Endocrine Pathology最新文献

{"title":"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/s12022-025-09889-6","DOIUrl":"10.1007/s12022-025-09889-6","url":null,"abstract":"<p><p>About 40% of non-functioning (NF) Pancreatic Neuroendocrine Tumors (PanNETs) harbour mutations in MEN1, often co-occurring with DAXX/ATRX. While the ADM group (MEN1 and DAXX/ATRX co-mutated) exhibits homogeneous genetic and epigenetic features and a consistent risk of relapse, it shows considerable variability in treatment response, suggesting an underlying molecular diversity. In this study we aimed to elucidate the molecular mechanisms underlying this heterogeneity of ADM PanNETs by integrating transcriptomic (n = 36) and DNA methylation (n = 93) data. First, DNA methylation discriminates ADM-PanNET from PanNET mutated only in MEN1 (α-like), revealing enhancer, peri-centromeric, and telomeric methylation changes associated with alternative lengthening of telomeres and increased chromosomal instability. Transcriptomic analysis further revealed three distinct ADM subtypes: ADM hypoxic, ADM NST (No Special Type), and ADM immunosuppressive. The ADM hypoxic subtype is characterized by strong hypoxia signature, likely regulated epigenetically. The ADM NST subtype appears to be primarily driven by epigenetic changes that promote proliferation. Notably, the ADM immunosuppressive subtype, although significantly smaller (< 2.5 cm, p = 0.023), exhibits strong immune and metastasis-like signatures, suggesting a uniquely aggressive biology despite its reduced size. By defining these three novel ADM subtypes, our study provides a refined framework for understanding PanNET heterogeneity. This classification underscores potential diagnostic markers and highlights distinct biological vulnerabilities that may inform the development of subtype-tailored therapeutic strategies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"44"},"PeriodicalIF":4.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483931","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":"Phenotypic Landscape of Pulmonary Neuroendocrine Tumors: Subtyped by OTP/ASCL1 Expression Correlated with Histology, Hormones and Outcome.","authors":"Ayako Ura, Katja Evert, Matthias Evert, Bruno Märkl, Marcus Kremer, Elisa Moser, Hironobu Sasano, Yoshinori Okada, Katja Steiger, Carolin Mogler, Moritz Jesinghaus, Alexander von Werder, Seyer Safi, Hans Hoffmann, Günter Klöppel, Atsuko Kasajima","doi":"10.1007/s12022-025-09882-z","DOIUrl":"10.1007/s12022-025-09882-z","url":null,"abstract":"<p><p>Recent studies have shown that pulmonary neuroendocrine tumor (NET) subgroups, defined by the transcription factors OTP and ASCL1, correlate with age, sex, and tumor location. Their relationships with histology and hormone production, however, remain unclear. We analyzed 170 pulmonary NETs classified by OTP (O) and ASCL1 (A) expression into four groups: O + /A + , O + /A-, O-/A + , and O-/A-. Subgroups were assessed for histology, hormone expression, therapy-related markers, outcomes, and matched metastases. Among 152 resected primaries, O + /A + tumors (38%) were most frequent, occurring mainly in females (median age 72 years), and typically showed central or peripheral location, solid/spindle morphology with diffuse gastrin-releasing peptide (GRP), and focal ACTH/calcitonin. They also showed strong DLL3 expression and pronounced neuroendocrine cell hyperplasia. O + /A- tumors (23%) occurred predominantly in females (median age 56 years) with solid/trabecular patterns, occasional/ACTH, and strong SSTR2A/5 expression. O-/A- tumors (25%) were more common in males (median age 70 years), often central with solid/trabecular or oncocytic histology, serotonin expression (24%), and frequently SSTR2A-positivity. O-/A + tumors (14%) occurred across both sexes (median age 58 years), were centrally located, and solid, sometimes oncocytic features with moderate DLL3/SSTR2A expression. Metastases mirrored their primaries in transcription factor and hormone profiles. In the univariate analysis, OTP-negative tumors were associated with poorer disease-free survival (DFS). However, the multivariate analysis identified Ki67-based WHO grades (G1-G3) as the only independent prognostic factors. In conclusion, integrating OTP and ASCL1 refines pulmonary NET classification into four histologically and biologically distinct subgroups, providing additional insight into tumor heterogeneity. O + /A + tumors showed solid-spindle features and diffuse GRP and frequent ACTH expression, trabecular patterns characterized ASCL1-negative tumors, while oncocytic histology predominated in OTP-negative tumors, highlighting their role in defining tumor heterogeneity.