Human pathology最新文献

{"title":"Challenges in papillary tumors of breast.","authors":"Raza S Hoda, Hannah Y Wen","doi":"10.1016/j.humpath.2025.105759","DOIUrl":"10.1016/j.humpath.2025.105759","url":null,"abstract":"<p><p>This review addresses common diagnostic challenges associated with papillary breast tumors-a rare but significant category of breast lesions. Despite their low incidence, papillary tumors are frequently encountered in breast pathology consultation practice due to their overlapping terminology and perplexing immunohistochemical results. Issues regarding assessment of invasive carcinoma in the setting of solid papillary carcinoma and encapsulated papillary carcinoma are covered. Emerging entities, such as tall cell carcinoma with reversed polarity and invasive lobular carcinoma mimicking solid papillary carcinoma, are discussed. Additionally, pragmatic guidance is provided for managing papillary breast tumors on needle core biopsy. Herein, we aim to provide clarity and confidence to surgical pathologists dealing with papillary breast tumors-mammary Medusa-equipping them with practical knowledge to better navigate this complex area of breast pathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105759"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary urethral adenocarcinoma harbors recurrent KRAS and EGFR alterations","authors":"Ting Zhao,&nbsp;A. John Iafrate,&nbsp;Chin-Lee Wu","doi":"10.1016/j.humpath.2025.105771","DOIUrl":"10.1016/j.humpath.2025.105771","url":null,"abstract":"<div><div>Primary urethral adenocarcinoma is an extremely rare malignancy with an unclear pathogenesis. Previously, we reported 4 brachytherapy-associated (BA) urethral mucinous adenocarcinomas that developed following treatment for prostate cancer. In the present study, we report one additional BA and 3 radiation-independent (RI) urethral adenocarcinomas. The aim of this study is to explore the molecular alterations and to compare the clinicopathologic features.</div><div>RNA sequencing was performed on 5 tumors, and a next-generation sequencing (NGS)-based fusion assay was used to identify gene fusions in 6 tumors. Additionally, NGS-based targeted genomic DNA sequencing was employed to analyze one metastatic BA tumor and one metastatic RI tumor.</div><div>The 8 patients had a mean age of 67 (range: 37–87) years, with one being female in the RI cohort. Cystoscopy revealed the following urethral findings: a papillary lesion (4/7), mass causing obstruction (1/7) and irregular friable tissue (2/7). Seven patients underwent urethrectomy with cystectomy/prostatectomy/hysterectomy. The mean tumor size was 3.4 cm (range: 1.5–6.5). Adenocarcinoma in situ was noted in 5 tumors. All 5 BA tumors originated from the prostatic urethra, with 4 showing mucinous morphology and one enteric morphology, and showed moderate to poor differentiation and tumor stages of pT2 (2/4), pT3 (1/3) and pT4 (1/4). Two patients developed metastasis, one at 3.3 and one at 4.2 years after diagnosis, and all patients were alive at a median follow-up of 4.5 (range: 2–14) years. In contrast, 3 RI tumors arose from bulbar, prostatic, or female mid/distal urethra, presenting as enteric, mucinous, and not otherwise specified (NOS) subtypes, with well to moderate differentiation and a tumor stage of pT4 (2/2). Two died of the disease, while one was alive without disease at a median follow-up of 4 (range: 2.2–14.5) years. All tumors were diffusely positive for CK20, CDX2 (7/7), and AMACR (3/3), and lacked nuclear β-catenin expression (5/5). Most expressed CK7 (5/7). <em>KRAS</em> mutations (p.Gly12Val and p.Gly13Asp) were observed in one BA mucinous tumor and one RI NOS tumor with the p.Gly13Asp mutation also detected in the metastatic RI tumor. The <em>EGFR</em> p.Ser784Phe mutation was detected in one RI enteric tumor. <em>TP53</em> p.Val172Phe, <em>CDKN2A</em> p.Leu32_Leu37del, and amplifications of <em>EGFR</em> and <em>MDM2</em>, were identified in a metastatic BA enteric tumor. No fusion transcripts were identified.