Pathology International最新文献

Genomic Alteration Patterns Across Histological Grades in BRAF p.V600E-Mutant Gliomas and Glioneuronal Tumors: An Analysis of 15 Cases. 15例BRAF p.v 600e突变型胶质瘤和神经细胞瘤的不同组织学级别的基因组改变模式分析

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70113

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

{"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":"https://doi.org/10.1111/pin.70113","url":null,"abstract":"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.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 4","pages":"e70113"},"PeriodicalIF":3.4,"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}

引用次数: 0

Eosinophilic Biliary Cystic Neoplasm of the Liver: A Case Report of an Unrecognized Subtype of Intrahepatic Biliary Neoplasm. 肝脏嗜酸性胆道囊性肿瘤：一种未被识别的肝内胆道肿瘤亚型1例报告。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70114

Mariko Tanaka, Daizo Koinuma, Munetoshi Hinata, Kimiko Takeshita, Yoichi Yasunaga, Kei Sakuma, Takeshi Takamoto, Yujiro Nishioka, Kiyoshi Hasegawa, Yudai Nakai, Tetsuo Ushiku

{"title":"Eosinophilic Biliary Cystic Neoplasm of the Liver: A Case Report of an Unrecognized Subtype of Intrahepatic Biliary Neoplasm.","authors":"Mariko Tanaka, Daizo Koinuma, Munetoshi Hinata, Kimiko Takeshita, Yoichi Yasunaga, Kei Sakuma, Takeshi Takamoto, Yujiro Nishioka, Kiyoshi Hasegawa, Yudai Nakai, Tetsuo Ushiku","doi":"10.1111/pin.70114","DOIUrl":"10.1111/pin.70114","url":null,"abstract":"We report a multicystic intrahepatic neoplasm in a 54-year-old Japanese woman, representing a previously unrecognized subtype. Grossly, the lesion was a well-demarcated multicystic tumor with focal papillary projections. Histologically, the cysts were lined by columnar to cuboidal neoplastic cells with brush border-like luminal microvilli, abundant granular eosinophilic cytoplasm, and small round nuclei. The cystic lumina contained colloid-like secretion, and bile-filled glands were occasionally observed. The septa were composed of thin hepatocellular parenchyma. Immunohistochemically, the tumor cells were positive for CD10, CK7, CK19, EpCAM, and SPINK1 and negative for HepPar1, MUC1, MUC2, MUC5AC, and MUC6. Whole-exome sequencing identified a pathogenic somatic KRAS p.G12V variant. RNA sequencing detected no PRKACA/B fusions. Single-cell spatial transcriptomics demonstrated that tumor cells clustered most closely with septal and medium-sized interlobular bile ducts. Gene set activity analysis showed significant suppression of gene sets downregulated by KRAS activation and upregulation of KRAS dependency signature gene sets in tumor cells. These findings distinguish this lesion from established entities of intrahepatic biliary cystic neoplasms, including intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, intraductal oncocytic papillary neoplasm, and mucinous cystic neoplasm. We propose the designation \"eosinophilic biliary cystic neoplasm of the liver\" for this distinct intrahepatic biliary neoplasm.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 4","pages":"e70114"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699453","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

Cortisol-Producing Oncocytic Adrenocortical Carcinoma Harboring a GNAS Mutation: An Integrated Histologic, Ultrastructural, and Genomic Analysis. 含有GNAS突变的促肾上腺皮质癌：综合组织学、超微结构和基因组分析。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70112

Naomi Sato, Yuta Tezuka, Taito Itoh, Yuko Omori, Taro Koike, Masaki Satou, Masaki Ogata, Yoshikiyo Ono, Masaaki Kitada, Yuto Yamazaki, Toru Furukawa, Takashi Suzuki, Yasuhiro Nakamura

