Rindi G, Klimstra DS, Abedi-Ardekani B et al (2018) 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 31:1770–1786. https://doi.org/10.1038/s41379-018-0110-y

Article  PubMed  PubMed Central  Google Scholar 

Klimstra D, Klöppel G, La Rosa S, Rindi G (2019) Classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumours Editorial Board. Digestive system tumours [Internet], 5th edn. International Agency for Research on Cancer, Lyon. https://tumourclassification.iarc.who.int/chapters/31. Accessed 5 Dec 2024

Marchiò C, Gatti G, Massa F, Bertero L, Filosso P, Pelosi G, Cassoni P, Volante M, Papotti M (2017) Distinctive pathological and clinical features of lung carcinoids with high proliferation index. Virchows Arch 471:713–720. https://doi.org/10.1007/s00428-017-2177-0

Article  PubMed  PubMed Central  Google Scholar 

Kasajima A, Konukiewitz B, Oka N et al (2019) Clinicopathological profiling of lung carcinoids with a Ki67 index > 20. Neuroendocrinology 108:109–120. https://doi.org/10.1159/000495806

Article  CAS  PubMed  Google Scholar 

Sazonova O, Manem V, Orain M, Khoshkrood-Mansoori B, Gaudreault N, Desmeules P, Bossé Y, Joubert P (2020) Transcriptomic data helps refining classification of pulmonary carcinoid tumors with increased mitotic counts. Mod Pathol 33:1712–1721. https://doi.org/10.1038/s41379-020-0538-8

Article  CAS  PubMed  Google Scholar 

Rubino M, Scoazec JY, Pisa E et al (2020) Lung carcinoids with high proliferative activity: further support for the identification of a new tumor category in the classification of lung neuroendocrine neoplasms. Lung Cancer 148:149–158. https://doi.org/10.1016/j.lungcan.2020.08.001

Article  CAS  PubMed  Google Scholar 

Cros J, Théou-Anton N, Gounant V et al (2021) Specific genomic alterations in high-grade pulmonary neuroendocrine tumours with carcinoid morphology. Neuroendocrinology 111:158–169. https://doi.org/10.1159/000506292

Article  CAS  PubMed  Google Scholar 

Vélayoudom-Céphise FL, Duvillard P, Foucan L et al (2013) Are G3 ENETS neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer 20:649–657. https://doi.org/10.1530/erc-13-0027

Article  PubMed  Google Scholar 

Basturk O, Yang Z, Tang LH et al (2015) The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol 39:683–690. https://doi.org/10.1097/pas.0000000000000408

Article  PubMed  PubMed Central  Google Scholar 

Crippa S, Partelli S, Belfiori G, Palucci M, Muffatti F, Adamenko O, Cardinali L, Doglioni C, Zamboni G, Falconi M (2016) Management of neuroendocrine carcinomas of the pancreas (WHO G3): a tailored approach between proliferation and morphology. World J Gastroenterol 22:9944–9953. https://doi.org/10.3748/wjg.v22.i45.9944

Article  PubMed  PubMed Central  Google Scholar 

Nuñez-Valdovinos B, Carmona-Bayonas A, Jimenez-Fonseca P et al (2018) Neuroendocrine tumor heterogeneity adds u to the World Health Organization 2010 classification: real-world data from the Spanish Tumor Registry (R-GETNE). Oncologist 23:422–432. https://doi.org/10.1634/theoncologist.2017-0364

Article  PubMed  PubMed Central  Google Scholar 

Pulvirenti A, Raj N, Cingarlini S et al (2021) Platinum-based treatment for well- and poorly differentiated pancreatic neuroendocrine neoplasms. Pancreas 50:138–146. https://doi.org/10.1097/mpa.0000000000001740

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luecke S, Fottner C, Lahner H et al (2022) Treatment approaches and outcome of patients with neuroendocrine neoplasia grade 3 in German real-world clinical practice. Cancers (Basel) 14:2718. https://doi.org/10.3390/cancers14112718

Article  CAS  PubMed  Google Scholar 

Elvebakken H, Perren A, Scoazec JY et al (2021) A consensus-developed morphological re-evaluation of 196 high-grade gastroenteropancreatic neuroendocrine neoplasms and its clinical correlations. Neuroendocrinology 111:883–894. https://doi.org/10.1159/000511905

