{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:56:19Z","timestamp":1792828579294,"version":"4.5.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018515","name":"Hamburger Krebsgesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018515","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinikum Hamburg-Eppendorf (UKE)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocr Pathol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats: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\u2019 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\u00a0PitNETs\/adenomas resemble NETs rather than adenomas on the epigenomic level\u00a0and 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.<\/jats:p>","DOI":"10.1007\/s12022-025-09879-8","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:15:49Z","timestamp":1759929349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let\u2019s Ask the Epigenome!"],"prefix":"10.1007","volume":"36","author":[{"given":"Matthias","family":"Dottermusch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"9879_CR1","unstructured":"Cushing H. The pituitary body and its disorders; clinical states produced by disorders of the hypophysis cerebri. 1912. Internet: https:\/\/archive.org. https:\/\/archive.org\/details\/pituitarybodyits00cushuoft\/page\/4\/mode\/2up. Accessed 23 Aug 2025"},{"key":"9879_CR2","doi-asserted-by":"publisher","unstructured":"Asa SL, Casar-Borota O, Chanson P, Delgrange E, Earls P, Ezzat S, Grossman A, Ikeda H, Inoshita N, Karavitaki N, et al. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr Relat Cancer. 2017;24:C5\u2013C8. https:\/\/doi.org\/10.1530\/ERC-17-0004","DOI":"10.1530\/ERC-17-0004"},{"key":"9879_CR3","doi-asserted-by":"publisher","unstructured":"Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, Busam KJ, de Krijger RR, Dietel M, El-Naggar AK, et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol. 2018;31:1770. https:\/\/doi.org\/10.1038\/S41379-018-0110-Y","DOI":"10.1038\/S41379-018-0110-Y"},{"key":"9879_CR4","unstructured":"WHO Classification of Tumours Editorial Board. Central nervous system tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 6)."},{"key":"9879_CR5","unstructured":"WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 8)."},{"key":"9879_CR6","doi-asserted-by":"publisher","unstructured":"Ho K, Fleseriu M, Kaiser U, Salvatori R, Brue T, Lopes MB, Kunz P, Molitch M, Camper SA, Gadelha M, et al. Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time? J Endocr Soc. 2021;5:1\u20139. https:\/\/doi.org\/10.1210\/JENDSO\/BVAA205","DOI":"10.1210\/JENDSO\/BVAA205"},{"key":"9879_CR7","doi-asserted-by":"publisher","unstructured":"Liu X, Wang R, Li M, Chen G. Pituitary adenoma or pituitary neuroendocrine tumor: a narrative review of controversy and perspective. Transl Cancer Res. 2021;10:1916. https:\/\/doi.org\/10.21037\/TCR-20-3446","DOI":"10.21037\/TCR-20-3446"},{"key":"9879_CR8","doi-asserted-by":"publisher","unstructured":"Giustina A. Pituitary adenoma\u2026nomen omen? Endocrine. 2021;74:1\u20134. https:\/\/doi.org\/10.1007\/S12020-021-02785-Z","DOI":"10.1007\/S12020-021-02785-Z"},{"key":"9879_CR9","doi-asserted-by":"publisher","unstructured":"Ho KKY, Gadelha M, Kaiser UB, Reincke M, Melmed S. The NETting of pituitary adenoma: a gland illusion. Pituitary. 2022;25:349. https:\/\/doi.org\/10.1007\/S11102-022-01235-X","DOI":"10.1007\/S11102-022-01235-X"},{"key":"9879_CR10","doi-asserted-by":"publisher","unstructured":"Capper D, Stichel D, Sahm F, Jones DTW, Schrimpf D, Sill M, Schmid S, Hovestadt V, Reuss DE, Koelsche C, et al. Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol. 2018;136:181\u2013210. https:\/\/doi.org\/10.1007\/s00401-018-1879-y","DOI":"10.1007\/s00401-018-1879-y"},{"key":"9879_CR11","doi-asserted-by":"publisher","unstructured":"Wu Z, Abdullaev Z, Pratt D, Chung HJ, Skarshaug S, Zgonc V, Perry C, Pack S, Saidkhodjaeva L, Nagaraj S, et al. Impact of the methylation classifier and ancillary methods on CNS tumor diagnostics. Neuro Oncol. 2022;24:571\u2013581. https:\/\/doi.org\/10.1093\/NEUONC\/NOAB227","DOI":"10.1093\/NEUONC\/NOAB227"},{"key":"9879_CR12","doi-asserted-by":"publisher","unstructured":"Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, et al. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016;164:1060\u20131072. https:\/\/doi.org\/10.1016\/J.CELL.2016.01.015","DOI":"10.1016\/J.CELL.2016.01.015"},{"key":"9879_CR13","doi-asserted-by":"publisher","unstructured":"Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555:469\u2013474. https:\/\/doi.org\/10.1038\/nature26000","DOI":"10.1038\/nature26000"},{"key":"9879_CR14","doi-asserted-by":"publisher","unstructured":"Dottermusch M, Ryba A, Ricklefs FL, Flitsch J, Schmid S, Glatzel M, Saeger W, Neumann JE, Sch\u00fcller U. Pituitary neuroendocrine tumors with PIT1\/SF1 co-expression show distinct clinicopathological and molecular features. Acta Neuropathol. 2024;147:16. https:\/\/doi.org\/10.1007\/s00401-024-02686-1","DOI":"10.1007\/s00401-024-02686-1"},{"key":"9879_CR15","doi-asserted-by":"publisher","unstructured":"Silva-J\u00fanior RMP da, Bueno AC, Martins CS, Coelli-Lacchini F, Ozaki JGO, Almeida-e-Silva DC de, Marrero-Guti\u00e9rrez J, Santos AC Dos, Garcia-Peral C, Machado HR, et al. Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors. J Clin Endocrinol Metab. 2023;108:1452\u20131463. https:\/\/doi.org\/10.1210\/clinem\/dgac703","DOI":"10.1210\/clinem\/dgac703"},{"key":"9879_CR16","doi-asserted-by":"publisher","unstructured":"Neou M, Villa C, Armignacco R, Jouinot A, Raffin-Sanson ML, Septier A, Letourneur F, Diry S, Diedisheim M, Izac B, et al. Pangenomic Classification of Pituitary Neuroendocrine Tumors. Cancer Cell. 2020;37:123-134.e5. https:\/\/doi.org\/10.1016\/j.ccell.2019.11.002","DOI":"10.1016\/j.ccell.2019.11.002"},{"key":"9879_CR17","doi-asserted-by":"publisher","unstructured":"Dottermusch M, Sch\u00fcller U, Hagel C, Saeger W. Unveiling the identities of null cell tumours: Epigenomics corroborate subtle histological cues in pituitary neuroendocrine tumour\/adenoma classification. Neuropathol Appl Neurobiol. 2023;49:e12870. https:\/\/doi.org\/10.1111\/NAN.12870","DOI":"10.1111\/NAN.12870"},{"key":"9879_CR18","doi-asserted-by":"publisher","unstructured":"Salomon MP, Wang X, Marzese DM, Hsu SC, Nelson N, Zhang X, Matsuba C, Takasumi Y, Ballesteros-Merino C, Fox BA, et al. The epigenomic landscape of pituitary adenomas reveals specific alterations and differentiates among acromegaly, Cushing\u2019s disease and endocrine-inactive subtypes. Clin Cancer Res. 2018;24:4126\u20134136. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-2206","DOI":"10.1158\/1078-0432.CCR-17-2206"},{"key":"9879_CR19","doi-asserted-by":"publisher","unstructured":"Ricklefs FL, Fita KD, Rotermund R, Piffko A, Schmid S, Capper D, Buslei R, Buchfelder M, Burkhardt T, Matschke J, et al. Genome-wide DNA methylation profiles distinguish silent from non-silent ACTH adenomas. Acta Neuropathol. https:\/\/doi.org\/10.1007\/s00401-020-02149-3","DOI":"10.1007\/s00401-020-02149-3"},{"key":"9879_CR20","doi-asserted-by":"publisher","unstructured":"Bhandari YR, Krishna V, Powers R, Parmar S, Thursby SJ, Gupta E, Kulak O, Gokare P, Reumers J, Van Wesenbeeck L, et al. Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers. Proc Natl Acad Sci U S A. 2023;120:e2301536120. https:\/\/doi.org\/10.1073\/pnas.2301536120","DOI":"10.1073\/pnas.2301536120"},{"key":"9879_CR21","doi-asserted-by":"publisher","unstructured":"Bueno AC, da Silva RMP, Stecchini MF, Marrero-Guti\u00e9rrez J, de Almeida e Silva DC, Cardinalli I, Scrideli CA, Junqueira T, Molina CAF, Ramalho FS, et al. DNA methylation is a comprehensive marker for pediatric adrenocortical tumors. Endocr Relat Cancer. 2022;29:599\u2013613. https:\/\/doi.org\/10.1530\/ERC-22-0145","DOI":"10.1530\/ERC-22-0145"},{"key":"9879_CR22","doi-asserted-by":"publisher","unstructured":"Chan CS, Laddha S V., Lewis PW, Koletsky MS, Robzyk K, Da Silva E, Torres PJ, Untch BR, Li J, Bose P, et al. ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup. Nat Commun. 2018;9:4158. https:\/\/doi.org\/10.1038\/S41467-018-06498-2","DOI":"10.1038\/S41467-018-06498-2"},{"key":"9879_CR23","doi-asserted-by":"publisher","unstructured":"Dos Reis MB, Barros-Filho MC, Marchi FA, Beltrami CM, Kuasne H, Pinto CAL, Ambatipudi S, Herceg Z, Kowalski LP, Rogatto SR. Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors. J Clin Endocrinol Metab. 2017;102:4089\u20134099. https:\/\/doi.org\/10.1210\/JC.2017-00881","DOI":"10.1210\/JC.2017-00881"},{"key":"9879_CR24","doi-asserted-by":"publisher","unstructured":"Fiedler D, Hirsch D, El Hajj N, Yang HH, Hu Y, Sticht C, Nanda I, Belle S, Rueschoff J, Lee MP, et al. Genome-wide DNA methylation analysis of colorectal adenomas with and without recurrence reveals an association between cytosine-phosphate-guanine methylation and histological subtypes. Genes Chromosomes Cancer. 2019;58:783. https:\/\/doi.org\/10.1002\/GCC.22787","DOI":"10.1002\/GCC.22787"},{"key":"9879_CR25","doi-asserted-by":"publisher","unstructured":"Jurmeister P, Leitheiser M, Arnold A, Capilla EP, Mochmann LH, Zhdanovic Y, Schleich K, Jung N, Chimal EC, Jung A, et al. DNA Methylation Profiling of Salivary Gland Tumors Supports and Expands Conventional Classification. Mod Pathol. 2024;37:100625. https:\/\/doi.org\/10.1016\/J.MODPAT.2024.100625","DOI":"10.1016\/J.MODPAT.2024.100625"},{"key":"9879_CR26","doi-asserted-by":"publisher","unstructured":"Kober P, Boresowicz J, Rusetska N, Maksymowicz M, Goryca K, Kunicki J, Bonicki W, Siedlecki JA, Bujko M. DNA methylation profiling in nonfunctioning pituitary adenomas. Mol Cell Endocrinol. 2018;473:194\u2013204. https:\/\/doi.org\/10.1016\/J.MCE.2018.01.020","DOI":"10.1016\/J.MCE.2018.01.020"},{"key":"9879_CR27","doi-asserted-by":"publisher","unstructured":"Laddha S V., Da Silva EM, Robzyk K, Untch BR, Ke H, Rekhtman N, Poirier JT, Travis WD, Tang LH, Chan CS. Integrative Genomic Characterization Identifies Molecular Subtypes of Lung Carcinoids. Cancer Res. 2019;79:4339\u20134347. https:\/\/doi.org\/10.1158\/0008-5472.CAN-19-0214","DOI":"10.1158\/0008-5472.CAN-19-0214"},{"key":"9879_CR28","doi-asserted-by":"publisher","unstructured":"Patte C, Pommier RM, Ferrari A, Fei-Lei Chung F, Ouzounova M, Moull\u00e9 P, Richaud M, Khoueiry R, Hervieu M, Breusa S, et al. Comprehensive molecular portrait reveals genetic diversity and distinct molecular subtypes of small intestinal neuroendocrine tumors. Nat Commun. 2025;16:2197. https:\/\/doi.org\/10.1038\/S41467-025-57305-8","DOI":"10.1038\/S41467-025-57305-8"},{"key":"9879_CR29","doi-asserted-by":"publisher","unstructured":"Rodr\u00edguez-Rodero S, Morales-S\u00e1nchez P, Tejedor JR, Coca-Pelaz A, Mangas C, Pe\u00f1arroya A, Fern\u00e1ndez-Vega I, Fern\u00e1ndez-Fern\u00e1ndez L, \u00c1lvarez-L\u00f3pez CM, Fern\u00e1ndez AF, et al. Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers. Eur J Endocrinol. 2022;187:335\u2013347. https:\/\/doi.org\/10.1530\/EJE-22-0012","DOI":"10.1530\/EJE-22-0012"},{"key":"9879_CR30","doi-asserted-by":"publisher","unstructured":"Tirosh A, Killian JK, Petersen D, Zhu YJ, Walker RL, Blau JE, Nilubol N, Patel D, Agarwal SK, Weinstein LS, et al. Distinct DNA Methylation Signatures in Neuroendocrine Tumors Specific for Primary Site and Inherited Predisposition. J Clin Endocrinol Metab. 