Modern Pathology最新文献

{"title":"Incidence, Clinicopathologic Features, and Follow-Up Results of human epidermal growth factor receptor-2–Ultralow Breast Carcinoma","authors":"Yan Hu,&nbsp;Daniel Jones,&nbsp;Weiqiang Zhao,&nbsp;Gary Tozbikian,&nbsp;Anil V. Parwani,&nbsp;Zaibo Li","doi":"10.1016/j.modpat.2025.100783","DOIUrl":"10.1016/j.modpat.2025.100783","url":null,"abstract":"<div><div>The preliminary result of DESTINY-Breast06 trial demonstrated the effectiveness of antibody-drug conjugate in patients with human epidermal growth factor receptor-2 (HER2)–ultralow breast carcinoma (BC), defined by the presence of ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining on HER2 immunohistochemistry. In this study, we investigated the pathologic features and clinical outcomes in patients with HER2-ultralow, HER2-null, and HER2-low expression. The incidence of HER2 ultralow was 17.5% (260/1486). The incidence of other groups is as follows: 7.7% for HER2 null, 56.8% for HER2 low, and 18% for HER2 positive. HER2-ultralow cases showed similarity to HER2-low cases but a significant difference from HER2-null cases, including older age (61.1 vs 57.3 years; <em>P</em> = .0099), fewer grade 3 BCs (18.1% vs 53.9%; <em>P</em> &lt; .0001), triple-negative BCs (16.2% vs 42.6%; <em>P</em> &lt; .0001), estrogen receptor (ER)–negative BCs (16.5% vs 47.8%; <em>P</em> &lt; .0001), and progesterone receptor–negative BCs (26.2% vs 54.8%; <em>P</em> &lt; .0001). When cases were stratified based on ER positivity, these differences between HER2-null and HER2-ultralow groups were confined to ER+ but not ER− cases. There were no discernible differences in response to neoadjuvant chemotherapy (n = 125) among HER2-null, HER2-ultralow, and HER2-low BCs. HER2-null/ER−BCs displayed a lower probability of overall survival than HER2-ultralow and HER2-low/ER−BCs, but no statistically significant difference was observed in disease-free survival among the 3 groups. HER2-ultralow BCs exhibit distinct features that align more closely with HER2-low BCs than HER2-null BCs. These findings contribute to the evolving classification of HER2 expression in BC and may have implications for refining treatment strategies in this subgroup.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100783"},"PeriodicalIF":7.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941835","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 Nectin-4 and Trop-2: Implications for Patient Outcomes and Therapy in Penile Cancer","authors":"Jan Niklas Mink ,&nbsp;Markus Eckstein ,&nbsp;Oybek Khalmurzaev ,&nbsp;Alexey Pryalukhin ,&nbsp;Carol Geppert ,&nbsp;Stefan Lohse ,&nbsp;Kristof Bende ,&nbsp;João Lobo ,&nbsp;Rui Henrique ,&nbsp;Hagen Loertzer ,&nbsp;Joachim Steffens ,&nbsp;Carmen Jerónimo ,&nbsp;Heiko Wunderlich ,&nbsp;Julia Heinzelbecker ,&nbsp;Rainer M. Bohle ,&nbsp;Michael Stöckle ,&nbsp;Vsevolod Matveev ,&nbsp;Arndt Hartmann ,&nbsp;Kerstin Junker","doi":"10.1016/j.modpat.2025.100781","DOIUrl":"10.1016/j.modpat.2025.100781","url":null,"abstract":"<div><div>Metastatic penile cancer (PC) continues to have a poor prognosis because of inadequate treatment options. Enfortumab vedotin and sacituzumab govitecan are antibody-drug conjugates (ADCs) that have significantly improved the prognosis of several other tumor types and are, therefore, promising candidates for the successful treatment of metastatic PC. We examined the expression of ADC targets Nectin-4 and Trop-2 in an international multicenter cohort of 203 PC patients both in the primary tumor and in metastases. In addition, we evaluated their prognostic values. Either intermediate or high Nectin-4 membrane expression was found in 28.0% of primary tumors and 18.8% of metastases. The expression in primary tumor decreased significantly with increasing T stage (<em>P</em> ≤ .001). It did not correlate with human papillomavirus status (<em>P</em> = .307) and was not associated with metastasis-free survival, cancer-specific survival, or overall survival. Nectin-4 expression levels at the tumor front and in metastases were significantly associated with each other (<em>P</em> = .005). Trop-2 was detected on the membrane of almost all samples with intermediate or high expression (primary tumor, 98.1%; metastasis, 100%). It was not associated with metastasis-free survival, cancer-specific survival, or overall survival. The expression at tumor front was significantly increased in human papillomavirus–positive tumors (<em>P</em> = .005). Neither Nectin-4 nor Trop-2 was found to be of prognostic value in PC. Enfortumab vedotin therapy seems promising for selected patients with high Nectin-4 expression, which should be confirmed in PC metastases before treatment is considered. Trop-2 is highly expressed in almost all PCs, and therefore, it is a very interesting potential target for sacituzumab govitecan therapy. Both ADCs warrant investigation in clinical trials focusing on PC.