Human pathology最新文献

{"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":"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":"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":"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}

{"title":"Estrogen receptor expression in human tumors: A tissue microarray study evaluating more than 18,000 tumors from 149 different entities","authors":"Florian Viehweger ,&nbsp;Justus Gusinde ,&nbsp;Nicolai Leege ,&nbsp;Lisa-Maria Tinger ,&nbsp;Natalia Gorbokon ,&nbsp;Anne Menz ,&nbsp;Ria Schlichter ,&nbsp;Andrea Hinsch ,&nbsp;David Dum ,&nbsp;Christian Bernreuther ,&nbsp;Sören Weidemann ,&nbsp;Florian Lutz ,&nbsp;Simon Kind ,&nbsp;Viktoria Chirico ,&nbsp;Katharina Möller ,&nbsp;Viktor Reiswich ,&nbsp;Andreas M. Luebke ,&nbsp;Morton Freytag ,&nbsp;Maximilian Lennartz ,&nbsp;Frank Jacobsen ,&nbsp;Sarah Minner","doi":"10.1016/j.humpath.2025.105757","DOIUrl":"10.1016/j.humpath.2025.105757","url":null,"abstract":"<div><div>Estrogen receptor (ER) is a ligand-activated transcription factor with a critical role in development and function of multiple organ systems and a well-established drug target for breast cancer. To comprehensively evaluate ER expression in normal and tumor tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). ER positivity was found in 55 different tumor types including 26 entities with at least one strongly positive tumor. ER positivity strongly predominated in breast neoplasms (81.1%) and in other gynecological tumors (39.4%) while only 0.8% of non-gynecological and non-mammary tumors showed ER positivity. Among these, ER staining – often at lower intensity – especially occurred in neuroendocrine neoplasms (up to 9.1%), salivary gland tumors (up to 8.3%), and in squamous cell carcinomas of different sites of origin (up to 6.7%). In invasive breast carcinoma (NST), reduced ER immunostaining was linked to high pT (p &lt; 0.0001), high grade (p &lt; 0.0001), distant metastasis (p = 0.0012), HER2 positivity (p &lt; 0.0001), PR negativity (p &lt; 0.0001) and shorter overall survival (p = 0.0576). In serous high-grade ovarian cancer, reduced ER staining was linked to nodal metastasis (p = 0.0012). ER staining was unrelated to histopathological features in 145 analyzable endometroid endometrial carcinomas. Within non-mammary, non-gynecological, non-prostate, and non-testicular tumors, ER positivity was more common in tumors from female (1.4% of 2528) than from male patients (0.6% of 3228; p = 0.0003). In summary, our data provide a ranking list of tumor entities according to their prevalence of ER positivity and shows that ER can be strongly expressed in a small number of non-breast and non-gynecological tumors which could potentially represent a diagnostic pitfall in a cancer of unknown primary but also represents a therapeutic opportunity.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105757"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYLD-mutated anal squamous cell carcinoma: An uncommon entity associated with cylindroma-like morphology and adverse clinical features","authors":"Xiaoqin Zhu ,&nbsp;Xiuling Meng ,&nbsp;Mark C. Mochel ,&nbsp;Erik A. Wiliams ,&nbsp;Karen Dresser ,&nbsp;Keith Tomaszewicz ,&nbsp;Lloyd Hutchinson ,&nbsp;Jacob R. Bledsoe","doi":"10.1016/j.humpath.2025.105765","DOIUrl":"10.1016/j.humpath.2025.105765","url":null,"abstract":"<div><div>Anal squamous cell carcinoma (SqCC) can be broadly divided into HPV-positive and HPV-negative groups, each with distinct clinicopathologic features and outcome. <em>CYLD</em>-mutant anal SqCC was recently characterized as having a strong association with cylindroma-like histologic features, HPV positivity, infrequent <em>PIK3CA</em> mutation, and low tumor mutational burden. The prognostic impact of <em>CYLD</em> mutation in this context has not been established. We performed <em>CYLD</em> mutational analysis on a cohort of 109 clinicopathologically well-characterized cases of anal SqCC including 98 HPV-positive and 11 HPV-negative carcinomas. <em>CYLD</em> mutation was present in 3 cases (2.8 % of total, 3.1 % of HPV-positive cases), all of which were HPV16-positive. <em>CYLD</em> mutation was significantly associated with more frequent cylindroma-like basement membrane inclusions (p = 0.0002) and basaloid cytomorphology (p = 0.017). Just 4 % of <em>CYLD</em>-wildtype carcinomas demonstrated cylindroma-like features, which were limited in extent relative to <em>CYLD</em>-mutant cases. Among the HPV-positive group, <em>CYLD</em> mutation and cylindroma-like