2020;105:3285\u20133294. https:\/\/doi.org\/10.1210\/CLINEM\/DGAA477","DOI":"10.1210\/CLINEM\/DGAA477"},{"key":"9879_CR31","doi-asserted-by":"publisher","unstructured":"Uro-Coste E, Nicaise Y, Akiki B, Decamps C, Chaltiel L, Siegfried A, Herbault-Barres B, Reboul H, Bassey E, Modesto A, et al. Malignant Transformation in Pleomorphic Adenoma: The Impact of DNA Methylation Profiling and Pathogenic Mutations. Mod Pathol. 2025;38:100786. https:\/\/doi.org\/10.1016\/J.MODPAT.2025.100786","DOI":"10.1016\/J.MODPAT.2025.100786"},{"key":"9879_CR32","doi-asserted-by":"publisher","unstructured":"Werr L, Bartenhagen C, Rosswog C, Cartolano M, Voegele C, Sexton-Oates A, Di Genova A, Ernst A, Kahlert Y, Hemstedt N, et al. TERT Expression and Clinical Outcome in Pulmonary Carcinoids. J Clin Oncol. 2024;43:214. https:\/\/doi.org\/10.1200\/JCO.23.02708","DOI":"10.1200\/JCO.23.02708"},{"key":"9879_CR33","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. 2024;"},{"key":"9879_CR34","doi-asserted-by":"publisher","unstructured":"Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA. Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363\u20131369. https:\/\/doi.org\/10.1093\/bioinformatics\/btu049","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"9879_CR35","doi-asserted-by":"publisher","unstructured":"Fortin JP, Triche TJ, Hansen KD. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics. 2016;33:558. https:\/\/doi.org\/10.1093\/BIOINFORMATICS\/BTW691","DOI":"10.1093\/BIOINFORMATICS\/BTW691"},{"key":"9879_CR36","doi-asserted-by":"publisher","unstructured":"McInnes L, Healy J, Melville J. UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. 2018;https:\/\/doi.org\/10.48550\/arxiv.1802.03426","DOI":"10.48550\/arxiv.1802.03426"},{"key":"9879_CR37","doi-asserted-by":"publisher","unstructured":"Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010;26:1572\u20131573. https:\/\/doi.org\/10.1093\/BIOINFORMATICS\/BTQ170","DOI":"10.1093\/BIOINFORMATICS\/BTQ170"},{"key":"9879_CR38","doi-asserted-by":"publisher","unstructured":"Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L, et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innov (Cambridge. 2021;2:100141. https:\/\/doi.org\/10.1016\/j.xinn.2021.100141","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"9879_CR39","doi-asserted-by":"publisher","unstructured":"Hu C, Li T, Xu Y, Zhang X, Li F, Bai J, Chen J, Jiang W, Yang K, Ou Q, et al. CellMarker 2.0: an updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data. Nucleic Acids Res. 2023;51:D870\u2013D876. https:\/\/doi.org\/10.1093\/NAR\/GKAC947","DOI":"10.1093\/NAR\/GKAC947"},{"key":"9879_CR40","doi-asserted-by":"publisher","unstructured":"Tian Y, Morris TJ, Webster AP, Yang Z, Beck S, Feber A, Teschendorff AE. ChAMP: updated methylation analysis pipeline for Illumina BeadChips. Bioinformatics. 2017;33:3982\u20133984. https:\/\/doi.org\/10.1093\/BIOINFORMATICS\/BTX513","DOI":"10.1093\/BIOINFORMATICS\/BTX513"},{"key":"9879_CR41","doi-asserted-by":"publisher","unstructured":"Yu Y, Mai Y, Zheng Y, Shi L. Assessing and mitigating batch effects in large-scale omics studies. Genome Biol 2024 251. 2024;25:1\u201327. https:\/\/doi.org\/10.1186\/S13059-024-03401-9","DOI":"10.1186\/S13059-024-03401-9"},{"key":"9879_CR42","doi-asserted-by":"publisher","unstructured":"Sill M, Plass C, Pfister SM, Lipka DB. Molecular tumor classification using DNA methylome analysis. Hum Mol Genet. 2020;29:R205\u2013R213. https:\/\/doi.org\/10.1093\/HMG\/DDAA147","DOI":"10.1093\/HMG\/DDAA147"},{"key":"9879_CR43","doi-asserted-by":"publisher","unstructured":"Papanicolau-Sengos A, Aldape K. DNA Methylation Profiling: An Emerging Paradigm for Cancer Diagnosis. Annu Rev Pathol. 