Modern Pathology最新文献

{"title":"Evidence for Unified Assessment Criteria of HER2 IHC in Colorectal Carcinoma.","authors":"Mark G Evans, Harris B Krause, Joanne Xiu, Andrew Elliott, Emil Lou, Hassan Ghani, Rhonda K Yantiss, Monica Garcia-Buitrago, Yuki Matsubara, Yoshiaki Nakamura, Jinru Shia, Rona Yaeger, Milan Radovich, David A Bryant, Matthew J Oberley, Jaclyn F Hechtman","doi":"10.1016/j.modpat.2024.100654","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100654","url":null,"abstract":"<p><p>HER2 expression is an important biomarker for the management of RAS wild-type metastatic colorectal carcinoma (CRC). Immunohistochemistry (IHC) with reflex in situ hybridization (ISH) is accepted as a standard method of assessment, yet there are currently two sets of criteria used to interpret results: the HERACLES criteria, and the My Pathway criteria. The HERACLES criteria require ISH confirmation when IHC staining is 3+ in 10-49% of cells, while the My Pathway criteria mirror those for gastric HER2 assessment and do not recommend ISH confirmation in the previously referenced scenario. We aimed to assess the prevalence of HER2 3+ heterogeneity and its association with ERBB2 copy number amplification (CNA) to evaluate the necessity of ISH testing when IHC staining is 3+ in <50% of cells. Next-generation sequencing (NGS) of DNA (592-gene panel or whole exome sequencing; WES) was performed for 13 208 colorectal carcinoma (CRC) tumors submitted to Caris Life Sciences (Phoenix, AZ). HER2 (4B5) expression was tested by IHC. A subset of tumors was tested for ERBB2 amplification via chromogenic ISH and/or via NGS (copy number amplification [CNA]). X²/Fisher-Exact tests were applied where appropriate, with p-values adjusted for multiple comparisons (p< 0.05). Of 13 208 CRCs with HER2 IHC, 87.4% (11 541/13 208) were negative for HER2 expression (intensity ≤3+ and < 10% tumor-cell staining) and 11.2% (1 473/13 208) demonstrated at least low HER2 expression (1-2+ and ≥10%). Only 1.5% (194/13 208) of all tested tumors were either positive or heterogeneously positive for HER2 overexpression (3+, ≥10%). Of these, 14% (28/194) had heterogenous HER2 overexpression (3+ staining of 10-49% of cells). Among 22 HER2-positive/heterogenous cases with successful ISH testing, 100% (22/22) demonstrated amplification via ISH. Because the classification of tumors as HER2-positive/heterogenous by IHC correlated very closely with ISH positivity, our results suggest that ISH is likely unnecessary for CRCs with 3+ HER2 overexpression in 10-49% of neoplastic cells.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100654"},"PeriodicalIF":7.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623740","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":"Superficial Neurocristic FET::ETS Fusion Tumor: Expanding the Clinicopathological and Molecular Genetic Spectrum of a Recently Described Entity.","authors":"Carina A Dehner, Laura M Warmke, Brandon Umphress, Faizan Malik, Jeffrey M Cloutier, Josephine K Dermawan, Mike Fritz, Syril Keena T Que, Baptiste Ameline, Karen J Fritchie, Darcy A Kerr, Konstantinos Linos, Daniel Baumhoer, Steven D Billings, Andrew L Folpe","doi":"10.1016/j.modpat.2024.100656","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100656","url":null,"abstract":"<p><p>Superficial neurocristic EWSR1::FLI1 fusion tumor is a very recently described, clinically indolent tumor of the skin and superficial soft tissues, which differs in essentially all ways from Ewing sarcoma, despite harboring an identical fusion event. The EWSR1 and FLI1 genes are members of the FET and ETS gene family, respectively, and very rare examples of Ewing sarcoma harbor alternative FET::ETS fusion events, such as EWSR1::ERG, FUS::FLI1, FUS::ERG, EWSR1::ETV4 and others. We report 5 new cases of this very rare entity, harboring in 3 cases alternative FET::ETS fusion events. The tumors occurred in 2 males and 3 females (median age 14 years; range 8-69 years) and presented as solitary dermal/ subcutaneous masses of the thigh, foot, shoulder, arm and back (median size 1.8 cm; range: 1-2 cm). All patients underwent wide excisions; one received adjuvant chemotherapy. Clinical follow-up on 3 patients (median: 24 months; range: 18-31 months) showed all to be without disease. Morphologically, all tumors displayed typical features of this entity as described, with nests of cytologically bland, diffusely S100 protein/SOX10-positive round cells without mitotic activity, surrounded by fibrous bands containing spindled cells with similar nuclear features. The tumors also showed membranous CD99 (4/5) and nuclear NKX2.2 (3/3) expression. RNA sequencing (4 cases) demonstrated FUS::FLI1, FUS::ERG, EWSR1::FLI1, EWSR1::ERG, and a novel FUS::ETV5. Methylation profiling (4 cases) showed all to cluster with previously reported superficial neurocristic EWSR1::FLI1 fusion tumors and apart from conventional and \"adamantinoma-like\" Ewing sarcoma. Our findings confirm the distinctive clinicopathological features of this very rare, recently described entity and expand its molecular genetic spectrum. Reflecting these findings, we propose modifying the name of this entity to \"superficial neurocristic FET::ETS fusion tumor\".