{"title":"Histological Features of Lung Squamous Cell Carcinoma According to Radiological Early-Phase Progression Patterns.","authors":"Masahiro Adachi, Jumpei Kashima, Haruto Sugawara, Satsuki Kishikawa, Hirokazu Watanabe, Masaya Yotsukura, Tomohiro Haruki, Yukihiro Yoshida, Hiroshi Igaki, Shun-Ichi Watanabe, Masahiko Kusumoto, Yasushi Yatabe","doi":"10.1111/pin.70124","DOIUrl":"10.1111/pin.70124","url":null,"abstract":"<p><p>We have previously reported radiological patterns of precursor lesions of lung squamous cell carcinoma (SqCCs) using computed tomography. SqCCs were found to develop from five unique precursor patterns. We histologically analyzed 61 cases from the previous cohort to evaluate whether these precursor patterns reflect possible developmental pathways. Of the precursor patterns, the endobronchial group demonstrated involvement of large bronchi in the hilar region. In the subsolid nodule pattern group, which exhibited ground-glass opacities radiologically, the tumors showed intra-alveolar wall infiltration, nuclear inclusion/vacuoles, low mitotic count, and absent atypical mitosis. In two of the seven cases in this group, lepidic growth, corresponding to ground-glass opacity, occurred at the tumor periphery. In the cyst wall thickening group, the tumors were located subpleurally, characterized by papillary growth structures. In the multiple-nodule group, all tumors displayed elastofibrous collapse and intra-alveolar wall infiltration. Overall and recurrence-free survival varied across the progression patterns. The radiological progression patterns were reflected in the histological features, highlighting the unique characteristics of subsolid and multiple nodule groups corresponding to peripheral-type SqCC. This study represented a new approach to the assessment of tumor evolutional pathways with histological features in combination with temporal radiographic changes.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70124"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Standardized Instance-Level Quantification of CD34-Positive Vessels in Lymph Node Whole-Slide Images Using U-Net.","authors":"Satomi Omotani, Natsumi Yonemoto, Akifumi Muramoto, Motohiro Kobayashi","doi":"10.1111/pin.70125","DOIUrl":"10.1111/pin.70125","url":null,"abstract":"<p><p>Deep learning enhances quantitative analysis of blood vessels in whole-slide images (WSIs), leading to precise and reliable counting. However, counting vessels in lymph nodes-which contain distinctive high endothelial venules (HEVs)-has not been systematically evaluated. Artificial intelligence (AI) approaches to vessel-counting fall into two categories: semantic segmentation, which provides a continuous mask, and instance segmentation, which treats each vessel as a separate object; prior work has emphasized the former. To address this gap, we adopted an instance-level approach to detect and count individual vessels. We developed a convolutional neural network (CNN) to quantify CD34-positive vessels in lymph-node WSIs, using U-Net, a widely used biomedical segmentation architecture. The model was trained over 4.0 million (4.0 M) iterations, followed by a fixed post-processing procedure to extract vessel instances. At 3.0 M, the model most faithfully captured CD34-positive vascular morphology. In the validation set, this checkpoint showed the highest morphological similarity. Furthermore, detection performance was robust with minimal variation across lymph nodes and training checkpoints. Using a simple fixed procedure, our method achieves accurate vessel detection and counting in lymph-node WSIs. This model provides a practical basis for standardized quantification and for studying lymph-node vascular morphology across normal, inflammatory, and lymphomatous states.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70125"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polypoid and Cystic Presentation of Type 1 Autoimmune Pancreatitis at the Duodenal Papilla: A Diagnostic Pitfall Mimicking Intraductal Papillary Mucinous Neoplasm.","authors":"Hirotake Fujii, Yuki Teramoto, Kenji Notohara, Takayuki Anazawa, Hiroto Nishino, Tomoaki Matsumori, Masahiro Shiokawa, Sachiko Minamiguchi, Hironori Haga","doi":"10.1111/pin.70121","DOIUrl":"10.1111/pin.70121","url":null,"abstract":"<p><p>We report a rare case of type 1 autoimmune pancreatitis (AIP) forming a polypoid mass at the major duodenal papilla in continuity with a cystic lesion of the pancreatic head, initially misdiagnosed as an intraductal papillary mucinous neoplasm (IPMN). A man in his 70s underwent pancreaticoduodenectomy after imaging revealed a mural nodule within a cystic lesion. Gross