Endocrine Pathology最新文献

{"title":"Impact of Co-Mutations and Genetic Variations on Malignancy Risk in RAS-Positive Indeterminate Thyroid Nodules: an Institutional Experience.","authors":"Lawrence Q Wong, Zubair W Baloch","doi":"10.1007/s12022-026-09910-6","DOIUrl":"10.1007/s12022-026-09910-6","url":null,"abstract":"<p><p>Mutations in RAS proto-oncogenes (NRAS, HRAS, KRAS) are common in thyroid nodules, though their prognostic significance remains unclear. This retrospective study analyzed 354 thyroid nodules from 346 patients (2018-2023) to investigate the clinical and pathological implications of isolated RAS mutations and RAS with co-occurring genetic alterations. Isolated RAS mutations were found in 41.0% (n = 145), while 54.8% (n = 194) had RAS with additional molecular alterations; NRAS was the most frequent subtype (62.1%). Among co-occurring mutations, EIF1AX (46.7%) and TERT (26.7%) were the most common, primarily in NRAS-positive cases. Surgical follow-up data from 302 cases revealed a malignancy rate of 52.3% (n = 158), with 60.1% (n = 95) being invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC). NRAS mutations appeared in 64.6% of malignant cases. Isolated RAS mutations were mainly associated with benign/low-risk neoplasms (47.0%), notably follicular adenomas and encapsulated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), or malignancies (41.0%). The malignancy rate was higher in nodules with a RAS mutation plus one concomitant molecular alteration (54.3%), and nearly 100% in those with three additional genetic alterations. Co-occurring genetic alterations with RAS mutations markedly increased the risk of malignancy compared with isolated RAS mutations (Fisher's exact test, two-tailed p = 0.0026) and were associated with more aggressive tumor phenotypes, whereas isolated RAS mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357544","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":"Reviewer Recognition.","authors":"","doi":"10.1007/s12022-026-09906-2","DOIUrl":"https://doi.org/10.1007/s12022-026-09906-2","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":""},"PeriodicalIF":14.7,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260076","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":"Validation of the Reticulin Algorithm for Adrenocortical Neoplasms: Assessing Diagnostic Accuracy Across All Age Groups and Histological Subtypes.","authors":"Hemlata Jangir, Sanjay Sriram, Sonali Dixit, Shipra Agarwal, Sameer Rastogi, Jagdish Prasad Meena, Yashdeep Gupta, Rajni Sharma, Rajeev Kumar, Om Prakash, Vishesh Jain, Sandeep Agarwala, Mehar Chand Sharma, Venkateswaran K Iyer","doi":"10.1007/s12022-026-09909-z","DOIUrl":"10.1007/s12022-026-09909-z","url":null,"abstract":"<p><p>Adrenocortical carcinoma is a rare and clinically heterogeneous malignancy, often posing difficulty in accurate prognostication. Existing clinicopathological scoring systems, the Weiss, AFIP/Wieneke, and Lin-Weiss-Bisceglia (LWB) criteria, are constrained by their age/subtype-specific applicability and are not suitable for evaluating the rare myxoid and sarcomatoid morphologies or needle biopsies. The Reticulin Algorithm (RA) is a simplified approach for the histopathological assessment of adrenocortical neoplasms, but its prognostic utility requires further validation. We evaluated the prognostic performance of RA and its pediatric-adaptation (pRA) in 157 adrenocortical neoplasms, comprising 140 resection specimens and 17 needle biopsies from 118 adult and 39 pediatric patients, representing all histomorphological subtypes. Among adult tumors, the RA demonstrated diagnostic accuracy exceeding 90%, comparable to the Weiss system but with higher specificity and a markedly superior positive likelihood ratio, highlighting its stronger prognostic value. Its greatest impact was observed in oncocytic tumors, where it outperformed the LWB criteria and correctly reclassified most lesions previously designated as having uncertain malignant potential. In pediatric cases, RA’s performance was comparable to the AFIP/Wieneke criteria. Notably, pRA further improved predictive precision. All myxoid and sarcomatoid tumors were appropriately classified using the algorithm. RA application to needle biopsies showed complete concordance with clinical outcomes. Survival analyses confirmed significant stratification between RA-defined benign and malignant groups. In this large single-center study, RA demonstrated broad applicability and prognostic utility across age groups, histologic subtypes, and specimen types, supporting its potential role in risk stratification of adrenocortical neoplasms.