{"title":"Immunohistochemical investigation of the transcription factor PROX1 emphasizing on neuroendocrine neoplasms.","authors":"Kanata Kojima, Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Mako Ochiai, Taku Kato, Hiroyasu Ito","doi":"10.1007/s00795-025-00437-z","DOIUrl":"10.1007/s00795-025-00437-z","url":null,"abstract":"<p><p>Prospero homeobox protein 1 (PROX1) is aberrantly expressed in tumors, including neuroendocrine neoplasms (NENs); however, the detailed expression pattern remains elusive. This study aimed to immunohistochemically assess PROX1 expression. Immunohistochemistry (IHC) for PROX1 was performed on tissue microarrays of normal tissues (n = 107), NENs (n = 152) (small cell lung carcinoma [SCLC], lung carcinoid [LC], gastroenteropancreatic-NEN [GEP-NEN], esophageal neuroendocrine carcinoma [ENEC], medullary thyroid carcinoma [MTC], neuroblastoma [NB], and pheochromocytoma [PHEO]), and non-NENs (n = 469). In normal tissues, PROX1 was expressed in lymphatic endothelial cells and a subset of epithelial cells in the gastrointestinal tract and the distal convoluted tubules. In NENs, the positive expression was observed in the nucleus of tumor cells in 19/26 SCLC (73.1%), 13/16 LC (81.3%), 10/15 GEP-NEN (66.7%), 2/2 ENEC (100%), 17/43 MTC (39.5%), 1/25 NB (4.0%), and 0/25 PHEO (0%). Although PROX1 was negative in many non-NENs, our analysis revealed high expression in certain cases with medulloblastoma and one case with juvenile granulosa cell tumor. PROX1 was expressed in specific cases with epithelial NENs and some cases with non-NENs. Analysis of PROX1 should provide insights into the molecular characteristics of distinct tumors.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"1-7"},"PeriodicalIF":1.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034515","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":"A rare case of thymoma with extensive clear cell components: a discussion of its clear cell transformation.","authors":"Hiroshi Sonobe, Rika Omote, Kenji Takahashi, Hiroyuki Yanai, Hiroki Kajihara, Hirofumi Nakayama, Ichiro Murakami, Yuki Hanamatsu","doi":"10.1007/s00795-025-00450-2","DOIUrl":"10.1007/s00795-025-00450-2","url":null,"abstract":"<p><p>We report a rare case of thymoma with extensive clear cell components, and discuss the histogenesis of clear cell transformation. Although thymic clear cell carcinoma is classified as a subtype of thymic carcinoma, thymoma with extensive clear cell components has not been recognized as a subtype in the World Health Organization classification (2021). Therefore, such thymomas may be erroneously misdiagnosed as clear cell carcinoma. Thymic clear cell carcinomas are positive for glycogen, with a high Ki67 index, whereas the clear cell component of the present tumor was negative, with a low index; this difference may help to distinguish thymomas with extensive clear cell components from thymic clear cell carcinomas. In this tumor, spindle cells predominantly proliferated in the center, whereas clear cells were densely distributed in the periphery. Hence, the initial tumor likely consisted of spindle cells, some of which transformed into clear cells as the tumor grew larger. In addition, nuclei of the clear cells were occasionally positive for autophagy-related 4 cysteine peptidase. Electron microscopically, clear cells with eccentrically located nuclei and cytoplasm contained large vacuoles, in which irregularly shaped membranous structures were observed. The histology, immunohistochemistry, and ultrastructure suggest that clear cell transformation represents a type of cellular degeneration.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"71-78"},"PeriodicalIF":1.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452386","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":"Epithelioid sarcoma originating in the chest wall: A case report.","authors":"Yuzo Oyama, Riko Furukawa-Kubota, Hiroko Kadowaki, Junnpei Wada, Kazuhiro Kawamura, Takashi Miura, Tsutomu Daa","doi":"10.1007/s00795-025-00445-z","DOIUrl":"10.1007/s00795-025-00445-z","url":null,"abstract":"<p><p>This report presents the sixth case of chest wall epithelioid sarcoma (ES) in a 71-year-old Japanese man. The patient was incidentally diagnosed with a soft tissue tumor between the eighth and ninth ribs, presenting with an associated bone fracture and osteolytic change. Marginal resection followed by chest wall reconstruction was performed for a definitive diagnosis. Histopathological examination revealed multinodular growth associated with collagenous stroma, mimicking a necrotizing granulomatous process. Various tumor cells were observed, including epithelioid, spindle-shaped, and rhabdoid cells. Immunohistochemical analysis, conducted on trimmed tumor samples without decalcification, revealed positivity for cytokeratin AE1/AE3, vimentin, and CD34, as well as negativity for CK7, CK20, CD31, calretinin, and D2-40. INI expression was completely absent in tumor cells. The patient was diagnosed with ES. The chest wall is an unusual location for ES, and its diagnosis requires differentiation from other epithelioid neoplasms. This case highlights the importance of trimming tumor samples before decalcification to preserve antigenicity and ensure accurate immunohistochemistry analysis.