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"43"},"PeriodicalIF":4.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12592246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453452","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":"Immunotherapy for Metastatic Pancreatic Neuroendocrine Tumors with High Mutational Burden and Mismatch Repair Alterations Following Treatment with Alkylating Chemotherapy.","authors":"Louis de Mestier, Thorvardur R Halfdanarson, Leonidas Apostolidis, Anna Koumarianou, Jorge Hernando, Rachel Riechelmann, Emily K Bergsland, Sara Cingarlini, Shagufta Shaheen, Joakim Crona, Simon Kreutzfeldt, Osama Mosalem, Taymeyah Al-Toubah, Jérôme Cros, Jonathan R Strosberg","doi":"10.1007/s12022-025-09887-8","DOIUrl":"10.1007/s12022-025-09887-8","url":null,"abstract":"<p><p>Alkylating agent-based chemotherapy is one of the main treatment options for patients with metastatic pancreatic neuroendocrine tumors (PanNETs).However, it favors the acquisition of a hypermutator phenotype, suggesting a potential benefit of immunotherapy.We aimed to describe the efficacy of immunotherapy in an international retrospective cohort of patients with metastatic well-differentiated PanNETs pretreated with alkylating therapy. The primary endpoint was progression-free survival (PFS) and the main secondary endpoint was the radiological objective response rate (ORR). We explored the impact of tumor mutation burden (TMB) and mismatch repair deficiency (MMRd), and evaluated variables associated with PFS.We included 64 patients with heavily pretreated PanNETs (median Ki-67 28%). Among 51 PanNETs with mutational profiling, 37 (73%) were TMB^high (median 35 mut/Mb). Among 46 PanNETs with available MMR status, 18 (39%) were MMRd, representing 49% of all TMB^high PanNETs. Immunotherapy consisted of a single (31%) or a dual (69%) immune checkpoint inhibitor. Median PFS was 3.2 months (95% CI, 1.3-5.0.3.0) and the ORR was 17%. Patients with TMB^high PanNETs had longer PFS (median 3.8 vs. 2.3 months, p = 0.015) and higher ORR (30% vs. 0%, p = 0.002) compared with TMB^low/unk cases. Patients with MMRd PanNETs had longer PFS (median 8.9 vs. 2.7 months, p = 0.003) and higher ORR (44% vs. 7%, p < 0.001) compared with MMRp/unk. On multivariable analyses, MMRd predicted longer PFS (HR 0.42, 95% CI [0.20-0.82], p = 0.015).Overall, immunotherapy may be effective against alkylating-pretreated metastatic PanNETs exhibiting TMB^high and MMRd. MMR immunohistochemistry and TMB assessment could be implemented in the routine assessment of alkylating-pretreated metastatic PanNETs.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"42"},"PeriodicalIF":4.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439611","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":"Correction to: TERT Amplification a Risk Stratification Marker in Papillary Thyroid Carcinoma, Significantly Correlated with Tumor Recurrence and Survival.","authors":"Sara Gil-Bernabé, Noa Feás-Rodríguez, Enrique Pérez-Riesgo, Miriam Corraliza-Gómez, Joaquín Fra Rodríguez, Ginesa García-Rostán","doi":"10.1007/s12022-025-09881-0","DOIUrl":"10.1007/s12022-025-09881-0","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"41"},"PeriodicalIF":14.