Modern Pathology最新文献

{"title":"Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in patients receiving Neoadjuvant Chemotherapy for HR-Positive HER2-Negative Breast Cancer.","authors":"Thais Perez Vazquez, Rodrigo Gonçalves, Juliana Pierobon Gomes da Cunha, Fernando Wladimir Silva Rivas, Fernando Nalesso Aguiar, Edmund Chada Baracat, José Roberto Filassi","doi":"10.1016/j.modpat.2025.100733","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100733","url":null,"abstract":"<p><p>Breast cancer (BC) presents significant molecular heterogeneity, complicating prognosis and treatment strategies. While molecular testing enhances our understanding of BC, high costs can limit accessibility in certain healthcare settings. This retrospective cohort study evaluates the prognostic value of Magee Equation 3 (ME3) and Residual Cancer Burden (RCB) in patients with HR-positive, HER2-negative BC treated at the Instituto do Câncer do Estado de São Paulo from January 2011 to January 2024. We included 203 women, with a mean age of 50.2 years, diagnosed with HR-positive, HER2-negative BC (stages I-III), who completed neoadjuvant chemotherapy (NAC) followed by surgery. ME3 scores were categorized as low (<18), intermediate (18-25), and high (>25), while RCB was classified into four groups (0, 1, 2, or 3). Associations between ME3 and RCB categories were analyzed using chi-square and Cochran-Mantel-Haenszel tests. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with log-rank tests. Prior to NAC, 60.1% of patients had tumors >5 cm, 69.5% had positive lymph nodes, and 85.7% had invasive carcinoma of non-special type, with a mean Ki67 index of 35.5%. Analysis revealed that 22.2% of patients had ME3 > 25, 39.9% had ME3 18-25, and 37.9% had ME3 < 18. A significant inverse association was found between RCB and ME3 (p<0.0001). At a median follow-up of 91.4 months (range: 8-157 months), significant associations were noted for OS (log-rank p=0.0059) and DFS (log-rank p=0.0028) with ME3 categories; patients with low ME3 showed better outcomes. In patients with RCB-3, those with ME3 < 18 had a lower risk of recurrence compared to those with ME3 18-25 (HR: 4.70, 95% CI 2.00-11.02; p = 0.0004) and ME3 > 25 (HR: 5.18, 95% CI 1.85-14.15; p = 0.0017). Similarly, lower risks of death were observed for ME3 < 18 versus higher ME3 categories. In conclusion, ME3 significantly correlates with OS and DFS, suggesting it may serve as a valuable alternative to molecular assays in resource-limited settings. Combining ME3 with RCB enhances individualized risk stratification, providing a more precise prognostic assessment for patients with high RCB.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100733"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382897","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":"MAD::NUT-fusion sarcoma: A sarcoma class with NUTM1, NUTM2A and NUTM2G fusions and possibly distinctive subtypes.","authors":"David J Papke, John S A Chrisinger, Christopher A French, Anthony Crymes, Thomas C Krivak, Ricardo E Estape, Mahesh Seetharam, Reema A Patel, William N O'Connor, Anthony W Chi, Pablo Gutman, Stephan Singer, Chul Kim, David A Bryant, Matthew J Oberley, Tolulope Adeyelu, Julia A Bridge, Mark G Evans","doi":"10.1016/j.modpat.2025.100729","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100729","url":null,"abstract":"<p><p>NUT-fusion-associated cancers are heterogeneous and include NUT carcinoma and an emerging group with non-BRD4/BRD3/NSD3 fusion partners. Here, we characterized 11 tumors harboring MAD::NUT-fusions (10/11 in females; median age: 48 yr; range: 1-67 yr), all histologically sarcomas. Eight cases were identified via sequencing database review and three were diagnosed prospectively. Eight patients (73%) presented with multifocal disease, including six with disseminated peritoneal tumors; three (27%) presented with solitary colonic, pulmonary, or orbital masses. Nine tumors (82%) harbored NUTM1 fusions, with MXI1 (5/9; 56%), MXD4 (2/9; 22%), and MGA (2/9; 22%). One tumor each harbored MXI1::NUTM2A and MXD4::NUTM2G. The nine MXD4/MXI1-rearranged sarcomas were high-grade, with epithelioid-to-spindle-cell cytomorphology, amphophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Histologic features included infiltrative growth (7/7 assessable tumors), rhabdoid morphology (7/9; 78%), prominent collagen (3/9; 33%), multinucleated tumor cells (2/9; 22%), and myxoid stroma (1/9, 11%). MXD4/MXI1-rearranged sarcomas