</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100656"},"PeriodicalIF":7.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623904","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":"Stromal tumor infiltrating lymphocytes in hormone receptor positive/HER2 negative metastatic breast cancer.","authors":"Anirudh Pabba, Gitte Zels, Maxim De Schepper, Tatjana Geukens, Karen Van Baelen, Marion Maetens, Sophia Leduc, Ha Linh Nguyen, Amena Mahdami, Josephine Van Cauwenberge, Kristien Borremans, Hava Izci, Sigrid Hatse, Patrick Neven, Hans Wildiers, Elia Biganzoli, Wouter Van Den Bogaert, François Richard, Giuseppe Floris, Christine Desmedt","doi":"10.1016/j.modpat.2024.100650","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100650","url":null,"abstract":"<p><p>The immune landscape of hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC), the most common subtype of BC, remains understudied. This is mainly due to reduced sample acquisition opportunities from metastases as compared to primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UPTIDER (NCT04531696). sTIL were scored as a continuous parameter according to international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2- mBC. ER-status was evaluated on 362 metastases with a cut-off for positivity set at 1% according to ASCO/CAP guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels >1% and >5% respectively. sTIL levels tended to be lower in metastases as compared to their respective primary tumor (Estimate: -2.83, 95%CI: -5.77-0.11, p:0.07). sTIL levels were lower in metastases from invasive lobular carcinoma than in metastases from invasive breast carcinoma of no special type (Estimate: -1.67, 95%CI: -2.35--0.98, p:<0.001). A loss of ER expression was observed in 14% of all metastases, yet a negative ER-status was not significantly associated with increased sTIL levels. Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100650"},"PeriodicalIF":7.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623891","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":"Exploring intratumoral budding in colorectal cancer using computational pathology: a biopsy- based evaluation.","authors":"Sonay Kuş Öztürk, John-Melle Bokhorst, Elias Baumann, Kieran Sheahan, Cornelis J H van de Velde, Corrie A M Marijnen, Geke A P Hospers, Michail Doukas, Michael Vieth, Alessandro Lugli, Iris D Nagtegaal","doi":"10.1016/j.modpat.2024.100655","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100655","url":null,"abstract":"<p><p>Due to insufficient evidence, tumor budding (TB) is not currently evaluated in colorectal cancer (CRC) biopsies. This study investigates TB in CRC by establishing the value of intratumoral budding (ITB) in resection specimens and assessing the feasibility and clinical value of TB in biopsies. TB was assessed using an algorithm in all cases. In a test cohort of 555 primarily surgically treated CRC patients, we assessed the prognostic impact of ITB compared to peritumoral budding (PTB). The distribution of ITB in the uppermost five millimeters of resection specimens was analyzed to validate TB counting in biopsies. We further validated the prognostic and predictive impact of TB in biopsies of 285 rectal cancer patients, focusing on overall survival and response to neoadjuvant therapy. High-grade TB, whether intratumoral or peritumoral and in biopsies or resections, was associated with advanced pathological stage, lymphatic invasion, infiltrative tumor border, and poor overall survival in the test cohort. Superficial ITBs (0-3 mm from the lumen) accurately predicted the final TB grade based on PTB in 87% of tumors, with 87% of tumors having at least one superficial ITB hotspot. ITB (hazard ratio 3.5, 95% CI 1.1-10.8) was an independent predictor of overall survival, unlike PTB. In the validation cohort, TB presence in biopsies significantly reduced the likelihood of achieving a pathological complete response (odds ratio 0.3, 95% CI 0.1-0.7, p=0.007). ITB is as prognostic as PTB, and evaluating both can improve risk stratification in CRC. TB assessment in biopsies can identify poor prognosis and predict response to neoadjuvant therapy.