Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation with Typical Carcinoid.

BACKGROUND 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 A retrospective series of TC with long-term follow-up data prospectively collected from two institutions was evaluated, and the outcome comparison between TC alone and MNEP+TC was investigated. Several baseline covariates were imbalanced between the MNEP+TC and TC groups, therefore, we have conducted 1:1 propensity score matching and inverse probability of treatment weighting (IPTW) in the full sample. In the matched group, association of clinical, respiratory and work-related factors with group was determined through univariable and multivariable conditional logistic regression analysis. RESULTS 234 TC patients have undergone surgery: 41 MNEP+TC(17.5%) and 193 TC alone(82.5%). In the MNEP+TC group older age(p<0.001), peripheral tumors(p=0.0032), smaller tumor size(p=0.011) and lymph-nodal spread(p=0.02) were observed in comparison with TC group. Relapses occurred in 8 patients (19.5%) of MNEP+TC group and in 7(3.6%) of TC group. After matching, in 36 pairs of patients a significantly higher 5-years progression-free rate was observed for TC group(p<0.01). Similar results were observed using IPTW in the full sample. Odds of being in the MNEP+TC group was higher with work-related exposure to inhalant agents(p=0.008), asthma/bronchitis(p=0.002), emphysema, fibrosis and inflammatory status(p=0.032), micronodules on the chest CT scan and respiratory insufficiency(p=0.036). CONCLUSIONS The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful pre-operative workup, systematic pathological evaluation, including non-tumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.