Human pathology最新文献

{"title":"Association between p16^INK4A expression and a treatment response to CDK4/6 inhibitor in advanced breast carcinoma.","authors":"Xiao Huang, Shuko Harada, Shi Wei, Gene P Siegal, Sarah A Anderson, Aysegul A Sahin, Katia Khoury, Ceren Yalniz","doi":"10.1016/j.humpath.2025.105905","DOIUrl":"10.1016/j.humpath.2025.105905","url":null,"abstract":"<p><strong>Introduction: </strong>Endocrine therapy combined with cyclin-dependent kinase 4 and 6 inhibitors (1) has been approved for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinomas. It has been known that the p16-CDK4/6-cyclin D1 axis regulates the S phase of the cell cycle. We investigated the association between p16 expression and the therapeutic response with CDK4/6i in advanced breast carcinoma.</p><p><strong>Methods: </strong>Patients diagnosed with invasive breast carcinoma between 2019 and 2024 whose tumors underwent next-generation sequencing (NGS) based analysis were identified. The expression of p16 was assessed in tumor cells and stromal cells within the invasive carcinoma by immunohistochemistry. In tumor cells, p16 expression was subclassified as cytoplasmic (TC), nuclear (TN), or cytoplasmic and nuclear staining (TCN). In stromal cells, p16 expression was assessed in tumor-associated fibroblasts (TAF) and tumor-infiltrating immune cells (TILs) in any cellular compartment.</p><p><strong>Results: </strong>Among the 35 cases, p16-TC, -TN, and -TCN were significantly associated with disease progression during CDK4/6i therapy. The positive association between p16-TC and progressive disease remained in the 24 CDK4/6i-treatment naïve tumors. In contrast, the tumors with p16 expression in TAF showed a numerically higher response rate than the p16-TAF-negative ones. We also observed a significant association between p16-TC expression and lymph node metastasis.</p><p><strong>Conclusion: </strong>Our study demonstrated a significant association between p16 expression in tumor cells and an unfavorable therapeutic response to CDK4/6i in advanced breast carcinoma. The clinical significance of p16 expression patterns as a predictive biomarker for CDK4/6i deserves further investigation.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105905"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803990","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":"Impact of neoadjuvant chemotherapy on PD-L1 expression in oral squamous cell carcinoma: A matched biopsy-resection study","authors":"Deeksha Agrawal ,&nbsp;Nidhi Anand ,&nbsp;Nuzhat Husain ,&nbsp;Pallavi Srivastava ,&nbsp;Akash Tamrakar ,&nbsp;Vikas Sharma ,&nbsp;Ashish Singhal ,&nbsp;Rohini Khurana","doi":"10.1016/j.humpath.2025.105927","DOIUrl":"10.1016/j.humpath.2025.105927","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death ligand 1 (PD-L1) is essential for immune evasion and serves as a significant biomarker for immunotherapy in oral squamous cell carcinoma (OSCC). Nevertheless, the changes in its expression after neoadjuvant chemotherapy (NACT) are not well understood. This research sought to assess the variations in PD-L1 expression between matched pretreatment biopsy samples and post-NACT surgical specimens, while also correlating these results with clinicopathological characteristics.</div></div><div><h3>Materials and methods</h3><div>The study comprised 130 patients with OSCC, of which 95 were treated with NACT while 35 acted as controls who did not receive NACT. PD-L1 expression was measured via immunohistochemistry (SP263 clone) on pretreatment biopsy samples and corresponding post-NACT resection specimens, employing Tumor Proportion Score (TPS), Immune Proportion Score (IPS), and Combined Positive Score (CPS) at several cut-off points (≥1 %, ≥10 %, ≥25 %, and ≥50 %). Statistical evaluations were performed using SPSS version 24.0.</div></div><div><h3>Results</h3><div>In post NACT, there was a significant variation in PD-L1 expression. A marked reduction in PD-L1 TPS was noted in T1 tumors, decreasing from 43.4 % to 13.0 % (p = 0.039), as well as in tumors with a depth of invasion (DOI) less than 5 mm, which dropped from 40.7 % to 14.8 %. Conversely, an increase in PD-L1 expression was observed in tumors at advanced nodal stages and those exhibiting lymphovascular invasion (LVI), perineural invasion (PNI), and tumor budding. The change in combined positive score (CPS) was significantly correlated with tumor budding (p = 0.008), the worst pattern of invasion (WPOI) (p = 0.036), DOI (p = 0.030), and prognostic stage (p = 0.026). In control cases, only minor alterations in PD-L1 status were detected between biopsy and resection specimens.