Modern Pathology最新文献

{"title":"Spatial Cancer-Immune Phenotypes Predict Shorter Recurrence-Free Survival in the No Specific Molecular Profile Molecular Subtype of Endometrial Carcinoma","authors":"Dario de Biase ,&nbsp;Jacopo Lenzi ,&nbsp;Claudio Ceccarelli ,&nbsp;Thais Maloberti ,&nbsp;Marco Grillini ,&nbsp;Camelia Alexandra Coadǎ ,&nbsp;Claudio Zamagni ,&nbsp;Pierandrea De Iaco ,&nbsp;Anna Myriam Perrone ,&nbsp;Donatella Santini ,&nbsp;Martin Köbel ,&nbsp;Cheng-Han Lee ,&nbsp;Giovanni Tallini ,&nbsp;Antonio De Leo","doi":"10.1016/j.modpat.2024.100624","DOIUrl":"10.1016/j.modpat.2024.100624","url":null,"abstract":"<div><div>Compartmentation of the immune response into 3 main spatial cancer-immune phenotypes (SCIs) – inflamed, excluded, and desert – has been proposed as the main predictor of response to immune checkpoint inhibitors in solid tumors. The objective of the study was to define and characterize the SCI in a consecutive series of 213 endometrial carcinomas (ECs) by correlating it with molecular subtypes, clinicopathologic features, and prognosis. Immunohistochemistry (IHC) and next-generation sequencing were used to assign surrogate molecular EC subtypes: <em>POLE</em> mutant (<em>POLE</em>), mismatch repair deficient (MMRd), <em>TP53</em> mutant (p53abn), and no specific molecular profile (NSMP). Immune cell markers (CD20, CD3, CD8, CD68, PD-L1) were assessed by IHC on whole sections and quantified by digital image analysis to define the 3 SCIs. ECs were stratified into 4 molecular subtypes: 17 (8.0%) <em>POLE</em>, 68 (31.9%) MMRd, 42 (19.7%) p53abn, and 86 (40.4%) NSMP. SCI determination showed 105 (49.3%) inflamed, 62 (29.1%) desert, and 46 (25.6%) excluded tumors. The inflamed phenotype was more prevalent in MMRd (64.7%) and <em>POLE</em> (76.5%) subtypes compared with NSMP (45.3%) and p53abn (21.4%). SCI revealed a strong correlation with disease-free survival in NSMP tumors: inflamed 96.2%, desert 83.2%, and excluded 40.5%. The SCI prognostic impact was also maintained in NSMP cases treated with adjuvant therapy resulting in a significant difference in recurrence between the inflamed and excluded phenotypes. To simplify SCI determination, a subset of immune cell markers was selected as appropriate to define the 3 SCI patterns: high intraepithelial CD8 for the inflamed phenotype; CD68, CD20, and PD-L1 to discriminate between desert and excluded tumors. The integration of SCI into molecular classification could be a promising opportunity to improve the prognostic risk stratification of patients and may guide the therapeutic approach, particularly in the NSMP subtype. Thus, the different patterns of immune response are a new prognostic parameter in the NSMP subtype.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100624"},"PeriodicalIF":7.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350235","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":"Histopathologic and Molecular Characterization of IDH-Mutant Prostatic Adenocarcinoma","authors":"Benzion Samueli,&nbsp;Hikmat Al-Ahmadie,&nbsp;Ying-Bei Chen,&nbsp;Anuradha Gopalan,&nbsp;Judy Sarungbam,&nbsp;Satish K. Tickoo,&nbsp;Victor E. Reuter,&nbsp;Samson W. Fine,&nbsp;Jie-Fu Chen","doi":"10.1016/j.modpat.2024.100616","DOIUrl":"10.1016/j.modpat.2024.100616","url":null,"abstract":"<div><div>Gain-of-function isocitrate dehydrogenase (<em>IDH</em>) mutations are pathogenically significant in many tumor types and are actionable in cholangiocarcinoma, low-grade glioma, and acute myeloid leukemia. Rare <em>IDH</em> mutations have been described in prostatic adenocarcinoma (PCa). Recent publications have suggested that psammomatous calcifications in PCa are associated with <em>IDH1</em> mutations. In this retrospective study, we queried our institutional clinical sequencing database (cohort 1), and previously published PCa data sets in cBioPortal (cohort 2). Samples were stratified based on oncogenic hotspot <em>IDH</em> mutations at <em>IDH1</em> R132 and <em>IDH2</em> R140/R172, and other nonhotspot <em>IDH</em> mutations. Seventeen (0.4%) cases were identified from 4033 PCa cases in cohort 1 harboring mutually exclusive oncogenic hotspot <em>IDH1</em> (N = 15, 1 of which was subclonal) or <em>IDH2</em> (N = 2) mutations, and 20 (0.5%) cases had nonhotspot <em>IDH1</em>/<em>2</em> mutations. A histologic review of 13 cases with <em>IDH1</em> hotspot mutations and available material showed grade group 3 or higher disease. Immunohistochemistry was performed on cases with <em>IDH1</em> hotspot mutations when possible and showed AR, PSA, PSMA, and NKX3.1 positive in all the 4 cases stained. In cohort 2, 9 cases (0.3%) harboring <em>IDH1</em> hotspot mutations were identified from 2749 patients, and 9 cases carried nonhotspot <em>IDH1/2</em> mutations. The combined cohorts of 23 PCa cases with clonal <em>IDH1</em> hotspot mutations had no ETS fusions, <em>SPOP</em> hotspot mutations, and somatic or germline alterations in <em>BRCA1/2, ATM, RB1,</em> or <em>AR</em>; 19 cases with successful microsatellite instability testing were all microsatellite stable. Conversely, among 29 cases with nonhotspot <em>IDH</em> mutations, there were 4 with <em>TMPRSS2::ERG</em> fusions, 6 with <em>SPOP</em> hotspot mutations, and 10 with <em>AR</em> amplifications/hotspot mutations; 8 were microsatellite instability high. Notably, two cases with <em>IDH1</em> hotspot mutations had psammomatous calcifications. Our findings provide evidence that <em>IDH1</em> hotspot mutations serve as driver alterations in this rare yet distinct molecular subset of PCa. Further studies are warranted to correlate response to androgen deprivation and IDH inhibitors.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100616"},"PeriodicalIF":7.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350233","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":"Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes—Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS])","authors":"Fnu Aakash ,&nbsp;Savanah D. Gisriel ,&nbsp;Amer M. Zeidan ,&nbsp;John M. Bennett ,&nbsp;Rafael Bejar ,&nbsp;Jan Philipp Bewersdorf ,&nbsp;Uma M. Borate ,&nbsp;Jacqueline Boultwood ,&nbsp;Andrew M. Brunner ,&nbsp;Rena Buckstein ,&nbsp;Hetty E. Carraway ,&nbsp;Jane E. Churpek ,&nbsp;Naval G. Daver ,&nbsp;Amy E. DeZern ,&nbsp;Fabio Efficace ,&nbsp;Pierre Fenaux ,&nbsp;Maria E. Figueroa ,&nbsp;Guillermo Garcia-Manero ,&nbsp;Steven D. Gore ,&nbsp;Peter L. Greenberg ,&nbsp;Sanam Loghavi","doi":"10.1016/j.modpat.2024.100615","DOIUrl":"10.1016/j.modpat.2024.100615","url":null,"abstract":"<div><div>Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of biologically distinct entities characterized by variable degrees of ineffective hematopoiesis. Recently, 2 classification systems (the 5th edition of the World Health Organization Classification of Haematolymphoid tTumours and the International Consensus Classification) further subcharacterized MDS into morphologically and genetically defined groups. Accurate diagnosis and subclassification of MDS require a multistep systemic approach. The International Consortium for MDS (icMDS) summarizes a contemporary, practical, and multimodal approach to MDS diagnosis and classification.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100615"},"PeriodicalIF":7.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350231","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":"RNA Sequencing May Call CEP170::RAD51B Fusion Because of Alignment Artifacts","authors":"Cheng Lei ,&nbsp;Peng Zhou ,&nbsp;Yi Sun ,&nbsp;Qingchun Liang","doi":"10.1016/j.modpat.2024.100597","DOIUrl":"10.1016/j.modpat.2024.100597","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 10","pages":"Article 100597"},"PeriodicalIF":7.