</div><div>In conclusion, urethral adenocarcinoma harbors recurrent <em>KRAS</em> and <em>EGFR</em> alterations, independent of prior radiotherapy. RI tumors appear to be associated with a worse prognosis compared to BA tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105771"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mapping in head and neck adenoid cystic carcinoma by pathological grade using whole-exome sequencing and spatial transcriptome","authors":"Yuelu Zhu ,&nbsp;Lin Li ,&nbsp;Shun Wang ,&nbsp;Bingzhi Wang ,&nbsp;Lin Dong,&nbsp;Zhe Zhang,&nbsp;Ying Wang,&nbsp;Jiangtao Li,&nbsp;Haifeng Zhang,&nbsp;Haizhen Lu","doi":"10.1016/j.humpath.2025.105758","DOIUrl":"10.1016/j.humpath.2025.105758","url":null,"abstract":"<div><div>Our previous study demonstrated that pathological grades of adenoid cystic carcinoma (ACC) correlate with distinct prognoses and treatment strategies. To explore the molecular alterations underlying these grades, we performed whole-exome sequencing (WES) on 20 head and neck ACC samples from 12 patients, categorized into grade I-II, grade III, and high-grade transformation (HGT). Comprehensive analyses, including somatic mutations, chromosomal structural variations, and phylogenetic tree construction, were conducted. Spatial transcriptome (ST) technology was further employed to analyze gene expression, pseudo-time trajectories, and copy number variations in a grade III sample. WES revealed that high-grade (grade III and HGT) ACC tissues frequently harbor mutations in TP53, PI3K pathway genes, and chromatin remodelers. Phylogenetic analysis showed that higher-grade regions exhibit more subclonal mutations or a larger proportion of intergenerational mutations. Copy number analysis identified recurrent deletions of 1p36.33 and amplifications of 8q24.21/9p24.1 in high-grade samples, along with significant deletions on chr12 in both WES and ST. ST pathway enrichment and cell trajectory analyses indicated that high-grade clusters are more primitive and proliferative, while low-grade clusters display greater microenvironmental stability and interstitial specialization. These findings highlight the complex spatial heterogeneity associated with ACC pathological grades, providing critical insights into disease progression and guiding therapeutic strategies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105758"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of the histogenesis of epithelial cysts in angiomyolipoma with epithelial cysts (AMLEC) using GPNMB and TSC2 immunostains","authors":"Huili Li ,&nbsp;Oluwademilade Dairo ,&nbsp;Tamara Lotan ,&nbsp;Pedram Argani ,&nbsp;Andres Matoso","doi":"10.1016/j.humpath.2025.105764","DOIUrl":"10.1016/j.humpath.2025.105764","url":null,"abstract":"<div><div>Angiomyolipoma with epithelial cysts (AMLECs) is an uncommon subtype of angiomyolipoma (AML), with both a classic AML component and a bland epithelial-lined cystic component. The histogenesis of the cysts in AMLECs is unclear. Two main hypotheses have been proposed: the cysts represent entrapped dilated native tubules versus the epithelial differentiation of AML. Mutations of tuberous sclerosis genes are frequently observed in AML. Glycoprotein non-metastatic melanoma protein B (GPNMB) exhibits a low expression in most normal tissues and is transcriptionally activated by TFE3 and TFEB. Loss of TSC1/2/mTOR function paradoxically activates TFE3 and TFEB, resulting in a strong diffuse GPNMB expression. We explored the histogenesis of epithelial cysts in five AMELC cases using HMB45, Cathepsin-K, GPNMB and TSC2 immunostains. GPNMB