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MiThyCA: A Computational Pathology Pipeline for the Identification of Microscopic Foci of Papillary Thyroid Carcinoma-Like Nuclear Features with AI in Whole-Slide Histological Images. MiThyCA:利用人工智能在全片组织学图像中识别甲状腺乳头状癌样核特征的显微病灶的计算病理管道。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-10-07 DOI: 10.1007/s12022-025-09877-w
Leone Bacciu, Mario Urso, Vasco Coelho, Giorgio Cazzaniga, Angela Ida Pincelli, Mattia Garancini, Daniele M Papetti, Daniela Besozzi, Giulia Capitoli, Stefania Galimberti, Alessia Vargiolu, Nicola Fusco, Andrea Gianatti, Fabio Pagni, Vincenzo L'Imperio, Marco S Nobile
{"title":"MiThyCA: A Computational Pathology Pipeline for the Identification of Microscopic Foci of Papillary Thyroid Carcinoma-Like Nuclear Features with AI in Whole-Slide Histological Images.","authors":"Leone Bacciu, Mario Urso, Vasco Coelho, Giorgio Cazzaniga, Angela Ida Pincelli, Mattia Garancini, Daniele M Papetti, Daniela Besozzi, Giulia Capitoli, Stefania Galimberti, Alessia Vargiolu, Nicola Fusco, Andrea Gianatti, Fabio Pagni, Vincenzo L'Imperio, Marco S Nobile","doi":"10.1007/s12022-025-09877-w","DOIUrl":"10.1007/s12022-025-09877-w","url":null,"abstract":"<p><p>The histological identification of papillary thyroid carcinoma (PTC) is straightforward for experienced endocrine pathologists. The increase in radical thyroidectomies led to a raise in the rate of postoperative incidental subcentimeter PTC foci and the recent introduction of the Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) as a less aggressive mimicker of PTC, which significantly complicated the histology screening of thyroid histology specimens. Artificial Intelligence (AI) applied to Whole Slide Images (WSI) can speed up these processes, aiding pathologists to improve diagnostic accuracy and turnaround times. Here we present a computational pathology pipeline for the identification of Microscopic foci of papillary Thyroid Carcinoma-like nuclear features using Artificial intelligence (MiThyCA). This algorithm relies on a tandem architecture consisting of a Convolutional Neural Network (CNN) designed to identify neoplastic areas within thyroid specimens, and a Vision Transformer (TinyViT) focused on detecting PTC-like areas within the neoplastic regions identified by the first model. The study was conducted on a multi-institutional cohort of 73 WSIs from 67 patients with normal thyroid tissue (n = 22 patients, 33%), NIFTP (n = 19, 28%), PTC (n = 23, 34%), and lymph nodes (n = 3, 5%). Cases were divided into training (n = 40 patients, 41 WSIs), validation (n = 13 patients, 14 WSIs) and test (n = 14 patients, 18 WSIs) sets. Each model singly demonstrated excellent performance at the tile-level on the validation set (accuracy = 0.95 and AUC-ROC = 0.95 for CNN, accuracy = 0.86 and AUC-ROC = 0.84 for TinyViT), with their tandem combination in MiThyCA showing accuracy = 0.85 and F1 score = 0.8 on the validation set at the whole WSI-level. The average total execution time of MiThyCA on the test set WSIs was 51 ± 27 s on average on workstations not equipped with GPU, and up to 16 ± 6 s and 11 ± 4 s per WSI with Nvidia GPU and Apple's laptop chip, respectively. Worthy of note, WSIs dimension did not significantly impact the algorithm processing time. Given its speed and accessibility, MiThyCA is a promising AI-based computer-aided diagnostic tool for the detection of subcentimeter PTC foci in histology.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"34"},"PeriodicalIF":4.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240328","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}
引用次数: 0
Presurgical Succinate MetAstatic Risk Tool (P-SMART) in Paragangliomas. 副神经节瘤手术前琥珀酸盐转移风险工具(P-SMART)。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-09-30 DOI: 10.1007/s12022-025-09878-9
Elena Rapizzi, Lorenzo Zanatta, Alice Santi, Fabio Staderini, Niccolò Galeotti, Tonino Ercolino, Francesca Amore, Clotilde Sparano, Mario Maggi, Letizia Canu
