Endocrine Pathology最新文献

{"title":"The Proteome of Bilateral Macronodular Adrenocortical Disease (BMAD) Shows Different Profiles Correlating with the Genetic Causes and Reveals Specific Dysregulation of RNA Polymerase II and Cholesterol Biosynthesis Enzymes.","authors":"Florian Violon, Anne Jouinot, Bruno Ragazzon, Patricia Vaduva, Lucas Bouys, Louis Thomeret, Johanna Bruce, Marjorie Leduc, Martin Gaillard, Guillaume Assié, Fidéline Bonnet-Serrano, Annabel Berthon, Mathilde Sibony, Jérôme Bertherat","doi":"10.1007/s12022-025-09898-5","DOIUrl":"10.1007/s12022-025-09898-5","url":null,"abstract":"<p><p>Bilateral macronodular adrenocortical disease (BMAD) is currently described as composed of 4 microscopic subtypes (subtype 1 to 4) and 3 molecular groups (ARMC5-altered, KDM1A-altered, and unknown). Little is known about protein heterogeneity and its links with BMAD characteristics. The aim of this work is to study the protein signatures of BMADs and their correlations with microscopy and genetics. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed on 24 BMADs: 7 ARMC5, 4 KDM1A, 13 non-KDM1A, non-ARMC5 BMADs and 2 normal adrenal glands and 10 adrenal adenomas as control. Unsupervised clustering divided BMAD samples into 3 proteomic groups. The first group is composed of ARMC5-altered BMADs (subtype 1) and is characterized by an accumulation of RNA polymerase II (Pol II) subunits. The second, composed of KDM1A-altered (subtype 2) patients and subtype 4 BMADs (oncocytic), is characterized by an accumulation of cholesterol biosynthesis enzymes (such as FDFT1). The last group has no specific signature detected and is composed of subtypes 1 and 3 BMAD without ARMC5 alteration. Immunohistochemical analyses with anti Pol II subunits and cholesterol biosynthesis enzymes correlate with the three proteomic groups. Proteins specifically accumulated in ARMC5-altered BMADS such as POLR2A could be used as biomarkers to detect ARMC5 alterations. Data are available via ProteomeXchange with identifier PXD070500. Our study explores BMAD proteome using LC-MS/MS. The 3 proteomic groups mostly overlap the 4 microscopic and 3 molecular groups of BMAD. Accumulation of Pol II subunits consistent with the described role of ARMC5 could play a role in the pathogenesis of these BMADs. KDM1A-altered (subtype 2) and subtype 4 BMADs showed an accumulation of proteins involved in lipid metabolism that could contribute to hypercortisolism. These results reveal specific protein patterns pointing to various cellular processes opening new perspectives to understand BMAD pathophysiology and provide new tools for the pathologists.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"3"},"PeriodicalIF":4.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights from the Expression of the Mismatch Repair System in Pituitary Neuroendocrine Tumors.","authors":"Francesca Carbonara, Francesca Gianno, Tiziana Feola, Francesco Mancinelli, Dario De Alcubierre, Mariana Moroni, Eleonora Lucantonio, Antonietta Arcella, Alba Di Pardo, Roberta Morace, Andrea M Isidori, Stefano Gambardella, Vincenzo Esposito, Marie-Lise Jaffrain-Rea","doi":"10.1007/s12022-025-09896-7","DOIUrl":"10.1007/s12022-025-09896-7","url":null,"abstract":"<p><p>Although defects in the mismatch repair (MMR) system have been occasionally reported in aggressive/metastatic pituitary neuroendocrine tumors (PitNETs), the potential role of MMR dysregulation in pituitary tumorigenesis is largely unknown. This study aimed to evaluate the expression of the four key MMR components in a large series of PitNETs. MMR gene expression was studied by RT-qPCR in 127 tumors (54 PIT1, 51 SF1, 22 TPIT), and semi-quantitative immunohistochemistry (score 0-12) in selected cases (n=46). MSH2/6 and MLH1 promoters methylation was studied in 96 tumors. Except for MLH1, tumor lineage of origin was the most significant factor influencing MMR transcripts (P=0.005, <0.001 and 0.039 for MSH2/6 and PMS2, respectively), the highest levels being observed in SF1 tumors. Within subgroups, MMR transcripts were significantly lower in large/invasive PIT1 and in functioning TPIT tumors. MSH2 promoter methylation was occasionally associated with reduced MSH2 expression. Global loss of MSH6 (score 0), defining MMR deficiency, was observed in a single silent lactotroph PitNET, unrelated to the Lynch's syndrome. Near global loss involving MSH6, MSH2 or PMS2 (score 1) was observed in 5 tumors (1 lactotroph, 1 SF1, 3 TPIT). MMR mutations were excluded in 4/5 cases but 2 had LOH at MSH2/MSH6 loci. Heterogeneous immunostaining for any MMR (score 2-4) was also observed in 15 cases. In conclusion, MMR deficiency was rarely observed (2.2%) but reduced MMR expression could be found, especially in functioning corticotroph and invasive lactotroph tumors. The molecular mechanisms and prognostic significance of such findings would deserve further investigation.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"2"},"PeriodicalIF":14.