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12572078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403202","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":"Performance of Immunohistochemistry to Detect Rb/p53 Alterations in High-Grade Neuroendocrine Neoplasms: Staining Patterns and Comparison with Genetic Testing.","authors":"Ruiqian Chen, Matthieu Tihy, Ludovic Lacroix, Ophelie de Rycke, Caroline Lacombe, Pierre Alexandre Just, Aurelie Cazes, Magali Svrcek, Vincent Thomas de Montpreville, Martine Antoine, Jean Yves Scoazec, Louis de Mestier, Anne Couvelard, Jérôme Cros","doi":"10.1007/s12022-025-09885-w","DOIUrl":"10.1007/s12022-025-09885-w","url":null,"abstract":"<p><p>Rb and p53 status helps distinguishing well from poorly differentiated high-grade neuroendocrine neoplasms (HG-NENs) and may predict response to platinum-based chemotherapy. Historically, gene and protein profile correlations for Rb and p53 were performed on frozen samples using high-throughput techniques efficient for copy number determination. This situation differs from routine practice in which NGS is not available everywhere and small deletions may be hard to detect on formalin-fixed paraffin-embedded (FFPE) samples with a gene panel approach. This study aimed at describing the immunohistochemical (IHC) staining patterns of Rb, p16, and p53 in a large cohort of well and poorly differentiated lung and pancreatic HG-NENs, and comparing the performance of Rb/p53 NGS profiling with IHC to detect molecular alterations. Rb, p16, and p53 protein status were determined by IHC in 132 HG-NENs (79 pulmonary and 53 pancreatic). NGS was performed on a subset of 63 tumors. Three IHC patterns were observed in HG-NENs: (i) loss of expression (Rb^loss = 45.4% with p16^strong expression in most cases, p53^loss = 32.6%), (ii) variable expression (Rb^var = 40.8% including 12 cases with p16^strong, p53^var = 37.1%), (iii) strong expression (Rb^strong = 13.6%, p53^strong = 30.3%). NGS testing and IHC agreed in 76.2% and 82.5% of cases for Rb and p53, respectively. Abnormal Rb & p53 IHC profiles, highly suggestive of a molecular alteration, were missed by NGS in 42% and 20.5% of cases, respectively. In conclusion, IHC is a reliable, rapid, and cost-effective screening method in HG-NENs for Rb/p53 status.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"40"},"PeriodicalIF":14.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403164","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":"Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.","authors":"Giovanni Centonze, Patrick Maisonneuve, Émilie Mathian, Federica Grillo, Giovanna Sabella, Vincenzo Lagano, Alessandro Mangogna, Sara Pusceddu, Paola Bossi, Paola Spaggiari, Alessandro Del Gobbo, Stefano Ferrero, Luigi Rolli, Ugo Pastorino, Luisa Bercich, Andrea Tironi, Mauro Roberto Benvenuti, Maria Sole Gallazzi, Rosalia Romano, Alfredo Berruti, Luca Roz, Carlo Capella, Matthieu Foll, Massimo Milione","doi":"10.1007/s12022-025-09886-9","DOIUrl":"10.1007/s12022-025-09886-9","url":null,"abstract":"<p><p>Atypical carcinoids (ACs) and large cell neuroendocrine carcinomas (LCNECs) are defined by the WHO as intermediate- and high-grade lung neuroendocrine neoplasms, respectively, based on morphological criteria; however, treatment strategies remain debated. Given the emerging role of the tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) in cancer prognosis and therapy response, this study aimed to characterize the immune landscape of ACs and LCNECs comprehensively. Immunohistochemistry for T-cell markers (CD3, CD8), immune checkpoints (PD-1, PD-L1), HLA molecules (HLA-DR, HLA-I), and fibroblasts (α-SMA) was performed on a re-evaluated cohort of 56 ACs and 104 LCNECs. Digital image analysis quantified intra-tumor (iTILs) and stromal (sTILs) CD3 and CD8 TILs in the whole slide and in specific tumor regions (invasive margin [IM] and central tumor [CT]). LCNECs exhibited significantly higher stromal T-cell infiltration, immune checkpoint expression, and HLA compared to ACs (p < 0.001), while α-SMA was more prominent in ACs. No ACs showed PD-L1 tumor expression. Digital quantification confirmed greater iTILs and sTILs in LCNECs across all regions, with moderate concordance to manual counts. Interestingly, TIL parameters were higher at the IM than in the CT (p < 0.001). Using Boruta feature selection algorithm, Principal