{"title":"Presurgical Succinate MetAstatic Risk Tool (P-SMART) in Paragangliomas.","authors":"Elena Rapizzi, Lorenzo Zanatta, Alice Santi, Fabio Staderini, Niccolò Galeotti, Tonino Ercolino, Francesca Amore, Clotilde Sparano, Mario Maggi, Letizia Canu","doi":"10.1007/s12022-025-09878-9","DOIUrl":"10.1007/s12022-025-09878-9","url":null,"abstract":"<p><strong>Introduction: </strong>Paragangliomas (PGLs) are rare malignant non-epithelial neuroendocrine neoplasms characterized by a strong genetic determinism and heterogeneous metastatic potential with no reliable histopathological predictors. In this retrospective study we investigated the role of serum succinate as a biomarker for metastatic risk and developed a novel preoperative scoring tool.</p><p><strong>Matherials and methods: </strong>Seventy patients with PGLs evaluated between 2006 and 2023 were analysed. Clinical, biochemical, imaging, and genetic data were collected. Germline genetic variants were analysed via Sanger sequencing or NGS through a targeted panel of susceptibility genes. Serum succinate concentrations were quantified by gas chromatography-mass spectrometry.</p><p><strong>Results: </strong>Succinate levels were significantly higher in patients with Cluster 1 genetic variants (p < 0.001), extra-adrenal PGLs (p = 0.006), and metastatic disease (p = 0.024). We developed a novel preoperative risk assessment tool, the P-SMART (Preoperative Succinate MetAstatic Risk Tool), combining serum succinate levels, tumour size, and location. P-SMART assigns: 3 points for extra-adrenal localization, 3.5 points for serum succinate ≥ 8.95 µM, and 3 points for tumour size ≥ 7.0 cm. In our cohort a P-SMART score > 4.75 predicted metastatic disease with 72.7% sensitivity and 83% specificity, outperforming the ASES score (Age, Size, Extra-adrenal, Secretory type; AUC 0.891 vs 0.752, p = 0.005).</p><p><strong>Conclusions: </strong>Though limited by sample size and retrospective design, our findings suggest that succinate is a minimally invasive biomarker that could enhance preoperative metastatic risk stratification, especially when integrated into a multiparametric score such as P-SMART. Larger prospective studies are needed to validate its role, but P-SMART could optimize clinical decision-making, refine patient selection for whole-body imaging, reduce unnecessary radiation exposure, and inform surveillance strategies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"33"},"PeriodicalIF":4.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201556","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}
引用次数: 0
Diagnostic Evaluation of Anaplastic Thyroid Carcinoma in Core Biopsy Specimens: Morphologic, Immunohistochemical, Molecular, and Therapeutic Considerations. 甲状腺间变性癌核心活检标本的诊断评估:形态学、免疫组织化学、分子和治疗考虑。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-09-04 DOI: 10.1007/s12022-025-09876-x
Maria Cristina Riascos, Justine A Barletta
{"title":"Diagnostic Evaluation of Anaplastic Thyroid Carcinoma in Core Biopsy Specimens: Morphologic, Immunohistochemical, Molecular, and Therapeutic Considerations.","authors":"Maria Cristina Riascos, Justine A Barletta","doi":"10.1007/s12022-025-09876-x","DOIUrl":"10.1007/s12022-025-09876-x","url":null,"abstract":"<p><p>Although a diagnosis of anaplastic thyroid carcinoma (ATC) can be rendered on fine needle aspiration (FNA), a core needle biopsy is often performed to provide sufficient material for immunohistochemical and molecular analysis. Rendering an ATC diagnosis on core biopsy can be challenging due to limited material. It is crucial that other diagnostic entities in the differential, such as poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, lymphoma, metastases, and NUT carcinoma (among others), are considered and that immunohistochemistry (IHC) is employed judiciously to support the diagnosis. IHC for BRAF V600E should also be performed for ATC to expeditiously assess BRAF V600E mutation status because BRAF-targeted therapy is a critical treatment option for patients with BRAF V600E-mutant ATC. Molecular testing utilizing next-generation sequencing (NGS) should also be initiated at the time of an ATC diagnosis both to confirm BRAF V600E mutation status and to evaluate for other actionable alterations in BRAF-wild-type ATC (such and NTRK or RET fusions or mismatch repair deficiency) and to assess tumor mutation burden. Additionally, IHC for PD-L1 is increasingly being utilized given the results of studies demonstrating the efficacy of checkpoint inhibitors in some ATC patients with PD-L1 expression in tumor cells (especially when utilized along with BRAF inhibitors in patients with BRAF V600E-mutant ATC). In this review, the morphologic and immunophenotypic features of ATC are outlined, the differential diagnosis is reviewed, and the therapeutic implications of key biomarkers are highlighted.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"32"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994417","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}
