{"title":"Hepatic adenosquamous carcinoma with sarcomatous transformation: a case report and review of the literature.","authors":"Quynh Thi Nguyen, Hiep Canh Nguyen, Kenta Takahashi, Kaori Yoshimura, Hiroko Ikeda, Kazuto Kozaka, Zihan Li, Dong Thanh Le, Rui Yang, Shintaro Yagi, Kenichi Harada","doi":"10.1007/s00795-024-00406-y","DOIUrl":"10.1007/s00795-024-00406-y","url":null,"abstract":"<p><p>Adenosquamous carcinoma (ASC) with the presence of a sarcomatous component is exceptionally uncommon in intrahepatic cholangiocarcinoma (iCCA). We report a case of hepatic ASC with rhabdoid transformation, one variation of sarcomatous change. A 72-year-old man was admitted to our hospital after being diagnosed with a 45 mm-diameter neoplastic lesion in the right hepatic duct on abdominal computed tomography. Laboratory findings showed increases in AST, ALT, ALP, gamma-GT, CA19-9 and DUPAN-II. The patient then underwent an extended right hepatectomy. Histopathologically, the tumor was composed of an ASC component within an abundant fibrous stroma and a sarcomatoid carcinoma component. By immunohistochemistry, keratin 7 and keratin 19 were expressed by all tumor cells. Expression of keratin 5/6, p40 and p63 was restricted to the squamous component. The sarcomatoid component was immunoreactive for vimentin with no loss of INI1 expression. This component also showed a loss of membranous E-cadherin expression and a reduction of membranous β-catenin expression. Staining for desmin, myoglobin and HepPar1 was negative in any tumor cells. The patient died of liver failure 3 months after surgery. This report aims to provide a better understanding of the clinicopathological characteristics and disease progression of the rare variants of iCCA to aid diagnosis and treatment.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"75-82"},"PeriodicalIF":1.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391707","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":"Primary hepatic alpha-fetoprotein-producing neuroendocrine neoplasm harboring FGFR2 and TP53 mutations: a case report and literature review.","authors":"Hirofumi Watanabe, Kodai Enda, Fumiyoshi Fujishima, Hidekazu Shirota, Masashi Ninomiya, Tetsuro Yamazaki, Hironobu Sasano, Takashi Suzuki","doi":"10.1007/s00795-024-00408-w","DOIUrl":"10.1007/s00795-024-00408-w","url":null,"abstract":"<p><p>This report presents a rare case of a 45-year-old man diagnosed with a primary hepatic alpha-fetoprotein-producing neuroendocrine neoplasm, a condition rarely reported in the literature. The patient presented with initial symptoms of back and epigastric pain, after which multiple liver lesions were discovered on contrast-enhanced computed tomography, suggesting intrahepatic cholangiocarcinoma. Histopathological and immunohistochemical analyses confirmed the diagnosis of alpha-fetoprotein-producing neuroendocrine neoplasm that was further supported by genetic testing, which revealed FGFR2 and TP53 mutations commonly encountered in intrahepatic cholangiocarcinoma. Despite receiving various chemotherapeutic regimens, the patient exhibited a progressive disease. This case underscores the importance of accurate differential diagnosis from hepatocellular carcinoma and intrahepatic cholangiocarcinoma due to differences in treatment approaches and prognoses and highlights the necessity for increased awareness of AFP-producing primary hepatic neuroendocrine neoplasms among clinicians and pathologists. It emphasizes the significance of comprehensive histopathological evaluation, immunohistochemical profiling, and genetic analysis for precise diagnosis and tailored therapeutic strategies. Further research is warranted to elucidate the molecular mechanisms underlying this rare liver tumor subtype and develop targeted treatments.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"83-86"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623551","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":"Element analysis applied to investigate acute kidney injury induced by red yeast rice supplement.","authors":"Makoto Abe, Tadayuki Ogawa, Nobuyuki Magome, Yuko Ono, Akihiro Tojo","doi":"10.1007/s00795-024-00411-1","DOIUrl":"10.1007/s00795-024-00411-1","url":null,"abstract":"<p><p>Silica nanoparticles are used in functional foods and tablets to increase drug stability and delivery. We investigated a patient with acute kidney injury with Fanconi syndrome after taking functional food tablets made from red yeast rice using low-vacuum scanning electron microscopy (LVSEM) with an element analysis system. Kidney biopsy revealed proximal tubular necrosis and vacuolization with 10-20 nm black granules, which were similar to the silica nanoparticles found in the functional food tablets and urinary samples, as determined via LVSEM with element analysis. Reabsorbed silica nanoparticles induce oxidative stress in the kidney. Element analysis by LVSEM is useful to investigate a possible cause of acute tubular necrosis in patients with Fanconi syndrome.