Endocrine Pathology最新文献

{"title":"Reticulin Framework Assessment in Neoplastic Endocrine Pathology.","authors":"Umberto Mortara, Giulia Orlando, Marco Volante, Mauro Papotti, Eleonora Duregon","doi":"10.1007/s12022-025-09867-y","DOIUrl":"https://doi.org/10.1007/s12022-025-09867-y","url":null,"abstract":"<p><p>The reticulin framework, composed mainly of type III collagen, is an essential structural component of biological tissues. Reticulin stains, particularly silver-based methods, enable detailed visualization of reticulin framework alterations, which have been proven to be quick, low-cost, and reliable solutions for highlighting quantitative and qualitative changes of reticulin framework and have been variably associated with neoplastic and non-neoplastic conditions. This review provides an updated overview of reticulin stain applications and reticulin framework assessment in endocrine and neuroendocrine neoplasms, including those of the pituitary, parathyroid, adrenal, and other neuroendocrine systems. In pituitary neuroendocrine tumors, reticulin framework loss serves as a distinguishing feature between normal and neoplastic adenohypophysis. Parathyroid neoplasms, including adenomas, atypical tumors, and carcinomas, exhibit varying degrees of reticulin framework disruption, which may aid in differential diagnosis. Similarly, in adrenocortical neoplasms, reticulin framework evaluation plays a crucial role in malignancy assessment, as defined in the reticulin algorithm, which incorporates reticulin framework alterations alongside three Weiss criteria: necrosis, high mitotic count (> 5/10 mm²), and venous invasion. Moreover, specific reticulin framework patterns help to distinguish the different morphological subtypes of bilateral macronodular adrenocortical disease. Pheochromocytomas and paragangliomas display a range of reticulin framework patterns which might be related to the genetic background of the tumor. Finally, different neuroendocrine neoplasms exhibit variable reticulin framework integrity, with a more significant disruption observed in high-grade carcinomas. Advancements in digital pathology and artificial intelligence offer promising avenues for automated reticulin framework quantification, enhancing diagnostic precision and prognostic assessments. The integration of computational approaches may further improve the clinical utility of reticulin framework evaluation in endocrine pathology.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"21"},"PeriodicalIF":11.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217631","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":"Focal High-Grade Areas with a Tumor-in-Tumor Pattern: Another Feature of Pediatric DICER1-Associated Thyroid Carcinoma?","authors":"Marco Schiavo Lena, María Sánchez-Ares, Emanuela Brunetto, Ihab Abdulkader-Nallib, Riccardo Maggiore, Diego Barbieri, Maria Cristina Vigone, Francesca Perticone, Roberto Lanzi, Silvia Presi, Paola Carrera, Maria Giulia Cangi, Gianluigi Arrigoni, Claudio Doglioni, José Manuel Cameselle-Teijeiro","doi":"10.1007/s12022-025-09863-2","DOIUrl":"10.1007/s12022-025-09863-2","url":null,"abstract":"<p><p>In the thyroid gland, during childhood or adolescence, DICER1-driven tumors include differentiated follicular thyroid carcinoma and, more rarely, poorly differentiated carcinoma. Herein, we describe the features of DICER1-associated thyroid carcinoma with the presence of high-grade areas within a differentiated tumor in four patients (median age 12.5 years, range 6-15 years), three of them carrying germline pathogenic variants of DICER1. A new tumor-in-tumor pattern characterized by intratumoral nodules with a higher histological grade (increased mitotic activity/Ki-67 and solid/trabecular/insular and/or microfollicular architecture) was detected in these DICER1-associated tumors. In two patients, the high-grade component also demonstrated the presence of CHEK2 p.(Tyr390Cys) likely pathogenic variants, suggesting a role for this gene and more generally for the ATM-CHECK2-TP53 pathway as a mechanism of malignant progression of DICER1-associated thyroid carcinomas. One of these two patients presented lymph node recurrence 8 months after surgery. An immunohistochemical study was also performed to explore the possible contribution of anti-DICER1 antibodies as well as thyroglobulin, Ki-67, p53, and PRAME in characterizing these tumors. DICER1 proved to be strongly expressed in mutated tumors compared to a control cohort (p < 0.001), deserving further validation to define its possible diagnostic role. Finally, well-demarcated ischemic-like areas with ghost cells embedded in a thick hyaline stroma (atrophic changes) were found within four tumors, whereas bunches of ectatic macrofollicles lined by flattened epithelium (involutional changes) were only detected in the background thyroid parenchyma of patients with germline DICER1 variants. These morphological features may alert pathologists to suspect a somatic and/or germline DICER1 alteration.