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260016","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":"Ampullary Mixed Adenoma and Well-Differentiated Neuroendocrine Tumor (MANET) with Aberrant Beta-Catenin Expression in a Patient with Neurofibromatosis Type 1.","authors":"Dimitrios P Bouklas, Vincenzo Guastafierro, Silvia Carrara, Alessandro Zerbi, Silvia Uccella","doi":"10.1007/s12022-026-09907-1","DOIUrl":"10.1007/s12022-026-09907-1","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260035","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":"Histopathological and Molecular Characteristics of Pediatric Adrenocortical Tumors: where Do we Stand?","authors":"Christianne C Swart, Ronald R de Krijger","doi":"10.1007/s12022-026-09905-3","DOIUrl":"10.1007/s12022-026-09905-3","url":null,"abstract":"<p><p>Pediatric adrenal cortical carcinoma (ACC) is a rare heterogeneous cancer type that is incompletely understood and differs from its adult counterpart in clinical presentation, histopathological characteristics, genomic landscape, and prognosis. Pediatric ACC has a bimodal age distribution for children with ACC, with the highest incidence in young children and adolescents. Tumors commonly present with an endocrine syndrome such as virilization or Cushing’s syndrome, associated with hormone overproduction. Surgical resection is the primary treatment. Adjuvant therapies such as mitotane or chemotherapy can lead to (severe) side effects in children and should be closely monitored. Histopathological assessment commonly relies on the AFIP/Wieneke classification, with the modified reticulin algorithm also providing predictive value. Recently, the two-step scoring system by Picard aimed to integrate the AFIP/Wieneke classification and the Children’s Oncology Group (COG) staging system into a two-step model. Molecularly, pediatric ACC is strongly associated with germline variants of TP53 and loss of heterozygosity of chromosomes 11 and 17. Somatic variants in several genes, including ATRX and CTNNB1, have been identified and are associated with poor prognosis. Multiple factors, such as age, tumor size, and biomarkers, with Ki67-labeling index being most important, are of prognostic value. Despite research advances, overall survival remains poor and worsens with older age at diagnosis and advanced disease. To improve survival rates of pediatric ACC further research is necessary aiming at optimizing therapeutic strategies in these patients. This review summarizes current knowledge of this challenging tumor and highlights recent advances in the field.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12920729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229996","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":"From Tissue Architecture To Genetic Signature: Artificial intelligence-based Analysis of Reticulin Framework and Clinical Variables Predicts Molecular Cluster in Paragangliomas.","authors":"Eleonora Duregon, Mirko Parasiliti-Caprino, Giulia Orlando, Anna Paola Ferrero, Martina Bollati, Rute Pedrosa, Darshan Kumar, Giuseppe Giraudo, Barbara Pasini, Ezio Ghigo, Emanuela Arvat, Marco Volante, Mauro Maccario, Mauro Papotti","doi":"10.1007/s12022-026-09904-4","DOIUrl":"10.1007/s12022-026-09904-4","url":null,"abstract":"<p><p>Paragangliomas (PGLs), encompassing pheochromocytomas and extra-adrenal paragangliomas, are genetically heterogeneous non-epithelial neuroendocrine neoplasms that segregate into molecular clusters with distinct biological and clinical behavior. Architectural correlates of genotype have not been systematically investigated. This study aimed to assess the reticulin framework as a potential morphologic structural surrogate of molecular background and to introduce a novel deep learning model for its spatially resolved quantitative analysis and genotype prediction. A total of 104 adrenal and extra-adrenal PGLs with complete clinical, pathological, and genetic data were retrospectively analyzed. Reticulin stain was evaluated qualitatively and quantitatively using a supervised convolutional neural network trained on expert-annotated reticulin-stained whole-slide images (WSIs) to map and quantify areas of intact framework and very small nest patterns. Two bias-reduced logistic regression models (Firth’s method) were developed to predict germline cluster 1 genotype, each combining clinical variables (age, tumor size, extra-adrenal presentation) with one artificial intelligence (AI)-derived morphometric feature-percentage of intact framework (Model-INTACT) or very