Component Analysis and Hierarchical Clustering, three patient clusters were identified: Cluster 1 (mainly ACs, low TILs, favorable prognosis), Cluster 2 (mixed histology, intermediate TILs, moderate prognosis), and Cluster 3 (mostly LCNECs, high TILs, poor prognosis), with distinct TME marker profiles. PD-L1 tumor expression was strongly linked to Cluster 3. These findings suggest that ACs and LCNECs may be stratified into three distinct immune clusters, highlighting the heterogeneity of their tumor microenvironment and providing a rationale for further translational studies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"39"},"PeriodicalIF":4.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12552328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369223","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":"High Prevalence of Potential Molecular Therapeutic Targets in Poorly Differentiated Thyroid Carcinoma.","authors":"Vanessa Zambelli, Giulia Orlando, Marta Fornaro, Giulia Vocino Trucco, Ida Rapa, Francesca Napoli, Susanna Cappia, Lorenzo Daniele, Simonetta Piana, Mauro Papotti, Marco Volante","doi":"10.1007/s12022-025-09883-y","DOIUrl":"10.1007/s12022-025-09883-y","url":null,"abstract":"<p><p>Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid cancer with aggressive clinical course and peculiar clinical/pathological characteristics but lacking effective therapeutic options, when surgery is not curative. We aimed at the molecular characterization of PDTC with a specific focus on the identification of potential therapeutic targets. A series of PDTC cases was selected from a multi-institutional network. Fifty-nine samples underwent wide targeted DNA and RNA next-generation sequencing (NGS) testing and immunohistochemical analysis for mismatch repair (MMR) proteins. Gene fusion analysis was enriched by 25 additional samples. Prevalence of MMR protein loss was 11.9%. The most prevalent mutations were in NRAS (25%) and TP53 (25%), mutually exclusive. TERT promoter (TERTp) mutations were detected in 19.6% of cases (10/51). NRAS-mutated cases were enriched for mutations in genes belonging to the same pathway. TP53-mutated samples lacked TERTp co-mutations, but were associated with mutations in PTEN and in genes related to MMR system and/or loss of MMR proteins. TERTp mutations were the most prevalent alterations (28%, 7/25) in a third group that lacked NRAS or TP53 mutations. Four cases harbored gene fusions, including two cases harboring the TBL1XR1::PIK3CA fusion that has never been reported in thyroid cancer, so far. In conclusion, PDTC may be genomically segregated in subgroups with specific molecular characteristics. Overall, targetable gene fusions have a prevalence of 9% (4/42). Moreover, 47% of cases are potential candidates for individualized target therapies since they harbor mutations in genes coding for potentially targetable molecules and/or have defects in the MMR system.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"38"},"PeriodicalIF":4.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12546271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350227","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: 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/s12022-025-09884-x","DOIUrl":"10.1007/s12022-025-09884-x","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"37"},"PeriodicalIF":14.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12546278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350212","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":"Intratumoral Heterogeneity of Ki67 Index and Its Impact on the Diagnosis and Prognostication of Pancreatic Neuroendocrine Tumors: Hot-Spot Count Differs Significantly from Random-Area Count.","authors":"Ozgur Can Eren, Nobuyuki Ohike, Deniz Tuncel, Pelin Bagci, Serdar Balci, David E Adsay, Rohat Esmer, Burcu Saka, Burcin Pehlivanoglu, Yue Xue, Juan Sarmiento, Shishir K Maithel, David A Kooby, Alyssa Krasinskas, Michelle D Reid, Olca Basturk, Volkan Adsay","doi":"10.1007/s12022-025-09880-1","DOIUrl":"10.1007/s12022-025-09880-1","url":null,"abstract":"<p><p>The