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Pancreatoblastoma: A Challenge in the Differential Diagnosis of Pancreatic Neuroendocrine Neoplasms.","authors":"Vincenzo Guastafierro, Dimitrios P Bouklas, Saverio Pancetti, Silvia Uccella","doi":"10.1007/s12022-025-09897-6","DOIUrl":"10.1007/s12022-025-09897-6","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"52"},"PeriodicalIF":4.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Assessment of Focus Quality in Whole-Slide Imaging of Thyroid Liquid-Based Cytology Using Laplacian Variance.","authors":"Chan Kwon Jung, Chankyung Kim, Sora Jeon, Andrey Bychkov","doi":"10.1007/s12022-025-09893-w","DOIUrl":"10.1007/s12022-025-09893-w","url":null,"abstract":"<p><p>Reliable focus is essential for digital cytopathology, yet three-dimensional cell clusters in liquid-based cytology (LBC) slides pose persistent challenges for single-plane whole-slide imaging. We sought to quantitatively compare focus performance among three whole-slide scanners and to evaluate the use of Laplacian variance as an objective focus quality metric. A total of 102,573 image tiles (512 × 512 pixels) were generated from 36 whole-slide images after scanning twelve thyroid LBC slides at 40× magnification using three scanners. Single-plane mode with automatic focusing was applied. Image sharpness for each tile was computed in Python using the variance of the Laplacian, quantified as a focus score and classified into five ordinal categories, ultimately dichotomized as in-focus (variance ≥ 10) versus out-of-focus. Statistical comparisons between scanners were performed. Laplacian variance scores showed strong concordance with visual assessments of focus quality made by pathologists. One scanner consistently achieved the highest median focus scores and the most uniform spatial distribution for SurePath slides, while the other two demonstrated lower median values and greater variability. ThinPrep slides exhibited high focus quality across all scanners (> 95% in-focus), with smaller but still measurable inter-scanner differences. Overall, more than 70% of tiles were in-focus across all scanners, suggesting preserved diagnostic usability. Laplacian variance is a practical and reproducible tool for assessing focus quality in digital cytology. Focus performance varied among scanners, particularly for slides with three-dimensional cell clusters, whereas differences were less pronounced for monolayer ThinPrep preparations. Quantitative focus assessment may support scanner selection, quality assurance, and computational cytopathology workflows.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"51"},"PeriodicalIF":4.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recipient of the 2025 Endocrine Pathology Society Lifetime Achievement Award: Dr. Arthur S. Tischler, M.D.","authors":"","doi":"10.1007/s12022-025-09895-8","DOIUrl":"https://doi.org/10.1007/s12022-025-09895-8","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"50"},"PeriodicalIF":14.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-center Assessment of DLL3 Expression by Immunohistochemistry in Medullary Thyroid Carcinoma.","authors":"Ignacio Ruz-Caracuel, Alejandra Rosell, Lucie Geryková, João Martins Gama, Teresa Alonso-Gordoa, Amanda Rodríguez-Villena, Rui Almeida, Marta Rosas, Rebeca Martínez-Hernández, Maria João Martins, Ales Ryska, Catarina Eloy, José Palacios","doi":"10.1007/s12022-025-09894-9","DOIUrl":"10.1007/s12022-025-09894-9","url":null,"abstract":"<p><p>Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy accounting for 1-2% of thyroid carcinomas. As a neuroendocrine neoplasm, it shares molecular features with other aggressive neuroendocrine carcinomas, including alterations in the Myc and Notch pathways. Delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch pathway and a validated therapeutic target in small cell lung carcinoma, has attracted interest as a biomarker and potential target in other neuroendocrine tumors; however, its relevance in MTC remains poorly characterized. We performed a multicenter retrospective study of 119 MTC cases resected between 2000 and 2024 across five European institutions. DLL3 immunohistochemistry was assessed on whole sections using the Ventana SP347 antibody, with expression categorized as null (< 1%), low (1-49%), or high (≥ 50%). Interobserver agreement between two endocrine pathologists was substantial (weighted kappa = 0.80). DLL3 positivity (≥ 1%) was observed in 89.1% of cases; 53.8% showed low and 35.3% high expression. DLL3-high expression correlated with adverse histopathological features, including larger tumor size, high-grade histology, desmoplasia, positive surgical margins, and lymph node metastases. In survival analyses, DLL3-high expression was associated with significantly shorter disease-free survival (HR 7.96, p = 0.05) and overall survival (HR 11.6, p = 0.01). Our findings indicate that DLL3 is frequently expressed in MTC and its high expression identifies tumors with aggressive pathological characteristics and poor clinical outcomes. These results support DLL3 as a potential prognostic biomarker and therapeutic target in MTC, highlighting the need for further validation and integration into clinical trials of DLL3-directed therapies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"49"},"PeriodicalIF":14.