Pathology International最新文献_第4页

A Unique WHSC1L1-FGFR1 Fusion in Follicular Dendritic Cell Sarcoma. 滤泡树突状细胞肉瘤中一种独特的WHSC1L1-FGFR1融合。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70169

Pedro Farrajota Neves da Silva, Felix Haglund de Flon, Clas Mercke, George Z Rassidakis

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Primary Biliary Cholangitis-Associated Granulomatous Interstitial Lung Disease: Pulmonary Epithelial-Interface Injury Supporting the Concept of Generalized Autoimmune Epithelitis. 原发性胆道胆管炎相关肉芽肿性间质性肺病：肺上皮-界面损伤支持全身性自身免疫性上皮炎的概念。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70166

Jiayao Liu, Yuki Kamikokura, Manami Hayashi, Akira Sakata, Naoko Aoki, Miki Saito, Yoshinori Minami, Takaaki Sasaki, Masahiro Kitada, Yukio Nakatani, Sayaka Yuzawa, Shin Ichihara, Mishie Tanino

{"title":"Primary Biliary Cholangitis-Associated Granulomatous Interstitial Lung Disease: Pulmonary Epithelial-Interface Injury Supporting the Concept of Generalized Autoimmune Epithelitis.","authors":"Jiayao Liu, Yuki Kamikokura, Manami Hayashi, Akira Sakata, Naoko Aoki, Miki Saito, Yoshinori Minami, Takaaki Sasaki, Masahiro Kitada, Yukio Nakatani, Sayaka Yuzawa, Shin Ichihara, Mishie Tanino","doi":"10.1111/pin.70166","DOIUrl":"10.1111/pin.70166","url":null,"abstract":"Primary biliary cholangitis (PBC) can be accompanied by interstitial lung disease (ILD) manifesting as granulomatous interstitial lung disease, but the mechanism of granuloma formation remains unclear. We report a case of PBC-ILD coexisting with anti-synthetase syndrome (ASS) in a 49-year-old woman who presented with persistent cough, facial rash, and arthritis. Laboratory tests demonstrated cholestatic enzyme elevation, anti-mitochondrial M2 positivity, and anti-aminoacyl-tRNA synthetase antibody positivity, with elevated KL-6 and SP-D levels. High-resolution CT revealed lower-lobe-predominant ground-glass opacities. Bronchoalveolar lavage fluid showed lymphocytosis with high CD4/CD8 ratio. Liver biopsy confirmed PBC. Surgical lung biopsies revealed epithelial-interface injury and focal apoptosis of bronchiolar and alveolar epithelium accompanied by CD4-dominant T-cell infiltration and non-caseating granulomas (NCGs). Segment 2 showed cellular NSIP pattern and segment 9 showed fibrotic NSIP pattern. NCGs were more prominent in the cellular NSIP areas and decreased in the fibrotic NSIP areas. These findings suggest a possible pathological continuum from active inflammation by epithelial-interface injury to fibrotic remodeling. These observations may highlight the potential relevance of generalized autoimmune epithelitis in the pathogenesis of PBC-ILD.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 8","pages":"e70166"},"PeriodicalIF":1.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796507","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}

引用次数: 0

Impact of Tissue Sampling Strategy on the Diagnostic Accuracy of DNA Methylation Profiling in Central Nervous System Tumors. 组织取样策略对中枢神经系统肿瘤DNA甲基化谱诊断准确性的影响。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70161

Jyotsna Singh, Shabnam Mansoori, Bharathi Prabakaran N S, Swati Singh, Supriya Bhardwaj, Srinidhi Vasant, Kirti Srivastava, Ashwinee Kumar, Swati Mahajan, Vaishali Suri