was strongly and diffusely positive in the classic spindle cell component in all five AMLECs, but not in the cystic epithelium and associated blood vessels. Correspondingly, loss of TSC2 labeling was only seen in the classic spindle cell AML but not in the cystic epithelium and vessels. HMB45 was positive in the classic spindle cell component and not in the cystic epithelium or blood vessels. Cathepsin-K stained both spindle and epithelial components but was weaker in the epithelium. Our study demonstrates that strong diffuse expression of GPNMB correlates with loss of TSC2 expression. The epithelial cysts and associated vessels in AMLECs do not harbor TSC pathway alteration, thus supporting the idea that they are entrapped native tubules and vasculatures, not part of the neoplasia.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105764"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological study of 34 cases of clear cell adenocarcinoma of the urinary tract and diagnostic value of SOX 17 in its differential diagnosis","authors":"Lan Zheng ,&nbsp;Georges Tabet ,&nbsp;Charles C. Guo ,&nbsp;Yasmeen Oamar Rizvi ,&nbsp;Maria Gabriela Raso ,&nbsp;Jinsong Liu ,&nbsp;Qingqing Ding ,&nbsp;Ezra Baraban ,&nbsp;Jianping Zhao","doi":"10.1016/j.humpath.2025.105767","DOIUrl":"10.1016/j.humpath.2025.105767","url":null,"abstract":"<div><div>Clear cell adenocarcinoma (CCA) of the urinary tract is a rare tumor with a female predominance. The morphological features and immunoprofile of urinary CCA, CCA of the gynecologic tract (Gyn CCA), and nephrogenic adenoma (NA) can show extensive overlap, and the differential diagnosis can be challenging especially in small biopsies. SOX17 is a newly identified sensitive and specific immunomarker for endometrial and ovarian carcinomas including Gyn CCA. However, its expression in urinary CCA and NA has not been studied. We studied clinical and pathological features of 34 cases of urinary CCA, the largest cohort in the literature to date. We analyzed the expression pattern of SOX17 in a cohort of 34 urinary CCA, 24 Gyn CCA, and 18 NA. Interestingly, 29 % (10/34) of urinary CCA showed high SOX17 expression, while all the NA cases (18/18) showed negative-low expression. In female, 51 % of urinary CCA cases (15/29) show negative-low expression of SOX17, whereas all Gyn CCA (24/24) showed high SOX17 positivity. Our study showed a unique expression pattern of SOX17 in urinary CCA and NA. These results suggest that SOX17 is a useful marker in distinguishing CCA from NA or urinary CCA from Gyn CCA. Moreover, our study suggests different pathogenic pathways for the histogenesis of urinary CCA.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105767"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-based analysis of gross features for ovarian epithelial tumors classification: A tool to assist pathologists for frozen section sampling","authors":"Dong He ,&nbsp;Longhai Jin ,&nbsp;Hanhan Geng ,&nbsp;Lanqing Cao","doi":"10.1016/j.humpath.2025.105762","DOIUrl":"10.1016/j.humpath.2025.105762","url":null,"abstract":"<div><div>Computational pathology has primarily focused on analyzing tissue slides, neglecting the valuable information contained in gross images. To bridge this gap, we proposed a novel approach leveraging the Swin Transformer architecture to develop a Swin-Transformer based Gross Features Detective Network (SGFD-network), which assist pathologists for locating diseased area in ovarian epithelial tumors based on their gross features. Our model was trained on 4129 gross images and achieved high accuracy rates of 88.9 %, 86.4 %, and 93.0 % for benign, borderline, and carcinoma group, respectively, demonstrating strong agreement with pathologist evaluations. Notably, we trained a new classifier to distinguish between borderline tumors