{"title":"Evaluation of PRDM10 gene rearrangement by immunohistochemistry and molecular methods in unclassifiable undifferentiated soft tissue tumors.","authors":"Merve Aksin, Kivilcim Eren Ates, Akif Mirioglu, Tugba Toyran, Gulfiliz Gonlusen","doi":"10.1007/s00795-025-00442-2","DOIUrl":"10.1007/s00795-025-00442-2","url":null,"abstract":"<p><p>Soft tissue sarcomas are heterogenous groups of tumors that show variable morphology as well as clinical behavior. Morphological features do not always directly reflect clinical behavior. Certain mesenchymal tumors exhibit an indolent clinical course. Among them are superficial CD34-positive fibroblastic tumors characterized by PRDM10 fusion. In our study, we aimed to detect PRDM10 gene rearrangement in superficial CD34-positive fibroblastic tumors and other pleomorphic sarcomas included in its differential diagnosis by immunohistochemistry and Fluorescence in situ hybridization. Totally, 33 cases were enrolled into this study. The results showed that two cases diagnosed as superficial CD34-positive fibroblastic tumor and two cases diagnosed as undifferentiated pleomorphic sarcoma have PRDM10 gene rearrangement. Immunohistochemically, not all rearranged tumors showed PRDM10 staining that suggests a low sensitivity of PRDM10 antibody. In conclusion, we suggested that PRDM10 gene rearrangement is not limited to superficial CD34-positive fibroblastic tumors; undifferentiated pleomorphic sarcomas may exhibit this molecular alteration and immunohistochemistry has lower sensitivity than fluorescence in situ hybridization.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"20-25"},"PeriodicalIF":1.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484964","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":"Anaplastic thyroid carcinoma with osteoclast-like giant cells: a case report and a study of a potential therapeutic approach.","authors":"Kaori Yukino, Yoshihiro Komohara, Shukang Zhao, Rin Yamada, Yukio Fujiwara, Akira Murakami, Yu Shimoda, Haruki Saito, Yorihisa Orita","doi":"10.1007/s00795-025-00443-1","DOIUrl":"10.1007/s00795-025-00443-1","url":null,"abstract":"<p><p>Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm with no effective treatment options. ATC with osteoclast-like giant cells (OGCs; ATC/OGC) is a rare variant of ATC, and no detailed pathological examination has been reported to date. A 59-year-old woman presented with sudden neck swelling. Computed tomography revealed a 5 cm tumor in the thyroid gland, which was surgically resected. Pathological examination revealed a diagnosis of ATC/OGC. The patient succumbed to progressive lung metastases within four months despite postoperative lenvatinib therapy. Immunohistochemical (IHC) examination indicated absence of PD-L1 expression in the OGCs, which comprised the majority of the tumor, with only sparse T cell infiltration in the area occupied by OGCs. Increased TGF-β expression was observed in the area containing OGCs, and both OGCs and infiltrating myeloid cells, including CD1a/CD11c-positive dendritic cells and CD68/CD163/CD204-positive macrophages, appeared to produce TGF-β. Pathological analysis of this case suggests that OGCs might be involved in immune suppression by secreting TGF-β, potentially serving as a critical cytokine in the immunosuppressive microenvironment of ATC/OGC. TGF-β-targeted therapy might be useful in the treatment of this very rare subtype of ATC.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"64-70"},"PeriodicalIF":1.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698981","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":"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":1.4,"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":1.4,"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":1.4,"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":1.4,"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":1.4,"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":"Aging potentially reduces CD169 expression in sinus macrophages of pelvic lymph nodes.","authors":"Yuki Ibe, Yojiro Ozaki, Toshiki Anami, Hiromu Yano, Yukio Fujiwara, Hidekazu Nishizawa, Ryoma Kurahashi, Takanobu Motoshima, Yoji Murakami, Junji Yatsuda, Yoshihiro Komohara, Tomomi Kamba","doi":"10.1007/s00795-025-00433-3","DOIUrl":"10.1007/s00795-025-00433-3","url":null,"abstract":"<p><p>The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant anti-cancer effects have been observed in patients with prostate cancer. Lymph node sinus macrophages (LSMs) are known to work as antigen-presenting cells, which are critical for anticancer immune responses. Previous