expressed desmin (3/7; 43%), and keratin(s) (3/7; 43%), and not p63 (6 tumors), CD34 (5), or S-100 (5). The adult MGA::NUTM1-fusion sarcoma exhibited some cytologic overlap with MXD4/MXI1-rearranged sarcomas but showed lower-grade myxoid spindle cell regions, microcystic spaces, and S-100 expression. The pediatric MGA::NUTM1-fusion sarcoma was low-grade with CD34/S-100 co-expression. Immunohistochemistry (IHC) demonstrated NUTM1 expression in NUTM1-rearranged sarcomas (5/5), and weak and no expression in NUTM2A- and NUTM2G-rearranged sarcomas, respectively. Gene expression profiling demonstrated sarcomas with MXD4/MXI1::NUTM1/NUTM2A/NUTM2G fusions clustered separately from NUT carcinoma. Follow-up was available for nine patients (82%; median: 1.8 yr; range: 2 mo-8.2 yr). Four of seven patients with MXD4/MXI-rearranged sarcomas died of disease (median: 1.3 yr; range: 5 mo-4.8 yr), one entered hospice at two months, and one was alive with pericardial masses at 2.8 years. The adult with the MGA::NUTM1-fusion sarcoma died of other causes at 4.5 years; the child was alive without disease at 11 months. We conclude that MAD::NUT-fusions define a sarcoma class distinct from NUT carcinoma. Among this group, MGA::NUTM1-fusion sarcomas might represent a distinctive subset. NUTM1 IHC does not reliably detect NUTM2A/NUTM2G-rearranged sarcomas.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100729"},"PeriodicalIF":7.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374448","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":"Integration of molecular testing with clinical criteria and histopathology improves diagnostic precision in immune-mediated liver diseases.","authors":"Esteban Arroyave, Omar A Saldarriaga, Sundus Bhatti, Isabelle Bergman, Rondell Graham, Michele Tana, Dana Balitzer, Kashif J Khan, Michael Kueht, Heather L Stevenson","doi":"10.1016/j.modpat.2025.100728","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100728","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are immune-mediated liver diseases (IMLDs) that are diagnosed by a combination of clinical, serologic, and histologic features. Diagnosis may be challenging, particularly when patients have mixed features of both AIH and PBC, a disease often called overlap syndrome (OS). In addition, many patients have refractory disease. We hypothesized that adding molecular testing to the current diagnostic criteria would provide an additional tool that could assist in correctly classifying patients. RNA was isolated from liver biopsies from patients with AIH (n=16), PBC (n=13), OS (n=8), drug-induced/serology-negative AIH (AIH-DI/Ser-neg, n=6), or controls (n=10). Gene expression was determined using a nCounter Sprint Profiler, and principal component analysis delineated distinct clusters for patients with an inflammatory profile due to AIH, PBC, and AIH-DI/Ser-neg. Two patients with minimal histologic features of PBC clustered with the control group, and two patients with predominantly AIH and minimal PBC features clustered with the PBC group. A patient with OS who received treatment for both conditions showed no disease progression, whereas a patient with OS treated solely for AIH failed to respond. Conversely, one of the gene signatures from a patient diagnosed with PBC fell within the AIH group. This patient did not respond to treatment with ursodiol and ultimately required liver replacement. These findings suggest that the IMLD initially diagnosed in these patients may have been incorrectly classified. As expected, molecular analysis could not identify a distinct cluster for patients diagnosed with OS, and these had variable gene signatures that fell throughout the identified AIH or PBC groups. In summary, gene expression analysis may assist in confirming the type of IMLD, especially when the diagnosis is unclear. Combining molecular testing with existing criteria could provide an additional diagnostic tool, improving patient care and response to treatment.