{"title":"Impact of Tissue Sampling Strategy on the Diagnostic Accuracy of DNA Methylation Profiling in Central Nervous System Tumors.","authors":"Jyotsna Singh, Shabnam Mansoori, Bharathi Prabakaran N S, Swati Singh, Supriya Bhardwaj, Srinidhi Vasant, Kirti Srivastava, Ashwinee Kumar, Swati Mahajan, Vaishali Suri","doi":"10.1111/pin.70161","DOIUrl":"10.1111/pin.70161","url":null,"abstract":"DNA methylation-based classification is a key adjunct to histopathology in CNS tumor diagnostics. Although both fresh-frozen and FFPE tissues are used, the impact of sampling strategy on classifier performance remains insufficiently characterized. We analyzed 179 CNS specimens (162 tumors and 17 controls), including 42 FFPE and 137 fresh-frozen samples with ≥ 50% tumor cellularity. Fresh-frozen cases were stratified into histology-validated and blind sampling groups. Genome-wide DNA methylation profiling was performed using Illumina EPIC/EPIC v2.0 arrays and classified using the DKFZ Brain Tumor Classifier, with independent validation using the NIH Methylscape platform. Results were categorized as confirmed, refined, changed, or unclassified and correlated with histopathological diagnoses. FFPE samples showed high diagnostic yield with minimal unclassified results (2%). Among fresh-frozen specimens, histology-validated samples demonstrated robust classification, whereas blind sampling showed higher discordance and unclassified rates (22%). Discordant results were confined to the blind-sampling group and were most consistent with sampling bias and variable tumor representation rather than technical limitations. Methylation profiling confirmed or refined diagnoses in most cases and led to clinically relevant reclassification in a subset. Classifier performance appeared to be influenced more by sampling strategy rather than preservation method, with histology-guided sampling associated with the most reliable diagnostic outcomes.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 8","pages":"e70161"},"PeriodicalIF":1.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722861","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}

引用次数: 0

A Case of an Inflammatory Myofibroblastic Tumor Harboring a Novel STRN3::ALK Fusion. 炎症性肌成纤维细胞肿瘤携带新型STRN3::ALK融合1例。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70163

Kurara Yamamoto, Ryota Miyata, Junko Kunieda, Yuki Togashi, Satoko Baba, Ayaka Asakawa, Kenichi Okubo, Kyoko Yamashita, Kenichi Ohashi, Kengo Takeuchi

引用次数: 0

Comparative Analysis of the Clinicopathological Features of Follicular Lymphoma With and Without EZH2 Y646 Mutation. EZH2 Y646突变伴与不伴滤泡性淋巴瘤临床病理特征的比较分析。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70167

Akira Satou, Kanae Yoshikawa, Ikki Mitsuda, Akari Iwakoshi, Makoto Minoshima, Masaharu Gunji, Hideki Murakami, Joaquim Carreras, Haruka Ikoma, Naoya Nakamura, Toyonori Tsuzuki, Masanori Sato, Kennosuke Karube

{"title":"Comparative Analysis of the Clinicopathological Features of Follicular Lymphoma With and Without EZH2 Y646 Mutation.","authors":"Akira Satou, Kanae Yoshikawa, Ikki Mitsuda, Akari Iwakoshi, Makoto Minoshima, Masaharu Gunji, Hideki Murakami, Joaquim Carreras, Haruka Ikoma, Naoya Nakamura, Toyonori Tsuzuki, Masanori Sato, Kennosuke Karube","doi":"10.1111/pin.70167","DOIUrl":"10.1111/pin.70167","url":null,"abstract":"Histone methyltransferase EZH2 is essential for germinal center formation, and gain-of-function mutations of EZH2 occur in approximately 20% of follicular lymphomas (FLs). Although EZH2 inhibitors are used for relapsed/refractory EZH2-mutated (EZH2mut) FLs, their clinicopathological characteristics remain incompletely understood. We assessed the EZH2 Y646 mutation by Sanger sequencing in 301 FLs and identified mutations in 17% (50/301). Compared with EZH2 wild-type (EZH2wt), EZH2mut FL showed a significantly higher proportion aged > 60 years (p = 0.033). Pathologically, EZH2mut FL more frequently exhibited clear neoplastic follicles (p < 0.0001) and grater interfollicular tumor cell distributions highlighted by CD20 immunohistochemistry (p < 0.0001). These cases also more often showed the typical FL immunophenotype (CD10+, BCL2+, BCL6+) (p = 0.027) and BCL2 rearrangement (p = 0.0060). Gene expression profiling revealed enrichment of TNF-α/NF-κB signaling in EZH2wt FL, whereas EZH2mut FL showed upregulation of cell-cycle programs, particularly the G2/M checkpoint. Concordance of EZH2 mutation status between primary and relapsed lesions was 94% (33/35). Even at relapse, EZH2mut FL retained its characteristic pathological features, including clear follicles and high interfollicular spread of tumor cells. In conclusion, EZH2mut FL exhibits distinctive clinicopathological and molecular features that may help identify patients most likely to benefit from EZH2-targeted therapy.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 8","pages":"e70167"},"PeriodicalIF":1.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808825","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}

