Hautzel Hubertus, Alnajdawi Yazan, Fendler Wolfgang P, Rischpler Christoph, Darwiche Kaid, Eberhardt Wilfried E, Umutlu Lale, Theegarten Dirk, Stuschke Martin, Schuler Martin, Aigner Clemens, Herrmann Ken, Plönes Till
Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
EJNMMI Res. 2021 Jul 22;11(1):68. doi: 10.1186/s13550-021-00811-9.
Large 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-[F]-fluoro-deoxyglucose ([F]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 [F]FDG PET/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [F]FDG PET/CT findings.
Between 03/2014 and 12/2020, 46 patients with LCNEC were included in this single center retrospective analysis. All underwent [F]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 [F]FDG PET/CT using the final histopathological N-staging (pN0 to pN3) as reference.
Per 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. [F]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 [F]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).
In LCNEC N-staging with [F]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 [F]FDG PET/CT. In [F]FDG PET/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [F]FDG uptake as compared to the LCNEC primary.
肺大细胞神经内分泌癌（LCNEC）是一种罕见的实体肿瘤，在所有肺癌中所占比例不到4%。由于其低分化和高葡萄糖转运蛋白1（GLUT1）表达，LCNEC表现出葡萄糖代谢增加。因此，2-[F]-氟脱氧葡萄糖（[F]FDG）PET/CT适用于LCNEC分期。根治性手术是早期LCNEC的首选治疗方法。其前提是准确的淋巴结分期。本研究旨在评估手术切除或纵隔镜检查后经组织病理学验证的[F]FDG PET/CT的诊断性能。评估了N分期的观察者间可靠性，以测试[F]FDG PET/CT结果的稳健性。
在2014年3月至2020年12月期间，46例LCNEC患者纳入了这项单中心回顾性分析。所有患者均接受[F]FDG PET/CT进行术前分期，随后接受手术（n = 38）或纵隔镜检查（n = 8）。关于淋巴结受累情况，以最终组织病理学N分期（pN0至pN3）为参考，计算[F]FDG PET/CT的敏感性、特异性、准确性、阳性预测值（PPV）和阴性预测值（NPV）。
每位患者切除并进行组织学处理的淋巴结为14±7个（范围4 - 32个）。46例患者中有31例LCNEC未扩散至淋巴结。46例患者中有8例最终分期为pN1，5例为pN2，2例为pN3。[F]FDG PET/CT诊断LCNEC淋巴结转移的敏感性为93%，特异性为87%，准确性为89%，PPV为78%，NPV为96%。在4例假阳性病例中，淋巴结的[F]FDG摄取比相应的LCNEC原发灶少33%至67%。观察者间可靠性高，一致性程度强（κ = 0.82）。
在LCNEC的N分期中，[F]FDG PET/CT显示出高敏感性和特异性，出色的NPV，但PPV略有降低。因此，对于[F]FDG PET/CT显示cN0疾病的病例，术前可省略侵入性纵隔分期。对于[F]FDG PET/CT显示cN1 - cN3期，尤其是与LCNEC原发灶相比[F]FDG摄取仅为中等程度的情况，需要进行组织学确认。
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