Modern Pathology最新文献

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Distinct Patterns of GLUT1 Expression in Human Papillomavirus Associated and Human Papillomavirus Independent Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma GLUT1在hpv相关和不依赖hpv的外阴上皮内瘤变和鳞状细胞癌中的不同表达模式
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-07-03 DOI: 10.1016/j.modpat.2025.100836
Gloria Zhang, Bin Yang
{"title":"Distinct Patterns of GLUT1 Expression in Human Papillomavirus Associated and Human Papillomavirus Independent Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma","authors":"Gloria Zhang,&nbsp;Bin Yang","doi":"10.1016/j.modpat.2025.100836","DOIUrl":"10.1016/j.modpat.2025.100836","url":null,"abstract":"<div><div>The expression of GLUT1 in vulvar squamous cell carcinoma (SCC) and its precursors remains largely unknown. We systematically investigated GLUT1 expression in human papillomavirus (HPV)–associated and HPV-independent vulvar intraepithelial neoplasia (VIN) and SCC. Our study had a total of 240 cases, including 40 cases of non-neoplastic vulva, 45 HPV-associated high-grade squamous intraepithelial lesions (HSILs), 65 HPV-independent VINs, and 90 invasive SCCs. Immunohistochemical analysis revealed that GLUT1 was expressed noncontinuously at the basal layer near stromal papillae in most non-neoplastic vulvar squamous epithelium. Overexpression of GLUT1 was observed in 82.2% and 88.9% of HPV-associated HSIL and SCC, respectively, compared with 96.9% and 100% of HPV-independent VIN and SCC. Two distinct patterns of the GLUT1 expression were observed in HPV-associated and HPV-independent VIN and SCC. In HPV-associated HSIL, overexpression of GLUT1 was mainly noted in the upper intermediate layers, accompanied by negative or weak immunostaining in the basal and parabasal layers. Similar patterns were also found in HPV-associated SCC, characterized by increased GLUT1 staining intensity in the centers of tumor sheets or nests with spared basal peripheral layers. Conversely, intense membranous GLUT1 staining was mainly observed in the basal and suprabasal layers in HPV-independent VIN, regardless of p53 status. Similar intense basal and parabasal GLUT1 staining patterns and no or weak staining intensity in central areas were seen in HPV-independent SCCs. In conclusion, overexpression of GLUT1 was found in most vulvar SCCs and their precursors. We identified 2 distinct GLUT1 patterns between HPV-associated and HPV-independent VINs and SCCs. Given its high sensitivity, immunohistochemistry for GLUT1 can be a valuable tool for facilitating accurate diagnosis of VIN, especially the HPV-independent type.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100836"},"PeriodicalIF":7.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564888","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}
引用次数: 0
Revisiting hepatic small vessel neoplasms and anastomosing hemangiomas as a unique capillary liver neoplasm: a 25-case series with pathomolecular correlations. 重新审视肝小血管肿瘤和吻合血管瘤作为一种独特的毛细血管肝脏肿瘤:25例病理分子相关性。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-07-02 DOI: 10.1016/j.modpat.2025.100835
Aurélie Beaufrère, Astrid Laurent-Bellue, Antoinette Lemoine, Agnès Bourillon, Nathalie Sturm, Pierre Gosset, Virginie Cahn, Valérie Vilgrain, Maité Lewin, Valérie Paradis, Catherine Guettier
{"title":"Revisiting hepatic small vessel neoplasms and anastomosing hemangiomas as a unique capillary liver neoplasm: a 25-case series with pathomolecular correlations.","authors":"Aurélie Beaufrère, Astrid Laurent-Bellue, Antoinette Lemoine, Agnès Bourillon, Nathalie Sturm, Pierre Gosset, Virginie Cahn, Valérie Vilgrain, Maité Lewin, Valérie Paradis, Catherine Guettier","doi":"10.1016/j.modpat.2025.100835","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100835","url":null,"abstract":"<p><p>Hepatic small vessel neoplasm (HSVN) and anastomosing hemangioma (AH), are two capillary liver neoplasms that are challenging to differentiate in clinical practice. This study aimed to refine their classification through integrated histopathologic and molecular analyses. We conducted a bicentric retrospective study of 25 cases (15 resections and 10 biopsies). Four