引用次数: 0

Muir-Torre Syndrome Associated With a Cryptic Intronic MSH2 Variant Identified via Whole-Genome Sequencing: A Case Report. Muir-Torre综合征与通过全基因组测序鉴定的隐性内含子MSH2变异相关：一个病例报告。

IF 1.9 4区医学

Pathology International Pub Date : 2026-08-01 DOI: 10.1111/pin.70164

Keisuke Noda, Hirokazu Kurohama, Katsuya Matsuda, Akira Kinoshita, Hiroyuki Mishima, Megumi Matsumoto, Riko Matsuda, Nozomi Ueki, Masao Kishikawa, Kiyonori Miura, Takashi Nonaka, Koh-Ichiro Yoshiura, Keitaro Matsumoto, Masahiro Nakashima

{"title":"Muir-Torre Syndrome Associated With a Cryptic Intronic MSH2 Variant Identified via Whole-Genome Sequencing: A Case Report.","authors":"Keisuke Noda, Hirokazu Kurohama, Katsuya Matsuda, Akira Kinoshita, Hiroyuki Mishima, Megumi Matsumoto, Riko Matsuda, Nozomi Ueki, Masao Kishikawa, Kiyonori Miura, Takashi Nonaka, Koh-Ichiro Yoshiura, Keitaro Matsumoto, Masahiro Nakashima","doi":"10.1111/pin.70164","DOIUrl":"10.1111/pin.70164","url":null,"abstract":"Tumors exhibiting mismatch repair deficiency without detectable germline mutations via standard multigene panel testing are often classified as Lynch-like syndrome. In the present report, we describe the case of a 47-year-old man presenting with synchronous axillary sebaceous carcinoma and colonic medullary carcinoma. Although initial germline multigene panel testing failed to identify pathogenic variants, a high degree of pathological suspicion for Muir-Torre syndrome remained. Immunohistochemistry revealed a concordant loss of MSH2 and MSH6 expression in both the extraocular sebaceous carcinoma and the colonic medullary carcinoma. This identical protein-loss pattern detected across anatomically distinct tumors served as decisive pathological evidence of an underlying germline defect rather than independent biallelic somatic mutations. Consequently, whole-genome sequencing was performed to resolve the discrepancy between the pathological findings and multigene panel testing results, successfully identifying a germline intronic MSH2 variant (NM_000251.3:c.2459-12A>G). Subsequent RNA analysis confirmed aberrant splicing with an 11-bp insertion. In conclusion, the present case illustrates that concordant mismatch repair protein loss across multiple tumors provides compelling morphological evidence to guide pathologists in reconsidering negative panel results and pursuing comprehensive genomic investigation to identify pathogenic intronic variants.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 8","pages":"e70164"},"PeriodicalIF":1.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726208","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}

引用次数: 0

AID and MUM1 Negativity Identifies a Prognostically Favorable Subgroup of Diffuse Large B-Cell Lymphoma/High-Grade B-Cell Lymphoma With Double-Hit MYC and BCL2 or BCL6 and Triple Hit. AID和MUM1阴性确定弥漫性大b细胞淋巴瘤/高级别b细胞淋巴瘤伴MYC和BCL2双重打击或BCL6和三重打击的预后有利亚组。

IF 1.9 4区医学

Pathology International Pub Date : 2026-07-01 DOI: 10.1111/pin.70145

Masashi Miyaoka, Joaquim Carreras, Yara Yukie Kikuti, Haruka Ikoma, Shunsuke Nagase, Atsushi Ito, Makoto Orita, Yuki Tanigaki, Yohei Masugi, Giovanna Roncador, Naoya Nakamura

引用次数: 0

Prevalence and Independence of p53 Signatures and β-Catenin Signatures in Risk-Reducing Salpingo-Oophorectomy Specimens. p53信号和β-Catenin信号在输卵管卵巢切除术标本中的普遍性和独立性。

IF 1.9 4区医学

Pathology International Pub Date : 2026-07-01 DOI: 10.1111/pin.70152

Kei Koyama, Hikaru Tsukita, Takahiro Ishinari, Ayana Takahashi, Ken Miyabe, Makoto Yoshida, Yukitsugu Kudo-Asabe, Hiroshi Nanjo, Masato Waga, Enami Kaneko, Takeo Hirakawa, Tae Sugawara, Kenichi Makino, Yukihiro Terada, Akiteru Goto

