Modern Pathology最新文献

{"title":"Frank Invasion in Tall Cell Carcinoma With Reversed Polarity of the Breast: Report of Two Cases","authors":"Rachel Han ,&nbsp;Fresia Pareja ,&nbsp;Dara S. Ross ,&nbsp;Anne Grabenstetter ,&nbsp;Hannah Y. Wen ,&nbsp;Edi Brogi","doi":"10.1016/j.modpat.2025.100714","DOIUrl":"10.1016/j.modpat.2025.100714","url":null,"abstract":"<div><div>Tall cell carcinoma with reversed polarity (TCCRP) is a rare neoplasm of the breast composed of columnar tumor cells arranged in solid and solid-papillary nests with evidence of apical nuclear polarity. No frank invasion is evident despite the lack of a myoepithelial cell layer throughout the tumor. TCCRP has a triple-negative or hormone receptor-low immunophenotype. Recurrent <em>IDH2</em> R172 hotspot mutation coexisting with genetic alterations in the PI3K pathway characterizes this tumor. Here, we report on 2 postmenopausal patients with TCCRP with frank stromal invasion. <em>IDH2</em> R172 mutations were detected in both tumors by immunohistochemistry. Targeted sequencing of case 2 demonstrated the presence of <em>IDH2</em> R172T and <em>RTEL1</em> E839K mutations. Both patients underwent breast conservation surgery, radiation therapy, and adjuvant endocrine therapy with anastrozole and demonstrated no evidence of disease at 65 and 25 months, respectively. This study suggests that TCCRP may give rise to frank invasive carcinoma, the prognostic significance of which is yet unknown.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100714"},"PeriodicalIF":7.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Color Calibration of Digital Pathology Scanners for Robust Artificial Intelligence–Assisted Cancer Diagnosis","authors":"Xiaoyi Ji ,&nbsp;Richard Salmon ,&nbsp;Nita Mulliqi ,&nbsp;Umair Khan ,&nbsp;Yinxi Wang ,&nbsp;Anders Blilie ,&nbsp;Henrik Olsson ,&nbsp;Bodil Ginnerup Pedersen ,&nbsp;Karina Dalsgaard Sørensen ,&nbsp;Benedicte Parm Ulhøi ,&nbsp;Svein R. Kjosavik ,&nbsp;Emilius A.M. Janssen ,&nbsp;Mattias Rantalainen ,&nbsp;Lars Egevad ,&nbsp;Pekka Ruusuvuori ,&nbsp;Martin Eklund ,&nbsp;Kimmo Kartasalo","doi":"10.1016/j.modpat.2025.100715","DOIUrl":"10.1016/j.modpat.2025.100715","url":null,"abstract":"<div><div>The potential of artificial intelligence (AI) in digital pathology is limited by technical inconsistencies in the production of whole slide images (WSIs). This causes degraded AI performance and poses a challenge for widespread clinical application, as fine-tuning algorithms for each site is impractical. Changes in the imaging workflow can also compromise diagnostic accuracy and patient safety. Physical color calibration of scanners, relying on a biomaterial-based calibrant slide and a spectrophotometric reference measurement, has been proposed for standardizing WSI appearance, but its impact on AI performance has not been investigated. We evaluated whether physical color calibration can enable robust AI performance. We trained fully supervised and foundation model–based AI systems for detecting and Gleason grading prostate cancer using WSIs of prostate biopsies from the STHLM3 clinical trial (n = 3651) and evaluated their performance in 3 external cohorts (n = 1161) with and without calibration. With physical color calibration, the fully supervised system’s concordance with pathologists’ grading (Cohen linearly weighted κ) improved from 0.439 to 0.619 in the Stavanger University Hospital cohort (n = 860), from 0.354 to 0.738 in the Karolinska University Hospital cohort (n = 229), and from 0.423 to 0.452 in the Aarhus University Hospital cohort (n = 72). The foundation model’s concordance improved as follows: from 0.739 to 0.760 (Karolinska), from 0.424 to 0.459 (Aarhus), and from 0.547 to 0.670 (Stavanger). This study demonstrated that physical color calibration provides a potential solution to the variation introduced by different scanners, making AI-based cancer diagnostics more reliable and applicable in diverse clinical settings.