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"53-61"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623545","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":"Is it really descemetocele? Morphology of extremely thin membrane that remained after severe corneal melting: a case report.","authors":"Yasser Helmy Mohamed, Masafumi Uematsu, Mao Kusano, Takashi Kitaoka, Teruo Nishida","doi":"10.1007/s00795-024-00405-z","DOIUrl":"10.1007/s00795-024-00405-z","url":null,"abstract":"<p><p>The aim of this study was to report transmission electron microscopic findings of a case with whole corneal descemetocele following infective corneal ulcer for the first time in literature. A 72-year-old male patient presented with infective corneal ulcer. After resolution of the infection, corneoscleral transplantation was performed. The excised very thin corneal membrane was processed for transmission electron microscopic examination. Transmission electron microscopic examination of the specimen revealed many layered structures that consisted of two different types of cells. The first type consisted of lighter staining polygonal cells, while the second consisted of elongated cells with relatively dense staining. All cells were connected with a large number of gap or adherens junctions with intercalation of the cell membranes of adjacent cells. A haphazard distribution of cytoplasmic microfilaments were also observed in all of the cell types. There was no evidence of the presence of endothelial cells throughout the specimen. There was also no evidence of Descemet membrane presence except for a small part adjacent to iris tissue that contained some melanosomes. Although we clinically diagnosed descemetocele, Descemet membrane was not present at the electron microscopic level, and thus, the expression \"descemetocele\" is inappropriate.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"69-74"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349661","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}
Hajime Masubuchi, Yasuko Imamura, Takumi Kawaguchi, Hironori Koga
{"title":"Leucine drives LAT1-related SNAIL upregulation in glucose-starved pancreatic cancer cells.","authors":"Hajime Masubuchi, Yasuko Imamura, Takumi Kawaguchi, Hironori Koga","doi":"10.1007/s00795-024-00404-0","DOIUrl":"10.1007/s00795-024-00404-0","url":null,"abstract":"<p><p>Pancreatic cancer, a highly fibrotic and hypovascular tumor, is thought to have unique metabolic characteristics in surviving and proliferating in malnutritional microenvironments. In this study, we compared the differences in the ability of pancreatic cancer cells to adapt to glucose-free conditions with liver cancer cells, which are representative of hypervascular tumors. Three pancreatic cancer cells and two liver cancer cells were used to examine the transcriptional expression levels of molecules involved in intracellular amino acid uptake, epithelial-mesenchymal transition (EMT), and cancer stemness under glucose deprivation. The results showed that the proliferative activity of pancreatic cancer cells under glucose deprivation was significantly lower than that of liver cancer cells, but the expression levels of amino acid transporters were significantly higher. Among them, L-type amino acid transporter 1 (LAT1) upregulation was unique in concert with increased expression of the EMT regulator SNAIL and the cancer stemness marker doublecortin-like kinase 1. LAT1 knockdown canceled the upregulation of SNAIL in glucose-starved pancreatic cancer cells, suggesting a mechanistic link between the two molecules. When LAT1 was stimulated by its substrate leucine, the SNAIL expression was upregulated dose-dependently. Collectively, pancreatic cancer cells reprogrammed metabolism to adapt to energy crises involving leucine-induced SNAIL upregulation.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"23-33"},"PeriodicalIF":1.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140500","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}
Peiqi Shen, Zeyi Ma, Xiaoqing Xu, Weiyu Li, Yaoyin Li
{"title":"Dental pulp stem cells promote malignant transformation of oral epithelial cells through mitochondrial transfer.","authors":"Peiqi Shen, Zeyi Ma, Xiaoqing Xu, Weiyu Li, Yaoyin Li","doi":"10.1007/s00795-024-00403-1","DOIUrl":"10.1007/s00795-024-00403-1","url":null,"abstract":"<p><p>Oral epithelial dysplasia includes a range of clinical oral mucosal diseases with potentially malignant traits. Dental pulp stem cells (DPSCs) are potential candidates for cell-based therapies targeting various diseases. However, the effect of DPSCs on the progression of oral mucosal precancerous lesions remains unclear. Animal experiments were conducted to assess the effect of human DPSCs (hDPSCs). We measured the proliferation, motility and mitochondrial respiratory function of the human dysplastic oral keratinocyte (DOK) cells cocultured with hDPSCs. Mitochondrial transfer experiments were performed to determine the role mitochondria from hDPSCs in the malignant transformation of DOK cells. hDPSCs injection accelerated carcinogenesis in 4NQO-induced oral epithelial dysplasia in mice. Coculture with hDPSCs increased the proliferation, migration, invasion and mitochondrial respiratory function of DOK cells. Mitochondria from hDPSCs could be transferred to DOK cells, and activated mTOR signaling pathway in DOK cells. Our study demonstrates that hDPSCs activate the mTOR signaling pathway through mitochondrial transfer, promoting the malignant transformation of oral precancerous epithelial lesions.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"306-319"},"PeriodicalIF":1.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913253","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}
Ning Zhu, Yu Pan, Liling Song, Na Li, Xiaolong Sui, Ping Yang, Xiaoqian Liu, Li Zhang, Guohua Yu
