PathobiologyPub Date : 2026-06-19DOI: 10.1159/000553118
Ayana Suzuki, Mitsuyoshi Hirokawa, Hidetaka Yamamoto, Takuya Higashiyama, Takashi Akamizu
{"title":"Solitary Fibrous Tumor Arising in Thyroid Follicular Nodular Disease: A Case Report.","authors":"Ayana Suzuki, Mitsuyoshi Hirokawa, Hidetaka Yamamoto, Takuya Higashiyama, Takashi Akamizu","doi":"10.1159/000553118","DOIUrl":"10.1159/000553118","url":null,"abstract":"<p><strong>Introduction: </strong>Herein, we present the first documented case of a solitary fibrous tumor (SFT) arising within thyroid follicular nodular disease and discuss its histogenesis.</p><p><strong>Case presentation: </strong>A man in his 60s presented with a left thyroid nodule. Histologically, the nodule was composed of spindle cells and thyroid follicles. The spindle cells were positive for CD34 and STAT6, negative for PAX8 and cytokeratin, and harbored a NAB2::STAT6 fusion, confirming the diagnosis of SFT. No extrathyroidal SFT was identified, and the Demicco model classified the tumor as low risk.</p><p><strong>Conclusion: </strong>This report suggests that SFT may arise de novo within the stromal component of thyroid follicular nodular disease. This underscores the need to consider SFT in the differential diagnosis of spindle-cell lesions occurring within thyroid nodules.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284173","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}
PathobiologyPub Date : 2026-06-05DOI: 10.1159/000552283
Boglárka Pósfai, Anna Jakab, Alex Jenei, Katalin Dezső, Tamás László, Attila Fintha, Tamás Micsik, Csaba Bödör, Gertrúd Forika, Áron Somorácz, Borbála Dénes, Dávid Semjén, Kornélia Eizler, Nándor Giba, Zsombor Melegh, Helga Engi, Ali Bassam, László Torday, Anikó Maráz, Krisztián Nagyiványi, Lajos Géczi, Zsófia Küronya, Krisztina Bíró, Ondrej Hes, Kristyna Pivovarcikova, Henriett Butz, Attila Patócs, Fanni Sánta, Levente Kuthi
{"title":"Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Multicentric Comprehensive Clinical, Pathological, and Molecular Analysis of 12 Cases.","authors":"Boglárka Pósfai, Anna Jakab, Alex Jenei, Katalin Dezső, Tamás László, Attila Fintha, Tamás Micsik, Csaba Bödör, Gertrúd Forika, Áron Somorácz, Borbála Dénes, Dávid Semjén, Kornélia Eizler, Nándor Giba, Zsombor Melegh, Helga Engi, Ali Bassam, László Torday, Anikó Maráz, Krisztián Nagyiványi, Lajos Géczi, Zsófia Küronya, Krisztina Bíró, Ondrej Hes, Kristyna Pivovarcikova, Henriett Butz, Attila Patócs, Fanni Sánta, Levente Kuthi","doi":"10.1159/000552283","DOIUrl":"10.1159/000552283","url":null,"abstract":"<p><strong>Introduction: </strong>Fumarate hydratase-deficient renal cell carcinoma (FHd RCC) is a rare, aggressive subtype of kidney cancer associated with hereditary leiomyomatosis and renal cell carcinoma syndrome.</p><p><strong>Methods: </strong>We retrospectively analyzed 12 FHd RCC cases from Hungarian patients, assessing clinical, histopathological, immunohistochemical, and molecular features.</p><p><strong>Results: </strong>The median age at diagnosis was 48.5 years, with a male-to-female ratio of 1.6:1. Most patients presented symptomatically and in an advanced stage; ten underwent surgery, and seven had metastatic disease at diagnosis. Tumors were unifocal, unilateral, and high-grade, displaying heterogeneous architectural patterns, often with eosinophilic cytoplasm and prominent viral inclusion-like nucleoli. Fumarate hydratase (FH) expression was lost in all but 1 tumor, while aberrant nuclear and cytoplasmic 2SC positivity was observed in all cases. CK7 was consistently negative, whereas AMACR and PAX8 were positive in all tested tumors. GATA3 expression was focal in 2 tumors. PD-L1 positivity was detected in 4 tumors, including 1 with high tumor mutational burden. Pathogenic FH mutations were confirmed in nine cases, including three germline alterations. Systemic therapy was administered in 7 patients, with variable responses.</p><p><strong>Conclusion: </strong>Our findings highlight the pronounced morphological heterogeneity of FHd RCC and the critical role of combined FH and 2SC immunohistochemistry for accurate diagnosis. FHd RCC should be recognized as a distinct, highly malignant renal neoplasm, warranting comprehensive histological, immunohistochemical, and genetic assessment, along with genetic counseling to identify potential hereditary background.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-15"},"PeriodicalIF":1.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176306","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}