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100715"},"PeriodicalIF":7.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin 18.2 Expression in 1404 Digestive Tract Adenocarcinomas Including 1175 Colorectal Carcinomas: Distinct Colorectal Carcinoma Subtypes Are Claudin 18.2 Positive","authors":"Kelsey E. McHugh ,&nbsp;Rish K. Pai ,&nbsp;Robert C. Grant ,&nbsp;Steven Gallinger ,&nbsp;Jon Davison ,&nbsp;Changqing Ma ,&nbsp;Reetesh K. Pai","doi":"10.1016/j.modpat.2025.100712","DOIUrl":"10.1016/j.modpat.2025.100712","url":null,"abstract":"<div><div>Claudin 18.2 (CLDN18.2) immunohistochemical (IHC) expression can be used to select patients with gastric/gastroesophageal junction adenocarcinomas for zolbetuximab (IMAB362) therapy, zolbetuximab (IMAB362) being a monoclonal antibody targeting CLDN18.2. The aim of this study was to correlate IHC expression of CLDN18.2 with clinicopathologic and molecular features in a large series of digestive tract cancers. IHC for CLDN18.2 was performed on tissue microarrays from 1404 adenocarcinomas including 155 gastric/gastroesophageal, 74 pancreatic ductal, and 1175 colorectal (576 in the initial test cohort; 599 in the subsequent validation cohort), and correlated with HER2 and mismatch repair (MMR) status. Cases were scored as CLDN18.2 positive or negative, with positivity defined as moderate-to-strong membranous staining in ≥75% of tumor cells. CLDN18.2 expression was correlated with clinicopathologic and molecular features for all colorectal adenocarcinomas. CLDN18.2 was positive in 39% (61/155) of gastric/gastroesophageal adenocarcinomas, 38% (28/74) of pancreatic ductal adenocarcinomas, and 3.4% (40/1175) of colorectal adenocarcinomas (<em>P</em> &lt; .001). For gastric/gastroesophageal and pancreatic ductal adenocarcinoma, there was no correlation between CLDN18.2 expression and either HER2 or MMR status. In contrast, CLDN18.2-positive colorectal adenocarcinomas had distinct clinicopathologic and molecular features. CLDN18.2-positive colorectal adenocarcinomas were more frequently proximally located and were more often MMR deficient and <em>BRAF</em> V600E positive (all with <em>P</em> &lt; .05). Quantitative pathologic analysis using the digital pathology biomarker QuantCRC (Aiforia) demonstrated marked differences in histologic features between CLDN18.2-positive and CLDN18.2-negative colorectal adenocarcinomas, with CLDN18.2-positive tumors having an increased tumor:stroma ratio and %mucin but decreased %immature stroma in both the test and validation cohorts (all with <em>P</em> &lt; .05). In conclusion, CLDN18.2-positive colorectal adenocarcinomas are frequently MMR deficient and <em>BRAF</em> V600E mutated, and demonstrate distinct histologic features. Future studies addressing the efficacy of zolbetuximab therapy in this subset of colorectal cancers are needed.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100712"},"PeriodicalIF":7.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Response to Anti-HER2 Therapy Using A Multigene Assay","authors":"Nehal Atallah ,&nbsp;Shorouk Makhlouf ,&nbsp;Xingmin Li ,&nbsp;Yuan Zhang ,&nbsp;Nigel P. Mongan ,&nbsp;Emad Rakha","doi":"10.1016/j.modpat.2025.100713","DOIUrl":"10.1016/j.modpat.2025.100713","url":null,"abstract":"<div><div>HER2-positive breast cancer (BC), which constitutes 13% to 15% of cases, shows variable response to anti-HER2 therapies. HER2 positivity, defined as protein overexpression (immunohistochemistry [IHC] score 3+) or equivocal expression (IHC 2+) with evidence of <em>HER</em>2 gene amplification, determines the eligibility for anti-HER2 therapy. The MammaTyper assay (Cerca Biotech GmbH) is an RT-qPCR BC subtyping platform based on the micro RNA expression of <em>ERBB2</em>, <em>ESR1</em>, <em>PGR</em>, and <em>MKI67.