liver pathologists independently reviewed histologic and immunohistochemical features. Targeted DNA next generation sequencing and RNA sequencing were performed on 21 and 15 cases, respectively. Seven lesions (28%) were diagnosed as AH, presenting as well-demarcated tumors with fibrotic stroma, often associated with cirrhosis (5/7, 71%). The remaining 18 lesions (72%) were identified as HSVN, typically infiltrative and occurring predominantly in non-cirrhotic livers (78%). Microscopically, HSVN displayed two distinct patterns: (1) a classic pattern (8/18, 44%) composed of small, thin-walled vessels, and (2) a hepatocellular-reactive pattern (7/18, 39%) with small vessels interwoven with regenerative hepatocellular trabeculae. A mixed pattern appeared in 3/18 cases (17%). No cytologic atypia or mitoses were observed. Tumor cells consistently expressed ERG, CD31, and CD34, with Ki67 indices <10% in all cases. Mutations in GNA genes were found in 20 of 21 cases (95%), distributed between GNA14 (81% overall: 4 AH and 13 HSVN, p=0.544) and GNAQ (19% overall: 2 AH and 2 HSVN, p=0.544). Transcriptomic analysis revealed no differentially expressed genes between AH and HSVN. After a median follow-up of 18 months, no recurrence was observed in resected tumors. Tumor growth was noted in three non- or partially resected cases (two AH and one HSVN). In conclusion, despite subtle pathological differences, HSVN and AH exhibit overlapping clinical and molecular features, supporting their reclassification as a single benign entity, namely AH. Notably, some lesions exhibit a hepatocellular-reactive pattern that closely mimics hepatocellular adenoma, posing a significant diagnostic challenge, particularly in biopsy specimens.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100835"},"PeriodicalIF":7.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564889","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}
引用次数: 0
Cyclin D1 Overexpression Predicts Poor Disease-Specific Survival in HPV-independent Vulvar Squamous Cell Carcinoma. Cyclin D1过表达预测hpv不依赖型外阴鳞状细胞癌的不良疾病特异性生存率。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-07-02 DOI: 10.1016/j.modpat.2025.100833
Núria Carreras-Dieguez, Oriol Ordi, Núria Peñuelas, Marta Del Pino, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Lorena Marimon, Naiara Vega, Aureli Torné, Adela Saco, Robert Albero, Lydia Gaba, Natalia Rakislova
{"title":"Cyclin D1 Overexpression Predicts Poor Disease-Specific Survival in HPV-independent Vulvar Squamous Cell Carcinoma.","authors":"Núria Carreras-Dieguez, Oriol Ordi, Núria Peñuelas, Marta Del Pino, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Lorena Marimon, Naiara Vega, Aureli Torné, Adela Saco, Robert Albero, Lydia Gaba, Natalia Rakislova","doi":"10.1016/j.modpat.2025.100833","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100833","url":null,"abstract":"<p><p>The amplification of CCND1 is associated with the development and progression of various cancers. In a recent study, we showed that almost all adverse outcomes in vulvar squamous cell carcinomas (VSCC) occurred in patients with human papillomavirus (HPV)-independent, TP53 mutated tumors harboring CCND1 gains. In this study, we analyzed the association between CCND1 gain, cyclin D1 immunohistochemistry (IHC), and disease-specific survival (DSS) in a series of patients with HPV-independent VSCC. All patients who underwent primary surgery for VSCC at the Hospital Clinic of Barcelona, Spain, from 1975 to 2023 were recruited (\"overall\" cohort, n=139). IHC for p53 and cyclin D1 was performed in all cases. In a subset of patients, we performed DNA sequencing to evaluate CCND1 copy number variations (\"sequencing\" cohort, n=54). Cyclin D1 IHC overexpression (≥50% of tumor cells) had 94% sensitivity and 67% specificity as a surrogate marker of CCND1 gain. In the \"sequencing\" cohort, only CCND1 gains were significantly associated with impaired DSS in the multivariate analysis (HR=4.15, 95%confidence interval (CI): 1.08-5.40; p=0.032), whereas stage or mutant TP53 status did not reach statistical significance. In the \"overall\" cohort, advanced stage (HR=2.41, 95%CI: 1.08-5.39; p=0.032) and cyclin D1 IHC overexpression (HR=4.89, 95%CI: 1.77-18.5; p=0.001) were associated with worse DSS in the multivariate analysis, whereas abnormal p53 IHC was not (HR=5.06, 95%CI: 0.68-647; p=0.138). In conclusion, cyclin D1 overexpression is an acceptable surrogate for CCND1 gain and has a much stronger adverse prognostic impact than altered p53 IHC in patients with HPV-independent VSCC.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100833"},"PeriodicalIF":7.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564887","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}