引用次数: 0
DICER1-Related Pediatric Thyroid Neoplasm with Follicular and Morular Growth: A Tumor that Did Not Read the Textbook. dicer1相关的儿童甲状腺肿瘤伴滤泡和毛囊生长:一个没有读过教科书的肿瘤。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-09-02 DOI: 10.1007/s12022-025-09874-z
José Manuel Cameselle-Teijeiro, Sangeeta Verma, Anthony Penn, Chitra Sethuraman, Isabel Amendoeira, Pablo Garrido-Gil, José Luís Labandeira-García, Beatriz Sobrino, Clara Ruíz-Ponte, Manuel Sobrinho-Simões
{"title":"DICER1-Related Pediatric Thyroid Neoplasm with Follicular and Morular Growth: A Tumor that Did Not Read the Textbook.","authors":"José Manuel Cameselle-Teijeiro, Sangeeta Verma, Anthony Penn, Chitra Sethuraman, Isabel Amendoeira, Pablo Garrido-Gil, José Luís Labandeira-García, Beatriz Sobrino, Clara Ruíz-Ponte, Manuel Sobrinho-Simões","doi":"10.1007/s12022-025-09874-z","DOIUrl":"10.1007/s12022-025-09874-z","url":null,"abstract":"<p><p>Thyroid lesions associated with DICER1 syndrome include multifocal hyperplastic and benign neoplastic proliferations (follicular nodular disease) with characteristic macrofollicular and/or intrafollicular centripetal papillary growth patterns, frequently associated with atrophic and involutional changes. There are also well-differentiated thyroid carcinomas showing intermediate-type nuclei, sometimes combining high-grade areas (tumor-in-tumor pattern) and poorly differentiated carcinomas. Here, for the first time, we describe an encapsulated follicular cell thyroid tumor showing a mixed follicular and morular growth pattern, which presented in an 11-year-old girl with follicular nodular disease and a constitutional (germline) DICER1 p.(Tyr1357fs*18) pathogenic variant. The tumoral follicular component showed colloid and tumor cells with round nuclei, frequent chromatin clearing, and overlapping without grooves or pseudoinclusions (intermediate-type nuclei). There were scattered mitotic figures, but no tumor necrosis, infiltration, or vascular invasion. The morular structures lacked keratinization. The follicular areas were positive for TTF1/NKX2, PAX8, thyroglobulin, thyroperoxidase, keratin clones CKAE1/AE3 and 34bE12, CK19, and vimentin, whereas the morular component was positive for CKAE1/AE3, CK19, CD10, and CDX2. Aberrant (nuclear and cytoplasmic) immunolabeling pattern for β-catenin was limited to the morular structures. The Ki67 proliferation index was 21% in the follicular component and less than 1% in the morulae. In addition to the constitutional DICER1 p.(Tyr1357fs*18) variant, the somatic DICER1 p.(Asp1910Tyr) oncogenic variant and the somatic CTNNB1 p.(Thr41Ala) oncogenic variant were also identified in this tumor. This \"DICER1-related pediatric thyroid neoplasm with follicular and morular growth\" expands the spectrum of DICER1-associated thyroid lesions. Indirectly, the absence of follicular markers only in the areas with WNT/β-catenin pathway activation (morular structures) in this neoplasm could explain the absence of follicular differentiation in cribriform morular thyroid carcinoma. The additional study of one of the accompanying thyroid nodules (follicular nodular disease) confirmed the constitutional DICER1 variant, along with DICER1 p.(Asp1709Gly) and p.(Asp1810Val) variants.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"31"},"PeriodicalIF":4.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979448","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}
引用次数: 0
Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas. 滤泡性甲状腺癌向间变性甲状腺癌的进展:分子和临床病理特征与乳头状甲状腺癌衍生的间变性甲状腺癌的比较。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-09-01 DOI: 10.1007/s12022-025-09875-y
Toru Odate, Tetsuo Kondo, Ryohei Katoh, Koichi Ito, Toshihide Ueno, Yasushi Yatabe, Taisuke Mori
{"title":"Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas.","authors":"Toru Odate, Tetsuo Kondo, Ryohei Katoh, Koichi Ito, Toshihide Ueno, Yasushi Yatabe, Taisuke Mori","doi":"10.1007/s12022-025-09875-y","DOIUrl":"10.1007/s12022-025-09875-y","url":null,"abstract":"<p><p>Although anaplastic thyroid carcinomas (ATCs) typically arise from papillary thyroid carcinomas (PTCs), follicular thyroid carcinomas (FTCs) can also progress to ATCs; however, histologically confirmed FTC-derived ATCs are relatively uncommon and remain poorly characterized. To clarify this phenomenon, we analyzed eight FTC-derived ATCs and compared them with 11 PTC-derived ATCs. Whole-exome sequencing (WES) was conducted on the