small nests (Model-VSN). PGLs harboring germline cluster 1 variants occurred at a younger age, were larger, more frequently extra-adrenal, and showed significant enrichment of intact reticulin and very small nest patterns compared with cases harboring germline cluster 2 variants and sporadic cases. The supervised AI model accurately mapped and quantified these architectural features across the WSIs. Predictive models integrating AI-derived morphometrics with clinical variables achieved excellent discrimination for germline cluster 1 genotype (AUC 0.981 for Model-INTACT; AUC 0.990 for Model-VSN). Preservation of the reticulin framework, particularly with very small nests, represents a histoarchitectural correlate of pseudohypoxic PGLs. Integration of AI-based morphometric descriptors with clinical parameters enables reliable pre-test prediction of germline cluster 1 genotype, bridging conventional histopathology and molecular classification.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"8"},"PeriodicalIF":4.6,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12916514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221866","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":"Immunohistochemical and Genetic Evidence of Lynch Syndrome-Related Well-Differentiated Pancreatic Neuroendocrine Tumor in Association with Peliosis of the Non-Tumorous Islets and Ductulo-Insular Complexes: An Expansion of Endocrine Manifestations of Lynch Syndrome.","authors":"Ozgur Mete, Raymond Jang, Steven Gallinger","doi":"10.1007/s12022-026-09903-5","DOIUrl":"10.1007/s12022-026-09903-5","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"7"},"PeriodicalIF":4.6,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094929","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":"Whole-Exome Profiling of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma of the Nasopharynx.","authors":"Xin-Chun Chen, Jian-Chang Fu, Ao Zhang, Yuan-Tao Liu, Shan Xing, Fang Wang, Xiao-Ying Zhang, Xiang-Wei Kong, Yan Li","doi":"10.1007/s12022-026-09902-6","DOIUrl":"10.1007/s12022-026-09902-6","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-positive neuroendocrine carcinoma (NEC) of the nasopharynx is a rare malignancy with poor prognosis and lacks squamous markers, rendering it biologically distinct from nasopharyngeal carcinoma (NPC) of squamous epithelial origin. However, its molecular features remain largely undefined, and the entity has not been formally recognized as a nasopharyngeal carcinoma subtype, substantially limiting advances in its diagnosis and treatment. In this study, we performed whole-exome sequencing on seven EBV-positive nasopharyngeal NECs. These tumors exhibited a high tumor mutational burden and recurrent mutations in TP53, APC, and PROK2, with enrichment of alterations in the TP53/WNT, NOTCH, and RTK/RAS/PI3K pathways-mimicking the genomic landscape of NECs at other anatomical sites but clearly diverging from that of NPC. In addition, we identified potentially actionable alterations involving TP53 and KMT2A, suggesting avenues for targeted therapeutic exploration. Collectively, our findings provide molecular evidence supporting EBV-positive NEC of the nasopharynx as a distinct clinicopathologic entity, and offer valuable insights into its oncogenesis and potential therapeutic vulnerabilities.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"6"},"PeriodicalIF":4.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042282","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":"Composite Gangliocytoma/Neuroma and Neuroendocrine Tumor (CoGNET) of the Duodenum: An Image in Endocrine Pathology Exploring Patterns of Biomarker Expression in Tumor Elements.","authors":"Ozgur Mete, Assem Alrumeh, Sara Hafezi Bakhtiari","doi":"10.1007/s12022-026-09901-7","DOIUrl":"10.1007/s12022-026-09901-7","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"5"},"PeriodicalIF":4.6,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985875","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":"Non-Invasive Follicular Cell-Derived Thyroid Neoplasm Composed Entirely of Spindle Cells Harboring NRAS p.Q61R Mutation and Variable Atypia.","authors":"Toru Odate, So Shimekake, Tatsuya Horiuchi, Daiju Sakurai, Tetsuo Kondo","doi":"10.1007/s12022-025-09900-0","DOIUrl":"10.1007/s12022-025-09900-0","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"37 1","pages":"4"},"PeriodicalIF":14.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12795892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954047","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}