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100781"},"PeriodicalIF":7.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948043","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":"Optimal Approaches to Grading Enteropancreatic Neuroendocrine Tumors Using Ki-67 Proliferation Index: Hotspot and Whole-Slide Digital Quantitative Analysis","authors":"Ibrahim Abukhiran ,&nbsp;Azfar Neyaz ,&nbsp;Michaela Kop ,&nbsp;Ihsan Baroudi ,&nbsp;Daniel Christensen ,&nbsp;M-Nasan A. Baki ,&nbsp;Hamdi Surakji ,&nbsp;Nuha Shaker ,&nbsp;Mariel L. Bedell ,&nbsp;Judy Jasser ,&nbsp;Rayan Rammal ,&nbsp;Mustafa Deebajah ,&nbsp;Reetesh Pai ,&nbsp;Liron Pantanowitz ,&nbsp;Andrew Bellizzi","doi":"10.1016/j.modpat.2025.100780","DOIUrl":"10.1016/j.modpat.2025.100780","url":null,"abstract":"<div><div>Grading neuroendocrine tumors using Ki-67 proliferation index (PI) is essential for prognostic assessment and therapeutic decision-making. However, the absence of standardized guidelines has led to methodological inconsistencies across pathology practices. This study aimed to establish more standardized approaches by evaluating grading methodologies and their impact on clinical outcomes using a large multisite data set. We analyzed 734 tissue sections from 325 patients, applying hotspot analysis (HSA) and whole-slide analysis (WSA) to determine Ki-67 PI and World Health Organization grade across primary tumors, regional metastases, and distant metastases. Ki-67 PI was quantified using digital image analysis, with WSA capturing the entire tumor proliferation profile and HSA focusing on the highest proliferating region. A patient-wise analysis was performed to determine the highest grade site per patient, and each case was assigned dual World Health Organization grades based on HSA and WSA. To evaluate the generalizability of our findings, we analyzed an external validation cohort of 74 patients, which was processed with independent image analysis software to ensure reproducibility. The analysis revealed that grading based solely on the primary tumor failed to predict clinical outcomes, as the highest grade site varied among the primary tumor (26.1%), regional metastases (39.1%), and distant metastases (34.8%). Within G2 tumors, survival outcomes differed significantly based on grading methodology, with diffuse G2 tumors (homogeneous Ki-67 distribution) demonstrating significantly worse survival compared with focal G2 tumors (84 vs 136 months; <em>P</em> &lt; .01). Cox proportional hazards regression identified the maximum WSA Ki-67 PI as the sole independent predictor of overall survival, whereas TNM stage and tumor location (pancreatic vs jejunoileal) were not statistically significant. The external validation cohort reinforced these findings, confirming that diffuse G2 tumors exhibited significantly worse progression-free survival than focal G2 tumors. These findings emphasize the necessity of integrating both HSA and WSA for grading neuroendocrine tumors, as well as evaluating all available disease sites to ensure accurate prognostication. Incorporating digital image analysis into grading workflows can provide a more standardized, reproducible approach, improving clinical decision-making and patient outcomes.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100780"},"PeriodicalIF":7.