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229452","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":"Regulatory Aspects of Artificial Intelligence and Machine Learning","authors":"Liron Pantanowitz ,&nbsp;Matthew Hanna ,&nbsp;Joshua Pantanowitz ,&nbsp;Joe Lennerz ,&nbsp;Walter H. Henricks ,&nbsp;Peter Shen ,&nbsp;Bruce Quinn ,&nbsp;Shannon Bennet ,&nbsp;Hooman H. Rashidi","doi":"10.1016/j.modpat.2024.100609","DOIUrl":"10.1016/j.modpat.2024.100609","url":null,"abstract":"<div><div>In the realm of health care, numerous generative and nongenerative artificial intelligence and machine learning (AI-ML) tools have been developed and deployed. Simultaneously, manufacturers of medical devices are leveraging AI-ML. However, the adoption of AI in health care raises several concerns, including safety, security, ethical biases, accountability, trust, economic impact, and environmental effects. Effective regulation can mitigate some of these risks, promote fairness, establish standards, and advocate for more sustainable AI practices. Regulating AI tools not only ensures their safe and effective adoption but also fosters public trust. It is important that regulations remain flexible to accommodate rapid advances in this field to support innovation and also not to add additional burden to some of our preexisting and well-established frameworks. This study covers regional and global regulatory aspects of AI-ML including data privacy, software as a medical device, agency approval and clearance pathways, reimbursement, and laboratory-developed tests.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100609"},"PeriodicalIF":7.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291430","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":"p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence—A Retrospective Study in a Longitudinal Cohort","authors":"Yen Chen Kevin Ko ,&nbsp;Kelly Yi Ping Liu ,&nbsp;Esther Chen ,&nbsp;Sarah Yuqi Zhu ,&nbsp;Catherine F. Poh","doi":"10.1016/j.modpat.2024.100613","DOIUrl":"10.1016/j.modpat.2024.100613","url":null,"abstract":"<div><div>Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ). Tissue microarrays were constructed from the most representative area of the pathology. Three consecutive sections were sectioned and stained for hematoxylin and eosin, p53 immunohistochemistry, and p16 immunohistochemistry. The staining results were reviewed by 2 pathologists (Y.C.K.K., C.F.P.) blinded to clinical outcome. Samples were categorized into p53 abnormal OED (n = 46), p53 conventional OED (n = 118), and p53 human papillomavirus (HPV) OED (HPV associated) (n = 12) using a previously published pattern-based approach. All cases of p53 HPV OED (HPV associated) were identified in HGLs. In contrast, cases of p53 abnormal OED were observed in mild OED (9.5%), moderate OED (23%), and severe OED/carcinoma in situ (51%). None of the 27 reactive or nondysplastic lesions showed abnormal p53 staining patterns. Among the 135 low-grade lesions, 23 cases (17.0%; 2 mild OEDs and 21 moderate OEDs) progressed to HGL or squamous cell carcinoma, with 11 cases showing progression within the first 3 years. Remarkably, 82% (9/11) of these faster progressors showed abnormal p53 patterns. Survival analysis revealed that p53 abnormal OED had significantly poorer progression-free probability (<em>P</em> &lt; .0001) with hazard ratio of 11.24 (95% CI, 4.26-29.66) compared with p53 conventional OED. Furthermore, p53 abnormal OED had poorer local recurrence–free survival compared with p53 wild-type OED (<em>P</em> = .03). The study supports that OED with p53 abnormal pattern is at high risk for progression and recurrence independent of the dysplasia grade.