar morphology, but positive pancytokeratin and PAX8 immunostaining confirmed metastatic renal cell carcinoma. Interestingly, sections of the detached nodules showed better tumor morphology. Patient two is an 81-year-old male with a history of urothelial carcinoma status post transurethral resection two years ago. He presented with right upper quadrant pain, and imaging showed emphysematous cholecystitis. The gallbladder was unremarkable grossly; however, histologic sections showed metastatic urothelial carcinoma. Patient three is a 55-year-old female with a history of metastatic melanoma three years ago. PET/CT showed a stable FDG-avid gallbladder lesion. Grossly the gallbladder wall showed pigmented areas and histologic sections showed metastatic melanoma. Our study shows that the clinical, gross, and frozen section diagnosis of gallbladder metastases can be challenging. Avoiding a diagnostic error will likely entail an integrated approach, inclusive of a thorough review of clinical history, a detailed gross inspection and adequate tissue sampling.
{"title":"Metastases to the gallbladder: Challenges of clinical and frozen section diagnosis","authors":"Taylor Barr, Erik Washburn, Guoli Chen, Xiaobang Hu","doi":"10.1016/j.anndiagpath.2025.152568","DOIUrl":"10.1016/j.anndiagpath.2025.152568","url":null,"abstract":"<div><div>Gallbladder metastases are rare and the clinical presentations are often nonspecific. Intra-operative gross and frozen section diagnosis can be particularly challenging. Here we present three cases and reviewed the patients' clinical, gross, frozen, and final pathology findings. Patient one is a 59-year-old male with a history of clear cell renal cell carcinoma status post partial nephrectomy seven years ago. Surveillance imaging showed two small gallbladder polyps. Intra-operative gross examination showed gallbladder with a firm, polypoid area and two detached nodules. Frozen sections of the polypoid area showed histiocytic appearing inflammation and was interpreted as chronic cholecystitis. Permanent sections showed similar morphology, but positive pancytokeratin and PAX8 immunostaining confirmed metastatic renal cell carcinoma. Interestingly, sections of the detached nodules showed better tumor morphology. Patient two is an 81-year-old male with a history of urothelial carcinoma status post transurethral resection two years ago. He presented with right upper quadrant pain, and imaging showed emphysematous cholecystitis. The gallbladder was unremarkable grossly; however, histologic sections showed metastatic urothelial carcinoma. Patient three is a 55-year-old female with a history of metastatic melanoma three years ago. PET/CT showed a stable FDG-avid gallbladder lesion. Grossly the gallbladder wall showed pigmented areas and histologic sections showed metastatic melanoma. Our study shows that the clinical, gross, and frozen section diagnosis of gallbladder metastases can be challenging. Avoiding a diagnostic error will likely entail an integrated approach, inclusive of a thorough review of clinical history, a detailed gross inspection and adequate tissue sampling.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152568"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.anndiagpath.2025.152570
Badr AbdullGaffar , Fatma B. Zarooni , Khalid Bamakramah
Intestinal-type adenomas of the ampullary duodenum are well-characterized and recognized entities, sharing similar clinicopathologic features to conventional colonic adenomas. However, gastric-type adenomas arising from the duodenal ampulla are less recognized and characterized due to limited available data. Our main aim is to investigate the clinical, histopathologic, histochemical and immunohistochemical features of gastric-type ampullary adenomas. We aim to compare gastric-type adenomas with intestinal-type adenomas and inflammatory hyperplastic reactive-type polyps of the ampullary duodenum. We have conducted a retrospective review study of ampullary polyps over 15-years. We found 17 patients [age range: 22–84, average age: 51.0 years, male to female ratio: 1.1:1.0] with polypoid lesions of the ampullary duodenum. Four lesions (24 %) were gastric-type adenomas [age range: 46–84, average age: 63 years, male to female ratio: 1.0:3.0, average size: 1.0 cm], eight lesions (47 %) were intestinal-type adenomas [age range: 22–76, average age: 45 years, male to female ratio: 1.5:1.0, average size: 1.2 cm], and five lesions (29 %) were reactive inflammatory hyperplastic polyps [age range: 41–76, average age: 53 years, male to female ratio: 1.5:1.0, average size: 0.7 cm]. One of the gastric-type adenomas was pure pyloric gland adenoma, one was pure foveolar adenoma, whereas two were mixed adenomas showing equal proportions of foveolar and pyloric cytoarchitectural features. The foveolar adenoma showed luminal mucin cap and expressed MUC5AC, the pyloric gland adenoma lacked apical mucin cap and expressed MUC6, whereas the mixed adenomas equally coexpressed MUC6 and MUC5AC. The intestinal-type adenomas expressed MUC2 and CDX2, but lacked MUC5AC and MUC6. Three gastric-type adenomas were originally misinterpreted as reactive polyps, whereas two other reactive polyps were originally misinterpreted as intestinal-type adenomas. Three patients with gastric-type adenomas had multiple sporadic colonic adenomas, and one recurred. Four patients with intestinal-type adenomas had colonic adenomas, three of which had familial adenomatous polyposis with recurrence, and one had sporadic colonic adenomas with recurrence. The reactive polyps were not associated with colonic adenomas and did not recur. Gastric-type adenomas are not uncommon among ampullary polyps when carefully examined. They should be distinguished from reactive polyps, because similar to intestinal-type adenomas, they are neoplastic polyps with dysplasia and a risk of recurrence.