引用次数: 0
Cover 封面
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-07-01 DOI: 10.1016/S0893-3952(25)00127-9
{"title":"Cover","authors":"","doi":"10.1016/S0893-3952(25)00127-9","DOIUrl":"10.1016/S0893-3952(25)00127-9","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 7","pages":"Article 100830"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634130","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}
引用次数: 0
Whole slide image versus microscope glass slide performance for evaluation of Programmed Death-Ligand 1 (PD-L1) expression in 14 tumor types using PD-L1 IHC 22C3 pharmDx. 利用PD-L1 IHC 22C3 pharmDx评估14种肿瘤类型中程序性死亡配体1 (PD-L1)表达的整片图像和显微镜玻片性能。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-07-01 DOI: 10.1016/j.modpat.2025.100832
Micki Adams, Deanna Moquin, Siena Tabuena-Frolli, Jim Ruvalcaba-Rodarte, Amber Morones, Ryan Marczak, Epiphani Simmons, Stephanie Hund
{"title":"Whole slide image versus microscope glass slide performance for evaluation of Programmed Death-Ligand 1 (PD-L1) expression in 14 tumor types using PD-L1 IHC 22C3 pharmDx.","authors":"Micki Adams, Deanna Moquin, Siena Tabuena-Frolli, Jim Ruvalcaba-Rodarte, Amber Morones, Ryan Marczak, Epiphani Simmons, Stephanie Hund","doi":"10.1016/j.modpat.2025.100832","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100832","url":null,"abstract":"<p><p>Agilent Technologies, Inc. investigated concordance of PD-L1 expression level results (binary: positive/negative) recorded by qualified study readers using microscope glass slide (MGS) and Aperio AT2 scanner-generated whole slide image (WSI) scoring for 14 tumor types and cutoffs. All study readers were qualified by completing Agilent training and certification testing specific to the tumor types and cutoffs they scored for the study. Formalin-fixed, paraffin embedded (FFPE) specimens were stained using the qualitative IHC assay, PD-L1 IHC 22C3 pharmDx, on Autostainer Link 48 and scored using the Tumor Proportion Score (TPS) or Combined Positive Score (CPS) algorithm at predefined cutoffs. The objective was to demonstrate comparable performance of scoring for MGS and WSI. Three study readers determined the numerical score and corresponding PD-L1 expression level for specimens of each tumor type using 1) MGS and 2) WSI viewed with Aperio ImageScope with a ≥14-day washout period between MGS and WSI reads. Agreement between MGS (reference condition) and WSI was evaluated for each individual tumor type and cutoff. Concordance Correlation Coefficient (CCC) analysis was also performed on individual tumor type MGS and WSI numerical score data. MGS and WSI percent agreement results for all individual tumor types and cutoffs were ≥ 89%. CCC value results for all tumor types and cutoffs were ≥ 0.80. The high concordance and the low variability and bias between scoring modalities demonstrates comparable performance between MGS and WSI scoring for PD-L1 expression evaluation across multiple tumor types and cutoffs.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100832"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560456","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}
引用次数: 0
Intratumoral Fibrotic Features Are Associated With Lymph Node Metastasis and Recurrence in Patients With Advanced Colon Cancer 晚期结肠癌患者瘤内纤维化特征与淋巴结转移和复发相关。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-06-24 DOI: 10.1016/j.modpat.2025.100828
Ayako Mine , Maiko Tabuchi , Yasuhiko Nakao , Nazigul Zhumagazhiyeva , Takahiro Motoyama , Keiichi Hashiguchi , Eri Yoshioka , Kanan Matsushima , Junya Shiota , Taro Akashi , Moto Kitayama , Hiroko Inomata , Kayoko Matsushima , Naoyuki Yamaguchi , Takashi Nonaka , Kazuhiko Nakao , Hisamitsu Miyaaki , Yuko Akazawa