pivotal role of Ki67 in grading pancreatic neuroendocrine tumors (PanNETs) is well recognized and firmly established in current WHO guidelines. Intratumoral heterogeneity is a well-known phenomenon, and it has also been documented for Ki67; however, the data on the magnitude of the impact of this heterogeneity on the final grade in primary NETs is relatively limited. In this study, Ki67 labeling index (KI) was calculated by using the manual count of camera-captured image method in 91 PanNETs both in hot-spots (KI(h)) as well as 6 different random-areas (KI(r)), each counted in a minimum of 2000 cells. The process was repeated for 29 samples from metastatic foci. Mean KI of the hot-spots was more than twofold higher than that of the random (5 vs 2.1%), with a low kappa agreement (0.2770). This changed the final grade in almost half of the cases (42/91; p < 0.001). Random counting missed all 4 G3 NETs as well as 6/7 of the Grade 2b cases (those with Ki67 10-≤ 20%). On the other hand, in only 4 cases, the difference in KI was > 10%. Similar heterogeneity was also observed in the 29 metastatic tumors analyzed with the final grade differing in 55% based on KI(h) versus KI(r). KI(h) had a stronger correlation with signs of aggressiveness including metastasis and tumor size and also trended with perineural invasion in tumors > 5 cm. The intratumoral heterogeneity in Ki67 in pancreatic NETs lead to a change in final grade in 46% of cases by hot-spot versus random count. This underscores the importance of both making a reliable Ki67 count and providing a numerical index in addition to the final grade, and interpretation of the results case-by-case basis for management purposes, rather than the rigid grade-based approach. This study also supports the usage of hot-spot rather than random count as the grade parameter. Reporting Ki67 in cytology and small biopsy specimens should be supplemented by a comment highlighting that the final grade may change when the entire tumor is evaluated but that the difference in the nominal count will seldom be higher than 10%.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"36"},"PeriodicalIF":4.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276663","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":"Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!","authors":"Matthias Dottermusch","doi":"10.1007/s12022-025-09879-8","DOIUrl":"10.1007/s12022-025-09879-8","url":null,"abstract":"<p><p>The introduction of the term pituitary neuroendocrine tumor (PitNET) to replace pituitary adenoma has sparked a versatile debate among experts. The controversy surrounding this nomenclature change includes the question of whether these tumors' biological identity truly corresponds to neuroendocrine tumors. In this meta-analysis, DNA methylation data were interrogated to clarify whether the old or new nomenclature more accurately reflects the epigenome of these tumors. Publicly available DNA methylation data of 100 NETs, 100 PitNETs/adenomas, and 100 adenomas of various origins and lineages were compiled from 18 different publications. Epigenomic signatures characteristic of NETs and adenomas were defined and compared to those of PitNETs/adenomas. Promoter CpG methylation levels were investigated for hallmarks of cellular differentiation. Comparative DNA methylation analyses demonstrated that all 100 PitNETs/adenomas aligned more closely with NETs than with adenomas. Focusing on promoter-associated CpGs moreover confirmed robust epigenomic features associated with neuroendocrine differentiation in PitNETs/adenomas. These findings indicate that PitNETs/adenomas resemble NETs rather than adenomas on the epigenomic level and support PitNET as the biologically more accurate term. Of note, appropriately addressing the broad spectrum of clinical behaviors in these tumors remains a critical issue in the current pituitary tumor classification framework and nomenclature.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"35"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253599","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}