</em> This study aimed to evaluate the accuracy of the MammaTyper assay in predicting the response of HER2-positive patients to therapy. A well-characterized HER2-positive BC cohort of 287 cases diagnosed at Nottingham University hospitals between 2006 and 2018 was included. The cohort was divided into 2 groups: a trastuzumab-treated group (n = 159) and a chemotherapy-only treated group (n = 128). Tumor clinicopathologic characteristics were matched between the 2 groups. Cases with discordant HER2 status were validated through staining of surgical excision specimens. <em>ERBB2</em> micro RNA identified 251/287 (87.5%) cases as HER2-positive, 10.8% (31/287) as HER2 low and 1.7% (5/287) as HER2 negative. According to the MammaTyper assay, <em>ERBB2</em>-positive patients treated with anti-HER2 therapy had significantly prolonged 5-year disease-free survival and distant metastasis-free survival (hazard ratio = 0.56, <em>P</em> = .003 and hazard ratio = 0.62, <em>P</em> = .023, respectively). MammaTyper-defined HER2-enriched subtype showed a better response to anti-HER2 therapy compared with IHC-defined subtypes, with significant differences in both 5-year disease-free survival and BC-specific survival (<em>P</em> = .01 and &lt; .001, respectively). Patients who were <em>ERBB2</em> negative did not show a survival difference between the group of patients who were treated with trastuzumab and those who were treated with chemotherapy only (<em>P</em> &gt; .05). Validation analysis revealed that 11/36 <em>ERBB2</em>-negative cases were IHC 2+/ISH positive with very low level of gene amplification and 25 cases were false classified as HER2-positive using current protocols. Combining the MammaTyper assay with IHC to assess HER2 status improves the identification of HER2-positive patients with BC who would benefit from anti-HER2 therapy.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 4","pages":"Article 100713"},"PeriodicalIF":7.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do I Diagnose Fibrolamellar Carcinoma?","authors":"Haukur Einarsson,&nbsp;Rondell P. Graham","doi":"10.1016/j.modpat.2025.100711","DOIUrl":"10.1016/j.modpat.2025.100711","url":null,"abstract":"<div><div>Fibrolamellar carcinoma (FLC) is a unique primary carcinoma of the liver that is characterized by distinct morphologic findings and a recurrent <em>DNAJB1::PRKACA</em> gene fusion. It typically presents in young individuals without underlying liver dysfunction. FLC is difficult to diagnose when based only on morphology, and misdiagnosis is common. Frequent differential diagnoses include conventional hepatocellular carcinoma and intrahepatic cholangiocarcinoma, both of which can show similar morphologic and immunohistochemical features. If based only on molecular analysis, other differential diagnoses have recently emerged, as the <em>DNAJB1::PRKACA</em> fusion has now been reported in cases of intraductal oncocytic papillary neoplasm and intraductal papillary mucinous neoplasm. In this article, we review our diagnostic approach to FLC, which relies on both morphologic and immunohistochemical features, as well as molecular analysis.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 4","pages":"Article 100711"},"PeriodicalIF":7.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse Large B-Cell Lymphoma/High-Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements: A Study of 60 Cases","authors":"Do H. Kim,&nbsp;L. Jeffrey Medeiros,&nbsp;Jie Xu,&nbsp;Guilin Tang,&nbsp;Lianqun Qiu,&nbsp;Sa A. Wang,&nbsp;Chi Y. Ok,&nbsp;Wei Wang,&nbsp;C. Cameron Yin,&nbsp;M. James You,&nbsp;Sofia Garces,&nbsp;Pei Lin,&nbsp;Shaoying Li","doi":"10.1016/j.modpat.2025.100710","DOIUrl":"10.1016/j.modpat.2025.100710","url":null,"abstract":"<div><div>Classification of cases of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) with <em>MYC</em> and <em>BCL6</em> rearrangements, referred to here as <em>BCL6</em> double-hit lymphoma (DHL), is controversial. We assessed 60 cases of <em>BCL6</em>-DHL and compared this cohort to 224 cases of DHL with <em>MYC</em> and <em>BCL2</em> rearrangements (<em>BCL2</em>-DHL) and 217 cases of DLBCL not otherwise specified. Compared with the DLBCL cohort, patients with <em>BCL6</em>-DHL had more aggressive clinical features such as frequent extranodal involvement, high-stage disease, a high International Prognostic Index score, and an elevated serum lactate dehydrogenase level (<em>P</em> &lt; .01 for all). Compared with the <em>BCL2</em>-DHL cohort, patients with <em>BCL6</em>-DHL had similarly aggressive clinical features but a lower frequency of germinal center B-cell (GCB) immunophenotype and <em>MYC</em> and <em>BCL2</em> double expression. Patients with <em>BCL6</em>-DHL showed overall survival (OS) intermediate between patients with DLBCL and <em>BCL2</em>-DHL. Following induction with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, patients with <em>BCL6</em>-DHL demonstrated poor OS similar to patients with <em>BCL2</em>-DHL and worse OS than that of patients with DLBCL (<em>P</em> = .024). However, among patients who received rituximab, etoposide phosphate, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH), there was no significant difference in OS among the 3 groups (<em>P</em> = .146). Gene expression profiling showed that 60% of <em>BCL6</em>-DHL cases had a double-hit (DH)-like signature compared with 10% of DLBCL-GCB and 93% of <em>BCL2</em>-DHL cases. The DH-like signature in <em>BCL6</em>-DHL cases was associated with a GCB immunophenotype. Based on these data, we suggest that <em>BCL6</em>-DHL cases are clinically more aggressive than DLBCL and patients may benefit from a more aggressive therapy than R-CHOP. The data also suggest that <em>BCL6</em>-DHL, as currently defined, is heterogeneous and that neoplasms with a GCB immunophenotype are more likely to have a DH-like signature and behave more aggressively. Last, we suggest that <em>BCL6</em>-DHL cases deserve to be recognized separately in a lymphoma classification to facilitate further understanding of these neoplasms and for optimal patient management.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100710"},"PeriodicalIF":7.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline Pathogenic Variants in Patients with Pancreatic Ductal Adenocarcinoma and Extra-Pancreatic Malignancies: A Nationwide Database Analysis","authors":"Valentyna Kryklyva ,&nbsp;Michael J. Pflüger ,&nbsp;Hicham Ouchene ,&nbsp;Hanneke Volleberg-Gorissen ,&nbsp;Arjen R. Mensenkamp ,&nbsp;Marianne A. Jonker ,&nbsp;Carlijn van de Water ,&nbsp;Iris D. Nagtegaal ,&nbsp;Marjolijn J.L. Ligtenberg ,&nbsp;Lodewijk A.A. Brosens","doi":"10.1016/j.modpat.2025.100709","DOIUrl":"10.1016/j.modpat.2025.100709","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Approximately 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies. In this study, we aimed to determine the prevalence and impact of germline pathogenic variants (gPVs) in patients with PDAC and extra-pancreatic malignancies. Using tissue samples and longitudinal data from a nationwide pathology database, we identified patients with PDAC and a set of 7 extra-pancreatic malignancies to investigate the presence of gPVs in 25 cancer susceptibility genes with targeted next-generation sequencing. Of 473 patients with PDAC and at least 1 extra-pancreatic malignancy, 75 (16%) had gPVs. These were predominantly in <em>ATM</em> (n = 22), <em>CDKN2A</em> (n = 14), <em>BRCA2</em> (n = 10), or <em>CHEK2</em> (n = 10) genes. The combination of PDAC and ovarian carcinoma carried the highest prevalence of gPVs (4 of 10; 40%), followed by PDAC and melanoma (15 of 53; 28%), and PDAC and gastric cancer (2 of 9; 22%). Patients with PDAC and certain extra-pancreatic malignancies carry a higher burden of gPVs than unselected PDAC cohorts. This is a group that very likely benefits from genetic testing because germline status can have important diagnostic and therapeutic implications for affected individuals and their family members.