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100728"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365505","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":"Characterization of esophageal biopsies from stem cell transplant patients with and without esophageal graft-versus-host disease.","authors":"Reem Youssef, Omer Saeed, Jingmei Lin, Iván A González","doi":"10.1016/j.modpat.2025.100727","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100727","url":null,"abstract":"<p><p>Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HSCT). Histologic diagnostic criteria and several grading systems have been described for colonic GVHD; however, for esophageal GVHD (eGVHD) limited reports exist to date. In this study, a total of 130 HSCT patients with esophageal biopsies were included, with a median age of 44 years (2-77) and a male predominance (54.6%). Of these, 82 (63%) had a clinical diagnosis of eGVHD. Cases were divided into two groups: those without apoptotic bodies, dyskeratotic cells or ulceration (group 1, no histologic evidence of eGVHD) (42%) and those with at least one of those features (group 2) (58%). Group 2 cases were associated with extra gastrointestinal tract GVHD (p=0.024), a clinical diagnosis of eGVHD (p=0.001), older age (p<0.001), stem cells derived from peripheral blood (p<0.001), higher number of intraepithelial lymphocytes (p=0.002), presence of acute inflammation (p<0.001) and basal cell hyperplasia (p=0.016). Apoptotic bodies were seen in 65 (89%), dyskeratotic cells in 27 (37%) and an ulcer in 28 (37%) of the group 2 cases. The sensitivity (Sn), specificity (Sp) and accuracy (acc) of the group 2 cases for a clinical diagnosis of eGVHD was 68.3%, 60.4% and 65.4%, respectively. Apoptotic bodies (p=0.012) and dyskeratotic cells (p<0.001) but not ulceration (p=0.881), were associated with a clinical diagnosis of eGVHD. The Sn, Sp and acc for apoptotic bodies, dyskeratotic cells and ulcer were 59.3%, 63.8% and 60.9%, 30.9%, 95.7% and 54.7%, 21.9%, 79.2% and 43.1%, respectively. Cases with only apoptotic bodies or ulceration were considered as possible GVHD, and those with dyskeratotic cells as likely GVHD, which were associated with GVHD specific survival (p=0.030). This study provides a comprehensive characterization of the esophageal histologic findings in HSCT patients. Further studies are needed to corroborate these findings in other patient populations.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100727"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255824","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":"Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis","authors":"Seyed Reza Taha,&nbsp;Fouad Boulos","doi":"10.1016/j.modpat.2024.100665","DOIUrl":"10.1016/j.modpat.2024.100665","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100665"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869554","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":"Evidence for Unified Assessment Criteria of HER2 Immunohistochemistry in Colorectal Carcinoma","authors":"Mark G. Evans ,&nbsp;Harris B. Krause ,&nbsp;Joanne Xiu ,&nbsp;Andrew Elliott ,&nbsp;Emil Lou ,&nbsp;Hassan Ghani ,&nbsp;Rhonda K. Yantiss ,&nbsp;Monica Garcia-Buitrago ,&nbsp;Yuki Matsubara ,&nbsp;Yoshiaki Nakamura ,&nbsp;Jinru Shia ,&nbsp;Rona Yaeger ,&nbsp;Milan Radovich ,&nbsp;David A. Bryant ,&nbsp;Matthew J. Oberley ,&nbsp;Jaclyn F. Hechtman","doi":"10.1016/j.modpat.2024.100654","DOIUrl":"10.1016/j.modpat.2024.100654","url":null,"abstract":"<div><div>Human epidermal growth factor receptor-2 (HER2) expression is an important biomarker for the management of <em>RAS</em> 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 the following 2 sets of criteria used to interpret results: the HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) criteria and the MyPathway criteria. The HER2 Amplification for Colorectal Cancer Enhanced Stratification criteria require ISH confirmation when IHC staining is 3+ in 10% to 49% of cells, whereas the MyPathway 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 <em>ERBB2</em> copy number amplification to evaluate the necessity of ISH testing when IHC staining is 3+ in &lt;50% of cells. Next-generation sequencing of DNA (592-gene panel or whole exome sequencing) was performed for 13,208 CRC tumors submitted to Caris Life Sciences. HER2 (4B5) expression was tested using IHC. A subset of tumors was tested for <em>ERBB2</em> amplification via chromogenic ISH and/or via next-generation sequencing (copy number amplification). χ² tests or Fisher exact tests were applied where appropriate, with <em>P</em> values adjusted for multiple comparisons (<em>P</em> &lt; .05). Of 13,208 CRCs with HER2 IHC, 87.4% (11,541/13,208) were negative for HER2 expression (≤3+ intensity and &lt;10% tumor-cell staining) and 11.2% (1473/13,208) demonstrated at least low HER2 expression (1 to 2+ and ≥10%). Only 1.5% (194/13,208) of all tested tumors were either positive or heterogeneously positive for HER2 overexpression (3+ and ≥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 using IHC correlated very closely with ISH positivity, our results suggest that ISH is likely unnecessary for CRCs with 3+ HER2 overexpression in 10% to 49% of neoplastic cells.