Article  CAS  PubMed  Google Scholar 

Kasajima A, Konukiewitz B, Schlitter AM, Weichert W, Klöppel G (2022) An analysis of 130 neuroendocrine tumors G3 regarding prevalence, origin, metastasis, and diagnostic features. Virchows Arch 480:359–368. https://doi.org/10.1007/s00428-021-03202-6

Article  PubMed  Google Scholar 

Uccella S, La Rosa S, Metovic J, Marchiori D, Scoazec JY, Volante M, Mete O, Papotti M (2021) Genomics of high-grade neuroendocrine neoplasms: well-differentiated neuroendocrine tumor with high-grade features (G3 NET) and neuroendocrine carcinomas (NEC) of various anatomic sites. Endocr Pathol 32:192–210. https://doi.org/10.1007/s12022-020-09660-z

Article  PubMed  Google Scholar 

Tang LH, Basturk O, Sue JJ, Klimstra DS (2016) A practical approach to the classification of WHO Grade 3 (G3) well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC) of the pancreas. Am J Surg Pathol 40:1192–1202. https://doi.org/10.1097/pas.0000000000000662

Article  PubMed  PubMed Central  Google Scholar 

Oka N, Kasajima A, Konukiewitz B et al (2020) Classification and prognostic stratification of bronchopulmonary neuroendocrine neoplasms. Neuroendocrinology 110:393–403. https://doi.org/10.1159/000502776

Article  CAS  PubMed  Google Scholar 

Scoazec JY, Couvelard A, Monges G, Guyétant S, Bisot-Locard S, Parot X, Lepage C (2017) Professional practices and diagnostic issues in neuroendocrine tumour pathology: results of a prospective one-year survey among French pathologists (the PRONET study). Neuroendocrinology 105:67–76. https://doi.org/10.1159/000448431

Article  CAS  PubMed  Google Scholar 

Konukiewitz B, Schlitter AM, Jesinghaus M et al (2017) Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20. Mod Pathol 30:587–598. https://doi.org/10.1038/modpathol.2016.217

Article  CAS  PubMed  Google Scholar 

Taboada R, Claro L, Felismino T, de Jesus VH, Barros M, Riechelmann RP (2022) Clinicopathological and molecular profile of grade 3 gastroenteropancreatic neuroendocrine neoplasms. J Neuroendocrinol 34:e13099. https://doi.org/10.1111/jne.13099

Article  CAS  PubMed  Google Scholar 

Simbolo M, Mafficini A, Sikora KO et al (2017) Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D. J Pathol 241:488–500. https://doi.org/10.1002/path.4853

Article  CAS  PubMed  Google Scholar 

Lacombe C, De Rycke O, Couvelard A, Turpin A, Cazes A, Hentic O, Gounant V, Zalcman G, Ruszniewski P, Cros J, de Mestier L (2021) Biomarkers of response to etoposide-platinum chemotherapy in patients with grade 3 neuroendocrine neoplasms. Cancers (Basel) 13:643. https://doi.org/10.3390/cancers13040643

Article  CAS  PubMed  Google Scholar 

Pelosi G, Bianchi F, Dama E et al (2018) Most high-grade neuroendocrine tumours of the lung are likely to secondarily develop from pre-existing carcinoids: innovative findings skipping the current pathogenesis paradigm. Virchows Arch 472:567–577. https://doi.org/10.1007/s00428-018-2307-3

Article  PubMed  Google Scholar 

Simbolo M, Barbi S, Fassan M et al (2019) Gene expression profiling of lung atypical carcinoids and large cell neuroendocrine carcinomas identifies three transcriptomic subtypes with specific genomic alterations. J Thorac Oncol 14:1651–1661. https://doi.org/10.1016/j.jtho.2019.05.003

Article  CAS  PubMed  Google Scholar 

Simbolo M, Bilotta M, Mafficini A et al (2021) Gene expression profiling of pancreas neuroendocrine tumors with different Ki67-based grades. Cancers (Basel) 13:2054. https://doi.org/10.3390/cancers13092054

Article  CAS  PubMed  Google Scholar 

Venizelos A, Elvebakken H, Perren A et al (2021) The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 29:1–14. https://doi.org/10.1530/erc-21-0152

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Riet J, van de Werken HJG, Cuppen E et al (2021) The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets. Nat Commun 12:4612. https://doi.org/10.1038/s41467-021-24812-3