PathobiologyPub Date : 2026-05-22DOI: 10.1159/000552636
Che Liu, Zhengrong Zhou, Tao Zeng, Jianpeng Hu, Huazhong Cai, Pan Huang
{"title":"Lactate and <italic>Akkermansia muciniphila</italic>: Emerging Roles in Inflammatory Bowel Disease and Colorectal Cancer.","authors":"Che Liu, Zhengrong Zhou, Tao Zeng, Jianpeng Hu, Huazhong Cai, Pan Huang","doi":"10.1159/000552636","DOIUrl":"10.1159/000552636","url":null,"abstract":"<p><strong>Background: </strong>Lactate levels are significantly elevated in the tissues of patients with inflammatory bowel disease (IBD) and colorectal cancer (CRC). In IBD, lactate promotes anti-inflammatory repair by inducing M2 macrophage polarization, whereas abnormal lactate levels in the CRC tumor microenvironment contribute to tumor initiation and progression through acidification, immune reprogramming, and activation of pro-angiogenic pathways. Akkermansia muciniphila (Akk) exhibits a distinct preference for lactate as a nutritional substrate, and its abundance increases significantly in the murine gut following lactate administration. As an important intestinal symbiont, Akk shows potential in the prevention and treatment of both IBD and CRC.</p><p><strong>Key messages: </strong>We hypothesize that targeting lactate metabolism and leveraging the active components of Akk may provide novel strategies for the prevention and therapy of IBD and CRC.</p><p><strong>Summary: </strong>This review aims to summarize the relationship among lactate, Akk, and inflammation-associated CRC, thereby offering new perspectives and approaches for the clinical management of CRC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":1.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005988","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}
PathobiologyPub Date : 2026-05-21DOI: 10.1159/000552666
Betül Öğüt, Mehmet Arda İnan, Özgür Ekinci, Meral Toker, Ceren Bilkan Öge, Osman Sütçüoğlu, Mualla İlknur Gündüz, Gülen Akyol
{"title":"Stromal Podoplanin Expression as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.","authors":"Betül Öğüt, Mehmet Arda İnan, Özgür Ekinci, Meral Toker, Ceren Bilkan Öge, Osman Sütçüoğlu, Mualla İlknur Gündüz, Gülen Akyol","doi":"10.1159/000552666","DOIUrl":"10.1159/000552666","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic cancer is known for its poor prognosis, characterized by early systemic dissemination and locally aggressive behavior. Podoplanin (PDPN) is a mucin-type transmembrane glycoprotein physiologically expressed in various tissues. In certain malignancies, overexpression of PDPN has been linked to enhanced tumor invasiveness, metastatic potential, and unfavorable clinical outcomes. In this study, we evaluated stromal PDPN expression in a cohort of patients diagnosed with pancreatic carcinoma and investigated its immunohistochemical profile in relation to patient survival.</p><p><strong>Methods: </strong>This retrospective study included 103 cases of pancreatic ductal adenocarcinoma (PDAC). Histological grade, perineural invasion, pathological tumor stage, lymph node status, and lymphovascular invasion were evaluated. Immunohistochemical expression of PDPN was evaluated as a percentage by calculating the proportion of PDPN-positive (of any staining intensity) tumor stroma relative to the total tumor stromal area.</p><p><strong>Results: </strong>Among 103 cases of PDAC, the median value of immunohistochemical expression of PDPN in tumor stroma was 20%. Complete absence of PDPN expression was observed in 7 patients (6.8%). The survival analysis indicated that higher stromal PDPN expression was associated with shorter overall survival (log-rank p = 0.0129). High PDPN expression in cancer-associated fibroblasts showed a borderline association with overall survival in multivariable Cox regression analysis (hazard ratio: 1.52, 95% confidence interval: 1.00-2.32, p = 0.05).</p><p><strong>Conclusion: </strong>PDPN expression may serve as a prognostic biomarker in PDAC and could contribute to future therapeutic stratification.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988662","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}
PathobiologyPub Date : 2026-04-29DOI: 10.1159/000552286
Claire W Michael, Ben Davidson