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100655"},"PeriodicalIF":7.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623641","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":"Detection of Alternative Lengthening of Telomeres via Chromogenic in situ Hybridization (ALT-CISH) for the Prognostication of PanNETs and Other Neoplasms.","authors":"Christopher M Heaphy, Simmi Patel, Katelyn Smith, Anne R Wondisford, Michelle L Lynskey, Roderick J O'Sullivan, Kimberly Fuhrer, Xiaoli Han, Raja R Seethala, Ta-Chiang Liu, Dengfeng Cao, Onur Ertunc, Qizhi Zheng, Marija Stojanova, Amer H Zureikat, Alessandro Paniccia, Kenneth Lee, Melanie C Ongchin, James F Pingpank, Herbert J Zeh, Melissa E Hogg, David Geller, J Wallis Marsh, Randall E Brand, Jennifer S Chennat, Rohit Das, Kenneth E Fasanella, Charles Gabbert, Asif Khalid, Kevin McGrath, Anne Marie Lennon, Savreet Sarkaria, Harkirat Singh, Adam Slivka, Dennis Hsu, Janie Y Zhang, Benjamin A Nacev, Marina N Nikiforova, Abigail I Wald, Neel Vaddi, Angelo M De Marzo, Anju H Singhi, Phoenix D Bell, Aatur D Singhi","doi":"10.1016/j.modpat.2024.100651","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100651","url":null,"abstract":"<p><p>Molecular studies have shown ALT to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A CISH assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a multi-institutional cohort of 360 surgically resected PanNETs and correlated with multiple clinicopathologic features, RFS, and FISH results. Separately, 109 leiomyosarcomas (LMS) were evaluated by both CISH and FISH, and, similarly, the prognostic significance of ALT status was assessed. Upon optimization, ALT-CISH was identified in 112 of 360 (31%) primary PanNETs and was 100% concordant with FISH testing. ALT correlated with several adverse prognostic findings and distant metastasis (all p<0.004). The 5-year RFS for patients with ALT-positive PanNETs was 35% as compared to 94% for ALT-negative PanNETs. By multivariate analysis, ALT was an independent prognostic factor for shorter RFS. Similarly, ALT was associated with shorter RFS in LMS patients and, analogous to PanNETs, a negative, independent prognostic factor. ALT-CISH was developed and validated in not only PanNETs, but also sarcomas, specifically LMS. CISH testing has multiple advantages over FISH that facilitate its widespread clinical use in the detection of ALT and prognostication of patients with diverse neoplasms.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100651"},"PeriodicalIF":7.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623722","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":"Weakly supervised multiple instance learning model with generalization ability for clinical adenocarcinoma screening on serous cavity effusion pathology.","authors":"Yupeng Zhang, Xiaolong Zhu, Li Zhong, Jingjing Wu, Jianling Chen, Hongqin Yang, Sheng Zhang, Kun Wang, Saifan Zeng","doi":"10.1016/j.modpat.2024.100648","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100648","url":null,"abstract":"<p><p>Accurate and rapid screening of adenocarcinoma cells in serous cavity effusion is vital in diagnosing the stage of metastatic tumors and providing prompt medical treatment. However, it is often difficult for pathologists to screen serous cavity effusion. Fixed agglutination cell block can help to improve diagnostic sensitivity in malignant tumor cells through analyzing larger volumes of serous cavity effusion, though it could accordingly lead to screening on more cells for pathologists. With the advent of whole slide imaging and development of artificial intelligence, advanced deep learning models are expected to assist pathologists in improving the diagnostic efficiency and accuracy. In this study, so far as we known, it is the first time to use cell block technology combined with a proposed weakly supervised deep learning model with multiple instance learning method to screen serous adenocarcinoma. The comparative experiments were implemented through five-fold cross-validation, and the results demonstrated that our proposed model not only achieves state-of-the-art performance under weak supervision while balancing the number of learnable parameters and computational costs and reduces the workload of pathologists, but also presents a quantitative and interpretable cellular pathological scene of serous adenocarcinoma with superior interpretability and strong generalization capability. The performances and features of the model indicate its effectiveness in the rapid screening and diagnosis of serous cavity effusion and its potential in broad clinical application prospects, e.g., in precision medical applications. Moreover, the constructed two real-world pathological datasets would be the first public WSI datasets of serous cavity effusion with adenocarcinoma based on cell block sections, which can help to assist colleagues.