morphology were associated with a higher rate of metastatic disease progression (p = 0.022 and p = 0.01, respectively), with 2 of 3 <em>CYLD</em>-mutant patients developing liver metastasis at 6 and 7 months after initial diagnosis. None of the <em>CYLD</em>-mutant cases had other mutations including <em>PIK3CA</em> and <em>TP53</em> mutations. Our findings further establish <em>CYLD</em>-mutant anal SqCC as an infrequent but distinct clinicopathologic entity with characteristic pathogenetic features and a possible association with adverse clinical outcomes. Among HPV-positive anal SqCC, <em>CYLD</em> mutation represents a potentially useful novel marker for this distinct entity and cylindroma-like morphology serves as a useful feature to identify such cases.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105765"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761339","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":"Solid basaloid adenoid cystic carcinoma of the breast: A high-grade triple negative breast carcinoma which rarely responds to neoadjuvant chemotherapy","authors":"Katharine Schulz-Costello ,&nbsp;Fang Fan ,&nbsp;Daniel Schmolze ,&nbsp;Javier A. Arias-Stella III ,&nbsp;Lesley Taylor ,&nbsp;Jennifer Tseng ,&nbsp;Michelle Afkhami ,&nbsp;Jamie G. Rand ,&nbsp;Veronica Jones ,&nbsp;Preeti Farmah ,&nbsp;Min Han","doi":"10.1016/j.humpath.2025.105760","DOIUrl":"10.1016/j.humpath.2025.105760","url":null,"abstract":"<div><div>Solid basaloid adenoid cystic carcinoma of the breast (SB-AdCC) is an exceedingly rare but important entity that warrants clear separation from classic AdCC (C-AdCC) for optimal treatment. This case series retrospectively reviewed the diagnosis and treatment of 20 breast AdCCs. While four breast pathologists reached consensus on the diagnosis of all C-AdCCs, there was considerable disagreement when diagnosing pure SB-AdCCs. The morphology and immunohistochemical profiles of SB-AdCC closely resemble those of basaloid triple-negative breast carcinoma (TNBC). Molecular profiling of SB-AdCC revealed frequent mutations in the Notch pathway and alterations in chromatin modifiers, such as <em>CREBBP</em> and <em>KMT2D</em>. <em>MYB-NFIB</em> fusion was rare and detected in only 2 of 9 (22.2 %) SB-AdCCs. Axillary lymph node metastasis was present in 2 of 10 patients with SB-AdCC at the time of surgery. During a median follow-up of 27 months, one patient with SB-AdCC developed axillary recurrence. Moreover, 6 of 12 (50.0 %) patients with SB-AdCC developed distant metastases. Of the three patients who underwent neoadjuvant chemotherapy for SB-AdCC, one achieved near-complete pathological response, while the remaining two had minimal response. In conclusion, this series underscores the aggressive clinical course of SB-AdCC, similar to conventional TNBC. Pathologically, SB-AdCC also closely mimics conventional TNBC. It is imperative for pathologists to clearly indicate C-AdCC or SB-AdCC or give a percentage of each component to ensure appropriate treatment strategies and avoid both over-treatment and under-treatment.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105760"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729566","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":"Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics","authors":"Wei Xie ,&nbsp;L. Jeffrey Medeiros ,&nbsp;Guang Fan ,&nbsp;Shaoying Li ,&nbsp;Jie Xu","doi":"10.1016/j.humpath.2024.105671","DOIUrl":"10.1016/j.humpath.2024.105671","url":null,"abstract":"<div><div>Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or <em>ALK</em> rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as “donut cells”, Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called “antigen loss”) and in some cases can have a “null” immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of <em>DUSP22</em>, <em>TP63, JAK2, FRK, MYC, ROS1</em> and <em>TYK2</em>; mutations of <em>JAK1, STAT3</em> and <em>MSCE</em>; and aberrant expression of <em>ERBB4</em>. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with <em>DUSP22</em> rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105671"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464054","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":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(25)00037-1","DOIUrl":"10.1016/S0046-8177(25)00037-1","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105750"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571482","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}