studies have suggested that CD169 expression in LSMs affects anticancer immune responses in several cancers, including prostate cancer. In the present study, we aimed to examine the correlation between the tumor immune microenvironment and activation status of LSMs in patients with prostate cancer. Forty-two cases of high-risk localized prostate cancer treated using robot-assisted laparoscopic radical prostatectomy and lymph node dissection between 2017 and 2021 were enrolled. CD169 expression in LSMs was examined by immunohistochemistry. The results indicated that CD169 expression in LSMs was significantly decreased in older (≥ 75 years) compared with younger patients. However, no significant correlation was found between CD169 expression and any other clinicopathological factors. In addition, CD3- and CD8-postitive lymphocytes in primary cancer tissues were evaluated in the same cases, and their correlations with CD169 expression in LSMs were tested. Although these lymphocytes tended to be higher in CD169<sup>high</sup> than in CD169<sup>low</sup> cases, the difference was not statistically significant. In conclusion, we found that CD169 expression was upregulated in older patients and tended to be related to T cell infiltration in cancer tissues. Therefore, the downregulation of CD169 in LSMs might be involved in the reduced anticancer immune response in prostate cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"290-297"},"PeriodicalIF":1.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12644165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700596","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":"Transmission electron microscopic analysis of pancreatic ductal adenocarcinoma cell spheres formed in 3D cultures.","authors":"Yuuki Shichi, Masakazu Fujiwara, Fujiya Gomi, Keisuke Nonaka, Fumio Hasegawa, Seiichi Shinji, Hirofumi Rokutan, Tomio Arai, Kimimasa Takahashi, Toshiyuki Ishiwata","doi":"10.1007/s00795-025-00435-1","DOIUrl":"10.1007/s00795-025-00435-1","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) cell lines are classified into two types: epithelial and mesenchymal protein-expressing. Using scanning electron microscopy, we reported that these two groups differ in terms of morphology when they formed tumor spheres under three-dimensional (3D) culturing. In this study, we used transmission electron microscopy (TEM) to examine the intracellular microstructures of five epithelial and three mesenchymal PDAC cell lines in 3D culture, and compared them to the morphologies of the same cell types in two-dimensional (2D) cultures. Microvilli were present in all PDAC cells cultured in 2D and 3D, and were well developed in epithelial PDAC cells. Desmosome-like structures were only observed in epithelial PDAC cells, and were more common in 3D cultures. Secretory granules were observed in epithelial PDAC and mesenchymal PANC-1 cells, and were more common in 3D cultures. Intracytoplasmic lumina were only observed in epithelial PK-59 and T3M-4 cells cultured in 3D. Abundant filamentous aggregates were observed in 2D-cultured T3M-4 and MIA PaCa-2 cells. By contrast, entosis was observed in 3D-cultured PK-59, PK-1, and KP4 cells. Microstructural differences enhanced by 3D culturing revealed significant phenotypic diversity among PDAC cells, and may provide key insights into curing intractable pancreatic cancer.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"298-306"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780173","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}
Hiroaki Kawano, Koichi Kawamura, Koji Maemura, Shinji Okano
{"title":"Ultrastructure of the small vessels in the myocardium in a patient with fatal systemic capillary leak syndrome.","authors":"Hiroaki Kawano, Koichi Kawamura, Koji Maemura, Shinji Okano","doi":"10.1007/s00795-025-00439-x","DOIUrl":"10.1007/s00795-025-00439-x","url":null,"abstract":"<p><p>A 29-year-old Japanese woman was admitted to our hospital with fever, cardiogenic shock, and cardiac arrest and died 18 h after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019. Electron microscopy of the biopsied right-ventricular myocardium revealed extensive interstitial leakage of blood cells and plasma, damaged capillaries, and reticular vessel drainage into the Thebesian vein. These findings indicate that severe capillary leak and lumen occlusion due to damaged capillaries are the main features of systemic capillary leak syndrome.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"325-330"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989646","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}