{"title":"Nodal T follicular helper cell lymphoma with aberrant CD20 expression and monoclonal TCR, IG rearrangements secondary to Classical Hodgkin Lymphoma: a case report.","authors":"Ning Zhu, Yu Pan, Liling Song, Na Li, Xiaolong Sui, Ping Yang, Xiaoqian Liu, Li Zhang, Guohua Yu","doi":"10.1007/s00795-024-00398-9","DOIUrl":"10.1007/s00795-024-00398-9","url":null,"abstract":"<p><p>Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6 years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"320-325"},"PeriodicalIF":1.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620396","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":"Identification of histopathological classification and establishment of prognostic indicators of gastric adenocarcinoma based on deep learning algorithm.","authors":"Zhihui Wang, Hui Peng, Jie Wan, Anping Song","doi":"10.1007/s00795-024-00399-8","DOIUrl":"10.1007/s00795-024-00399-8","url":null,"abstract":"<p><p>The aim of this study is to establish a deep learning (DL) model to predict the pathological type of gastric adenocarcinoma cancer based on whole-slide images(WSIs). We downloaded 356 histopathological images of gastric adenocarcinoma (STAD) patients from The Cancer Genome Atlas database and randomly divided them into the training set, validation set and test set (8:1:1). Additionally, 80 H&E-stained WSIs of STAD were collected for external validation. The CLAM tool was used to cut the WSIs and further construct the model by DL algorithm, achieving an accuracy of over 90% in identifying and predicting histopathological subtypes. External validation results demonstrated the model had a certain generalization ability. Moreover, DL features were extracted from the model to further investigate the differences in immune infiltration and patient prognosis between the two subtypes. The DL model can accurately predict the pathological classification of STAD patients, and provide certain reference value for clinical diagnosis. The nomogram combining DL-signature, gene-signature and clinical features can be used as a prognostic classifier for clinical decision-making and treatment.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"286-298"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860172","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 transcription factors involved in odontoblast differentiation mechanism.","authors":"Haruka Nakazato, Shoko Onodera, Natsuko Aida, Masahiro Furusawa, Toshifumi Azuma","doi":"10.1007/s00795-024-00389-w","DOIUrl":"10.1007/s00795-024-00389-w","url":null,"abstract":"<p><p>Primary cultured odontoblasts rapidly lose their tissue-specific phenotype. To identify transcription factors (TF) that are important for the maintenance of the odontoblast phenotype, primary cultures of C57BL/6 J mouse dental mesenchymal cells (DMC) were isolated, and expression of TF and odontoblast marker genes in cells immediately after isolation and 2 days after culture were comprehensively evaluated and compared using RNA-sequencing (RNA-seq). The expression of odontoblast markers in mouse dental mesenchymal cells decreased rapidly after isolation. In addition, the expression of Hedgehog-related, Notch-related, and immediate- early gene (IEG)-related transcription factors significantly decreased. Forced expression of these genes in lentiviral vectors, together with fibroblast growth factor 4 (FGF4), fibroblast growth factor 9 (FGF9), and the Wnt pathway activator CHIR99021, significantly induced the expression of odontogenic marker genes. These results indicate, for the first time, that Notch signaling and early genes may be important for maintaining odontoblast cultures. Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"253-267"},"PeriodicalIF":1.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580196","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":"High ambient temperature may induce presbyopia via TRPV1 activation.","authors":"Yosuke Nakazawa, Yumika Kuno, Hibiki Shimada, Noriaki Nagai, Noriko Hiramatsu, Shun Takeda, Naoki Yamamoto, Megumi Funakoshi-Tago, Hiroshi Sasaki","doi":"10.1007/s00795-024-00391-2","DOIUrl":"10.1007/s00795-024-00391-2","url":null,"abstract":"<p><p>The prevalence of presbyopia and nuclear cataracts (NUC) is reported to be higher in tropical areas than that in other regions, suggesting a potential influence of high temperatures on lens health. Transient receptor potential vanilloid (TRPV) channels play a crucial role in detecting ambient temperatures across various species, with TRPV1 and TRPV4 expressed in lens epithelial cells. In this study, we investigated whether ambient temperatures affect TRPV1 and TRPV4 activity in the lens, potentially contributing to the development of presbyopia and NUC. We conducted experiments using cultured human lens epithelial cell lines under different temperature conditions. Our results revealed that the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and p38 pathways, downstream molecules of TRPV1, were activated, while Src family kinase, a downstream molecule of TRPV4, was inhibited at 37.5 °C culture compared to 35.0 °C. Confocal microscope images demonstrated higher expression of TRPV1 in 3D-structured cells under high-temperature culture conditions. Additionally, in organ culture lenses, higher elasticity was observed at elevated temperatures compared to that at lower temperatures. These results suggest that high ambient temperatures may induce lens sclerosis via TRPV1 activation, potentially contributing to the development of presbyopia and NUC.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"268-276"},"PeriodicalIF":1.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559079","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}