differentiated thyroid carcinoma (DTC) and ATC components within the same tumors to examine mutational profiles; three additional cases underwent FoundationOne® testing. The demographic features were similar between FTC- and PTC-derived ATCs. Histologically, spindle-cell morphology was more common in FTC-derived ATCs (3/8), whereas PTC-derived ATCs exhibited squamoid (5/11) and giant cell features (5/11), including osteoclast-like cells. WES was successfully performed on both the ATC and FTC components in seven of the eight FTC-derived ATCs. Common alterations included TERT promoter (5/7), NRAS (4/7), and HRAS (2/7) mutations in both components. TP53 mutations were observed only in the ATC component (5/7). EIF1AX mutations co-occurred with TERT and HRAS mutations in two cases. PTEN mutations were found in two FTCs with solid/trabecular patterns but were absent in the corresponding ATC components. One tumor harbored a DGCR8 p.E518K mutation that was retained during progression. By contrast, PTC-derived ATCs consistently showed concurrent BRAF and TERT promoter mutations (11/11). Immunohistochemistry for BRAF V600E, RAS Q61R, p53, PTEN, and MTAP showed high concordance with the corresponding mutation status. These findings revealed significant histological and genetic differences between FTC- and PTC-derived ATCs, providing new insights into the molecular basis of FTC dedifferentiation into ATC.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"30"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979545","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}
引用次数: 0
Exploring Intratumoral Heterogeneity in Mixed Neuroendocrine-Nonneuroendocrine Neoplasms with Spatial Transcriptomics: Even More Diverse Than Anticipated. 利用空间转录组学探索混合神经内分泌-非神经内分泌肿瘤的肿瘤内异质性:比预期的更加多样化。
IF 14.7 2区 医学
Endocrine Pathology Pub Date : 2025-08-20 DOI: 10.1007/s12022-025-09869-w
Annika Weiß, Julia Teply-Szymanski, Maxime Schmitt, Sebastian Foersch, Paul Jank, Joscha Griger, Uwe Wagner, Detlef K Bartsch, Carsten Denkert, Moritz Jesinghaus
{"title":"Exploring Intratumoral Heterogeneity in Mixed Neuroendocrine-Nonneuroendocrine Neoplasms with Spatial Transcriptomics: Even More Diverse Than Anticipated.","authors":"Annika Weiß, Julia Teply-Szymanski, Maxime Schmitt, Sebastian Foersch, Paul Jank, Joscha Griger, Uwe Wagner, Detlef K Bartsch, Carsten Denkert, Moritz Jesinghaus","doi":"10.1007/s12022-025-09869-w","DOIUrl":"10.1007/s12022-025-09869-w","url":null,"abstract":"<p><p>Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN) are usually highly aggressive tumors characterized by marked histological heterogeneity, most commonly represented by mixed adenocarcinoma and poorly differentiated neuroendocrine carcinoma (NEC). However, beyond morphological observations, the biological basis and implications of this heterogeneity remain incompletely understood. In this study, we combined component-specific next-generation sequencing and spatial transcriptomics to investigate three mixed adenocarcinoma-NEC cases from different anatomical sites (ileocecal, ovarian, gastric), tracing tumor progression from precursor lesions to invasive NEC. Genomic analyses revealed a shared trunk of driver mutations across all tumor compartments, confirming their clonal origin, while also uncovering additional compartment-specific alterations. Spatial transcriptomics, together with gene set enrichment analysis (GSEA), revealed distinct transcriptional profiles aligned with histologically annotated compartments (e.g., adenocarcinoma, NEC, precursor). In NECs, GSEA consistently showed downregulation of immune-related pathways and upregulation of proliferation-associated pathways compared to non-neuroendocrine tumor areas. Moreover, distinct transcriptomic subclusters were identified within morphologically homogeneous NEC regions in two of the three cases. These subclusters exhibited significant differences in immune regulation, proliferation signaling, and cell-cycle control, and were associated with divergent predicted chemotherapy-response signatures, suggesting clinically relevant implications for treatment sensitivity and resistance. In summary, our findings indicate that despite a shared clonal origin, MiNEN develop distinct genetic and transcriptomic features across tumor compartments. The inconsistent presence of transcriptomic subclusters within morphologically similar regions underscores the complexity of intratumoral heterogeneity in these aggressive neoplasms. By connecting morphological and molecular layers of tumor architecture, spatial profiling may aid in translating biological complexity into more targeted clinical strategies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"29"},"PeriodicalIF":14.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979500","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}