{"title":"Gastric-type ampullary adenomas","authors":"Badr AbdullGaffar , Fatma B. Zarooni , Khalid Bamakramah","doi":"10.1016/j.anndiagpath.2025.152570","DOIUrl":"10.1016/j.anndiagpath.2025.152570","url":null,"abstract":"<div><div>Intestinal-type adenomas of the ampullary duodenum are well-characterized and recognized entities, sharing similar clinicopathologic features to conventional colonic adenomas. However, gastric-type adenomas arising from the duodenal ampulla are less recognized and characterized due to limited available data. Our main aim is to investigate the clinical, histopathologic, histochemical and immunohistochemical features of gastric-type ampullary adenomas. We aim to compare gastric-type adenomas with intestinal-type adenomas and inflammatory hyperplastic reactive-type polyps of the ampullary duodenum. We have conducted a retrospective review study of ampullary polyps over 15-years. We found 17 patients [age range: 22–84, average age: 51.0 years, male to female ratio: 1.1:1.0] with polypoid lesions of the ampullary duodenum. Four lesions (24 %) were gastric-type adenomas [age range: 46–84, average age: 63 years, male to female ratio: 1.0:3.0, average size: 1.0 cm], eight lesions (47 %) were intestinal-type adenomas [age range: 22–76, average age: 45 years, male to female ratio: 1.5:1.0, average size: 1.2 cm], and five lesions (29 %) were reactive inflammatory hyperplastic polyps [age range: 41–76, average age: 53 years, male to female ratio: 1.5:1.0, average size: 0.7 cm]. One of the gastric-type adenomas was pure pyloric gland adenoma, one was pure foveolar adenoma, whereas two were mixed adenomas showing equal proportions of foveolar and pyloric cytoarchitectural features. The foveolar adenoma showed luminal mucin cap and expressed MUC5AC, the pyloric gland adenoma lacked apical mucin cap and expressed MUC6, whereas the mixed adenomas equally coexpressed MUC6 and MUC5AC. The intestinal-type adenomas expressed MUC2 and CDX2, but lacked MUC5AC and MUC6. Three gastric-type adenomas were originally misinterpreted as reactive polyps, whereas two other reactive polyps were originally misinterpreted as intestinal-type adenomas. Three patients with gastric-type adenomas had multiple sporadic colonic adenomas, and one recurred. Four patients with intestinal-type adenomas had colonic adenomas, three of which had familial adenomatous polyposis with recurrence, and one had sporadic colonic adenomas with recurrence. The reactive polyps were not associated with colonic adenomas and did not recur. Gastric-type adenomas are not uncommon among ampullary polyps when carefully examined. They should be distinguished from reactive polyps, because similar to intestinal-type adenomas, they are neoplastic polyps with dysplasia and a risk of recurrence.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152570"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.anndiagpath.2025.152567
Jing Jia , Ying Zhou , Ajin Hu , Yuxiang Wang , Yue Wang , Yan Liu , Xinlan Shi , Caixia Ren , Congrong Liu
In this study, to evaluate the diagnostic accuracy and clinical reliability of intraoperative frozen sections (IFS) compared with paraffin-embedded sections (PS) in guiding surgical decision-making for endometrial carcinoma (EC) patients, we retrospectively analyzed the clinical data of 165 EC patients who underwent surgical resection with IFS evaluation. Diagnostic concordance between IFS and final PS pathology was assessed across six parameters: 1) tumor histological type, 2) tumor grade, 3) depth of myometrial invasion (MI), 4) cervical stromal involvement, 5) lymphovascular space invasion (LVSI) status, and 6) lymph node metastasis risk stratification. The data were statistically analyzed using Kappa coefficient and chi-square test. The IFS results concurred with the PS in 95.3 % for histological type (kappa 0.859, p = 0.125), 94.0 % for tumor grade (kappa 0.848, p = 0.039), 97.6 % for depth of MI (kappa 0.929, p = 0.046), 95.2 % for cervical involvement (kappa 0.481, p = 0.008), and 88.5 % for LVSI (kappa 0.155, p < 0.001). Risk assessment was accurately determined in 92.1 % of cases (kappa 0.796, p < 0.001). Final histopathology confirmed pelvic and paraaortic lymph node metastases in two patients whose metastatic risk had been underestimated based on the IFS risk stratification. High-intermediate/high-risk patients showed significantly higher lymph node involvement compared to low/intermediate-risk groups. IFS analysis demonstrates reliability and clinical utility in assessing disease extent and guiding surgical decisions regarding the need for complete staging procedures in EC patients.