{"title":"Intratumoral Fibrotic Features Are Associated With Lymph Node Metastasis and Recurrence in Patients With Advanced Colon Cancer","authors":"Ayako Mine ,&nbsp;Maiko Tabuchi ,&nbsp;Yasuhiko Nakao ,&nbsp;Nazigul Zhumagazhiyeva ,&nbsp;Takahiro Motoyama ,&nbsp;Keiichi Hashiguchi ,&nbsp;Eri Yoshioka ,&nbsp;Kanan Matsushima ,&nbsp;Junya Shiota ,&nbsp;Taro Akashi ,&nbsp;Moto Kitayama ,&nbsp;Hiroko Inomata ,&nbsp;Kayoko Matsushima ,&nbsp;Naoyuki Yamaguchi ,&nbsp;Takashi Nonaka ,&nbsp;Kazuhiko Nakao ,&nbsp;Hisamitsu Miyaaki ,&nbsp;Yuko Akazawa","doi":"10.1016/j.modpat.2025.100828","DOIUrl":"10.1016/j.modpat.2025.100828","url":null,"abstract":"<div><div>Fibrosis is a significant pathological feature of advanced colon adenocarcinomas. However, objective and systematic assessments of fibrosis signatures in colon cancer remain underexplored. This study evaluated the phenotypic histologic features of fibrosis within the tumor, which reflect lymph node (LN) metastasis and predict recurrence, to identify fibrosis signatures in patients with advanced colon adenocarcinoma. Of 499 patients who underwent surgical resection for colorectal cancer, 38 patients with stage T3 colon adenocarcinoma were selected by propensity score matching. Paraffin-embedded tissues were stained with Azan-Mallory and converted to digital pathological images. The histologic phenotypes of fibrosis were quantified based on collagen content and structure in primary tumors using the FibroNest quantitative digital pathology platform. Quantitative fibrosis traits, describing most of the variability between consecutive groups, were integrated into a phenotypic fibrosis composite score (Ph-FCS). Overall, Ph-FCS, which encompasses collagen content, fiber morphology, and fiber structure, differed significantly between the T3 colon cancer with LN metastasis and nonmetastasis groups, distinguishing between the metastasis and nonmetastasis groups with 89.5% sensitivity and 89.5% specificity (area under the curve, 0.95). Among all the parameters, kurtosis, a texture analysis component indicating the concentration of histogram data, was the most significantly different individual factor between the 2 groups. Furthermore, among the 19 patients with LN metastasis, Ph-FCS could distinguish between the recurrence and nonrecurrence groups after chemotherapy with 71.4% sensitivity and 100% specificity (area under the curve, 0.88). Detailed analysis revealed that the number of fiber branches was significantly higher in the recurrence group compared with the nonrecurrence group. In conclusion, among patients with advanced colon cancer who underwent colon surgery, the fibrotic histologic phenotype differed significantly between those with and without LN metastasis, as well as between patients with and without recurrence following chemotherapy. Phenotypic analysis of collagen in nontumor lesions may be an effective method for predicting outcomes.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100828"},"PeriodicalIF":7.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506828","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}
引用次数: 0
Attention-Based Whole-Slide Image Compression Achieves Pathologist-Level Prescreening of Multiorgan Routine Histopathology Biopsies 基于注意力的全片图像压缩实现了病理水平的多器官常规组织病理学活检的预筛选。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-06-23 DOI: 10.1016/j.modpat.2025.100827
Witali Aswolinskiy , Rachel S. van der Post , Michela Campora , Carla Baronchelli , Laura Ardighieri , Simona Vatrano , Jeroen van der Laak , Enrico Munari , Michiel Simons , Iris Nagtegaal , Francesco Ciompi