{"title":"Cellular Plasticity in Malignant Transformation: Mesothelial Cells.","authors":"Claire W Michael, Ben Davidson","doi":"10.1159/000552286","DOIUrl":"10.1159/000552286","url":null,"abstract":"<p><strong>Background: </strong>Mesothelial proliferations range from reactive lesions to benign and malignant tumors, bearing witness to the plasticity of these cells. Their diagnosis often requires combination of morphological assessment, immunohistochemistry, and molecular testing.</p><p><strong>Summary: </strong>Considerable progress has been made in recent years in all the above aspects. The separation of reactive from neoplastic mesothelial proliferations has become more robust. Mesothelioma in situ is now recognized as precursor of invasive mesothelioma and better tools exist for its differentiation from benign mimics. Differentiating mesothelial tumors from other malignancies, including metastatic carcinomas, sarcomas, and other tumors, is now more easily achieved. Genetic conditions which predispose to development of mesothelioma at a young age have been identified and characterized. These issues are discussed in this review.</p><p><strong>Key messages: </strong>Mesothelial pathology is an evolving field and more knowledge of these processes is likely to be gained in coming years. The diagnosis of these tumors requires experts with subspecialty in cytology, thoracic, soft tissue/bone, and gynecologic pathology, cooperating with surgeons, radiologists, and oncologists at specialized centers.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777792","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}
PathobiologyPub Date : 2026-04-27DOI: 10.1159/000551677
Mariana O Nunes, Diana Luísa Almeida-Nunes, Ana E C de Lima, Verónica Ferreira, Cláudia Lobo, Paula M Monteiro, Sara Carvalho, Miguel Henriques Abreu, Carla Bartosch, Sara Ricardo
{"title":"Tracking Chemotherapy Effects via ALDH1A1, SOX2, CD44v6, and P-gp Expression in Malignant Ascites from High-Grade Serous Carcinoma.","authors":"Mariana O Nunes, Diana Luísa Almeida-Nunes, Ana E C de Lima, Verónica Ferreira, Cláudia Lobo, Paula M Monteiro, Sara Carvalho, Miguel Henriques Abreu, Carla Bartosch, Sara Ricardo","doi":"10.1159/000551677","DOIUrl":"10.1159/000551677","url":null,"abstract":"<p><strong>Introduction: </strong>Malignant ascites is frequently observed in high-grade serous carcinoma (HGSC), yet its value as a dynamic source for molecular profiling across treatment stages remains underexplored. The main aim of this study was to evaluate the feasibility of immunocytochemical analysis of malignant ascites (MA) samples from patients with high-grade serous carcinoma. A goal was to determine whether marker expression varies before and after chemotherapy and between clinical response groups.</p><p><strong>Methods: </strong>A cohort of 37 MA samples from 33 HGSC patients was analysed by immunocytochemistry for ALDH1A1, SOX2, CD44v6, and P-glycoprotein. Full-volume centrifugation of MA (1-4 L) was used to maximize tumour cell recovery. A biomarker profile was considered positive if ≥1 marker showed >10% tumour cell expression.</p><p><strong>Results: </strong>This profile was significantly more frequent in post-chemotherapy samples (72.2%) than in pre-chemotherapy samples (21.1%; p = 0.003). Stratified analysis revealed increased expression in platinum-sensitive patients following chemotherapy (60% vs. 14.3%, p = 0.032), suggesting chemotherapy-induced reprogramming rather than selection alone. Expression of p-glycoprotein was more frequent in resistant cases, though often limited to <25% of tumour cells. Survival analysis showed no significant difference in overall survival between biomarker-positive patients (p = 0.176).</p><p><strong>Conclusion: </strong>Our findings suggest that chemotherapy modulates the expression of cancer stem cells and resistance-related markers in HGSC, potentially contributing to adaptive resistance mechanisms. MA, particularly when processed in full, represents a valuable, minimally invasive source of tumour cells for real-time biomarker monitoring. This approach may support early identification of resistance phenotypes and inform personalized therapeutic strategies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777783","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}
PathobiologyPub Date : 2026-01-01Epub Date: 2025-07-26DOI: 10.1159/000547335
Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M van Deurzen, Martine Berlière, Mieke R Van Bockstal