</div></div><div><h3>Conclusion</h3><div>NACT did not lead to uniform or widespread changes in PD-L1 expression in OSCC. Significant alterations were limited to TPS in T1 tumors and CPS associations with certain pathological features, while most other comparisons showed no statistical significance. These findings suggest that PD-L1 expression after NACT should be interpreted cautiously, and larger studies are needed to clarify its clinical relevance. <strong>Keywords</strong>: Oral Squamous Cell Carcinoma; PD-L1 expression; Neoadjuvant treatment; Prognosis; Tumor proportion score; Combined positive score.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105927"},"PeriodicalIF":2.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952177","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":"High-grade endometrioid carcinomas with pilomatrix-like features lacking CTNNB1 Mutations: Clinicopathologic characteristics and novel molecular events","authors":"Lei Qin ,&nbsp;Wanrun Lin ,&nbsp;Suming Huang ,&nbsp;Wenxin Zheng ,&nbsp;Feng Zhou","doi":"10.1016/j.humpath.2025.105928","DOIUrl":"10.1016/j.humpath.2025.105928","url":null,"abstract":"<div><h3>Context</h3><div>Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) represents a recently described, aggressive variant of endometrial carcinoma. Prior reports have linked PiMHEC with <em>CTNNB1</em> exon 3 mutations and abnormal nuclear β-catenin expression.</div></div><div><h3>Objective</h3><div>We aimed to expand the understanding a potential subclassification of PiMHEC by analyzing three new cases that lack <em>CTNNB1</em> mutations and β-catenin nuclear accumulation.</div></div><div><h3>Design</h3><div>Three cases of high-grade endometrioid carcinomas with pilomatrix-like features were identified and their clinical presentations and pathologic features reviewed. Immunohistochemistry (IHC) and targeted next-generation sequencing (NGS) were performed.</div></div><div><h3>Results</h3><div>All tumors demonstrated two components: a high-grade basaloid component with solid sheets of atypical basaloid cells, geographic necrosis, and focal “ghost” cells, and an associated low-grade FIGO grade 1 endometrioid carcinoma component. Notably, none of the three cases showed nuclear β-catenin expression by IHC, and all lacked <em>CTNNB1</em> exon 3 mutations. Despite this, the tumors fulfilled the morphologic criteria for PiMHEC described in prior studies and displayed aggressive clinical behavior. All the patients presented with advanced-stage disease (stages IIC–IVB), and two patients had a recurrence within 12 months. NGS revealed no <em>CTNNB1</em> mutations in any case, but identified alternative likely oncogenic alterations: one tumor harbored an <em>FGFR4 p.</em></div><div><em>T259A</em> mutation, two tumors had pathogenic <em>TSC2</em> mutations, one had a <em>KRAS p.G12D</em> mutation, and two showed <em>MYC</em> amplification, among other genetic changes.</div></div><div><h3>Conclusions</h3><div>High-grade endometrioid carcinomas with pilomatrix-like features lacking CTNNB1 mutations may represent a potential subclassification of PiMHEC, which exhibit aggressive behavior. CTNNB1-wildtype cases appear to rely on alternative oncogenic drivers, indicating that <em>CTNNB1</em> mutation maybe not an absolute requirement for the PiMHEC phenotype.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105928"},"PeriodicalIF":2.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926222","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)00208-4","DOIUrl":"10.1016/S0046-8177(25)00208-4","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"163 ","pages":"Article 105921"},"PeriodicalIF":2.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911464","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":"Inside front cover - Masthead","authors":"","doi":"10.1016/S0046-8177(25)00205-9","DOIUrl":"10.1016/S0046-8177(25)00205-9","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"163 ","pages":"Article 105918"},"PeriodicalIF":2.