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"79-84"},"PeriodicalIF":1.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804419","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":"Fascin-1 expression is associated with EMT and recurrence in thymic carcinoma: a clinicopathologic study.","authors":"Hironobu Okada, Yoshihiro Hayashi, Naoki Furukawa, Yujirou Bunno, Marino Yamamoto, Ryohei Miyazaki, Mitsuko Iguchi, Makoto Toi, Ichiro Murakami, Masaya Tamura","doi":"10.1007/s00795-025-00446-y","DOIUrl":"10.1007/s00795-025-00446-y","url":null,"abstract":"<p><p>Fascin-1, an actin-bundling protein, plays a crucial role in cancer cell motility, invasion, and epithelial-mesenchymal transition (EMT). While its significance has been demonstrated in several malignancies, its clinical relevance in thymic carcinoma remains unclear. We retrospectively analyzed 10 surgically resected thymic carcinoma cases treated at Kochi University Hospital from 2008 to 2024. Immunohistochemical staining was performed to evaluate Fascin-1 expression using the Allred scoring system. Expression of EMT-related markers (TGF-β, pSmad3, Snail, and E-cadherin) was also assessed. Associations between Fascin-1 expression and postoperative recurrence were analyzed. Fascin-1 was highly expressed in tumor regions with low E-cadherin expression and co-localized with EMT-inducing markers such as TGF-β and Snail. Patients with postoperative recurrence showed significantly higher Fascin-1 scores than those without recurrence (P = 0.048). Double immunofluorescence confirmed an inverse relationship between Fascin-1 and E-cadherin expression. High Fascin-1 expression may serve as a potential marker for postoperative recurrence in thymic carcinoma and is closely associated with EMT. These findings suggest Fascin-1 as a promising prognostic biomarker and therapeutic target, although further studies with larger cohorts and functional analyses are warranted.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"57-63"},"PeriodicalIF":1.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959783","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":"Heat stroke-induced hepatic lipid dysregulation: histological and lipidomic insights.","authors":"Takahiro Deguchi, Hiroki Tanaka, Kie Horioka, Chihiro Matsuhisa, Akira Hayakawa, Shuhei Takauji, Shimpei Watanabe, Masanori Goto, Yumiko Fujii, Kumi Takasawa, Akira Takasawa","doi":"10.1007/s00795-025-00441-3","DOIUrl":"10.1007/s00795-025-00441-3","url":null,"abstract":"<p><p>Global warming has increased summer temperatures, leading to a rise in heat stroke-related deaths in Japan. Heat stroke disrupts the body's adaptation to high temperatures, often resulting in severe complications, including liver damage and even death. However, despite the increasing incidence, pathological autopsies remain rare, and the histological changes associated with heat stroke are poorly understood. In this study, we investigated the pathogenesis of heat stroke using a mouse model. Mice were exposed to 45 °C for 30 min and dissected immediately or 24, 48, and 72 h post-exposure. Histological analysis revealed significant lipid accumulation in hepatocytes surrounding the central vein at 24, 48, and 72 h. At 24 h, hepatocytes also exhibited features of early degeneration, including cytoplasmic lysis and chromatin condensation. Lipidomics analysis of liver tissue collected 24 h post-exposure demonstrated a marked increase in 27-hydroxycholesterol levels. These results indicate that heat stress rapidly disrupts hepatic lipid homeostasis, causing cellular damage and metabolic remodeling. The observed lipid accumulation, including elevated 27-hydroxycholesterol, may play dual roles in mediating inflammation and serving as a protective response. Our findings provide new insight into the pathogenesis of heat stroke-induced liver injury and suggest potential molecular targets for early diagnosis and intervention.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"34-41"},"PeriodicalIF":1.