{"title":"Prevalence and Independence of p53 Signatures and β-Catenin Signatures in Risk-Reducing Salpingo-Oophorectomy Specimens.","authors":"Kei Koyama, Hikaru Tsukita, Takahiro Ishinari, Ayana Takahashi, Ken Miyabe, Makoto Yoshida, Yukitsugu Kudo-Asabe, Hiroshi Nanjo, Masato Waga, Enami Kaneko, Takeo Hirakawa, Tae Sugawara, Kenichi Makino, Yukihiro Terada, Akiteru Goto","doi":"10.1111/pin.70152","DOIUrl":"10.1111/pin.70152","url":null,"abstract":"Clusters of epithelial cells of the fallopian tube exhibiting aberrant p53 expression, termed \"p53 signatures,\" are detected at a relatively high frequency and have been regarded as putative precursors of high-grade serous carcinoma (HGSC). In contrast, the recently proposed \"β-catenin signature\" represents a distinct tubal epithelial alteration characterized by the aberrant expression of β-catenin, the biological significance of which remains unclear. To clarify the frequency and spatial relationship between the two lesions, we analyzed 30 consecutive risk-reducing salpingo-oophorectomy specimens from BRCA1/2 mutation carriers using the sectioning and extensively examining the fimbriated end protocol and performed immunohistochemical evaluation for p53, β-catenin, and Ki-67. p53 signatures and β-catenin signatures were each identified in seven cases (23%). Two cases (6.7%) harbored both lesions; however, no spatial overlap or histological continuity was observed. Neither lesion demonstrated significant associations with BRCA mutation subtype, age, body mass index, or parity. Furthermore, no cases showed serous tubal intraepithelial lesion, serous tubal intraepithelial carcinoma, or HGSC. These findings suggest that p53 signatures and β-catenin signatures may represent distinct localized epithelial alterations in the fallopian tube, although further molecular and spatial analyses are required to clarify their biological relationship.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 7","pages":"e70152"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550101","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}

引用次数: 0

IF 1.9 4区医学

Pathology International Pub Date : 2026-07-01 DOI: 10.1111/pin.70159

Toshihiro Gi, Hiroki Tanaka, Sayaka Moriguchi-Goto, Kensaku Nishihira, Yujiro Asada, Koichi Kaikita, Atsushi Yamashita

引用次数: 0

Effects of Nicotine on Urinary Bladder Carcinogenesis. 尼古丁对膀胱癌发生的影响。

IF 1.9 4区医学

Pathology International Pub Date : 2026-07-01 DOI: 10.1111/pin.70151

Shugo Suzuki, Samuel M Cohen

{"title":"Effects of Nicotine on Urinary Bladder Carcinogenesis.","authors":"Shugo Suzuki, Samuel M Cohen","doi":"10.1111/pin.70151","DOIUrl":"10.1111/pin.70151","url":null,"abstract":"Epidemiological evidence has consistently demonstrated an association between tobacco smoking and an increased risk of urinary bladder cancer. However, the specific role of nicotine, independent from established genotoxic carcinogens such as aromatic amines, has not been clarified. This review summarises experimental evidence regarding the carcinogenic effects of nicotine and the underlying molecular mechanisms in urinary bladder carcinogenesis. In a two-stage rat carcinogenesis model, nicotine administration significantly increased the incidence and multiplicity of invasive urothelial carcinoma. In contrast, nicotine treatment alone increased hyperplasia but did not induce the formation of tumors, suggesting that nicotine functions as an enhancing agent for tumorigenesis, rather than as a DNA reactive agent. Mechanistically, nicotine has been shown to induce cell proliferation through two distinct pathways. One involves the activation of nicotinic acetylcholine receptors (nAChRs), particularly the α7 subunit, leading to activation of STAT3 and ERK1/2 signalling pathway. The other involves urothelial cytotoxicity followed by regenerative increased cell proliferation. In addition, cotinine, the major urinary metabolite of nicotine, was found to induce proliferation via nAChRs, without inducing cytotoxicity. These findings indicate that nicotine exposure may contribute to bladder cancer risk through mechanisms involving increased cell proliferation, either due to direct mitogenesis or secondary to cytotoxicity and regeneration.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 7","pages":"e70151"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456350","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}

引用次数: 0