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912952","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":"A real-world study on the expression and clinical application of IMP3 immunohistochemistry in bone tumors","authors":"Qingzhu Wei,&nbsp;Lin Zhong,&nbsp;Hui Zhou,&nbsp;Lucen Jiang,&nbsp;Qi Wang,&nbsp;Dan Li,&nbsp;Qiao Yang","doi":"10.1016/j.humpath.2025.105911","DOIUrl":"10.1016/j.humpath.2025.105911","url":null,"abstract":"<div><div>Previous studies have confirmed that insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) is widely expressed in various malignant tumors. However, no systematic study has assessed the expression of IMP3 in bone tumors. We immunohistochemically examined 1381 bone tumor specimens for IMP3 expression, analyzed its differential expression among various types of bone tumors, and evaluated its potential application in surgical pathology. Our results demonstrated that IMP3 positivity was observed in 7.5 % (55/732) of benign bone tumors and 55.2 % (358/649) of malignant bone tumors, with statistically significant differences (<em>P</em> &lt; 0.0001). Notably, higher levels of IMP3 expression were observed in high-grade malignant bone tumors than in their low-grade counterparts. The incidence of IMP3 positivity exceeds 80 % in diffuse large B-cell lymphoma, high-grade osteosarcoma, lymphoblastic lymphoma, and undifferentiated pleomorphic sarcoma. Additionally, we detected IMP3 positivity in 63.5 % (80/126) of metastatic bone cancers, specifically in 83.6 % (46/55) of lung cancers, 70 % (7/10) of liver cancers, and 87.5 % (7/8) of colorectal cancers. We also observed high levels of IMP3 expression in three benign bone tumor types: chondroblastoma, epithelioid hemangioma, and Langerhans cell histiocytosis. In conclusion, IMP3 immunostaining may serve as a diagnostic biomarker for malignant bone tumors, especially osteosarcoma and lymphoma. The high expression of IMP3 observed in bone metastases of lung cancer, liver cancer, and colorectal cancer indicates that IMP3 could be associated with bone metastasis in these malignancies. Future research should focus on elucidating the relationship between IMP3 expression and various clinicopathological parameters as well as prognostic outcomes in malignant bone tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105911"},"PeriodicalIF":2.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903707","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":"Eosinophil-rich esophagitis pattern in patients with allogenic hematopoietic stem cell transplantation: a multicenter experience","authors":"Reem Youssef ,&nbsp;Kwun Wah Wen ,&nbsp;Zahra Alipour ,&nbsp;Shaomin Hu ,&nbsp;Shula Schechter ,&nbsp;Jerome Cheng ,&nbsp;Iván A. González","doi":"10.1016/j.humpath.2025.105915","DOIUrl":"10.1016/j.humpath.2025.105915","url":null,"abstract":"<div><div>Eosinophil-rich esophagitis is a pattern of inflammation characterized by increased intraepithelial eosinophils which is associated with a wide range of disorders including eosinophilic esophagitis (EoE). In hematopoietic stem cell transplant (HSCT) patients, eosinophil-rich esophagitis is exceedingly rare and associated in one prior case to transplant-acquired allergy (TAA). The goal of this multicenter study was to characterize the clinical and pathologic features of esophageal biopsies with an eosinophil-rich esophagitis pattern in HSCT patients. 10 cases were identified presenting with a median age of 45 years (range: 10–76), including 7 men. The median time lapsed from HSCT to biopsy was 6 months (range: 0–3). 3 patients presented within 21 days of HSCT, 2 of which showed apoptotic bodies. The median number of eosinophils/HPF was 25 (range: 16–102), 6 cases showed eosinophilic degranulation, 3 cases had eosinophilic abscesses, 5 cases showed apoptotic bodies, and 3 cases had dyskeratotic cells. Of the 5 patients presenting after 21 days of HSCT, features of GVHD were seen in 2 patients (apoptotic bodies and dyskeratotic cells) and 1 patient (apoptotic bodies only), with all of them having extra-gastrointestinal GVHD. 2 patients developed TAA to medications, levofloxacin and diphenhydramine, and 1 patient had an allergic transfusion reaction. Only 1 patient met diagnostic criteria for EoE. Based on these limited cases, HSCT patients presenting with an eosinophilic-rich esophagitis pattern were associated with conditioning regimen-induced injury and GVHD and seen in patients with TAA.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105915"},"PeriodicalIF":2.