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100613"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291428","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":"Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery","authors":"Tami Yu-Yu Lin ,&nbsp;Kelly Yi Ping Liu ,&nbsp;Rachel Novack ,&nbsp;Pushwant S. Mattu ,&nbsp;Tony L. Ng ,&nbsp;Lynn N. Hoang ,&nbsp;Eitan Prisman ,&nbsp;Catherine F. Poh ,&nbsp;Yen Chen Kevin Ko","doi":"10.1016/j.modpat.2024.100614","DOIUrl":"10.1016/j.modpat.2024.100614","url":null,"abstract":"<div><div>Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in <em>TP53</em>. The presence of <em>TP53</em> mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery. A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: midepithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, and cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing midepithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), whereas 40 of 79 p53-abnormal cases had positive lymph nodes (<em>P</em> &lt; .001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; <em>P</em> = .008).</div><div>p53-Abnormal OSCCs were significantly more likely to be associated with positive lymph node status than p53 wild-type OSCCs at the time of surgery. Further investigation with long-term follow-up is required to determine its clinical application before surgery planning.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100614"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291426","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":"Unraveling the Molecular Landscape of Uterine Tumor Resembling Ovarian Sex Cord Tumor: Insights From A Clinicopathological, Morphologic, Immunohistochemical, and Molecular Analysis of 35 Cases","authors":"Miroslava Flídrová ,&nbsp;Nikola Hájková ,&nbsp;Jan Hojný ,&nbsp;Jiří Dvořák ,&nbsp;Romana Michálková ,&nbsp;Eva Krkavcová ,&nbsp;Jan Laco ,&nbsp;W. Glenn McCluggage ,&nbsp;Giovanna Giordano ,&nbsp;Enrico Maria Silini ,&nbsp;Květoslava Michalová ,&nbsp;Magdalena Bizoń ,&nbsp;Kristýna Němejcová ,&nbsp;Pavel Dundr ,&nbsp;Michaela Kendall Bártů","doi":"10.1016/j.modpat.2024.100611","DOIUrl":"10.1016/j.modpat.2024.100611","url":null,"abstract":"<div><div>Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving <em>NCOA1</em>-<em>3</em>. We performed a comprehensive clinicopathological, morphologic, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with coexpression of sex cord–stromal, smooth muscle, and epithelial markers, as well as hormone receptors. Next-generation sequencing RNA analysis revealed recurrent <em>NCOA1</em>-<em>3</em> gene fusions in 22/32 analyzed cases (69%), including <em>ESR1</em>::<em>NCOA3</em> (11/22), <em>GREB1</em>::<em>NCOA2</em> (7/22), <em>ESR1</em>::<em>NCOA2</em> (3/22), and <em>GREB1</em>::<em>NCOA1</em> (1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and <em>GREB1</em> alterations, but the <em>NCOA2</em>-altered tumors were associated with pseudoglandular architecture. The <em>GREB1</em>-altered cases occurred in older patients and tended to be more often intramural masses compared with <em>ESR1</em>-altered cases. On the contrary, the <em>ESR1</em>-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a <em>GREB1</em>::<em>NCOA2</em> fusion. Unsupervised hierarchical cluster analysis of our cohort revealed 2 main clusters. The tumors with <em>GREB1</em> or <em>NCOA2</em> fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with <em>ESR1</em>::<em>NCOA3</em> fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100611"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291435","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":"MYC Rearrangement Prediction From LYSA Whole Slide Images in Large B-Cell Lymphoma: A Multicentric Validation of Self-supervised Deep Learning Models","authors":"Charlotte Syrykh ,&nbsp;Valentina Di Proietto ,&nbsp;Eliott Brion ,&nbsp;Christiane Copie-Bergman ,&nbsp;Fabrice Jardin ,&nbsp;Peggy Dartigues ,&nbsp;Philippe Gaulard ,&nbsp;Thierry Jo Molina ,&nbsp;Josette Briere ,&nbsp;Lucie Oberic ,&nbsp;Corine Haioun ,&nbsp;Hervé Tilly ,&nbsp;Charles Maussion ,&nbsp;Mehdi Morel ,&nbsp;Jean-Baptiste Schiratti ,&nbsp;Camille Laurent","doi":"10.1016/j.modpat.2024.100610","DOIUrl":"10.1016/j.modpat.2024.100610","url":null,"abstract":"<div><div>Large B-cell lymphoma (LBCL) is a heterogeneous lymphoid malignancy in