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912237","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":"ELOC-Mutated Renal Cell Carcinoma is a Rare Indolent Tumor With Distinctive Genomic Characteristics","authors":"Jasmine J. Wang ,&nbsp;Rong Rong Huang ,&nbsp;Brian D. Cone ,&nbsp;Sung-Hae L. Kang ,&nbsp;Reza Setoodeh ,&nbsp;Anthony E. Sisk ,&nbsp;Dipti P. Sajed ,&nbsp;Brian M. Shuch ,&nbsp;Adam G. Sowalsky ,&nbsp;Huihui Ye","doi":"10.1016/j.modpat.2025.100777","DOIUrl":"10.1016/j.modpat.2025.100777","url":null,"abstract":"<div><div><em>ELOC</em>-mutated renal cell carcinoma (<em>ELOC</em>-RCC) is a subtype of RCC first recognized by the World Health Organization in 2022, molecularly defined by the presence of <em>ELOC</em> mutations and the lack of <em>VHL</em> mutations. Here, we present an institutional series of <em>ELOC</em>-RCC and provide an in-depth genetic comparison to <em>VHL</em>-null clear cell RCC (<em>VHL</em>-ccRCCs). Among 1209 RCCs in our institutional cytogenetics database, we identified 16 candidate cases that were originally classified as ccRCC and exhibited monosomy 8 and intact chromosome 3p. Seven of these 16 candidate cases were diagnosed as <em>ELOC</em>-RCCs based on histomorphology, immunohistochemistry, and whole-exome sequencing results. By contrast, <em>ELOC</em>-RCCs had a simpler karyotype of monosomy 8 with few other alterations. Adding 6 additional <em>ELOC</em>-RCC cases identified from The Cancer Genome Atlas cohort, all 13 <em>ELOC</em>-RCCs exhibited biallelic <em>ELOC</em> inactivation without <em>VHL</em> mutations. These <em>ELOC</em> mutations (Y79C/L/S/N, E92K, A106D, and C112Vfs∗3) were all located within or close to the VHL-binding domains in ELOC protein; 69% of the <em>ELOC</em>-RCC cases exhibited its characteristic histomorphology. Compared with stage- and grade-matched <em>VHL</em>-ccRCCs, patients with <em>ELOC</em>-RCCs had superior overall survival (hazard ratio, 0.32; 95% confidence intervals, 0.16-0.61; <em>P</em> = .02) and progression-free survival (hazard ratio, 0.16; 95% confidence intervals, 0.06-0.42; <em>P</em> = 0.04). <em>ELOC</em>-RCCs had significantly fewer somatic copy number alterations and a greater abundance of the mutational signature SBS1 than <em>VHL</em>-ccRCCs. <em>ELOC</em>-RCCs lacked common chromosomal alterations or gene mutations seen in ccRCC, including <em>PBRM1</em>, <em>SETD2</em>, <em>BAP1</em>, <em>TSC1</em>, <em>TSC2</em>, or <em>mTOR</em>. Most <em>ELOC-RCC</em>s had linear phylogenetic trees with clonal and truncal <em>ELOC</em> mutations, whereas additional alterations to <em>ELOC</em> or 8q losses occurred as a subclonal event. Although 11 of 13 <em>ELOC</em>-RCCs were confined to the kidney, 2 <em>ELOC</em>-RCCs were high-stage and exhibited a large solid alveolar pattern, tumor necrosis, more somatic copy number alterations, and an additional monoallelic <em>VHL</em> copy loss. Taken together, <em>ELOC</em>-RCCs exhibit distinctive genomic features and indolent behavior in general, supporting it as an independent diagnostic entity.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100777"},"PeriodicalIF":7.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917341","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":"Impact of Hormone Receptor Status and HER2 Expression on Neoadjuvant Targeted Therapy Response in HER2-Positive Breast Cancer: A Multicenter Retrospective Study","authors":"Dechuang Jiao ,&nbsp;Hao Dai ,&nbsp;Junchao Fei ,&nbsp;Dandan Wang ,&nbsp;Jingyang Zhang ,&nbsp;Jiao Zhang ,&nbsp;Jia Wang ,&nbsp;Xuhui Guo ,&nbsp;Yajie Zhao ,&nbsp;Zhenzhen Liu","doi":"10.1016/j.modpat.2025.100778","DOIUrl":"10.1016/j.modpat.2025.100778","url":null,"abstract":"<div><div>Previous studies indicate that HER2 protein expression and hormone receptor (HoR) status affect the sensitivity of HER2-positive breast cancer to neoadjuvant therapy, but it is unclear if sensitivity varies among subgroups defined by HER2 and HoR status. We examined 2 cohorts of patients, aged 18 to 80 years, with HER2-positive early breast cancer who underwent neoadjuvant therapy followed by surgery between January 1, 2009, and December 31, 2022: cohort 1 included 2648 patients, and cohort 2 had 141 patients with RNA expression data. Patients were divided into 4 groups based on immunohistochemical HER2 and HoR status: HER2(3+)/HoR−, HER2(3+)/HoR+, HER2(2+)/HoR−, and HER2(2+)/HoR+. We evaluated total pathological complete response (TpCR, defined as ypT0/is ypN0) rates, disease-free survival (DFS), and variations in PAM50 intrinsic subtypes across different subgroups. In