and those with microinvasion or microinvasive carcinoma, addressing a significant challenge in frozen section sampling. Our study was the first to propose a solution to this challenge, showcasing high accuracy rates of 85.0 % and 92.2 % for each group, respectively. To further elucidate the decision-making process, we employed Class Activation Mapping-grad to identify high-contribution zones and applied <em>k</em>-means clustering to summarize these features. The resulting clustered features can effectively complement existing knowledge of gross examination, improving the distinction between borderline tumors and those with microinvasion or microinvasive carcinoma. Our model identifies high-risk areas for microinvasion or microinvasive carcinoma, enabling pathologists to target sampling more effectively during frozen sections. Furthermore, SGFD-network requires only a single 4090 graphics card and completes a single interpretation task in 3 min. This study demonstrates the potential of deep learning-based analysis of gross features to aid in ovarian epithelial tumors sampling, especially in frozen section.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105762"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic alterations are common in Monogenic Disease patients with ‘healthy’ endoscopy: Results from a GIPAD-GIPPI multicenter study","authors":"Jacopo Ferro ,&nbsp;Paola Francalanci ,&nbsp;Valentina Angerilli ,&nbsp;Barbara Cafferata ,&nbsp;Maria D'Armiento ,&nbsp;Anna Maria Buccoliero ,&nbsp;Raduan Ahmed Franca ,&nbsp;Alessandro Vanoli ,&nbsp;Maria Cristina Macciomei ,&nbsp;Luisa Santoro ,&nbsp;Rita Alaggio ,&nbsp;Matteo Fassan ,&nbsp;Luca Mastracci ,&nbsp;Diana Sacchi ,&nbsp;Carla Giordano ,&nbsp;Emanuela Pilozzi ,&nbsp;Maria Cristina Giustiniani ,&nbsp;Iacopo Panarese ,&nbsp;Federica Grillo ,&nbsp;Paola Parente","doi":"10.1016/j.humpath.2025.105763","DOIUrl":"10.1016/j.humpath.2025.105763","url":null,"abstract":"<div><h3>Objective</h3><div>Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before 6 years of age, encompassing ‘pure’ IBD (Crohn's Colitis/Ulcerative Colitis)/non IBD colitis, and monogenic diseases (MDs), the latter often related to primary immunodeficiency disorders. A multidisciplinary approach is imperative for correct therapeutic management, as endoscopy and histology are not always completely informative. In this setting, the study aims to describe the extent/features of histologic lesions in both endoscopically damaged mucosa and otherwise endoscopically healthy (normal/near normal) mucosa.</div></div><div><h3>Methods</h3><div>Endoscopic data were retrospectively recorded, and histologic slides were collegially re-evaluated in a 93 VEO-IBD multicenter cohort, 76 (76/93 - 81,7 %) of which with complete endoscopic/histologic data.</div></div><div><h3>Results</h3><div>At endoscopy, lesions were reported by the clinician in 66/76 (86,8 %) cases. When endoscopic lesions were reported, histologic damage was also seen. Interestingly, histologic mucosal damage was also documented in 43,3 % (13/30) of cases with endoscopically healthy/nearly healthy mucosa. This misalignment between endoscopy and pathology was seen in about a third of (29,1 % - 7/24) ‘true’ IBD and all MDs (100 % - 6/6) (p = 0.0029).