引用次数: 0
Expression of DLL3 and SEZ6 in the Spectrum of Neuroendocrine Neoplasia. DLL3和SEZ6在神经内分泌肿瘤谱中的表达。
IF 14.7 2区 医学
Endocrine Pathology Pub Date : 2025-07-23 DOI: 10.1007/s12022-025-09873-0
Iqbal Ahmed, Amr Mohamed, Omid Savari, Yue Xue, Sylvia L Asa
{"title":"Expression of DLL3 and SEZ6 in the Spectrum of Neuroendocrine Neoplasia.","authors":"Iqbal Ahmed, Amr Mohamed, Omid Savari, Yue Xue, Sylvia L Asa","doi":"10.1007/s12022-025-09873-0","DOIUrl":"10.1007/s12022-025-09873-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Delta-like protein 3 (DLL3), a Notch ligand, has been identified in high-grade small- and large-cell lung carcinomas and prostate neuroendocrine carcinomas (NECs). SEZ6 (Seizure-related 6 homolog), a membrane-associated protein, has also been identified neuroendocrine neoplasms (NENs). Both DLL3 and SEZ6 are targets of novel antibody-drug conjugates (ADCs). Their expression in the broader family of NENs remains to be clarified. We examined a series of NENs of all types as well as several non-neuroendocrine neoplasms using immunohistochemistry for DLL3 and SEZ6. Staining was scored with the semi-quantitative assessment of intensity and percentage of stained cells that yields a histoscore (H-score from 0 to 300). We identified strong expression of DLL3 in all lung NECs (average H-score 180) and SEZ6 in 1 of 3 (H-score 70). Merkel cell carcinomas (n = 13) expressed DLL3 strongly and diffusely (H-score 178, range 10-300) and 10 of 13 had positivity for SEZ6 (H-score 128). Both DLL3 and SEZ6 were expressed in medullary thyroid carcinomas (10 of 11 cases, H-scores 199 for DLL3 and 224 for SEZ6). Two thymic neuroendocrine tumors (NETs) had weak expression of DLL3 (H-score 20) and SEZ6 (H-score 70). Nine of 11 lung NETs expressed DLL3 (H-score 191), while only two had focal weak staining for SEZ6 (H-score 45). DLL3 was negative in nine of 11 pancreatic NETs; two grade 3 pancreatic NETs had variable weak positivity (H-score 5). In contrast, seven of 11 pancreatic NETs expressed SEZ6 (H-score 45). DLL3 was positive in two pancreatic NECs (H-score 197), and SEZ6 was positive in 1 (H-score 60). One of 13 gastric NETs, a metastatic grade 3 tumor, expressed both DLL3 and SEZ6 (H-score 200 for each) and one other expressed SEZ6 at lower levels. A gastric NEC was weakly positive for both markers (H-scores 50 and 40). All 10 duodenal, 10 ileal, and nine rectal NETs were negative for DLL3; eight duodenal, six ileal, and four rectal NETs expressed SEZ6 (average H-scores 206, 78 and 45, respectively). Among 10 appendiceal NETs, two expressed DLL3 focally and weakly (H-score 45); eight were positive for SEZ6 (H score 109). Duodenal NECS (n = 2) were negative for DLL3; one duodenal NEC expressed SEZ6 (H-score 110). Among five colonic NECs, two expressed DLL3 (H-score 50) and one expressed SEZ6 (H-score 40). Pituitary NETs also expressed DLL3 with eight of 18 positive (H-scores from 10 to 180), and 11 of 18 expressed SEZ6 (average H-score 65). Three of 20 paragangliomas expressed DLL3 weakly (H-score 43), and six expressed SEZ6 (H-score 73). One of four parathyroid carcinomas expressed DLL3 weakly (H-score 30), and all four were negative for SEZ6; five parathyroid adenomas were negative for both. In 43 non-neuroendocrine neoplasms of the GI tract, pancreas, and liver and 10 non-neuroendocrine thyroid carcinomas, there was only weak focal reactivity for DLL3 in three and two cases, respectively, and for SEZ6 in one case each. These results suggest that expression ","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"27"},"PeriodicalIF":14.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692520","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}
引用次数: 0
Reappraisal of Neuroendocrine Tumor Classification of the Prostate Gland: Translating Molecular Insights into Clinical Practice. 前列腺神经内分泌肿瘤分类的重新评估:将分子见解转化为临床实践。
IF 14.7 2区 医学
Endocrine Pathology Pub Date : 2025-07-23 DOI: 10.1007/s12022-025-09871-2
Anandi Lobo, Liang Cheng