cohort 1, HER2(3+)/HoR− had a higher TpCR rate (44.5%) than HER2(3+)/HoR+ (33.8%) (<em>P</em> &lt; .001), HER2(2+)/HoR− (31.7%) (<em>P</em> = .013), and HER2(2+)/HoR+ (13.8%) (<em>P</em> &lt; .001). DFS was similar across groups (<em>P</em> = .445). Trastuzumab or trastuzumab plus pertuzumab significantly improved TpCR rates and DFS in HER2(3+)/HoR− and HER2(3+)/HoR+ but not in HER2(2+)/HoR− and HER2(2+)/HoR+. Cohort 2 showed significant PAM50 subtype differences across these groups (<em>P</em> &lt; .001). In conclusion, the responsiveness of HER2-positive breast cancer to neoadjuvant targeted therapy is significantly influenced by HER2 expression levels and HoR status, emphasizing the necessity of precision medicine approaches to tailor therapeutic strategies for improved clinical outcomes.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100778"},"PeriodicalIF":7.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906935","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":"Telepathology in Hematopathology Diagnostics: A Collaboration Between the Ho Chi Minh City Oncology Hospital and the University of Texas Health-McGovern Medical School","authors":"Uyen Ly ,&nbsp;Quang Nguyen ,&nbsp;Dang Nguyen ,&nbsp;Tu Thai ,&nbsp;Binh Le ,&nbsp;Duong Gion ,&nbsp;Alexander Banerjee ,&nbsp;Brenda Mai ,&nbsp;Amer Wahed ,&nbsp;Andy Nguyen","doi":"10.1016/j.modpat.2025.100779","DOIUrl":"10.1016/j.modpat.2025.100779","url":null,"abstract":"<div><div>Digital pathology in the form of whole-slide imaging has been used to support diagnostic consultation through telepathology. Previous studies have mostly addressed the technical aspects of telepathology and general pathology consultation. In this study, we focus on our experience at the University of Texas Health-McGovern Medical School in Houston, Texas, in providing hematopathology consultation to the Pathology Department at the Ho Chi Minh City Oncology Hospital in Vietnam. Over a 32-month period, 71 hematopathology cases were submitted for telepathology. Consensus was reached for a definitive diagnosis in 97% of all cases. Diagnostic efficiency significantly improved with average turnaround times reduced by 30% compared with traditional on-site consultations with local pathologists using glass slides. A significant educational metric was recorded for the improved diagnostic skills by the Ho Chi Minh City Oncology Hospital pathologists in the course of this teleconference series. A website has been established in this telepathology project to retain information of the most recently discussed cases for further review after the teleconference. Telepathology provides an effective platform for real-time consultations, allowing remote subspecialty experts to interact with local pathologists for comprehensive case reviews. This process also fosters ongoing education, facilitating knowledge transfer in regions where specialized hematopathology expertise is limited.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100779"},"PeriodicalIF":7.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904302","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":"Meningiomas With Chromosomal Polysomies Reveal Nonrandom Gain of Chromosomes, Distinct Methylation Signature, and Lower Risk of Recurrence","authors":"Erica Vormittag-Nocito ,&nbsp;Drew Duckett ,&nbsp;Rudolph J. Castellani ,&nbsp;Jared T. Ahrendsen ,&nbsp;Xinyan Lu ,&nbsp;Lawrence J. Jennings ,&nbsp;Rimas V. Lukas ,&nbsp;Stephen T. Magill ,&nbsp;Lucas Santana-Santos ,&nbsp;Daniel J. Brat ,&nbsp;Pouya Jamshidi ,&nbsp;Madina Sukhanova","doi":"10.1016/j.modpat.2025.100775","DOIUrl":"10.1016/j.modpat.2025.100775","url":null,"abstract":"<div><div>Meningiomas are the most common primary central nervous system tumors in adults. Although the majority of meningiomas are benign, certain clinical and histopathological factors are associated with an increased risk of tumor progression and recurrence. Advances in genomic characterization of brain tumors have revealed that certain molecular characteristics such as <em>TERT</em> promoter mutation and chromosomal losses on 1p, 6p/q, 9p, 10p/q, 14q, and 18p/q as genomic markers are associated with aggressive behavior. However, the significance of chromosomal polysomies in meningiomas is not clear. We performed