examination revealed a papillary polypoid lesion with continuity to a firm nodule in the pancreatic head. Histologically, the lesion exhibited glandular proliferation with pyloric and Brunner's gland-like differentiation in the fibrotic stroma, with dense IgG4-positive plasma cell infiltration and obliterative phlebitis. An incidental 6-mm high-grade pancreatic intraepithelial neoplasia was also identified adjacent to the IgG4-rich fibroinflammatory lesion. The surrounding pancreas showed acinar atrophy, vanishing duct change, and features consistent with resolving inflammation. The postoperative serum IgG4 levels remained elevated. Awareness of this unusual papillary, lumen-extending morphology may prompt consideration of type 1 AIP in the differential diagnosis and guide preoperative evaluation, including serum IgG4 testing and tissue sampling when clinically feasible.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70121"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A H Lim, A Ruszkiewicz, N Rodgers, J E Thomson, E L Neo, N Singhal, D Bartholomeusz, C K Rayner, E Tse, N Q Nguyen
{"title":"Histopathological Examination of Pancreatectomy Specimens From Patients With Locally Advanced Pancreatic Adenocarcinoma Following Endoscopic Ultrasound-Guided Phosphorus-32 (<sup>32</sup>P) Implantation and Chemotherapy.","authors":"A H Lim, A Ruszkiewicz, N Rodgers, J E Thomson, E L Neo, N Singhal, D Bartholomeusz, C K Rayner, E Tse, N Q Nguyen","doi":"10.1111/pin.70131","DOIUrl":"10.1111/pin.70131","url":null,"abstract":"<p><p>Despite increasing utilisation of brachytherapy for pancreatic cancer, literature on its histopathological effect is sparse. We evaluated the histopathological response and distribution of phosphorus-32 (<sup>32</sup>P) microparticles in resected locally advanced pancreatic cancer (LAPC). Distribution was confined to tumour tissue, maximising therapeutic effect whilst minimising systemic and peri-tumour exposure and potentially permitting optimisation of dosing and implantation strategies.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70131"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radwa Abd El Moneim Awad, Nehal Abd El-Ghaffar Heabah, Alshimaa Maged Eltawab
{"title":"Doublecortin-Like Kinase 1 Expression in HER2-Positive Breast Cancer: Relation to Clinicopathological Characteristics and Response to Subcutaneous Injection of Pertuzumab-Trastuzumab (Phesgo) as a Part of Neoadjuvant Chemotherapy.","authors":"Radwa Abd El Moneim Awad, Nehal Abd El-Ghaffar Heabah, Alshimaa Maged Eltawab","doi":"10.1111/pin.70119","DOIUrl":"10.1111/pin.70119","url":null,"abstract":"<p><p>Neoadjuvant therapy is backbone strategy for breast cancer (BC). Neoadjuvant subcutaneous administration of combined Pertuzumab and Trastuzumab (Phesgo) was approved in HER2-positive BC. Pathologic complete response (pCR) to neoadjuvant therapy indicates favorable patients' prognosis. Doublecortin-like kinase 1 (DCLK1) could promote chemoresistance. Little is known about the relation of DCLK1 to neoadjuvant therapy response in HER2-positive BC. Assessment of pCR, toxicity profile to Phesgo subcutaneous administration, and DCLK1 immunohistochemical expression in 104 cases of HER2-positive BC were done. Kaplan-Meier curves were used to estimate overall survival (OS) and progression free survival (PFS) in relation to pCR and DCLK1 expression. High DCLK1 expression (46.2%) was associated with large tumor size, grade III tumors, lymph node metastasis, high Ki-67 index, and poor neoadjuvant therapy response. pCR (62.5%) was related to older age, negative lymph node status, and low DCLK1 expression. Phesgo was tolerable and didn't cause cardiac toxicity or anaphylaxis. OS and PFS were higher in patients showed pCR and low DCLK1 expression. Dual blockade of HER2 using Phesgo is associated with pCR and better OS/PFS without adding more toxicity. High DCLK1 expression is related to unfavorable clinicopathologic parameters and poor response to neoadjuvant therapy, together with shorter OS/PFS.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70119"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akiko Kunita, Aya Shinozaki-Ushiku, Sachiyo Nagumo, Tetsuo Ushiku