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100648"},"PeriodicalIF":7.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623909","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":"Proximal and classic epithelioid sarcomas are distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial markers, respectively.","authors":"Luca Sigalotti, Anna Maria Frezza, Marta Sbaraglia, Elisa Del Savio, Davide Baldazzi, Beatrice Valenti, Elena Bellan, Ilaria De Benedictis, Michele Doni, Marco Gambarotti, Bruno Vincenzi, Antonella Brunello, Giacomo Giulio Baldi, Emanuela Palmerini, Sandro Pasquali, Maria Elena Ciuffetti, Veronica Varano, Filippo Cappello, Viviana Appolloni, Chiara Pastrello, Igor Jurisica, Alessandro Gronchi, Silvia Stacchiotti, Paolo Giovanni Casali, Angelo Paolo Dei Tos, Roberta Maestro","doi":"10.1016/j.modpat.2024.100647","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100647","url":null,"abstract":"<p><p>Epithelioid sarcoma (ES) is a rare tumor hallmarked by the loss of INI1/SMARCB1 expression. Apart from this alteration, little is known about the biology of ES. Despite recent advances in treatment, the prognosis of ES remains unsatisfactory. To elucidate the molecular underpinnings of ES, and to identify diagnostic biomarkers and potential therapeutic vulnerabilities, we performed an integrated omics profiling (RNA sequencing and methylation array) of 24 primary, untreated ESs. Transcriptome and methylome analysis identified two distinct molecular clusters that essentially corresponded to the morphologic variants of ES, classic ES (C-ES) and the more aggressive proximal ES (P-ES). The P-ES group was characterized by hyperactivation of GATA3 and MYC pathways, with extensive epigenetic rewiring associated with EZH2 overexpression. Both DNA methylation and gene expression analysis indicated a striking similarity with the \"MYC subgroup\" of ATRT, another SMARCB1-deficient tumor, implying a shared molecular background and potential therapeutic vulnerabilities. Conversely, the C-ES group exhibited an endothelial-like molecular profile, with expression of vascular genes and elevated pro-angiogenic SOX17 signaling. Immunohistochemistry validated the overexpression of the chromatin regulators GATA3 (9/12 vs. 0/16) and EZH2 (7/7 vs. 2/6) in P-ESs, and of the vascular factors SOX17 (8/8 vs. 1/10) and N-cadherin (5/9 vs 0/10) in C-ESs. Therefore, these molecules emerge as potential diagnostic tools to fill the gap represented by the lack of ES subtype-specific biomarkers. In summary, our study shows that P-ES and C-ES represent distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial molecular traits, respectively. Besides providing insights into the biology of ES, our study pinpoints subtype-specific biomarkers and potential therapeutic vulnerabilities.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100647"},"PeriodicalIF":7.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567680","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":"Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach.","authors":"Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal","doi":"10.1016/j.modpat.2024.100646","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100646","url":null,"abstract":"<p><p>Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including T_FH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) and PTCL-TBX21 (n=41; 66%), and a significant association (p < 0.02) with overall survival (OS) was reaffirmed. Histopathological assessment showed PTCL-GATA3 cases were characterized by monotonous medium-sized or large transformed cells with a minimal tumor microenvironment (TME) compared to PTCL-TBX21 cases, which consisted of pleomorphic cells in a polymorphous TME (p < 0.05). GEP analysis validated these TME distinctions. Immunophenotypic analysis showed that PTCL-GATA3 cases were predominantly CD4+CD8- and associated with significantly higher LEF1, MYC, and CD30 expression (p < 0.05). PTCL-TBX21 displayed a more diverse biomarker profile with two subgroups: one expressing cytotoxic antigens and enriched in CD8+CD4- or CD8-CD4- phenotype, and another lacking cytotoxic markers but showing a CD4+CD8- phenotype with increased ICOS expression, but devoid of other T_FH markers. The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100646"},"PeriodicalIF":7.