{"title":"Cortisol-Producing Oncocytic Adrenocortical Carcinoma Harboring a GNAS Mutation: An Integrated Histologic, Ultrastructural, and Genomic Analysis.","authors":"Naomi Sato, Yuta Tezuka, Taito Itoh, Yuko Omori, Taro Koike, Masaki Satou, Masaki Ogata, Yoshikiyo Ono, Masaaki Kitada, Yuto Yamazaki, Toru Furukawa, Takashi Suzuki, Yasuhiro Nakamura","doi":"10.1111/pin.70112","DOIUrl":"https://doi.org/10.1111/pin.70112","url":null,"abstract":"Oncocytic adrenal neoplasms are rare adrenocortical tumors characterized by abundant eosinophilic cytoplasm due to massive mitochondrial accumulation. Their biological behavior is often difficult to predict, and various diagnostic systems-including the Lin-Weiss-Bisceglia system, the Helsinki score, and the reticulin algorithm-are used to assess their malignant potential. We report a case of an oncocytic adrenocortical carcinoma associated with Cushing's syndrome and hyperandrogenemia in a 34-year-old woman. Histologically, the tumor showed diffuse growth of eosinophilic cells with marked pleomorphism and focal capsular invasion. Immunohistochemistry confirmed adrenocortical origin and cortisol production, with a Ki-67 labeling index of 25%. Ultrastructural examination revealed densely packed mitochondria with lamellar and tubulovesicular cristae, accompanied by numerous whorled smooth endoplasmic reticulum formations, suggesting active remodeling of the endoplasmic reticulum. Whole-exome sequencing identified a pathogenic GNAS R201S mutation, together with copy number losses of ARID1A, CDKN2A, and ZNRF3 with widespread copy number alteration. Despite multiple adverse prognostic indicators, the patient has remained disease-free for over 5 years following adrenalectomy and adjuvant low-dose mitotane therapy. These findings suggest that GNAS activation may drive steroidogenesis while attenuating malignant progression, as demonstrated by integrated morphologic and genomic assessment in this case.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 4","pages":"e70112"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623365","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}

引用次数: 0

Association of Smoothelin, a Cytoskeletal Component of Smooth Muscle Cells, With the Proliferative Features of Uterine Smooth Muscle Tumors. 平滑素，平滑肌细胞的一种细胞骨架成分，与子宫平滑肌肿瘤增生特征的关联。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70110

Sayaka Shimodai-Yamada, Kenta Uto, Guillaume van Eys, Yuya Denda, Mayumi Suzuki, Kei Kawana, Hiroyuki Hao

{"title":"Association of Smoothelin, a Cytoskeletal Component of Smooth Muscle Cells, With the Proliferative Features of Uterine Smooth Muscle Tumors.","authors":"Sayaka Shimodai-Yamada, Kenta Uto, Guillaume van Eys, Yuya Denda, Mayumi Suzuki, Kei Kawana, Hiroyuki Hao","doi":"10.1111/pin.70110","DOIUrl":"https://doi.org/10.1111/pin.70110","url":null,"abstract":"Smoothelin, a cytoskeletal protein expressed in smooth muscle cells (SMCs), colocalizes with α-smooth muscle actin and is typically restricted to the cytoplasm. Interestingly, in malignant smooth muscle tumors (SMTs), particularly uterine leiomyosarcoma (LMS), aberrant nuclear localization of smoothelin has been observed, though the underlying mechanism remains unclear. To investigate, 99 uterine SMT cases were analyzed, comprising 26 LMS and 73 non-LMS (typical leiomyoma, cellular leiomyoma, mitotically active leiomyoma, and tumors of uncertain malignant potential). Histopathological and immunohistochemical evaluations included mitotic activity, Ki-67 index, and smoothelin expression. In vitro, two humans uterine LMS cell lines (SK-LMS-1, SK-UT-1) and a primary uterine SMC line under proliferative conditions were examined. Nuclear smoothelin expression was significantly more frequent in LMS compared with non-LMS. Within LMS tissues, both cytoplasmic and nuclear positivity were noted. Smoothelin-positive regions exhibited significantly higher mitotic activity, whereas Ki-67 labeling and nuclear size variation showed no association with localization. In cultured LMS cells, proliferation correlated with increased nuclear smoothelin positivity. These findings suggest that smoothelin is linked to proliferative capacity in SMTs, and its altered subcellular distribution may have potential utility in the pathological evaluation of SMTs.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 4","pages":"e70110"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623437","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}

引用次数: 0

Helicobacter felis-Associated Acute Gastric Mucosal Lesion: Ultrastructure by Low-Vacuum Scanning Electron Microscopy. 幽门螺杆菌引起的急性胃黏膜病变：低真空扫描电镜的超微结构。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70109

Murasaki Aman, Toshihiro Gi, Kazunari Maekawa, Tomoaki Kimura, Akira Sawaguchi, Atsushi Yamashita

引用次数: 0

Abstracts of Presentation by the Winners of the Japanese Society of Pathology; Japan Pathology Award in 2026 (in Program Order). 日本病理学会获奖者演讲摘要获2026年日本病理学奖（按项目顺序）。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70116