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100709"},"PeriodicalIF":7.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Morphologic, and Genomic Differences in Deep-Penetrating Nevi and Deep-Penetrating Nevus-like Melanomas","authors":"Lu Chen ,&nbsp;Alice Chen ,&nbsp;Natasha Sharma ,&nbsp;Pragi Patel ,&nbsp;Afua Konadu Addo ,&nbsp;Julia Edwin Jeyakumar ,&nbsp;Haya Mary Beydoun ,&nbsp;Shantel Olivares ,&nbsp;David Dittmann ,&nbsp;Erica Vormittag-Nocito ,&nbsp;Lucas Santana dos Santos ,&nbsp;Lawrence Jennings ,&nbsp;Pedram Gerami","doi":"10.1016/j.modpat.2025.100707","DOIUrl":"10.1016/j.modpat.2025.100707","url":null,"abstract":"<div><div>Deep-penetrating nevi (DPNs) are characterized by activating mutations in the MAP kinase and Wnt/β-catenin pathways that result in large melanocytes with increased nuclear atypia, cytoplasmic pigmentation, and often mitotic activity. Together with a lack of maturation, this constellation of findings creates challenges for pathologists to distinguish DPN from DPN-like melanoma. To assess the utility of next-generation sequencing (NGS) in resolving this diagnostic dilemma, we performed NGS studies on 35 lesions including 24 DPNs and 11 DPN-like melanomas to characterize the specific genomic differences between the 2 groups and elucidate the genetic events involved in malignant transformation of DPNs. Compared with DPNs, DPN-like melanomas were clinically larger in size (1.1 vs 0.6 cm, <em>P</em> = .02) and on histopathologic examination more frequently showed high-grade nuclear atypia (11/11 vs 9/24; <em>P</em> = .00052), increased mitotic activity (mean 3.9 vs 1.3 per mm²; <em>P</em> = .0004), sheet-like growth pattern (5/11 vs 2/24; <em>P</em> = .01), and involvement of the subcutis (4/5 vs 3/13; <em>P</em> = .026). From a genomic standpoint, DPN-like melanomas had a higher tumor mutation burden (mean 37.1 vs 7.8 mutations/megabase; <em>P</em> = .002) than DPNs and more frequently harbored <em>NRAS</em> mutation (3/11 vs 1/24; <em>P</em> = .046), whereas <em>MAP2K1</em> in-frame deletions were only identified in DPNs (0/11 vs 5/24). There was no statistically significant difference in the frequency or type of <em>CTNNB1</em> or <em>APC</em> mutations between the 2 groups. Within progression genes, DPN-like melanomas were more frequently found to have pathogenic variants in <em>TERT</em> promoter (7/11 vs 0/24; <em>P</em> &lt; .00001), <em>CDKN2A</em> (4/11 vs 0/24; <em>P</em> = .0008), and protein subunits of the SWI/SNF complex (7/11 vs 3/24; <em>P</em> = .02) compared with DPNs. Our findings provide a framework for employing NGS in the evaluation of deep-penetrating melanocytic tumors.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100707"},"PeriodicalIF":7.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of Histologic Features with Gene Alterations in Pleural Mesothelioma","authors":"Rachel E. Fanaroff ,&nbsp;Soo-Ryum Yang ,&nbsp;Kay See Tan ,&nbsp;Prasad S. Adusumilli ,&nbsp;Francis Bodd ,&nbsp;Anita Bowman ,&nbsp;Jason Chang ,&nbsp;Michael D. Offin ,&nbsp;Allison Reiner ,&nbsp;Natasha Rekhtman ,&nbsp;Valerie W. Rusch ,&nbsp;William D. Travis ,&nbsp;Marjorie G. Zauderer ,&nbsp;Marc Ladanyi ,&nbsp;Jennifer L. Sauter","doi":"10.1016/j.modpat.2025.100706","DOIUrl":"10.1016/j.modpat.2025.100706","url":null,"abstract":"<div><div>Histologic features, including architectural patterns, cytologic features, and 2021 World Health Organization nuclear grade have been shown to have prognostic significance in epithelioid diffuse pleural mesothelioma (DPM). Biphasic and sarcomatoid DPM, regardless of morphology, have worse outcomes. These prognostic findings are well established but the correlation of architectural patterns, cytologic features, and nuclear grade with genetic alterations has not been well studied. To investigate relationships between histologic findings and genomic alterations, 128 treatment-naïve DPM specimens (70% epithelioid, 23% biphasic, and 6.3% sarcomatoid) with