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540801","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":"Comprehensive analysis of DNA repair, morphological remodeling and immune-gene expression in patient-derived biliary tract carcinoma organoids following ionizing radiation.","authors":"Ken Okuda, Shunji Haruna, Toshihide Muramatsu, Kohei Tateno, Mayu Isono, Kunihiro Miyazaki, Takahiro Oike, Haruka Okami, Takehiko Yokobori, Keiji Suzuki, Kensuke Otsuka, Akiko Takahashi, Yoshimasa Saito, Atsushi Shibata","doi":"10.1007/s00795-026-00456-4","DOIUrl":"https://doi.org/10.1007/s00795-026-00456-4","url":null,"abstract":"<p><p>Biliary tract carcinoma (BTC) is a malignancy with poor prognosis. Current molecular targeted therapies benefit only a limited subset of patients, underscoring the need for novel approaches, such as combining DNA-damaging chemoradiotherapy with an immune checkpoint inhibitor. Although cellular responses following chemoradiotherapy-induced DNA damage are essential, they remain poorly understood in the context of three-dimensional tumor structures. This study aimed to investigate the effects of ionizing radiation, a DNA-damaging cancer therapy, on patient-derived BTC organoids. DNA repair and gene expression regulation was integrally examined by immunofluorescence and RNA-Seq analysis following 10 Gy of X-rays. X-ray irradiation caused significant morphological changes. In addition, X-ray irradiation upregulated extracellular matrix-related gene expression as revealed by RNA sequencing. DNA damage response analysis indicated that non-homologous end joining was the primary repair pathway in patient-derived BTC organoids. Moreover, X-ray irradiation activated immune-related pathways, such as cGAS/STING, RIG-I/MDA-5, and JAK/STAT, suggesting potential immune activation following radiotherapy. Our study revealed that DNA damage response altered the tumor structure and modulated the expression of multiple genes, including extracellular matrix- and immune-related genes. Studies using in vitro organoid models can be useful for investigating three-dimensional cellular responses after DNA-damaging cancer therapies, such as chemoradiotherapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157793","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":"Relationship between nutritional indicators and clinicopathological factors, including immune cell densities in the tumor microenvironment, in patients with colorectal cancer.","authors":"Natsuko Sakaida, Rin Yamada, Kota Arima, Kohei Yamashita, Norihisa Hanada, Daiki Yoshii, Yukio Fujiwara, Chihiro Nakashita, Seiya Shimoda, Masaaki Iwatsuki, Yoshihiro Komohara","doi":"10.1007/s00795-025-00454-y","DOIUrl":"https://doi.org/10.1007/s00795-025-00454-y","url":null,"abstract":"","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934073","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":"Acute liver failure as the first symptom of childhood systemic lupus erythematosus: a case report and review of the literature.","authors":"Yutong Song, Jing Hao","doi":"10.1007/s00795-025-00452-0","DOIUrl":"https://doi.org/10.1007/s00795-025-00452-0","url":null,"abstract":"<p><p>Although systemic lupus erythematosus (SLE) can affect multiple organ systems, manifestations within the digestive tract are not typically conspicuous during the early phase of the disease. The liver damage caused by SLE is mild and insidious. Patients with SLE presenting with acute liver failure as the primary manifestation are significantly rarer in clinical diagnosis. The absence of diagnostic criteria for digestive system manifestation in SLE complicates the diagnosis of lupus as the underlying cause, particularly during the initial presentation. Timely recognition of the disease and commencement of immunosuppressive treatment are crucial for enhancing clinical outcomes. This article reports a rare case of SLE in a 9-year-old Chinese girl presenting with acute liver failure as the initial symptom. The child lacked typical lupus features such as skin and joint manifestations, making the initial diagnosis extremely challenging. The diagnosis relied on key liver pathological examinations and positive serological lupus-specific antibodies, and gene sequencing identified the c.740C > T (p.A247V) mutation of the TREX1 gene. After treatment, her condition improved. This case highlights the importance of early immunological and genetic screening in pediatric patients with unexplained acute liver failure to identify potential SLE. This case represents the first reported instance of pediatric SLE presenting with acute liver failure as the initial manifestation, associated with the c.740C > T (p.A247V) mutation. These findings highlight the critical importance of a multi-modal diagnostic approach-encompassing immunological, pathological (biopsy), and genetic assessments-for the evaluation of children with such atypical presentations.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708472","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}