引用次数: 0

Developmental Odontogenic Cyst With Characteristic Features of Glandular Odontogenic Cyst and Odontogenic Keratocyst. 以腺性牙源性囊肿和牙源性角化囊肿为特征的发育性牙源性囊肿。

IF 3.4 4区医学

Pathology International Pub Date : 2026-04-01 DOI: 10.1111/pin.70111

Nanako Kataoka, Yasuyuki Asada, Taeko Fukutani, Yukina Kobayashi, Ryouji Tani, Yoshikazu Suei, Naoya Kakimoto, Souichi Yanamoto, Ikuko Ogawa, Mutsumi Miyauchi, Mikihito Kajiya, Toshinori Ando

引用次数: 0

Establishment of a Patient-Derived Xenograft Model of a Testicular Yolk Sac Tumor. 患者来源睾丸卵黄囊肿瘤异种移植模型的建立。

IF 3.4 4区医学

Pathology International Pub Date : 2026-03-01 Epub Date: 2026-01-04 DOI: 10.1111/pin.70079

Nobuhiko Shimizu, Taku Naiki, Aya Naiki-Ito, Yosuke Sugiyama, Takashi Nagai, Toshiki Etani, Toshiharu Morikawa, Masakazu Gonda, Maria Aoki, Daiki Ishikawa, Yukihiro Umemoto, Satoru Takahashi, Takahiro Yasui

引用次数: 0

Appendiceal Goblet Cell Adenocarcinoma With Mismatch Repair Deficiency and Microsatellite Instability-High Status: A Novel Molecular Signature Guiding Immuno-Oncology Strategy. 具有错配修复缺陷和微卫星不稳定-高状态的阑尾杯状细胞腺癌：一种新的分子特征指导免疫肿瘤策略。

IF 3.4 4区医学

Pathology International Pub Date : 2026-03-01 DOI: 10.1111/pin.70108

Hirotsugu Hashimoto, Hirotomo Koda, Kentaro Nakajima, Takuro Mizukami, Masashi Kusakabe, Shouichi Satou, Teppei Morikawa

{"title":"Appendiceal Goblet Cell Adenocarcinoma With Mismatch Repair Deficiency and Microsatellite Instability-High Status: A Novel Molecular Signature Guiding Immuno-Oncology Strategy.","authors":"Hirotsugu Hashimoto, Hirotomo Koda, Kentaro Nakajima, Takuro Mizukami, Masashi Kusakabe, Shouichi Satou, Teppei Morikawa","doi":"10.1111/pin.70108","DOIUrl":"https://doi.org/10.1111/pin.70108","url":null,"abstract":"Appendiceal goblet cell adenocarcinoma (GCA) is a rare amphicrine neoplasm, which recent studies have characterized as mismatch repair proficient and microsatellite stable. A 49-year-old male presented to our hospital with a Borrmann type 3-like ileocecal tumor extending continuously from a markedly swollen appendix. The patient underwent ileocecal resection. Pathologically, the tumor was diagnosed as high-grade appendiceal GCA, accompanied by lymphocytic infiltration, staged as pStage IVB. Immunohistochemistry revealed loss of MSH2 and MSH6 expression, indicating mismatch repair deficiency (dMMR), and molecular analysis confirmed microsatellite instability (MSI)-high status. Postoperatively, the patient was treated with chemotherapy, including immune checkpoint inhibitors as second-line therapy, which provided temporary relief of duodenal stenosis caused by tumor metastasis. However, the patient died of disease progression 37 months after surgery. To our knowledge, this is the first report of appendiceal GCA with dMMR and MSI-high status. Our findings underscore the necessity of incorporating MMR/MSI testing into the diagnostic workup of rare tumors such as GCA, particularly in young patients or those with a family history suggestive of Lynch syndrome, to optimize personalized treatment strategies.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 3","pages":"e70108"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504570","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}

引用次数: 0

Heterologous Rhabdomyoblastic Differentiation in Dedifferentiated Liposarcoma Is Significantly Associated With Loss of H3K27 Trimethylation. 去分化脂肪肉瘤的异源横纹肌母细胞分化与H3K27三甲基化缺失显著相关

IF 3.4 4区医学

Pathology International Pub Date : 2026-03-01 DOI: 10.1111/pin.70103

Fleur Cordier, Nadine Van Roy, Liesbeth Ferdinande, David Creytens

引用次数: 0