Recent advances in the molecular landscape of lung neuroendocrine tumors

Pelosi, Giuseppe; Bianchi, Fabrizio; Hofman, Paul; Pattini, Linda; Ströbel, Philipp; Calabrese, Fiorella; Naheed, Salma; Holden, Chloe; Cave, Judith; Bohnenberger, Hanibal; Dinter, Helen; Harari, Sergio; Albini, Adriana; Sonzogni, Angelica; Papotti, Mauro; Volante, Marco; Ottensmeier, Christian

doi:10.1080/14737159.2019.1595593

Cited by 41 publications

(50 citation statements)

References 179 publications

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“…3. In this scenario, two subsets of neuroendocrine carcinomas are identified [21]. Primary neuroendocrine carcinomas feature undifferentiated tumor cells characterized by severe gene alterations (e.g., biallelic inactivation of RB1 and TP53) responsible for de novo pathogenetic mechanisms.…”

Section: Molecular Sub-classification Of Thoracic Neuroendocrine Neopmentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

et al. 2021

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Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.

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Section: Molecular Sub-classification Of Thoracic Neuroendocrine Neopmentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

et al. 2021

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“…Consequently, the concept of NET G3 (well differentiated tumors with high proliferation) was successively integrated into the WHO classifications of GEP neoplasms, leaving the definition of NEC to NENs with poorly differentiated morphology [12,13]. Similar observations have been described in thoracic sites [14], where a proliferative grading system has still not been officially adopted in the WHO classification [15]. The fact that NETs (including NET G3) and NECs are distinct clinico-pathological entities has been supported for a long time [16], and molecular findings have confirmed this assumption, showing that these two families of neoplasms follow different pathogenetic pathways [17].…”

Section: Evolution Of Their Understandingmentioning

confidence: 91%

Challenges in High-grade Neuroendocrine Neoplasms and Mixed Neuroendocrine/Non-neuroendocrine Neoplasms

Rosa

2021

Endocr Pathol

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The growth in knowledge of the pathogenesis, molecular background, and immunohistochemical profile of neuroendocrine neoplasms (NENs) has led not only to an increased awareness of these diseases but also to several changes of the nomenclature. In particular, the concept and terminology of high-grade (grade 3) NENs and mixed neoplasms have changed considerably over the last 20 years, creating some confusion among pathologists and clinicians. The aim of this review is to elucidate the diagnostic criteria, including the most important differential diagnoses of high-grade NENs and mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs). The role of the Ki67 labelling index and morphology, used to define grade 3 NENs of the digestive system and lungs, is also discussed. The evolution of the concepts and terminology of MiNENs is revised, including the most important differential diagnoses.

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“…Neuroendocrine neoplasms are genomically and clinically heterogeneous. This heterogeneity occurs between cancers originating from different organs, within the cancers originating in the same organ, and between primary and metastatic lesions [4,11,12,13]. For instance, small intestine NENs are genomic stable cancers, with a low mutational load compared with NENs originated from different organs, such as the lung and pancreas.…”

Section: Neuroendocrine Neoplasms and Molecular Heterogeneitymentioning

confidence: 99%

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms

Arx

Capozzi

López‐Jiménez

et al. 2019

JCM

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Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies, mainly originating from hormone-secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout the multiple endocrine neoplasia type 1 (MEN-1) gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signalling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the role and the potential therapeutic implications of gene mutations and NOTCH signalling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential role across all NEN subtypes is required.

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Recent advances in the molecular landscape of lung neuroendocrine tumors

Cited by 41 publications

References 179 publications

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

Challenges in High-grade Neuroendocrine Neoplasms and Mixed Neuroendocrine/Non-neuroendocrine Neoplasms

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms

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