which <em>MYC</em> gene rearrangement (<em>MYC</em>-R) is associated with a poor prognosis, prompting the recommendation for more intensive treatment. <em>MYC</em>-R detection relies on fluorescence in situ hybridization method which is time consuming, expensive, and not available in all laboratories. Automating <em>MYC</em>-R detection on hematoxylin-and-eosin–stained whole slide images of LBCL would decrease the need for costly molecular testing and improve pathologists’ productivity. We developed an interpretable deep learning algorithm to detect <em>MYC</em>-R considering recent advances in self-supervised learning and providing an extensive comparison of 7 feature extractors and 6 multiple instance learning models, themselves. Four different multicentric cohorts, including 1247 patients with LBCL, were used for training and validation. The best deep learning model reached an average area under the receiver operating characteristic curve score of 81.9% during crossvalidation on the largest LBCL cohort, and area under the receiver operating characteristic curve scores ranging from 62.2% to 74.5% when evaluated on other unseen cohorts. In addition, we demonstrated that using this model as a prescreening tool (with a false-negative rate of 0%), fluorescence in situ hybridization testing would be avoided in 35% of cases. This work demonstrates the feasibility of developing a medical device to efficiently detect <em>MYC</em> gene rearrangement on hematoxylin-and-eosin–stained whole slide images in daily practice.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100610"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291427","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":"Pathologic Features of Malignancies Presenting as Asymmetry on Mammography","authors":"Mohamed M.H. Kahila ,&nbsp;Allyson L. Chesebro ,&nbsp;Catherine S. Giess ,&nbsp;Esther Rhei ,&nbsp;Xuefei Hong ,&nbsp;Susan C. Lester","doi":"10.1016/j.modpat.2024.100612","DOIUrl":"10.1016/j.modpat.2024.100612","url":null,"abstract":"<div><div>The majority of breast cancers have a solid tumor growth pattern and are seen on mammography as dense masses with defined borders. Cancers detected as asymmetry are rare, and little has been published about their pathologic features. These cancers do not form discrete masses, and a border is not evident. This retrospective case series was undertaken to identify malignancies presenting as asymmetry, to describe their histologic and biologic features and to correlate these features with the mammographic appearance. During the 7.5 years of the study, 18,419 coreneedle biopsies were performed and 42 cases of malignancy presenting as asymmetry were diagnosed (0.2%). The majority were invasive carcinomas (30% or 71%), followed by ductal carcinoma in situ (9% or 21%) and lymphoma (3% or 7%). The invasive carcinomas could be divided into 3 groups: very small unifocal (T1a) carcinomas, larger unifocal carcinomas, and cases with multiple foci of invasion. The latter group had a higher rate of lymph node metastases and more stage III cancers. The invasive carcinomas were predominantly of special histologic types and associated with a minimal stromal response. In contrast, the cases of ductal carcinoma in situ tended to be of higher grade and elicited periductal fibrosis, which likely contributed to the increased density seen on mammography. Although most of the invasive carcinomas were of favorable biologic type (97%) and were stage I (67%), triple-negative carcinomas and stage III carcinomas were also detected. When evaluating core needle biopsies performed for asymmetry, pathologists should be aware that these cancers can have a subtle infiltrative appearance with little or no desmoplastic response, mirroring their appearance by imaging.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100612"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291429","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}