{"title":"Predictive Histopathological Markers for Upstaging to Invasive Carcinoma after a Biopsy Diagnosis of Ductal Carcinoma in situ of the Breast: A Hypothesis-Generating Systematic Review.","authors":"Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M van Deurzen, Martine Berlière, Mieke R Van Bockstal","doi":"10.1159/000547335","DOIUrl":"10.1159/000547335","url":null,"abstract":"<p><strong>Introduction: </strong>Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear. This PROSPERO-registered systematic review aims to identify which biopsy-based histopathological markers can predict the presence of IBC in the subsequent resection. These results might help to reserve SLNPs for selected high-risk patients, aiming to personalize treatment.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched for content using predefined search queries. Three reviewers independently screened the literature in Rayyan by applying predefined criteria and retained 36 reports. Studies including DCIS with micro-invasion were excluded.</p><p><strong>Results: </strong>This systematic review comprised 18,475 patients. The median cohort size was 267 patients (range: 67-3,780). Most studies were retrospective (33/36). The median upstaging risk was 26% (range: 8-52%). The reports studied twenty-three histopathological and immunohistochemical features. Only seven features were investigated in multiple studies, all yielding contradictory results. For instance, thirty-three studies investigated nuclear grade, but only 18 reports demonstrated a significant association with upstaging, independent from cohort size.</p><p><strong>Conclusion: </strong>No robust histopathological features can be recommended at present to reliably predict the upstaging risk to IBC after a biopsy diagnosis of pure DCIS. We discuss several hypotheses, aiming to explain these contradictory data. Ideally, large-scale multicentre prospective studies should be organized to answer this unmet clinical need.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"34-47"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732644","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}
PathobiologyPub Date : 2026-01-01Epub Date: 2025-09-24DOI: 10.1159/000548452
Meejeong Kim, Miseon Lee, Jun Kang, Sung Jong Lee, Sook Hee Hong, Keun Ho Lee, Ahwon Lee
{"title":"HPV ctDNA as a Biomarker for Monitoring Disease Progression in HPV16/18-Associated Cervical Cancer.","authors":"Meejeong Kim, Miseon Lee, Jun Kang, Sung Jong Lee, Sook Hee Hong, Keun Ho Lee, Ahwon Lee","doi":"10.1159/000548452","DOIUrl":"10.1159/000548452","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer, primarily driven by oncogenic HPV16/18, often relapses despite standard treatments. HPV circulating tumor DNA (ctDNA), which reflects tumor-derived genetic material in the bloodstream, has emerged as a promising noninvasive biomarker for monitoring disease progression.</p><p><strong>Methods: </strong>A prospective study was conducted on 20 patients with HPV16/18-associated cervical cancer. Posttreatment blood samples were collected, and HPV ctDNA levels were measured using droplet digital PCR. The correlation between HPV ctDNA levels and disease progression was examined.</p><p><strong>Results: </strong>HPV ctDNA was detected in 21% (18/85) of samples, with 6% (5/85) showing positivity. Patients without disease progression (n = 15) were HPV ctDNA negative, indicating a false positivity rate of zero. HPV ctDNA concentrations appeared higher in samples collected before or during disease progression, suggesting a potential association with disease status. Patients with positive HPV ctDNA tended to have shorter progression-free survival compared to those with negative ctDNA.</p><p><strong>Conclusions: </strong>This study suggests that HPV ctDNA may aid in monitoring disease progression in patients with HPV16/18-associated cervical cancer, highlighting the need for further validation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"87-95"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137908","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}
PathobiologyPub Date : 2026-01-01Epub Date: 2025-12-31DOI: 10.1159/000550086
Carlos López, Laia Reverté, Ramon Bosch Príncep, Esther Sauras, Noèlia Gallardo-Borràs, Alba Fischer-Carles, Anna Korzynska, Marcial García-Rojo, Gloria Bueno, Lukasz Roszkowiak, Albert Roso-LLorach, Andrea Gras Navarro, Montserrat Llobera, Daniel Mata, Laia Adalid Llansa, Salomé Martínez-González, Joan F Garcia-Fontgivell, Meritxell Arenas, Junior Gómez, José Antonio Izuel, Jordi Baucells, Marylène Lejeune
