Molecular Pathology of Pulmonary Large Cell Neuroendocrine Carcinoma: Novel Concepts and Treatments.

Published on Apr 22, 2021in Frontiers in Oncology6.244
· DOI :10.3389/FONC.2021.671799
Masayo Yoshimura , Kurumi Seki + 1 AuthorsJunya Fukuoka43
Estimated H-index: 43
(Nagasaki University)
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with poor prognosis. Histologic diagnosis of LCNEC is not always straightforward. In particular, it is challenging to distinguish small cell lung carcinoma (SCLC) or poorly differentiated carcinoma from LCNEC. However, histological classification for LCNEC as well as their therapeutic management has not changed much for decades. Recently, genomic and transcriptomic analyses have revealed different molecular subtypes raising hopes for more personalized treatment. Two main molecular subtypes of LCNEC have been identified by studies using next generation sequencing, namely type I with TP53 and STK11/KEAP1 alterations, alternatively called as non-SCLC type, and type II with TP53 and RB1 alterations, alternatively called as SCLC type. However, there is still no easy way to classify LCNEC subtypes at the actual clinical level. In this review, we have discussed histological diagnosis along with the genomic studies and molecular-based treatment for LCNEC.
#1Ann E. Walts (Cedars-Sinai Medical Center)H-Index: 29
#2James Mirocha (Cedars-Sinai Medical Center)H-Index: 52
Last. Alberto M. Marchevsky (Cedars-Sinai Medical Center)H-Index: 34
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Aims To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC. Methods and results Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments. Using the Kaplan-Meier...
#1Michael J. Giffin (Amgen)H-Index: 3
#2Keegan Cooke (Amgen)H-Index: 15
Last. Paul E. Hughes (Amgen)H-Index: 32
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Purpose: Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a high relapse rate, limited therapeutic options, and poor prognosis. We investigated the antitumor activity of AMG 757, a half-life extended bispecific T-cell engager molecule targeting delta-like ligand 3 (DLL3)—a target that is selectively expressed in SCLC tumors, but with minimal normal tissue expression. Experimental Design: AMG 757 efficacy was evaluated in SCLC cell lines and in orthotopic and patient-deriv...
#1Come Sesboue (University of Bordeaux)H-Index: 1
#2François Le Loarer (University of Bordeaux)H-Index: 18
Abstract The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages. Malignant rhabdoid tumors were the first malignancies linked to deregulation of these complexes with the involvement of SMARCB1 in their development but genetic alterations affect all subunits in other malignancies. In the chest and lung regions, SMARCA4 (BRG1) is the most frequently altered subunit and is involved in the path...
#1Marina K Baine (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2Min-Shu Hsieh (NTU: National Taiwan University)H-Index: 19
Last. Natasha Rekhtman (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 60
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Abstract Introduction Recent studies have identified subtypes of small cell lung carcinoma (SCLC) defined by the RNA expression of ASCL1, NEUROD1, POU2F3, and YAP1 transcriptional regulators. There are only limited data on the distribution of these markers at the protein level and associated pathologic characteristics in clinical SCLC samples. Methods The expression of ASCL1, NEUROD1, POU2F3, and YAP1 was analyzed by immunohistochemistry in 174 patient samples with SCLC. Subtypes defined by thes...
#1Xin Zhang (PRC: China Medical University (PRC))H-Index: 5
#2Yanbin SunH-Index: 3
Last. Shun XuH-Index: 2
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Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achiev...
#1Simon Papillon-Cavanagh (BMS: Bristol-Myers Squibb)H-Index: 17
#2Parul Doshi (BMS: Bristol-Myers Squibb)H-Index: 3
Last. Alice M. Walsh (BMS: Bristol-Myers Squibb)H-Index: 13
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INTRODUCTION: Somatic mutations in STK11 and KEAP1, frequently comutated in non-squamous non-small cell lung cancer (NSQ NSCLC), have been associated with poor response to immune checkpoint blockade (ICB). However, previous reports lack non-ICB controls needed to properly ascertain the predictive nature of those biomarkers. The objective of this study was to evaluate the predictive versus prognostic effect of STK11 or KEAP1 mutations in NSQ NSCLC. METHODS: Patients diagnosed with stage IIIB, III...
#1Connor J. Kinslow (Columbia University)H-Index: 8
#2Michael S. May (Columbia University)H-Index: 2
Last. Simon K. Cheng (Columbia University)H-Index: 15
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Abstract: Introduction Large-cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung malignancies. There are limited data on the epidemiology and best treatment practices for this malignancy. This study aims to be the largest cohort with the most up-to-date analysis of the epidemiology of LCNEC. Methods The SEER database was queried to identify cases of LCNEC diagnosed from 2010 through 2015, reflecting years the American Joint Committee on Cancer 7th Edition Staging was in u...
#1Natasha Rekhtman (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 60
#2Joseph Montecalvo (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
Last. William D. Travis (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 154
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Abstract Background Highly aggressive thoracic neoplasms characterized by SMARCA4 (BRG1) deficiency and undifferentiated round cell or rhabdoid morphology have been recently described, and proposed to represent thoracic sarcomas. However, it remains unclear whether such tumors may instead represent sarcomatoid carcinomas, and how their clinicopathologic characteristics compare to those of non-sarcomatoid SMARCA4-deficient non-small cell lung carcinomas (SD-NSCC). Methods We identified 22 thoraci...
#1Marina K Baine (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2John H. Sinard (Yale University)H-Index: 24
Last. Robert J. Homer (Yale University)H-Index: 83
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OBJECTIVES: The aim of this study was to devise reproducible biopsy criteria for distinguishing pulmonary large cell neuroendocrine carcinoma (LCNEC) from non-small cell lung carcinoma (NSCLC). METHODS: Tissue microarrays of LCNEC and NSCLC were generated from resection specimens and used as biopsy surrogates. They were stained for neuroendocrine markers, Ki-67, napsin-A, and p40, and independently analyzed by standardized morphologic criteria by four pathologists. Tumors were scored based on mo...
#6Guanghui Wang (SDU: Shandong University)H-Index: 11
Abstract Objectives The rarity of atypical carcinoid (AC) of lung and the lack of prospective clinical trials lead to limited knowledge of its biology, treatment information and prognosis. The current study analyzed AC patients from the Surveillance, Epidemiology, and End Results (SEER) database to better understand the clinical characteristics of this disease and build a prognostic nomogram for clinical practice. Materials and methods A total of 507 AC patients with pathological confirmation fr...
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