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12678581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Molecular Subtypes of Pancreatic Neuroendocrine Tumors Mutated in MEN1/DAXX/ATRX Explain Biological Variability.","authors":"Simona Avanthay, Annunziata Di Domenico, Philipp Kirchner, Konstantin Bräutigam, Aziz Chouchane, Renaud Maire, Christina Thirlwell, Corina Kim-Fuchs, Aurel Perren, Ilaria Marinoni","doi":"10.1007/s12022-025-09892-x","DOIUrl":"10.1007/s12022-025-09892-x","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"47"},"PeriodicalIF":14.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Utility of Cabozantinib in the Therapy of Endocrine Tumours.","authors":"Eleni Armeni, Tu-Vinh Luong, Ashley Grossman","doi":"10.1007/s12022-025-09890-z","DOIUrl":"10.1007/s12022-025-09890-z","url":null,"abstract":"<p><p>Endocrine and neuroendocrine malignancies, including epithelial neuroendocrine neoplasms (NENs), phaeochromocytoma/paraganglioma (PPGL), adrenocortical carcinoma (ACC) and thyroid cancers, represent a heterogeneous group of tumours often characterised by dysregulated receptor tyrosine kinase signalling and with limited systemic treatment options. Cabozantinib is a multikinase inhibitor implicated in tumour angiogenesis, growth, and therapeutic resistance, and its use has been reported in many of these tumours. We performed a narrative review assessing cabozantinib monotherapy or combination regimens in patients with progressive neuroendocrine neoplasms. In NENs, monotherapy achieved a disease control rate (DCR) of up to 83% and a progression-free survival (PFS) of 8.4 months in extra-pancreatic subtypes, and 13.8 months in pancreatic subtypes. Combination therapies yielded modest efficacy with a PFS up to 13.0 months. In metastatic PPGLs, monotherapy achieved an objective response rate (ORR) of 25%, a median PFS of 16.6 months and overall survival (OS) of 24.9 months; combination with atezolizumab showed an ORR of 15.4% and a PFS of 8.4 months. In adrenocortical cancer, the DCR reached 78%, PFS up to 7.2 months, and OS up to 23.9 months. In differentiated thyroid cancer, PFS 11.4 months and OS 26.3 months; in RET M918T-mutant medullary thyroid cancer, OS improved to 44.3 months. Cabozantinib represents a promising therapeutic option across endocrine and neuroendocrine malignancies, particularly in settings with limited treatment alternatives, although the reported rates of control have not been dramatic and adverse effects not insignificant. However, it offers the possibility of exploring more effective molecular approaches, especially with biomarker-based stratification and combinatorial approaches.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"48"},"PeriodicalIF":4.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular Thyroid Carcinoma Relapse Cases - Revisited by X-ray 3D Virtual Histology.","authors":"Kiarash Tajbakhsh, Olga Stanowska, Jonas Bossart, Marija Buljan, Antonia Neels, Martina T Mogl, Catarina Alisa Kunze, Guenther Klein, Wolfgang Hulla, Rene Brillmann, Sabine Kirchnawy, Michael Hermann, Reto Kaderli, Robert Zboray, Aurel Perren","doi":"10.1007/s12022-025-09891-y","DOIUrl":"10.1007/s12022-025-09891-y","url":null,"abstract":"<p><p>The diagnosis and prognosis of follicular thyroid neoplasms are based on the identification of capsular and vascular invasion. Although conventional histology allows accurate classification in most cases, its inherent limitations in tissue sampling can result in misjudgment of both the presence and extent of invasion, and occasionally result in diagnostic inaccuracies. Consequently, unexpected tumor recurrence or overtreatment still represent significant clinical challenges. To mitigate these limitations, emerging diagnostic approaches are exploring advanced imaging modalities. X-ray 3D virtual histology has been reported to enable non-destructive and comprehensive sampling of the entire tumor volume embedded in formalin-fixed paraffin-embedded blocks. In thisstudy, the X-ray 3D virtual histology technique is first evaluated by classifying 99 follicular thyroid carcinomas and 31 follicular adenomas, achieving an accuracy of 89.2%. It is then applied to tissue blocks from five relapse cases that were postoperatively diagnosed as adenomas using conventional histology. Three of five tumors exhibited at least one unequivocal focus of vascular invasion, reinforcing that even a single well-defined focus portends significant risk of recurrence and distant metastasis. Although histological confirmation at this stage remained necessary, X-ray 3D virtual histology proved to be a valuable screening method.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"46"},"PeriodicalIF":4.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine Pathology Society Hubert Wolfe Award for 2025: Call for Nominations.","authors":"","doi":"10.1007/s12022-025-09888-7","DOIUrl":"https://doi.org/10.1007/s12022-025-09888-7","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"45"},"PeriodicalIF":14.7,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}