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"20"},"PeriodicalIF":11.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192562","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":"Three Synchronous Pituitary Neuroendocrine Tumors-Epigenomics Confirm an Exceptional Triple PitNET.","authors":"Temor Rafiq, Jakob Matschke, Jörg Flitsch, Matthias Dottermusch","doi":"10.1007/s12022-025-09864-1","DOIUrl":"10.1007/s12022-025-09864-1","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"19"},"PeriodicalIF":11.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082212","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":"Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases.","authors":"Alessandro Vanoli, Nestor Piva, Frediano Socrate Inzani, Federica Grillo, Catherine Klersy, Silvia Uccella, Paola Spaggiari, Luca Albarello, Marco Schiavo Lena, Massimo Milione, Caterina Antoniacomi, Anna Caterina Milanetto, Alessandro Zerbi, Antonio Di Sabatino, Massimo Falconi, Andrea Anderloni, Paola Mattiolo, Claudio Luchini, Aldo Scarpa, Matteo Fassan, Paola Parente, Ombretta Luinetti, Guido Rindi, Marco Paulli, Stefano La Rosa","doi":"10.1007/s12022-025-09861-4","DOIUrl":"10.1007/s12022-025-09861-4","url":null,"abstract":"<p><p>Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"18"},"PeriodicalIF":11.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060574","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":"ABCC3 Is a Differential Marker of CYP11B2-Negative Zona Glomerulosa Cells in Human Adrenal Cortex.","authors":"Yingxian Pang, Sanas Mir-Bashiri, Zhuolun Sun, Yuhong Yang, Isabella Castellano, Thomas Knösel, Martin Reincke, Tracy Ann Williams","doi":"10.1007/s12022-025-09862-3","DOIUrl":"https://doi.org/10.1007/s12022-025-09862-3","url":null,"abstract":"<p><p>ATP Binding Cassette Subfamily C Member 3 (ABCC3) is a membrane transporter that exports diverse compounds, influencing drug resistance in cancers and impacting metabolic and malignant diseases. We previously reported ABCC3 upregulation in human adrenal cells under lipid peroxidation-induced oxidative stress. We investigated ABCC3 expression and function in the human adrenal cortex in the context of primary aldosteronism, focusing on its relationship to CYP11B2 (aldosterone synthase) in zona glomerulosa (ZG) cells and aldosterone-producing lesions. ABCC3 expression in aldosterone-producing adenomas (APAs) was markedly reduced compared to the adjacent adrenal cortex, cortisol-producing adenomas, and non-functioning adenomas. The reduction in APAs showed genotypic variability: in APAs harboring KCNJ5 mutations-known drivers of autonomous aldosterone production via altered potassium channel function-ABCC3 mRNA/protein levels were significantly higher than in wild-type KCNJ5 APAs. Spatial transcriptomics and immunofluorescence colocalization revealed an inverse expression pattern between ABCC3 and CYP11B2 (aldosterone synthase) in APAs and aldosterone-producing micronodules (APMs). Notably, high ABCC3 expression was exclusively observed in adrenal ZG cells that lacked CYP11B2 expression. This expression pattern distinguishes ABCC3 from common ZG markers such as KCNJ5 and DAB2, which are expressed across adrenal ZG cells, APMs, and APA tumor cells. In cultured human adrenocortical cells, both angiotensin II stimulation and induced expression of the KCNJ5-L168R mutation resulted in upregulation of CYP11B2 transcription while concomitantly suppressing ABCC3 expression. In conclusion, ABCC3 serves as a novel marker of CYP11B2-negative ZG cells, providing a histopathological tool to differentiate normal adrenal zonation from aldosterone-producing lesions in primary aldosteronism, as well as from cortisol-producing and nonfunctional adenomas.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"17"},"PeriodicalIF":11.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043009","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":"Is Ectopic Cushing Syndrome Commonly Associated with Small Cell Lung Cancer (SCLC)? Critical Review of the Literature and ACTH Expression in Resected SCLC.","authors":"Ayako Ura, Elisa Moser, Matthias Evert, Katja Evert, Bruno Märkl, Eva Sipos, Marcus Kremer, Hironobu Sasano, Yoshinori Okada, Katja Steiger, Carolin Mogler, Hans Hoffmann, Alexander von Werder, Daniel Kaemmerer, Silvia Uccella, Stefano La Rosa, Günter Klöppel, Atsuko Kasajima","doi":"10.1007/s12022-025-09860-5","DOIUrl":"10.1007/s12022-025-09860-5","url":null,"abstract":"<p><p>The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs. The literature search revealed that 90% of the 205 ECS-SCLC patients identified between 1952 and 2023 had no or poor-quality histologic images, so the diagnosis of SCLC could not be confirmed. Review of the 20 reports (10%) with histologic images revealed that 18/20 (90%) had to be reclassified as \"probable NET\", of which 5/18 (28%) showed spindle cell morphology, while only 2 cases were qualified as \"SCLC compatible\" due to their pleomorphic cell features. Immunohistochemically, 5/155 (3%) resected SCLCs, all without ECS, showed weak single cell ACTH expression, whereas in the NET cohort, 61/158 (39%) tumors expressed ACTH, of which 4 (3%) were associated with ECS. Both observations, the literature review, which casts doubt on previously reported data regarding the frequency of SCLC in ECS, and the immunohistochemical study, suggest that there is limited evidence that SCLC is the cause of ECS.