next-generation sequencing data were retrospectively reviewed. Alterations in <em>BAP1</em> were the most common genomic alteration (n = 62, 48%), followed by <em>CDKN2A</em> (n = 49, 38%) and <em>NF2</em> (n = 38, 30%). <em>NF2</em> alterations were significantly more frequent in biphasic DPM (53% in biphasic vs 25% in sarcomatoid and 22% in epithelioid DPM; <em>P</em> = .005). In epithelioid DPM, <em>TP53</em> alterations were associated with the presence of prognostically unfavorable histology, including micropapillary or solid architecture, pleomorphic features, and high nuclear grade. Tumors with low tumor-infiltrating lymphocytes (TILs) had a higher rate of <em>BAP1</em> alterations than tumors with higher levels of TILs (67% vs 30%; <em>P</em> = .002). The findings of this study enhance our understanding of the relationships among prognostically significant histologic and molecular features of DPM and provide preliminary data to support increased integration of these findings in clinical diagnosis of pleural mesothelioma.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100706"},"PeriodicalIF":7.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective and Retrospective Analysis of Whole-Slide Images of Sentinel and Targeted Lymph Node Frozen Sections in Breast Cancer","authors":"Qiqi Ye ,&nbsp;Timothy Law ,&nbsp;Dianna Klippel ,&nbsp;Constance Albarracin ,&nbsp;Hui Chen ,&nbsp;Alejandro Contreras ,&nbsp;Qingqing Ding ,&nbsp;Lei Huo ,&nbsp;Laila Khazai ,&nbsp;Lavinia Middleton ,&nbsp;Erika Resetkova ,&nbsp;Aysegul Sahin ,&nbsp;Hongxia Sun ,&nbsp;Keith Sweeney ,&nbsp;William Fraser Symmans ,&nbsp;Yun Wu ,&nbsp;Esther Yoon ,&nbsp;Savitri Krishnamurthy","doi":"10.1016/j.modpat.2025.100708","DOIUrl":"10.1016/j.modpat.2025.100708","url":null,"abstract":"<div><div>Different digital modalities are currently available for frozen section (FS) evaluation in surgical pathology practice. However, there are limited studies that demonstrate the potential of whole-slide imaging (WSI) as a robust digital pathology option for FS diagnosis. In the current study, we compared the diagnostic accuracy achieved with WSI to that achieved with light microscopy (LM) for evaluating FSs of axillary sentinel lymph nodes (SLNs) and clipped lymph nodes (LNs) from patients with breast cancer using 2 modalities. Initially, a retrospective analysis evaluated hematoxylin and eosin (H&amp;E)-stained FSs of 109 SLNs using WSI followed by LM after a washout period ranging from 2 to 6 weeks. Subsequently, a prospective analysis assessed FSs of 132 SLNs using LM by the first pathologist, and then H&amp;E-stained FSs were scanned and interpreted remotely in real time by a different pathologist. In the retrospective analysis, the diagnostic accuracy utilizing WSI ranged from 96% to 99% and exhibited similarity to those achieved with LM, ranging from 94% to 99%. Similarly, the prospective analysis also demonstrated comparable diagnostic accuracy between WSI (96.2%) and LM (97%). Pathologists in the retrospective study required an additional 0.8 to 5.4 minutes to render diagnoses using WSI compared with LM (<em>P</em> &lt; .0001). In the prospective study conducted 2 years later, pathologists only took slightly longer to provide WSI FS diagnoses (3.95 minutes) compared with LM (3.51 minutes) (<em>P</em> &gt; .05). In conclusion, our study indicated that WSI-based evaluation showed comparable diagnostic accuracy to LM for assessing LN FSs. Furthermore, the prospective study demonstrated the feasibility of real-time acquisition of high-quality WSIs for remote FS diagnosis of SLNs. These findings substantiate the promising potential of using WSIs of SLNs and clipped LNs in real-time FS evaluation of patients with breast cancer as a standard-of-care in surgical pathology practice.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 4","pages":"Article 100708"},"PeriodicalIF":7.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}