a comparative analysis of clinical, cytogenomic, and methylation profiles of a series of 25 meningioma cases with gains of multiple chromosomes and compared with 2 low-risk groups with either no copy number alterations or isolated monosomy 22. No high-risk morphologic subtypes of meningioma were linked to the polysomy group, and there were no differences in the World Health Organization Grade or progression-free survival between the study groups. Noteworthy was a nonrandom pattern of chromosomal gains, with most cases showing tetrasomy of chromosomes 5 and 20 with concurrent trisomy of chromosomes 12 and 17. Methylation profiling showed that meningiomas with polysomies had a distinct methylation signature and were predominantly Merlin-intact meningiomas. These results suggest that meningiomas with multiple polysomies are an uncommon subclass of benign meningioma that have a low rate of progression after resection and a unique genetic architecture.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100775"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907876","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":"Corrigendum to \"Pan-Cancer Molecular Biomarkers: Practical Considerations for the Surgical Pathologist\" [Modern Pathology 38 (2025) 100752].","authors":"Pari Jafari, Megan E Forrest, Jeremy Segal, Peng Wang, Melissa Yuwono Tjota","doi":"10.1016/j.modpat.2025.100773","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100773","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100773"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079114","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":"Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort","authors":"Jorja Braden ,&nbsp;Alison Potter ,&nbsp;Robert V. Rawson ,&nbsp;Nurudeen A. Adegoke ,&nbsp;Serigne N. Lo ,&nbsp;Jordan W. Conway ,&nbsp;Alexander M. Menzies ,&nbsp;Matteo S. Carlino ,&nbsp;George Au-Yeung ,&nbsp;Robyn P.M. Saw ,&nbsp;Andrew J. Spillane ,&nbsp;Kerwin F. Shannon ,&nbsp;Thomas E. Pennington ,&nbsp;Sydney Ch’ng ,&nbsp;David E. Gyorki ,&nbsp;Julie R. Howle ,&nbsp;James S. Wilmott ,&nbsp;Richard A. Scolyer ,&nbsp;Georgina V. Long ,&nbsp;Ines Pires da Silva","doi":"10.1016/j.modpat.2025.100776","DOIUrl":"10.1016/j.modpat.2025.100776","url":null,"abstract":"<div><div>Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination <em>BRAF</em>-targeted therapy with anti–programmed cell death-1 in the neoadjuvant setting. However, research on longitudinal histopathologic changes during this treatment period remains limited. Analysis of hematoxylin and eosin slides from 60 patients across 4 matched neoadjuvant timepoints revealed dynamic changes in a number of treatment response features. Females achieved significantly higher rates of major pathologic response (<em>P</em> = .002) and displayed higher levels of inflammatory fibrosis (<em>P</em> = .04) and hyalinized fibrosis (<em>P</em> = .01). The presence of tertiary lymphoid structures (<em>P</em> = .013) and plasma cells (<em>P</em> = .02) at resection was significantly associated with response. Combination scoring of histopathologic features (composite score and the immune-related pathologic response [irPR] score) was significantly associated with response early during the neoadjuvant period (composite score at week 2 on-treatment, <em>P</em> = .03; high irPR score at week 2 on-treatment, <em>P</em> = .01). A high irPR score at week 2 on-treatment was also found to be significantly associated with a lower chance of recurrence at this early neoadjuvant timepoint (<em>P</em> = .02). Other features associated with a lower likelihood of recurrence included increased hyalinized fibrosis (<em>P</em> = .015) and the presence of extensive lymphocyte density score (<em>P</em> = .01), tertiary lymphoid structures (<em>P</em> = .03), and plasma cells (<em>P</em> = .01). This study deepens our understanding of treatment response markers and their dynamic changes during neoadjuvant therapy. It underscores the significance of these features, particularly given their early emergence and strong associations with response and recurrence.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100776"},"PeriodicalIF":7.