</div></div><div><h3>Conclusion</h3><div>In VEO-IBD, histologic lesions can be present in endoscopically ‘healthy’ intestinal mucosa. This finding is more frequent in MDs, suggesting the need to accurately sample all the mucosal tract in VEO-IBD patients, even when no endoscopic lesions are seen at endoscopy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105763"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyalinizing trabecular tumor of the thyroid: Interest of GLIS3 immunohistochemical study to detect PAX8::GLIS3 rearrangement","authors":"Ziyad Alsugair ,&nbsp;Francoise Descotes ,&nbsp;Jonathan Lopez ,&nbsp;Myriam Decaussin-Petrucci","doi":"10.1016/j.humpath.2025.105761","DOIUrl":"10.1016/j.humpath.2025.105761","url":null,"abstract":"<div><h3>Background</h3><div><u>&amp; Objective</u>: Hyalinizing trabecular tumor of the thyroid (HTT) is a rare, low-risk neoplasm that poses diagnostic challenges. Very recently, <em>PAX8::GLIS3</em> rearrangements were found to characterize HTT. We aimed to explore HTT's genetic profile, focusing on <em>PAX8::GLIS3</em> rearrangements and GLIS3 immunohistochemical staining.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study involving 8 cases histologically diagnosed as HTT. RNA sequencing and immunohistochemical staining for GLIS3 were performed on all cases.</div></div><div><h3>Results</h3><div>The study included five females and three males, with a tumor size ranging from 3 to 45 mm. RNA sequencing analysis showed <em>PAX8::GLIS3</em> rearrangement in 6 cases (86 %). No other molecular alterations were found. However, one case failed due to the tissue quality, and one case did not show any gene fusion. Immunohistochemical staining for GLIS3 revealed nuclear positive expression in tumor cells for all cases where gene fusion was detected (100 %). A control group of 20 HTT mimickers showed no immunostaining for GLIS 3.</div></div><div><h3>Conclusion</h3><div>Our study confirms the consistent presence of <em>PAX8::GLIS3</em> rearrangement in hyalinizing trabecular tumor (HTT) of the thyroid. Additionally, our novel finding of GLIS3 expression via immunohistochemistry enhances diagnostic precision for these tumors. Notably, our series demonstrates the correlation between positive GLIS3 expression and detection of <em>PAX8::GLIS3</em> fusion by RNA sequencing, potentially expediting HTT diagnosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105761"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFE3-rearranged ossifying fibromyxoid tumors are uniquely negative for glycoprotein non-metastatic melanoma protein B: A study of 13 TFE3-rearranged mesenchymal tumors","authors":"Burak Tekin Instructor in Pathology ,&nbsp;Andrew L. Folpe Professor of Pathology ,&nbsp;Surendra Dasari Associate Professor of Biomedical Informatics ,&nbsp;Christopher D. Hofich Principal Developer, Department of Lab Medicine and Pathology ,&nbsp;Michael McCarthy Resident Physician, Pathology ,&nbsp;Saba Alvand Visiting Research Fellow, Pathology ,&nbsp;Ganesh P. Pujari Visiting Research Fellow, Pathology ,&nbsp;Kevin C. Halling Professor of Pathology ,&nbsp;John C. Cheville Professor of Pathology ,&nbsp;Rumeal D. Whaley Assistant Professor of Pathology ,&nbsp;Sounak Gupta Associate Professor of Laboratory Medicine and Pathology","doi":"10.1016/j.humpath.2025.105768","DOIUrl":"10.1016/j.humpath.2025.105768","url":null,"abstract":"<div><h3>Objectives</h3><div>Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transcriptional target of <em>MiTF/TFE3</em>. Prior studies have shown that immunohistochemistry for GPNMB is a sensitive screening tool for renal cell carcinomas with alterations of <em>TSC1/TSC2/MTOR</em>, <em>TFE3</em>, and <em>TFEB</em> genes, as well as alveolar soft part sarcomas (ASPS) and perivascular epithelioid cell neoplasms (PEComas). However, GPNMB expression has not been systematically evaluated in a diverse group of molecularly confirmed, <em>TFE3</em>-rearranged mesenchymal tumors.</div></div><div><h3>Methods</h3><div>Our archive was interrogated for <em>TFE3</em>-rearranged non-renal neoplasms previously assessed with our RNA NGS panel. For each case, a whole-slide section was immunostained for GPNMB, and quantified using H-scores. The methylation profiles of the included tumor types were retrieved from our database.