本研究为评价术中冷冻切片（IFS）与石蜡包埋切片（PS）在指导子宫内膜癌（EC）患者手术决策中的诊断准确性和临床可靠性，回顾性分析了165例经IFS评估的子宫内膜癌手术切除患者的临床资料。IFS与最终PS病理诊断的一致性通过以下六个参数进行评估：1)肿瘤组织学类型，2)肿瘤分级，3)肌层浸润深度（MI）， 4)宫颈间质累及，5)淋巴血管间隙浸润（LVSI）状态，6)淋巴结转移风险分层。采用Kappa系数和卡方检验对数据进行统计学分析。IFS结果与PS的一致性为：组织学类型95.3% (kappa 0.859, p = 0.125)，肿瘤分级94.0% (kappa 0.848, p = 0.039)，心肌梗死深度97.6% (kappa 0.929, p = 0.046)，宫颈受损伤95.2% (kappa 0.481, p = 0.008), LVSI 88.5% （kappa 0.155, p = 0.046）
{"title":"Accuracy and clinical value of intraoperative frozen section assessment in endometrial carcinoma","authors":"Jing Jia , Ying Zhou , Ajin Hu , Yuxiang Wang , Yue Wang , Yan Liu , Xinlan Shi , Caixia Ren , Congrong Liu","doi":"10.1016/j.anndiagpath.2025.152567","DOIUrl":"10.1016/j.anndiagpath.2025.152567","url":null,"abstract":"<div><div>In this study, to evaluate the diagnostic accuracy and clinical reliability of intraoperative frozen sections (IFS) compared with paraffin-embedded sections (PS) in guiding surgical decision-making for endometrial carcinoma (EC) patients, we retrospectively analyzed the clinical data of 165 EC patients who underwent surgical resection with IFS evaluation. Diagnostic concordance between IFS and final PS pathology was assessed across six parameters: 1) tumor histological type, 2) tumor grade, 3) depth of myometrial invasion (MI), 4) cervical stromal involvement, 5) lymphovascular space invasion (LVSI) status, and 6) lymph node metastasis risk stratification. The data were statistically analyzed using Kappa coefficient and chi-square test. The IFS results concurred with the PS in 95.3 % for histological type (kappa 0.859, <em>p</em> = 0.125), 94.0 % for tumor grade (kappa 0.848, <em>p</em> = 0.039), 97.6 % for depth of MI (kappa 0.929, <em>p</em> = 0.046), 95.2 % for cervical involvement (kappa 0.481, <em>p</em> = 0.008), and 88.5 % for LVSI (kappa 0.155, <em>p</em> < 0.001). Risk assessment was accurately determined in 92.1 % of cases (kappa 0.796, p < 0.001). Final histopathology confirmed pelvic and paraaortic lymph node metastases in two patients whose metastatic risk had been underestimated based on the IFS risk stratification. High-intermediate/high-risk patients showed significantly higher lymph node involvement compared to low/intermediate-risk groups. IFS analysis demonstrates reliability and clinical utility in assessing disease extent and guiding surgical decisions regarding the need for complete staging procedures in EC patients.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152567"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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