Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Multidisciplinary NET Group, Umbria Regional Cancer Network and University of Perugia, Perugia, Italy.
Ann Thorac Surg. 2022 Mar;113(3):966-974. doi: 10.1016/j.athoracsur.2021.03.069. Epub 2021 Apr 5.
The clinical significance of multifocal pulmonary neuroendocrine proliferation (MNEP), including tumorlets and pulmonary neuroendocrine cell hyperplasia, in association with typical carcinoid (TC), is still debated.
We evaluated a retrospective series of TC with long-term follow-up data prospectively collected from 2 institutions and compared the outcome between TC alone and MNEP plus TC. Several baseline covariates were imbalanced between the MNEP plus TC and TC groups; therefore, we conducted 1:1 propensity score matching and inverse probability of treatment weighting in the full sample. In the matched group, the association of clinical, respiratory, and work-related factors with the group was determined through univariable and multivariable conditional logistic regression analysis.
A total of 234 TC patients underwent surgery: 41 MNEP plus TC (17.5%) and 193 TC alone (82.5%). In the MNEP plus TC group, older age (P < .001), peripheral tumors (P = .0032), smaller tumor size (P = .011), and lymph node spread (P = .02) were observed compared with the TC group. Relapses occurred in 8 patients in the MNEP plus TC group (19.5%) and 7 in the TC group (3.6%). After matching, in 36 pairs of patients, a significantly higher 5-year progression-free rate was observed for the TC group (P < .01). Similar results were observed using inverse probability of treatment weighting in the full sample. The odds of being in the MNEP plus TC group was higher for those with work-related exposure to inhalant agents (P = .008), asthma or bronchitis (P = .002), emphysema, fibrosis, and inflammatory status (P = .032), or micronodules on the chest computed tomography scan and respiratory insufficiency (P = .036).
The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful preoperative workup, systematic pathologic evaluation, including nontumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.
多灶性肺神经内分泌增生（MNEP），包括肿瘤小体和肺神经内分泌细胞增生，与典型类癌（TC）相关的临床意义仍存在争议。
我们评估了 2 家机构前瞻性收集的 TC 长期随访数据的回顾性系列，并比较了 TC 单独与 MNEP 加 TC 的结果。MNEP 加 TC 组和 TC 组之间存在多个基线协变量不均衡；因此，我们在全样本中进行了 1:1 倾向评分匹配和治疗反概率加权。在匹配组中，通过单变量和多变量条件逻辑回归分析确定临床、呼吸和与工作相关的因素与组的关联。
共 234 例 TC 患者接受手术：41 例 MNEP 加 TC（17.5%）和 193 例 TC 单独（82.5%）。在 MNEP 加 TC 组中，与 TC 组相比，年龄较大（P<0.001）、肿瘤位于外周（P=0.0032）、肿瘤较小（P=0.011）和淋巴结扩散（P=0.02）。MNEP 加 TC 组中有 8 例（19.5%）和 TC 组中有 7 例（3.6%）患者复发。在匹配后，在 36 对患者中，TC 组的 5 年无进展生存率明显更高（P<0.01）。在全样本中使用治疗反概率加权也观察到了类似的结果。与工作相关的吸入剂暴露（P=0.008）、哮喘或支气管炎（P=0.002）、肺气肿、纤维化和炎症状态（P=0.032）或胸部 CT 扫描上的微结节和呼吸功能不全（P=0.036）的患者，更有可能处于 MNEP 加 TC 组。
与 MNEP 的关联似乎是 TC 的临床和预后相关因素。因此，建议对这些患者进行仔细的术前检查、系统的病理评估，包括非肿瘤性肺实质，并进行长期术后随访。