{"title":"Reappraisal of Neuroendocrine Tumor Classification of the Prostate Gland: Translating Molecular Insights into Clinical Practice.","authors":"Anandi Lobo, Liang Cheng","doi":"10.1007/s12022-025-09871-2","DOIUrl":"10.1007/s12022-025-09871-2","url":null,"abstract":"<p><p>Neuroendocrine tumors (NETs) of the prostate gland represent a distinct entity within the spectrum of prostate cancer, characterized by neuroendocrine differentiation on morphology and unique clinical behavior. Despite their clinical significance, there remains a lack of consensus regarding their diagnosis, classification, immunohistochemical evaluation, and management. A comprehensive understanding of the molecular and clinical heterogeneity of prostate NETs is essential for developing tailored treatment strategies and improving patient outcomes. Over the years, there has been a continuous effort to refine the terminology and classification of neuroendocrine tumors of the prostate. The current WHO 2022 classification scheme for genitourinary neuroendocrine neoplasms provides a standardized framework. However, given the substantial clinical and molecular heterogeneity of prostate NETs, there is an emerging need for an organ-specific classification system that better captures the biological and clinical diversity of these tumors. In this review, we propose a novel classification system for neuroendocrine neoplasms (NENs) of the prostate that integrates both histomorphology and clinical context. With the growing role of liquid biopsy and molecular biomarkers, there is a shift towards more precise, real-time detection of disease progression and treatment resistance. This review highlights the importance of a more nuanced, biologically and clinically informed approach to the diagnosis and management of prostate NETs. A dedicated classification system, combined with advancements in precision genomics and targeted therapies, holds significant promise for improving outcomes in patients with these rare and challenging tumors.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"28"},"PeriodicalIF":14.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692521","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}
引用次数: 0
Correction: Impact of Tissue Thickness on Computational Quantification of Features in Whole Slide Images for Diagnostic Pathology. 校正:组织厚度对病理诊断全切片图像特征计算量化的影响。
IF 14.7 2区 医学
Endocrine Pathology Pub Date : 2025-07-19 DOI: 10.1007/s12022-025-09872-1
Manav Shah, António Polónia, Mónica Curado, João Vale, Andrew Janowczyk, Catarina Eloy
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引用次数: 0
Roadmap to Challenges in Limited Cellularity Specimens from Pancreatic Neuroendocrine Neoplasms: Diagnostic Tools for the Most Appropriate Management of Limited Material. 胰腺神经内分泌肿瘤有限细胞标本的挑战路线图:有限材料最适当管理的诊断工具。
IF 4.6 2区 医学
Endocrine Pathology Pub Date : 2025-07-16 DOI: 10.1007/s12022-025-09870-3
Stefano La Rosa, Roberta Maragliano, Deborah Marchiori
{"title":"Roadmap to Challenges in Limited Cellularity Specimens from Pancreatic Neuroendocrine Neoplasms: Diagnostic Tools for the Most Appropriate Management of Limited Material.","authors":"Stefano La Rosa, Roberta Maragliano, Deborah Marchiori","doi":"10.1007/s12022-025-09870-3","DOIUrl":"10.1007/s12022-025-09870-3","url":null,"abstract":"<p><p>Fine needle aspiration (FNA) and fine needle biopsy (FNB) procedures are increasingly employed in the diagnostic work-up of pancreatic masses. These procedures represent a challenge for pathologists who have to adapt to handling specimens of limited cellularity. In several cases, FNA and FNB specimens are the only available material, as many pancreatic neoplasms are surgically unresectable at the time of the initial diagnosis. In the present review paper, the diagnosis of pancreatic neuroendocrine neoplasms in limited cellularity specimens is presented using a morphology-based approach. The aim is to provide a practical guide for pathologists to select the most appropriate ancillary techniques to be used for the diagnostic work-up, while conserving precious material. The integration of morphology, immunohistochemistry, and molecular biology will be discussed to provide the reader with practical tools to solve the main differential diagnostic problems encountered in routine practice when working with cytological samples or small biopsies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"25"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12681476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644191","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}
引用次数: 0
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