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100654"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","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":"Fast Processing of Electron Microscopic Specimen Preserved Ultrastructure of Glomeruli and Electron-Dense Deposits in Diagnostic Renal Biopsies: A Prospective and Retrospective Comparative Study","authors":"Aranza Pinedo ,&nbsp;Prerna Rastogi ,&nbsp;Abdullah Thayyil ,&nbsp;Matthew Gosse ,&nbsp;Amy Trent ,&nbsp;Serena M. Bagnasco ,&nbsp;Avi Rosenberg ,&nbsp;Lois J. Arend ,&nbsp;Dao-Fu Dai","doi":"10.1016/j.modpat.2024.100662","DOIUrl":"10.1016/j.modpat.2024.100662","url":null,"abstract":"<div><div>Optimization of electron microscopy (EM) tissue processing protocols is essential to handle the global increase in the number of renal biopsies requiring EM for accurate diagnosis. The conventional EM processing method (CEM) is the standard method used by &gt;95% of laboratories worldwide and it takes at least 48 to 52 hours for completion. In contrast, a fast-processing EM (FEM) method using microwave irradiation can be completed in 8 hours, allowing EM findings to be reported within 24 hours for most cases. There is widespread concern about the suboptimal quality of the FEM that may compromise its diagnostic roles; however, qualitative and quantitative data supporting the noninferiority of FEM compared with CEM has not been reported. We performed both prospective and retrospective studies. The prospective analysis compares FEM and CEM images from the same biopsy samples. For each case, the tissue was divided into 2 pieces: 1 piece for FEM processing and the second for CEM processing. The retrospective study compares the EM images of renal cases with electron-dense deposits from our archives that were processed either by FEM or CEM. The prospective analysis included 4 cases: lupus membranous nephropathy, IgA nephropathy, immune complex–mediated glomerulonephritis, and acute tubular injury. Both FEM and CEM methods obtained high-resolution images with comparable quality. A quantitative morphometric analysis of the glomerular basement membrane (GBM) in the IgA nephropathy case showed similar GBM thickness when processed by the FEM and the CEM, suggesting that FEM did not affect GBM thickness. The retrospective study of 42 cases with electron-dense deposits showed that the ultrastructural features of electron-dense deposits were indistinguishable between the FEM and the CEM. This included microtubular substructures in immunotactoid glomerulonephritis, the \"fingerprint\" deposits in cryoglobulinemic glomerulonephritis, fibril deposits in the light chain amyloidosis as well as fibrillary glomerulonephritis, with comparable morphometric measurements of the deposits. The FEM is efficient, consistent, reproducible, and delivers comparable high-quality sections and images for diagnostic assessment of renal biopsies, compared with those attained by the CEM while decreasing turnaround time significantly, making it possible to provide faster and accurate diagnostic results.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100662"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693199","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":"Making Pathologists Ready for the New Artificial Intelligence Era: Changes in Required Competencies","authors":"Shoko Vos ,&nbsp;Konnie Hebeda ,&nbsp;Megan Milota ,&nbsp;Martin Sand ,&nbsp;Jojanneke Drogt ,&nbsp;Katrien Grünberg ,&nbsp;Karin Jongsma","doi":"10.1016/j.modpat.2024.100657","DOIUrl":"10.1016/j.modpat.2024.100657","url":null,"abstract":"<div><div>In recent years, there has been an increasing interest in developing and using artificial intelligence (AI) models in pathology. Although pathologists generally have a positive attitude toward AI, they report a lack of knowledge and skills regarding how to use it in practice. Furthermore, it remains unclear what skills pathologists would require to use AI adequately and responsibly. However, adequate training of (future) pathologists is essential for successful AI use in pathology. In this paper, we assess which entrustable professional activities (EPAs) and associated competencies pathologists