{"title":"Influence of the Molecular Subtype-Dependent Immune Microenvironment of Metastatic Axillary Lymph Nodes on Breast Cancer Patient Outcomes.","authors":"Carlos López, Laia Reverté, Ramon Bosch Príncep, Esther Sauras, Noèlia Gallardo-Borràs, Alba Fischer-Carles, Anna Korzynska, Marcial García-Rojo, Gloria Bueno, Lukasz Roszkowiak, Albert Roso-LLorach, Andrea Gras Navarro, Montserrat Llobera, Daniel Mata, Laia Adalid Llansa, Salomé Martínez-González, Joan F Garcia-Fontgivell, Meritxell Arenas, Junior Gómez, José Antonio Izuel, Jordi Baucells, Marylène Lejeune","doi":"10.1159/000550086","DOIUrl":"10.1159/000550086","url":null,"abstract":"<p><p><p>Introduction: Metastasis in the axillary lymph nodes (ALNs) occurs in 30-50% of breast cancers (BCs), where residing immune cells play a crucial role in disease progression. Specifically at diagnosis, the immune elements infiltrating the primary tumour are among the best established prognostic factors. However, their prognostic value in the metastatic ALNs (ALNs+) is poorly understood.</p><p><strong>Methods: </strong>We aimed to retrospectively assess the immune populations of ALNs+ in luminal A (LA) and triple-negative BC (TNBC) patients using immunohistochemistry, to compare it with non-metastatic ALNs (ALNs-), and to determine their relationship with patient outcomes.</p><p><strong>Results: </strong>We found differences in the immune concentrations of matched ALNs (ALNs- vs. ALNs+) from patients with positive nodal status in either LA or TNBC subtypes. In contrast, compared with LA, the levels of immune cells in ALNs- of the TNBC profile differ much more from ALNs+ than in the LA subtype, regardless of the nodal status. In addition, TNBC patients with higher levels of CD4 and CD8 lymphocytes in ALNs+ have worse cancer-specific survival (CSS) and higher levels of CD83 dendritic cells (DCs) are related to worse CSS and time to progression (TTP). Conversely, LA patients with higher levels of CD21 DC showed better TTP.</p><p><strong>Conclusion: </strong>Our results showed that ALN immune profiles and their influence on disease evolution vary by molecular BC subtype and nodal status, suggesting that accurate ALN immune profiling at diagnosis could provide new insights into the immune BC landscape. These observations require validation in larger, prospective cohorts before they can be reliably used to inform clinical decision-making. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"147-159"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878760","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":"Establishment of a Novel Organoid Line from Esophageal Squamous Cell Carcinoma with Cytoplasmic Vacuoles: Association of Autolysosome Swelling with Vacuole Formation.","authors":"Shunsuke Fujita, Tomotaka Shibata, Haruto Nishida, Sawa Matsumoto, Shusaku Kurogi, Shinji Yano, Shoichi Fumoto, Yusuke Itai, Yuki Shitomi, Tomonori Akagi, Shigeo Ninomiya, Tsuyoshi Etoh, Chisato Nakada, Takafumi Fuchino, Yuka Hirashita, Kazuhiro Mizukami, Tsutomu Daa, Masafumi Inomata, Masatsugu Moriyama, Naoki Hijiya, Yoshiyuki Tsukamoto","doi":"10.1159/000548788","DOIUrl":"10.1159/000548788","url":null,"abstract":"<p><strong>Introduction: </strong>We experienced a case of esophageal squamous cell carcinoma (ESCC) exhibiting mucus-negative cytoplasmic vacuoles. The carcinoma cells with vacuoles were positive for p63, a marker of squamous cell carcinoma (SCC). Since the first description by Cramer and Heggeness in 1989, 24 cases of SCC with mucus-negative vacuoles have been reported to date. However, little is known about the clinical course of SCC with vacuoles (SCCVs) and the nature of the cytoplasmic vacuoles themselves, due to its rarity and the lack of suitable models.</p><p><strong>Methods: </strong>We established a novel organoid line - designated ECO_Vac - from residual cancer tissue of a patient with esophageal SCCV (ESCCV) after neoadjuvant chemotherapy, evaluated its applicability as a model of ESCCV, and characterized its cytoplasmic vacuoles by electron microscopic and organelle-specific fluorescent probe uptake assays.</p><p><strong>Results: </strong>ECO_Vac was successfully established and was found to be applicable to in vitro drug assays and experiments involving in vivo tumor formation. We also found that the vacuoles in ESCCV were enlarged autolysosomes.</p><p><strong>Conclusion: </strong>We established a novel organoid line, ECO_Vac, as a useful model for investigating the molecular pathogenesis of ESCCV. By using ECO_Vac, we demonstrated that the cytoplasmic vacuoles in ESCCV were unphysiologically enlarged autolysosomes.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"123-134"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471596","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}