{"title":"Attention-Based Whole-Slide Image Compression Achieves Pathologist-Level Prescreening of Multiorgan Routine Histopathology Biopsies","authors":"Witali Aswolinskiy ,&nbsp;Rachel S. van der Post ,&nbsp;Michela Campora ,&nbsp;Carla Baronchelli ,&nbsp;Laura Ardighieri ,&nbsp;Simona Vatrano ,&nbsp;Jeroen van der Laak ,&nbsp;Enrico Munari ,&nbsp;Michiel Simons ,&nbsp;Iris Nagtegaal ,&nbsp;Francesco Ciompi","doi":"10.1016/j.modpat.2025.100827","DOIUrl":"10.1016/j.modpat.2025.100827","url":null,"abstract":"<div><div>Screening programs for the early detection of cancers, such as colorectal and cervical cancers, have led to an increased demand for histopathological analysis of biopsies. Advanced image analysis with deep learning has shown the potential to automate cancer detection in digital pathology whole-slide images. In particular, weakly supervised learning can achieve whole-slide image classification without the need for tedious, manual annotations, using only slide-level labels. Here, we used data from n = 12,580 whole-slide images from n = 9141 tissue blocks to train and validate a weakly supervised deep learning approach based on Neural Image Compression with Attention (NIC-A) using labels extracted from pathology reports. We also introduced slide packing, a method that merges tissue from multiple slides of the same tissue block into a single “packed” image linked to block-level labels. NIC-A classifies colon and cervical tissue slides into cancer, high-grade dysplasia, low-grade dysplasia, and normal tissue and detects celiac disease in duodenal biopsies. We validated NIC-A for colon and cervix against panels of 4 and 3 pathologists, respectively, on cohorts from 2 European centers. We show that the proposed approach reaches pathologist-level performance in detecting and classifying abnormalities, suggesting its potential to assist pathologists in prescreening workflows by reducing workload in routine digital pathology diagnostics.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100827"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497496","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}
引用次数: 0
Extragonadal Urinary Tract Neoplasms With Yolk Sac Differentiation: Clinical, Histologic, and Molecular Evidence of Derivation From Underlying Urothelial Carcinoma 卵黄囊分化的性腺外泌尿道肿瘤:源自潜在尿路上皮癌的临床、组织学和分子证据。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-06-21 DOI: 10.1016/j.modpat.2025.100829
Léonie Beauchamp , Roy Elias , Adam D. Toll , Huili Li , Aparna Pallavajjala , Jing Zhu , Ying S. Zou , James R. Eshleman , Pedram Argani , Jonathan I. Epstein , Ezra G. Baraban
{"title":"Extragonadal Urinary Tract Neoplasms With Yolk Sac Differentiation: Clinical, Histologic, and Molecular Evidence of Derivation From Underlying Urothelial Carcinoma","authors":"Léonie Beauchamp ,&nbsp;Roy Elias ,&nbsp;Adam D. Toll ,&nbsp;Huili Li ,&nbsp;Aparna Pallavajjala ,&nbsp;Jing Zhu ,&nbsp;Ying S. Zou ,&nbsp;James R. Eshleman ,&nbsp;Pedram Argani ,&nbsp;Jonathan I. Epstein ,&nbsp;Ezra G. Baraban","doi":"10.1016/j.modpat.2025.100829","DOIUrl":"10.1016/j.modpat.2025.100829","url":null,"abstract":"<div><div>Extragonadal yolk sac tumors are rare and can be difficult to distinguish from somatically derived, non-germ cell tumors such as carcinomas with yolk sac differentiation, and there are very limited data available on this phenomenon in the urinary tract. A cohort of 10 tumors primary to the urinary tract with pure or extensive yolk sac differentiation was assembled to clarify their relationship to germ cell tumors, and herein, we describe the clinical, histologic, and molecular features of these lesions. The predilection for older males (8:2 male:female ratio, mean age = 78 years), the epicenter of disease along the urinary tract mucosa, association with prior pelvic radiation (40%), and frequent previous or subsequent diagnosis of conventional urothelial carcinoma (40%) mirrored the typical clinical and demographic features of urothelial carcinoma. Pathologically, all tumors demonstrated typical morphologic and immunohistochemical features of glandular yolk sac tumors and were not associated with other germ cell tumor subtypes. A subset of cases harbored additional histologic elements including sarcomatoid or squamous features (20%) or conventional urothelial carcinoma (10%). Most tumors showed aggressive clinical behavior with 7/8 cases with available follow-up demonstrating recurrence, metastasis, or death from disease. Molecular analysis, including panel-based DNA sequencing (n = 8) and fluorescence in situ hybridization (n = 2) on a subset of cases, showed no evidence of isochromosome 12p but did reveal recurrent mutations in <em>TP53</em> (8/8, 100%), the <em>TERT</em> promoter (3/8, 38%), and one of several genes involved in chromatin remodeling including <em>KDM6A</em>, <em>CREBBP</em>, and <em>KMT2D</em> (5/8, 63%), and recurrent deletions involving chromosome 9p, including homozygous deletion encompassing the <em>CDKN2A/MTAP</em> locus (3/8, 38%)—a constellation of findings strikingly similar to the established molecular landscape of urothelial carcinoma. These findings indicate that primary extragonadal tumors with yolk sac differentiation involving the urinary tract frequently represent a rare, diagnostically deceptive, and clinically aggressive form of urothelial carcinoma.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100829"},"PeriodicalIF":7.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475976","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}
引用次数: 0
Intraoperative Margin Analysis Does Not Improve Outcomes in Treatment-Naive or Neoadjuvantly-Treated Patients With Pancreatic Ductal Adenocarcinoma 术中切缘分析不能改善Treatment-Naïve或新辅助治疗的胰腺导管腺癌患者的预后。
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-06-20 DOI: 10.1016/j.modpat.2025.100826
Xing Li , Preeti Malik , Amarpreet Bhalla , John C. McAuliffe , Nicole C. Panarelli
{"title":"Intraoperative Margin Analysis Does Not Improve Outcomes in Treatment-Naive or Neoadjuvantly-Treated Patients With Pancreatic Ductal Adenocarcinoma","authors":"Xing Li ,&nbsp;Preeti Malik ,&nbsp;Amarpreet Bhalla ,&nbsp;John C. McAuliffe ,&nbsp;Nicole C. Panarelli","doi":"10.1016/j.modpat.2025.100826","DOIUrl":"10.1016/j.modpat.2025.100826","url":null,"abstract":"<div><div>The prognostic relevance of intraoperative frozen section (IOF) margin analysis for patients with pancreatic ductal adenocarcinoma (PDAC) is debatable in both those treated with upfront surgery and neoadjuvant therapy. We analyzed the impact of intraoperative and final microscopic margin clearance in neoadjuvantly treated (n = 71) and treatment-naive (n = 109) patients with PDAC. Overall survival (OS) was longer in the treatment-naive (43 months) compared with the neoadjuvant (27 months) cohort (<em>P</em> = .02). Overall, 24 (34%) patients in the neoadjuvant and 22 (20%) patients in the treatment-naive groups had positive final margins, 13 and 10 of which were detected intraoperatively, respectively. At a median follow-up of 21 months, recurrence rates were 65% in the treatment-naive and 66% in the neoadjuvant cohorts and were similar regardless of margin status assessed via IOF or permanent sections. Disease-free survival (DFS) was significantly shorter in treatment-naive patients with positive (11 months) compared with negative (30 months) final margins (<em>P</em> = .03). Neither IOF nor final margin status was significantly associated with DFS in neoadjuvantly treated patients nor were they associated with OS in either cohort. Multivariate analysis showed that lymphovascular and perineural invasion were significantly associated with DFS, and lymphovascular invasion was significantly associated with OS. Our results suggest that IOF of the selected margins does not correlate with survival and is of limited utility in treatment-naive and neoadjuvantly treated PDAC patients.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 11","pages":"Article 100826"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369071","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}
引用次数: 0
Corrigendum to “Prognostic Model for Patient Survival in Primary Anorectal Mucosal Melanoma: Stage at Presentation Determines Relevance of Histopathologic Features” [Modern Pathology 33 (2020) 496–513] “原发性肛肠粘膜黑色素瘤患者生存的预后模型:表现阶段决定组织病理学特征的相关性”的勘误[现代病理学33 (2020)496-513]
IF 7.1 1区 医学
Modern Pathology Pub Date : 2025-06-19 DOI: 10.1016/j.modpat.2025.100819
Priyadharsini Nagarajan , Jin Piao , Jing Ning , Laura E. Noordenbos , Jonathan L. Curry , Carlos A. Torres-Cabala , A. Hafeez Diwan , Doina Ivan , Phyu P. Aung , Merrick I. Ross , Richard E. Royal , Jennifer A. Wargo , Wei-Lien Wang , Rashmi Samdani , Alexander J. Lazar , Asif Rashid , Michael A. Davies , Victor G. Prieto , Jeffrey E. Gershenwald , Michael T. Tetzlaff
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