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924240","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":"Cytogenomic and Clinicopathologic Comparison of MYC-Positive and MYC-Negative High-Grade B-Cell Lymphoma With 11q Aberration in the Context of Other Aggressive Lymphomas With MYC Rearrangement","authors":"Beata Grygalewicz ,&nbsp;Lukasz M. Szafron ,&nbsp;Laura A. Szafron ,&nbsp;Renata Woroniecka ,&nbsp;Joanna Parada ,&nbsp;German Ott ,&nbsp;Heike Horn ,&nbsp;Barbara Pienkowska-Grela ,&nbsp;Jolanta Rygier ,&nbsp;Natalia Malawska ,&nbsp;Katarzyna Wojtkowska ,&nbsp;Zbigniew Bystydzienski ,&nbsp;Katarzyna Blachnio ,&nbsp;Beata Nowakowska ,&nbsp;Grzegorz Rymkiewicz","doi":"10.1016/j.modpat.2025.100774","DOIUrl":"10.1016/j.modpat.2025.100774","url":null,"abstract":"&lt;div&gt;&lt;div&gt;According to the 2022 World Health Organization Classification, high-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a &lt;em&gt;MYC&lt;/em&gt;-negative lymphoma with 11q duplication and terminal deletion as specific chromosomal aberrations for this neoplasm. However, there is a growing number of reports defying this definition, describing cases with the co-occurrence of 11q aberration and &lt;em&gt;MYC&lt;/em&gt; rearrangement (HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R). This research has 2 aims. First, to compare the unique HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R group of 9 cases with 26 HGBCL-11q cases on chromosomal, mutational, and clinicopathological levels. The second objective was to investigate the association of the new HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R group with HGBCL-11q and 2 other closely related &lt;em&gt;MYC-&lt;/em&gt;positive aggressive lymphoma subtypes: Burkitt lymphoma (BL) (n = 17) and HGBCL, not otherwise specified with &lt;em&gt;MYC&lt;/em&gt;R (n = 10). Genetic results were obtained by classical cytogenetics, fluorescence in situ hybridization, microarrays, and whole exome sequencing. In parallel histopathologic/immunohistochemical analyses (HP/IHC)with flow cytometry (FCM), in conjunction with clinical presentation and treatment outcomes, are presented. Our findings reveal that HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R exists as an independent nosologic entity, distinct from BL and HGBCL-11q at the cytogenetic, molecular, and clinicopathological levels, although it contains common features of both lymphoma subtypes. Common features with BL include following: &lt;em&gt;MYC&lt;/em&gt;R with the immunoglobulin (Ig) genes, patterns of secondary chromosomal aberrations like dup(1q), del(17p), and high number of &lt;em&gt;MYC&lt;/em&gt; and &lt;em&gt;CCND3&lt;/em&gt; mutations. Other BL features are: frequent extranodal abdominal presentation, morphology, germinal center B-cell-like cell of origin determined by IHC and FCM, immunophenotypical features such as MYC(+)/LMO2(–) detected by following flow cytometric features: CD45(+)&lt;sup&gt;weaker&lt;/sup&gt;, more cases with CD43(+) and CD44(–) expression, only expression of IgD and IgM heavy chain, and CD38(+)&lt;sup&gt;higher&lt;/sup&gt; overexpression, which correlates with &lt;em&gt;MYC&lt;/em&gt;R assessed by FCM. Similarity to HGBCL-11q includes the existence of 11q aberration, presence of &lt;em&gt;DDX3X&lt;/em&gt;, &lt;em&gt;ETS1&lt;/em&gt;, &lt;em&gt;GNA13&lt;/em&gt;, &lt;em&gt;NFRKB&lt;/em&gt;, and &lt;em&gt;KMT2D&lt;/em&gt;&lt;em&gt;,&lt;/em&gt; and the lack of &lt;em&gt;TCF3&lt;/em&gt; and &lt;em&gt;ID3&lt;/em&gt; mutations. Additionally, frequent nodal and tonsillar presentation, morphology, germinal center B-cell-like cell of origin, and immunophenotypical features, including CD56(+) expression measured using FCM, are observed, which are associated with &lt;em&gt;NCAM&lt;/em&gt; duplication/amplification on 11q, and pathogenesis not associated with Epstein-Barr virus infection. The distinctive chromosomal change of HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R was the gain or amplification of 3q29. Our cohort of patients with HGBCL-11q,&lt;em&gt;MYC&lt;/em&gt;R had similar relapse-free survival to that of patients with HGBCL-11q and BL, if treated with BL-direct","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 8","pages":"Article 100774"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924241","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}