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911655","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":"Idiopathic cholestasis in adults: Genetics as another lens for liver pathologists.","authors":"Cecelia Tamburro, Anne Mentzinger, Dhanpat Jain, Sílvia Vilarinho","doi":"10.1016/j.humpath.2025.105916","DOIUrl":"https://doi.org/10.1016/j.humpath.2025.105916","url":null,"abstract":"<p><p>Chronic liver disease (CLD) is a significant global health problem, responsible for approximately two million deaths annually. Despite extensive diagnostic evaluations, a proportion of patients with CLD remain undiagnosed, making the study and quantification of these cases challenging. Genetic testing has emerged as a critical diagnostic tool, identifying monogenic causes in a substantial portion of undiagnosed cases. In addition, nearly 50 % of known genetic liver diseases were identified in the past 20 years, underscoring the rapid expansion of genetic knowledge. Notably, recent data demonstrates that genetic testing provides diagnoses in up to nearly half of adult patients with idiopathic cholestasis. Furthermore, wide application of genetic testing in adult populations is revealing that genetic cholestatic liver diseases primarily thought to be of pediatric presentation are now often recognized in adulthood. As genomic medicine continues to evolve rapidly in the context of cholestatic liver disease, pathologists must stay informed about genetic diseases and their implications for liver biopsy interpretation. Interdisciplinary efforts merging hepatologists, clinical geneticists and pathologists' expertise, such as Hepatology Genome Rounds, are envisioned to become standard practice, enhancing disease understanding and patient care.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105916"},"PeriodicalIF":2.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952112","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":"Continuous cast-like intrabiliary extension of biliary neoplasm associated with mass-forming invasive carcinoma may be a hitherto poorly-described progression of intraductal tubulopapillary neoplasm of the bile duct.","authors":"Yasuni Nakanuma, Yuko Kakuda, Hiroyuki Matsubayashi, Takuma Oishi","doi":"10.1016/j.humpath.2025.105908","DOIUrl":"10.1016/j.humpath.2025.105908","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105908"},"PeriodicalIF":2.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821293","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":"Intracranial low-grade tumors with ALK rearrangement: diverse tumor types with shared molecular alterations","authors":"Kun Mu ,&nbsp;Yu Zhang ,&nbsp;Yuyu Yang ,&nbsp;Weiqing Wang ,&nbsp;Ranran Ma ,&nbsp;Yanzhao Wang ,&nbsp;Jie Gong","doi":"10.1016/j.humpath.2025.105910","DOIUrl":"10.1016/j.humpath.2025.105910","url":null,"abstract":"<div><div>Although <em>anaplastic lymphoma kinase (ALK)</em> gene fusions are increasingly recognized in newly classified pediatric high-grade gliomas, intracranial low-grade tumors harboring <em>ALK</em> rearrangements remain under characterized in the literature. Herein, we present five cases of low-grade intracranial tumors with <em>ALK</em> rearrangements that were diagnosed at a single institution over a continuous 24-month period. Comprehensive clinicopathological evaluation integrating morphological analysis, immunohistochemical profiling, and molecular characterization of fusion partners was performed. Microscopic examination was performed to assess histologic features. A panel of antibodies were used to evaluate protein expression including ALK, desmin, GFAP, Olig2, S100, NeuN, EMA, and CD34. DNA and RNA sequencing was performed, and potential fusion transcripts were analyzed using seed count and structural chromosomal aberrations. All five tumors harbored structural aberrations involving the <em>ALK</em> locus 2p23, and no additional pathogenic mutations, amplifications, deletions, or fusions were identified in all the cases. Among them, two tumors were inflammatory myofibroblastic tumors (IMT) with <em>SQSTM1</em>::<em>ALK</em>, and <em>NPM1</em>::<em>ALK</em> fusion, respectively. One was a tanycytic supratentorial ependymoma (ST-EPN) with <em>HNRNPA1</em>::<em>ALK</em> fusion, and another was ganglioglioma (GG) with <em>PPP1CB</em>::<em>ALK</em> fusion. Interestingly, one case presented as a low-grade myxoid mesenchymal neoplasm with <em>ATIC</em>::<em>ALK</em> rearrangement that did not fit any existing tumor category. All patients underwent complete tumor resection, and were alive with no signs of recurrence during a follow-up period ranging from 1 to 18 months. In summary, ALK fusions may be shared features of a group of low-grade intracranial tumors including IMT, tanycytic ST-EPN, GG, and ALK-rearranged low-grade myxoid mesenchyma neoplasm. Future studies using larger cohorts are warranted to further characterize their clinical and pathological features.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105910"},"PeriodicalIF":2.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821294","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}