</div></div><div><h3>Results</h3><div>Thirteen <em>TFE3</em>-rearranged tumors were identified, including 6 ossifying fibromyxoid tumors (OFMTs) (<em>PHF1::TFE3</em>), 3 PEComas/PEComa-like neoplasms (<em>ASPSCR1::TFE3</em>, <em>DVL2::TFE3</em>, and <em>PRCC::TFE3</em>, one case each), 2 <em>YAP1::TFE3</em>-rearranged hemangioendotheliomas, one ASPS (<em>ASPSCR1::TFE3</em>), and one unclassified <em>CBX4::TFE3</em>-rearranged sarcoma. Tumors harboring <em>ASPSCR1</em>, <em>PRCC</em>, <em>YAP1</em>, and <em>DVL2</em> as the fusion partner had a mean H-score of 300, 300, 290 and 280, respectively. All 6 <em>PHF1</em>::<em>TFE3</em>-rearranged OFMTs and the <em>CBX4</em>::<em>TFE3</em>-rearranged sarcoma were GPNMB-negative, despite having similar <em>TFE3</em> breakpoints to the positive cases (exon 6–7). <em>PHF1::TFE3</em>-rearranged OFMT showed relative hypermethylation of the <em>GPNMB</em> promoter locus cg02203656 compared to ASPS (<em>p</em> = 0.027).</div></div><div><h3>Conclusions</h3><div>Although study of additional cases is necessary, these findings suggest that the downstream effects of <em>TFE3</em>-rearrangement are different in <em>PHF1::TFE3</em>-rearranged OFMTs, compared to other known <em>TFE3</em>-rearranged neoplasms. <em>TFE3</em>-rearranged OFMTs are epigenetically distinct, implying that the impact of <em>TFE3</em>-rearrangement may be lineage-dependent.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105768"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and molecular characterization of primitive neuroectodermal tumors (PNET) in the female genital tract: a retrospective study of 8 cases","authors":"Zhiyang Zhang ,&nbsp;Haiyan Shi ,&nbsp;Ying Shao ,&nbsp;Bingjian Lu","doi":"10.1016/j.humpath.2025.105769","DOIUrl":"10.1016/j.humpath.2025.105769","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the molecular alterations in primitive neuroectodermal tumors (PNET) of the female genital tract.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the clinicopathologic and immunohistochemical features of 8 gynecologic PNET cases (3 cervical, 1 vaginal, and 4 ovarian). Fluorescence in situ hybridization and targeted next-generation sequencing (NGS) were performed to identify molecular alterations in these tumors.</div></div><div><h3>Results</h3><div>The cohort included 5 FIGO stage I, 1 stage III, and 2 stage IV tumors. Two patients with stage IV disease died at 8 and 12 months. The cervical/vaginal tumors consisted of small round blue cells arranged in sheets, with EWSR1 rearrangements and concurrent diffuse expression of membranous CD99 and nuclear FLI1. The ovarian tumors displayed diverse morphologic features resembling central nervous system (CNS) tumors, including embryonal tumor with multilayered rosettes (case 5), medulloblastoma (case 6), glioblastoma (case 7), and ependymoma (case 8). Three ovarian tumors were associated with teratomas. None of the ovarian tumors exhibited <em>EWSR1</em> rearrangements or <em>i(12p)/12p</em> overrepresentation. NGS identified an <em>EWSR1::exon11∼FLI1::exon6</em> fusion in one cervical PNET, with no additional molecular alterations. In contrast, three ovarian tumors lacked common genetic changes seen in CNS tumors but harbored several significant variants, including <em>NTRK2 exon11 c.1019C &gt; T (p.T340 M)</em> (case 6), <em>INPP4B exon23 c.2221G &gt; A (p.V741 M)</em> (case 7), and <em>FANCG exon7 c.882_883insA (p.D2</em>95Rfs<em>∗14)</em> with <em>MET 7q31</em> polysomy (case 8).</div></div><div><h3>Conclusions</h3><div>Our findings confirm that cervical/vaginal and ovarian PNET represent two distinct tumor types. Ovarian PNET have different pathogenetic pathways from their CNS and testicular counterparts most likely.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105769"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}