2022;17:295\u2013321. https:\/\/doi.org\/10.1146\/ANNUREV-PATHOL-042220-022304","DOI":"10.1146\/ANNUREV-PATHOL-042220-022304"},{"key":"9879_CR44","doi-asserted-by":"publisher","unstructured":"Huang H, Wang Y, Rudin C, Browne EP. Towards a comprehensive evaluation of dimension reduction methods for transcriptomic data visualization. Commun Biol. 2022;5:719. https:\/\/doi.org\/10.1038\/S42003-022-03628-X","DOI":"10.1038\/S42003-022-03628-X"},{"key":"9879_CR45","doi-asserted-by":"publisher","unstructured":"Shigematsu K, Nishida N, Sakai H, Igawa T, Toriyama K, Nakatani A, Takahara O, Kawai K. Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression. Eur J Endocrinol. 2009;161:939\u2013945. https:\/\/doi.org\/10.1530\/EJE-09-0596","DOI":"10.1530\/EJE-09-0596"},{"key":"9879_CR46","doi-asserted-by":"publisher","unstructured":"Satoh F, Umemura S, Yasuda M, Osamura RY. Neuroendocrine marker expression in thyroid epithelial tumors. Endocr Pathol. 2001;12:291\u2013299. https:\/\/doi.org\/10.1385\/EP:12:3:291\/METRICS","DOI":"10.1385\/EP:12:3:291\/METRICS"},{"key":"9879_CR47","doi-asserted-by":"publisher","unstructured":"Kriegsmann K, Zgorzelski C, Muley T, Christopoulos P, Thomas M, Winter H, Eichhorn M, Eichhorn F, von Winterfeld M, Herpel E, et al. Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: a retrospective large-scale study on 1170 tissue samples. BMC Cancer. 2021;21:486. https:\/\/doi.org\/10.1186\/S12885-021-08140-9","DOI":"10.1186\/S12885-021-08140-9"},{"key":"9879_CR48","doi-asserted-by":"publisher","unstructured":"Uhlig R, Dum D, Gorbokon N, Menz A, B\u00fcscheck F, Luebke AM, Hube-Magg C, Hinsch A, H\u00f6flmayer D, Fraune C, et al. Synaptophysin and chromogranin A expression analysis in human tumors. Mol Cell Endocrinol. 2022;555:111726. https:\/\/doi.org\/10.1016\/J.MCE.2022.111726","DOI":"10.1016\/J.MCE.2022.111726"},{"key":"9879_CR49","doi-asserted-by":"publisher","unstructured":"Lloyd R V., Scheithauer BW, Kovacs K, Roche PC. The Immunophenotype of Pituitary Adenomas. Endocr Pathol. 1996;7:145\u2013150. https:\/\/doi.org\/10.1007\/BF02739974","DOI":"10.1007\/BF02739974"},{"key":"9879_CR50","doi-asserted-by":"publisher","unstructured":"Gheorghi\u0219an-G\u0103l\u0103\u021beanu AA, Ilie\u0219iu A, Lambrescu IM, \u021a\u0103poi DA. The Complex Histopathological and Immunohistochemical Spectrum of Neuroendocrine Tumors\u2014An Overview of the Latest Classifications. Int J Mol Sci. 2023;24:1418. https:\/\/doi.org\/10.3390\/IJMS24021418","DOI":"10.3390\/IJMS24021418"}],"container-title":["Endocrine Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12022-025-09879-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12022-025-09879-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12022-025-09879-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:25:40Z","timestamp":1767860740000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12022-025-09879-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["9879"],"URL":"https:\/\/doi.org\/10.1007\/s12022-025-09879-8","relation":{},"ISSN":["1046-3976","1559-0097"],"issn-type":[{"value":"1046-3976","type":"print"},{"value":"1559-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"assertion":[{"value":"1 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All data processed in this study was retrieved from publicly accessible external data deposits. All analyses were conducted using anonymized data and were in accordance with local and national ethical standards and with the 1964 Helsinki declaration and its later amendments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The author declares no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35"}}