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567702","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":"Clinicopathologic Characteristics and Follow-Up Outcomes of Invasive Breast Carcinoma With Different Positive HER2 Fluorescence In Situ Hybridization Patterns: Experience From a Single Academic Institution","authors":"Zaibo Li,&nbsp;Yan Hu,&nbsp;Dan Jones,&nbsp;Weiqiang Zhao,&nbsp;Gary Tozbikian,&nbsp;Anil V. Parwani","doi":"10.1016/j.modpat.2024.100637","DOIUrl":"10.1016/j.modpat.2024.100637","url":null,"abstract":"<div><div>Human epidermal growth factor receptor 2 (HER2)-positive breast carcinoma (BC) encompasses a spectrum of molecular subtypes, characterized by varying <em>HER2/CEP17</em> ratios and <em>HER2</em> copy numbers, influencing responses to anti-HER2 therapy. This study stratified <em>HER2</em> fluorescence in situ hybridization (FISH)-positive patients into 3 distinct groups—group 1 with high copy number (G1-HC: ratio ≥2, copy number ≥6), group 1 with low copy number (G1-LC: ratio ≥2, copy number ≥4 and &lt;6), and group 3 (G3: ratio &lt;2.0, copy number ≥6.0)—and evaluated their clinicopathologic features, response to anti-HER2 therapy, and outcomes. In a cohort of 2702 continuous primary BCs, G1-HC BCs accounted for 304 cases (11.3%), G1-LC for 37 cases (1.4%), and G3 for 75 cases (2.8%). G1-HC BCs were associated with younger age, higher tumor grade, and estrogen receptor negativity compared with G1-LC BCs. Furthermore, G1-HC BCs exhibited increased progesterone receptor negativity and HER2 immunohistochemistry 3+ compared with G1-LC and G3 BCs. Analysis of the subgroup of HER2 immunohistochemistry 2+-only cases (n = 166) showed similar results. Notably, G1-HC patients exhibited significantly enhanced responses to anti-HER2 neoadjuvant chemotherapy compared with G1-LC and G3 patients. Conversely, G1-LC patients displayed a lower likelihood of disease-free status compared with G1-HC and G3 patients, albeit with no significant differences in overall survival, distant metastasis, or local recurrence among the groups. These findings offer valuable clinicopathologic insights into different <em>HER2</em> FISH positive subgroups, potentially informing future criteria for interpreting <em>HER2</em> FISH results.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100637"},"PeriodicalIF":7.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567507","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":"Evaluation of a task specific self-supervised learning framework in digital pathology relative to transfer learning approaches and existing foundation models.","authors":"Tawsifur Rahman, Alexander S Baras, Rama Chellappa","doi":"10.1016/j.modpat.2024.100636","DOIUrl":"https://doi.org/10.1016/j.modpat.2024.100636","url":null,"abstract":"<p><p>An integral stage in typical digital pathology workflows involves deriving specific features from tiles extracted from a tessellated whole slide image. Notably, various computer vision neural network architectures, particularly the ImageNet pre-trained, have been extensively used in this domain. This study critically analyzes multiple strategies for encoding tiles to understand the extent of transfer learning and identify the most effective approach. The study categorizes neural network performance into three weight initialization methods: random, ImageNet-based, and self-supervised learning. Additionally, we propose a framework based on task-specific self-supervised learning (TS-SSL) which introduces a shallow feature extraction method, employing a spatial-channel attention block to glean distinctive features optimized for histopathology intricacies. Across two different downstream classification tasks (patch classification, and weakly supervised whole slide image classification) with diverse classification datasets, including Colorectal cancer histology, Patch Camelyon, PANDA, TCGA and CIFAR-10, our task specific self-supervised encoding approach consistently outperforms other CNN-based encoders. The better performances highlight the potential of task-specific-attention based self-supervised training in tailoring feature extraction for histopathology, indicating a shift from utilizing pretrained models originating outside the histopathology domain. Our study supports the idea that task-specific self-supervised learning allows domain-specific feature extraction, encouraging a more focused analysis.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100636"},"PeriodicalIF":7.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504223","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}