Neuroendocrine carcinomas
2023-05-07 Yin (Rex) Hung, MD Affiliation1.Massachusetts General Hospital and Harvard Medical School, Boston
Classification
Definition
Primary neuroendocrine carcinomas of the lung are by definition high grade and include small cell carcinoma and large cell neuroendocrine carcinoma. Combined small cell carcinoma is a composite tumor consisting of both small cell carcinoma and non-small cell carcinoma(s), which can be adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma, or others. Given the morphologic overlap between small cells and large cells, the large cell component needs to comprise at least 10% of the tumor to qualify a diagnosis of combined small cell carcinoma-large cell neuroendocrine carcinoma or combined small cell carcinoma-large cell carcinoma. This 10% minimum requirement is not applicable to combined small cell carcinoma with other types of non-small cell elements, e.g. adenocarcinoma or squamous cell carcinoma. Large cell neuroendocrine carcinoma of lung is a high-grade non-small cell carcinoma with neuroendocrine histomorphology, mitotic count of >10 per 2 mm2, and evidence of neuroendocrine differentiation (by immunohistochemistry with expression of at least one neuroendocrine marker). Combined large cell neuroendocrine carcinoma is a composite tumor consisting of both large cell neuroendocrine carcinoma and other non-small cell carcinoma(s), such as adenocarcinoma, squamous cell carcinoma, spindle cell carcinoma, or others.
| Neuroendocrine carcinomas | Genetic marker(s) |
|---|---|
| Small cell carcinoma | Most tumors are characterized by bi-allelic inactivating mutations involving TP53 and RB1, along with mutations involving components of chromatin regulation, cell cycle regulation, and NOTCH signaling pathway.1,2 SOX2 gene amplification and MYC gene amplification are present in a subset of tumors.3,4 Driver mutations typical of lung adenocarcinoma, such as EGFR mutations, have been identified in rare cases, particularly in patients with no history of smoking.5,6 In addition, germline variants in cancer predisposition genes have been identified in a subset of patients.7 |
| Combined small cell carcinoma | See above in Small cell carcinoma |
| Large cell neuroendocrine carcinoma | Genomically heterogeneous with multiple distinct subgroups, including: 1) a small cell carcinoma-like subset with TP53 and RB1 co-mutations, 2) a non-small cell lung carcinoma-like subset with frequent STK11 and/or KEAP1 alterations, and 3) a caricnoid-like subset with MEN1 mutations.8-10 Driver mutations typical of lung adenocarcinoma, such as EGFR mutation and ALK rearrangement, are uncommon but can be identified in some cases.11,12 |
| Combined large cell neuroendocrine carcinoma | See above in Large cell neuroendocrine carcinoma |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 26168399 | 2015 | Comprehensive genomic profiles of small cell lung cancer. | George J et al |
| 2 | 22941188 | 2012 | Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. | Peifer M et al |
| 3 | 22941189 | 2012 | Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. | Rudin CM et al |
| 4 | 25407018 | 2015 | Myc protein expression correlates with MYC amplification in small-cell lung carcinoma. | Hwang DH et al |
| 5 | 32191822 | 2021 | Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations. | Ogino A et al |
| 6 | 32464188 | 2020 | Clinical and Genomic Characteristics of Small Cell Lung Cancer in Never Smokers: Results From a Retrospective Multicenter Cohort Study. | Thomas A et al |
| 7 | 33504652 | 2021 | Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair-targeted therapies. | Tlemsani C et al |
| 8 | 26960398 | 2016 | Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma-like and Non-Small Cell Carcinoma-like Subsets. | Rekhtman N et al |
| 9 | 29535388 | 2018 | Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. | George J et al |
| 10 | 31694833 | 2020 | The Prognostic and Therapeutic Role of Genomic Subtyping by Sequencing Tumor or Cell-Free DNA in Pulmonary Large-Cell Neuroendocrine Carcinoma. | Zhuo M et al |
| 11 | 22042963 | 2011 | Large-cell neuroendocrine carcinoma of the lung harboring EGFR mutation and responding to gefitinib. | De Pas TM et al |
| 12 | 32651063 | 2021 | Next-Generation Sequencing Identified a Novel Crizotinib-Sensitive PLB1-ALK Rearrangement in Lung Large-Cell Neuroendocrine Carcinoma. | Wang S et al |
Citation
Yin (Rex) Hung, MD
Neuroendocrine carcinomas
Atlas Genet Cytogenet Oncol Haematol. 2023-05-07
Online version: http://atlasgeneticsoncology.org/solid-tumor/209133/neuroendocrine-carcinomas