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"16"},"PeriodicalIF":11.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057584","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":"TERT Amplification a Risk Stratification Marker in Papillary Thyroid Carcinoma, Significantly Correlated with Tumor Recurrence and Survival.","authors":"Gil-Bernabé Sara, Feás-Rodríguez Noa, Pérez-Riesgo Enrique, Corraliza-Gómez Miriam, Fra Rodríguez Joaquín, García-Rostán Ginesa","doi":"10.1007/s12022-025-09853-4","DOIUrl":"https://doi.org/10.1007/s12022-025-09853-4","url":null,"abstract":"<p><p>Few studies have analyzed the prevalence of TERT amplification in thyroid cancer, showing discrepancies in various topics. The impact on tumor recurrence and patient survival in papillary thyroid carcinoma (PTC) remains unknown. Thirteen cancer cell lines and 215 tumor samples from 91 patients, who underwent surgery for PTC (41), poorly differentiated thyroid carcinoma (PDC = 15), or anaplastic thyroid carcinoma (ATC = 35), were analyzed. Clonality, spread with tumor dedifferentiation or metastatic PTC cells, and coexistence with TERTp, BRAF, RAS, and PIK3CA mutations were also investigated. TERT amplification was found in 17%, 20%, and 17% of the PTC, PDC, and ATC, respectively. It was more frequent in follicular variant PTC and PTC with distant metastases (86%, P = 0.0448). The cell lines HTh74, SW1736, and T242 had amplification. In PTC, TERT amplification was a subclonal event. The increase in TERT copy number spread in all cases with metastatic PTC cells. In 67% of the PDC and 100% of the ATC, TERT activation segregated with tumor dedifferentiation. TERT amplification correlated with TERTp mutations in PTC (P = 0.0313) and PIK3CA mutations in ATC (P = 0.0272). TERT amplification significantly correlated with vascular invasion (P = 0.03637), distant metastases at diagnosis and/or follow-up (P = 0.04482), metachronous distant metastases (P = 0.03131), death patient status (P = 0.000829), stage at diagnosis (P = 0.01995), and stage III/IV at last follow-up (P = 0.01552). TERT amplification associated independently with tumor-related recurrence and death. Our study shows that PTC can be stratified into clinically prognostic relevant categories based on the presence or not of TERT amplification in the cells.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"15"},"PeriodicalIF":11.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054517","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":"Identification of Specific Biomarkers for Anaplastic Thyroid Carcinoma Through Spatial Transcriptomic and Immunohistochemical Profiling.","authors":"Faridul Haq, Andrey Bychkov, Ozgur Mete, Sora Jeon, Chan Kwon Jung","doi":"10.1007/s12022-025-09858-z","DOIUrl":"https://doi.org/10.1007/s12022-025-09858-z","url":null,"abstract":"<p><p>Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with a poor prognosis. Despite its rarity, identifying predictive molecular markers that distinguish ATC from follicular cell-derived non-anaplastic thyroid carcinomas is critical for improving diagnosis and treatment strategies. This study aimed to identify and validate key mRNA and protein markers associated with ATC progression and dedifferentiation. We performed spatial transcriptomic analysis on an index case of ATC coexisting with papillary thyroid carcinoma (PTC) and identified eight differentially expressed mRNA markers. These findings were validated in a large cohort using immunohistochemistry on tissue microarrays across various thyroid tumor types, including follicular adenoma, PTC, poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, and ATC. Additionally, the impact of BRAF p.V600E mutation status on these markers was evaluated. COL7A1, LAMC2, SPHK1, and SRPX2 mRNA and protein levels were significantly overexpressed in ATCs. Conversely, CD24, EPHX1, GPX3, and RBM47 mRNA and protein levels were markedly downregulated in ATCs. Functional enrichment analysis, based on mRNA expression data, identified the role of these proteins in tumor invasion, epithelial-mesenchymal transition, extracellular matrix remodeling, and immune evasion. The expression levels of these markers were independent of BRAF p.V600E mutation status, highlighting their potential as diagnostic markers. In summary, this study identified eight molecular markers that can distinguish ATC from other thyroid tumors. The validation of these markers at both the mRNA and protein levels underscores their clinical relevance in ATC diagnosis and tumor characterization. These findings provide a foundation for future biomarker-driven diagnostic and therapeutic strategies for ATC.