Abstract

BackgroundLarge cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Due to its low differentiation and high glucose transporter 1 (GLUT1) expression, LCNEC demonstrates an increased glucose turnover. Thus, PET/CT with 2-[18F]-fluoro-deoxyglucose ([18F]FDG) is suitable for LCNEC staging. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. This study aimed at evaluating the diagnostic performance of [18F]FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [18F]FDG PET/CT findings.MethodsBetween 03/2014 and 12/2020, 46 patients with LCNEC were included in this single center retrospective analysis. All underwent [18F]FDG PET/CT for pre-operative staging and subsequently either surgery (n = 38) or mediastinoscopy (n = 8). Regarding the lymph node involvement, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for [18F]FDG PET/CT using the final histopathological N-staging (pN0 to pN3) as reference.ResultsPer patient 14 ± 7 (range 4–32) lymph nodes were resected and histologically processed. 31/46 patients had no LCNEC spread into the lymph nodes. In 8/46 patients, the final stage was pN1, in 5/46 pN2 and in 2/46 pN3. [18F]FDG PET/CT diagnosed lymph node metastasis of LCNEC with a sensitivity of 93%, a specificity of 87%, an accuracy of 89%, a PPV of 78% and a NPV of 96%. In the four false positive cases, the [18F]FDG uptake of the lymph nodes was 33 to 67% less in comparison with that of the respective LCNEC primary. Interrater-reliability was high with a strong level of agreement (κ = 0.82).ConclusionsIn LCNEC N-staging with [18F]FDG PET/CT demonstrates both high sensitivity and specificity, an excellent NPV but a slightly reduced PPV. Accordingly, preoperative invasive mediastinal staging may be omitted in cases with cN0 disease by [18F]FDG PET/CT. In [18F]FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [18F]FDG uptake as compared to the LCNEC primary.

Highlights

  • Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers

  • We retrospectively reviewed patients with Large cell neuroendocrine lung cancer (LCNEC) who underwent [­18F]FDG Positron emission tomography (PET)/Computer tomography (CT) and subsequently either surgery with curative intent or mediastinoscopy for lymph node sampling in cases of discordant diagnostic findings

  • Aim of this study was to assess the performance of ­[18F]FDG PET/CT N-staging in LCNEC as compared to the lymph node histopathology representing the diagnostic gold standard

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Summary

Introduction

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. One characteristic of LCNEC and discriminating it from typical and atypical bronchial carcinoids is the high expression of the glucose transporter 1 (GLUT1) making this entity suitable for fluorine-18-fluoro-deoyglucose ­([18F]FDG) imaging [5,6,7]. We retrospectively reviewed patients with LCNEC who underwent [­18F]FDG PET/CT and subsequently either surgery with curative intent or mediastinoscopy for lymph node sampling in cases of discordant diagnostic findings. Aim of this study was to assess the performance of ­[18F]FDG PET/CT N-staging in LCNEC as compared to the lymph node histopathology representing the diagnostic gold standard

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