{"title":"Preanalytical Determinants of DNA and RNA Quality in FFPE Tissues: Practical Recommendations for Molecular Testing.","authors":"Akiko Kunita, Aya Shinozaki-Ushiku, Sachiyo Nagumo, Tetsuo Ushiku","doi":"10.1111/pin.70118","DOIUrl":"10.1111/pin.70118","url":null,"abstract":"<p><p>FFPE tissue is essential for molecular testing, but nucleic acid quality is affected by preanalytical factors. Using porcine models, we systematically examined how formalin concentration, fixation duration, cold ischemia time, and tissue size affect DNA and RNA quality. Fresh liver was trimmed to 2, 10, or 50 mm and fixed in 10% or 20% neutral-buffered formalin (NBF) for 1, 3, or 7 days. In small samples, 10% NBF preserved DNA quality better than 20% NBF, while this difference was absent in large samples. RNA quality showed minimal susceptibility to formalin concentration. Both DNA and RNA deteriorated as fixation duration increased from 1 to 3 to 7 days. We next evaluated the impact of post-section storage using clinical FFPE specimens. DNA and RNA fragmentation increased after > 1 month and > 3 months, respectively, which was prevented by storage at ≤ 4°C. FFPE blocks < 1 year old yielded optimal DNA quality. These findings provide practical recommendations: (1) use 10% NBF with ≤ 24-h fixation; 20% NBF may be acceptable for large specimens, although its applicability to diverse specimen types remains unverified, (2) select blocks < 1 year old, (3) section within 1 month before testing, (4) store sections at ≤ 4°C when storage exceeds 1 month.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70118"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reinvigorating the Cancer-Immunity Cycle With Combined Oncolytic Virus and CAR-T Cell Therapies in Solid Tumors.","authors":"Keisuke Watanabe, Hiroyoshi Nishikawa","doi":"10.1111/pin.70117","DOIUrl":"10.1111/pin.70117","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T-cell therapies have shown remarkable clinical efficacy in hematological malignancies. However, objective clinical responses in solid tumors are limited. Various obstacles, such as the lack of ideal tumor-specific antigens and the immunosuppressive tumor microenvironment (TME), which impairs multiple immunological steps required to achieve effective cancer control, compromise the antitumor efficacy of CAR-T-cell therapy in solid tumors. To address this issue, combination treatment with oncolytic viruses (OVs) and CAR-T cells is being explored. OVs can modulate immunosuppression in the TME and invigorate both endogenous and adoptively transferred T cells, in addition to directly killing tumor cells. The immunomodulatory effect is further augmented by the use of OVs with therapeutic transgenes as payloads. Many preclinical evaluations have provided promising evidence for the combination approach, and clinical studies are ongoing. In this review, the mechanisms underlying resistance to CAR-T-cell therapies and recent advances in combination therapy with OVs and CAR-T cells are discussed from the perspective of the cancer-immunity cycle.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 5","pages":"e70117"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Alteration Patterns Across Histological Grades in BRAF p.V600E-Mutant Gliomas and Glioneuronal Tumors: An Analysis of 15 Cases.","authors":"Seiji Yamada, Tetsuya Takimoto, Mina Ikeda, Eiji Sugihara, Junya Yamaguchi, Shoichi Deguchi, Kosuke Aoki, Fumiharu Ohka, Kazuya Motomura, Mayu Takeda, Shigeo Ohba, Sachiko Minamiguchi, Kennosuke Karube, Ryuta Saito, Yuichi Hirose, Hideyuki Saya","doi":"10.1111/pin.70113","DOIUrl":"10.1111/pin.70113","url":null,"abstract":"<p><p>BRAF p.V600E-mutant gliomas and glioneuronal tumors comprise a wide clinicopathological spectrum, yet the relationship between genomic alteration burden and histological grade remains incompletely defined. We analyzed 15 BRAF p.V600E-mutant gliomas and glioneuronal tumors across histological grades using the PleSSision Rapid sequencing platform. Single-nucleotide variants (SNVs) and copy-number alterations were assessed in parallel to characterize genomic alteration profiles. Low-grade tumors generally exhibited limited genomic alterations; however, a subset of low-grade tumors showed increased numbers of SNVs. High-grade tumors demonstrated more extensive genomic alterations, characterized predominantly by copy-number gains. A trend toward increased copy-number gains with higher WHO grade was observed. Homozygous deletion of CDKN2A was observed in pleomorphic xanthoastrocytoma, including both CNS WHO grade 2 and grade 3 tumors, and epithelioid glioblastoma. These findings indicate substantial genomic heterogeneity among BRAF p.V600E-mutant gliomas and glioneuronal tumors. While low-grade tumors are generally genomically quiet, a subset shows increased alterations, and high-grade tumors tend to acquire copy-number changes, highlighting the limitations of genomic event counts alone as a surrogate for malignant potential.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 4","pages":"e70113"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}