Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid

Background: 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. Methods: 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. Results: 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). Conclusions: 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.