should acquire in order to use AI in their daily practice. We make use of the available academic literature, including literature in radiology, another image-based discipline, which is currently more advanced in terms of AI development and implementation. Although microscopy evaluation and reporting could be transferrable to AI in the future, most of the current pathologist EPAs and competencies will likely remain relevant when using AI techniques and interpreting and communicating results for individual patient cases. In addition, new competencies related to technology evaluation and implementation will likely be necessary, along with knowing one’s own strengths and limitations in human-AI interactions. Because current EPAs do not sufficiently address the need to train pathologists in developing expertise related to technology evaluation and implementation, we propose a new EPA to enable pathology training programs to make pathologists fit for the new AI era “using AI in diagnostic pathology practice” and outline its associated competencies.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100657"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623644","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":"Stromal Tumor-Infiltrating Lymphocytes in Hormone Receptor–Positive/HER2 Negative Metastatic Breast Cancer","authors":"Anirudh Pabba ,&nbsp;Gitte Zels ,&nbsp;Maxim De Schepper ,&nbsp;Tatjana Geukens ,&nbsp;Karen Van Baelen ,&nbsp;Marion Maetens ,&nbsp;Sophia Leduc ,&nbsp;Ha-Linh Nguyen ,&nbsp;Amena Mahdami ,&nbsp;Josephine Van Cauwenberge ,&nbsp;Kristien Borremans ,&nbsp;Hava Izci ,&nbsp;Sigrid Hatse ,&nbsp;Patrick Neven ,&nbsp;Hans Wildiers ,&nbsp;Elia Biganzoli ,&nbsp;Wouter Van Den Bogaert ,&nbsp;François Richard ,&nbsp;Giuseppe Floris ,&nbsp;Christine Desmedt","doi":"10.1016/j.modpat.2024.100650","DOIUrl":"10.1016/j.modpat.2024.100650","url":null,"abstract":"<div><div>The immune landscape of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer (HR+/HER2− mBC), the most common subtype of BC, remains understudied. This is mainly because of reduced sample acquisition opportunities from metastases as compared with primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UZ/KU Leuven Post-mortem Tissue Donation program to Enhance Research (NCT04531696). sTIL were scored as a continuous parameter according to the international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2− mBC. Estrogen receptor (ER) status was evaluated on 362 metastases with a cutoff value for positivity set at 1% according to the American Society of Clinical Oncology/College of American Pathologists guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels of ≥1% and ≥5%, respectively. sTIL levels tended to be lower in metastases as compared with their respective primary tumors (estimate, -2.83; 95% CI, -5.77 to 0.11; <em>P</em> = .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 to -0.98; <em>P</em> &lt; .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 with all metastases. Although these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provide novel and valuable insights into the state of immune infiltration in patients with HR+/HER2− mBC.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100650"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","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":"OA","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 ,&nbsp;Xiaolong Zhu ,&nbsp;Li Zhong ,&nbsp;Jingjing Wu ,&nbsp;Jianling Chen ,&nbsp;Hongqin Yang ,&nbsp;Sheng Zhang ,&nbsp;Kun Wang ,&nbsp;Saifan Zeng","doi":"10.1016/j.modpat.2024.100648","DOIUrl":"10.1016/j.modpat.2024.100648","url":null,"abstract":"<div><div>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, although it could accordingly lead to screening of 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 diagnostic efficiency and accuracy. In this study, so far as we know, 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 5-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 pathologic 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, eg, in precision medical applications. Moreover, the constructed 2 real-world pathologic data sets would be the first public whole slide imaging data sets of serous cavity effusion with adenocarcinoma based on cell block sections, which can help assist colleagues.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 2","pages":"Article 100648"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}