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"14"},"PeriodicalIF":11.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041288","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":"Prevalence and Clinical Impact of BRAF p.V600E Mutation in Papillary Thyroid Carcinoma.","authors":"Alexandria Brumfield, Sara Abou Azar, Rachel Nordgren, Ronald N Cohen, David Sarne, Xavier M Keutgen, Megan Applewhite, Peter Angelos, Nicole A Cipriani","doi":"10.1007/s12022-025-09859-y","DOIUrl":"https://doi.org/10.1007/s12022-025-09859-y","url":null,"abstract":"<p><p>Identifying risk factors in papillary thyroid carcinoma (PTC) that warrant more aggressive treatment is paramount. Importantly, the prevalence and clinical significance of BRAF p.V600E mutation in PTC remain debatable. This study aims to determine the association of BRAF p.V600E with demographic and clinicopathologic characteristics, including recurrence. Single institution data from consecutive PTC patients with BRAF p.V600E immunohistochemistry and/or molecular testing was collected between 2018 and 2022, including BRAF status, morphologic subtype, TN category, tumor size, nodal disease burden, tumor multifocality, extrathyroidal extension, treatment, follow-up time, loco-regional and distant recurrence, and mortality. This study included 301 patients, 30% male. The majority had BRAF p.V600E mutation (78.7%), and BRAF p.V600E was associated with morphologic subtype (p < 0.001), with 88% of classic subtype PTCs, 38% of PTCs with extensive follicular growth, and 100% of tall cell subtype expressing BRAF p.V600E. BRAF p.V600E was not associated with tumor size (p = 0.696) or nodal disease burden (p = 0.962). On multivariate analysis using Cox proportional hazard model, large volume nodal disease burden (HR 3.37, 95%CI 1.49-7.64, p = 0.004) and male gender (HR 2.29, 95%CI 1.23-4.26, p = 0.009) were significantly associated with recurrence. BRAF p.V600E (HR 0.71, 95% CI 0.31-1.65, p = 0.4) was not significantly associated with recurrence. In conclusion, presence of BRAF p.V600E in the absence of high risk histologic features does not have an impact on PTC recurrence, and thus, its utility in risk stratification is questionable in the setting of other clinicopathologic risk factors.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"13"},"PeriodicalIF":11.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019416","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":"Subclassifying \"Atypia of Undetermined Significance (AUS)\" Category in the 2023 Bethesda System for Thyroid Cytopathology: Analyzing K-TIRADS, BRAF V600E Mutation, and Risk of Malignancy.","authors":"Heejin Bang, Chulshin Cho, Mi Young Kim, Jiyeon Hyeon, Seung Eun Lee","doi":"10.1007/s12022-025-09856-1","DOIUrl":"https://doi.org/10.1007/s12022-025-09856-1","url":null,"abstract":"<p><p>The 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) update refines the atypia of undetermined significance (AUS) category by subclassifying it into AUS-nuclear atypia (AUS-N) and AUS-other atypia (AUS-O) based on risk of malignancy, to enhance clarity of diagnosis and patient management. This study evaluates the impact of AUS subclassification on malignancy risk prediction in thyroid nodules. A total of 118 AUS cases were analyzed for subclassification using the nuclear scoring (NS) system to evaluate nuclear features, along with the ultrasonography-based Korean Thyroid Imaging Reporting and Data System (K-TIRADS) for risk stratification, and BRAF V600E mutation testing. Logistic regression and ROC curve analyses were used to identify predictors of malignancy and to assess model performance. The AUS category was divided into AUS-N and AUS-O, with AUS-N having a significantly higher risk of malignancy (ROM) (78.1%) compared to AUS-O (27.3%). The subcategories AUS-N1, N2, and N5 showed significantly high ROM (96.9%, 71.7%, and 90.0%), whereas AUS-N3 and N4 showed lower ROM (20.0% and 33.3%). The NS system standardized the assessment of nuclear atypia, reducing interobserver variability and improving diagnostic reproducibility. BRAF V600E mutation, present in 28.1% of AUS-N cases but absent in AUS-O cases, was a strong predictor of malignancy. Models integrating imaging, detailed cytologic subclassification, and molecular findings achieved high specificity (81.0-86.5%) but moderate sensitivity (58.0-61.3%). These findings support the use of AUS subclassification and molecular testing for BRAF V600E mutation to improve ROM prediction and are consistent with the 2023 TBSRTC emphasis on tailored risk stratification.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"12"},"PeriodicalIF":11.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052802","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}