Next‐generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNETs) comprising the four World Health Organization classification categories: 53 typical carcinoid (TCs), 35 atypical carcinoid (ACs), 27 large‐cell neuroendocrine carcinomas, and 33 small‐cell lung carcinomas. A discovery screen was conducted on 46 samples by the use of whole‐exome sequencing and high‐coverage targeted sequencing of 418 genes. Eighty‐eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen, and validated on additional 102 LNETs by targeted NGS; their prevalence was then evaluated on the whole series. Thirteen of these 88 genes were also evaluated for copy number alterations (CNAs). Carcinoids and carcinomas shared most of the altered genes but with different prevalence rates. When mutations and copy number changes were combined, MEN1 alterations were almost exclusive to carcinoids, whereas alterations of TP53 and RB1 cell cycle regulation genes and PI3K/AKT/mTOR pathway genes were significantly enriched in carcinomas. Conversely, mutations in chromatin‐remodelling genes, including those encoding histone modifiers and members of SWI–SNF complexes, were found at similar rates in carcinoids (45.5%) and carcinomas (55.0%), suggesting a major role in LNET pathogenesis. One AC and one TC showed a hypermutated profile associated with a POLQ damaging mutation. There were fewer CNAs in carcinoids than in carcinomas; however ACs showed a hybrid pattern, whereby gains of TERT, SDHA, RICTOR, PIK3CA, MYCL and SRC were found at rates similar to those in carcinomas, whereas the MEN1 loss rate mirrored that of TCs. Multivariate survival analysis revealed RB1 mutation (p = 0.0005) and TERT copy gain (p = 0.016) as independent predictors of poorer prognosis. MEN1 mutation was associated with poor prognosis in AC (p = 0.0045), whereas KMT2D mutation correlated with longer survival in SCLC (p = 0.0022). In conclusion, molecular profiling may complement histology for better diagnostic definition and prognostic stratification of LNETs. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

In our experience radio-guided surgery has therefore been proven efficacious in the diagnosis of solitary pulmonary nodule and video-assisted thoracoscopic surgery allows the removal of pulmonary nodules without complications. Hookwire was also shown to be efficacious but demonstrated complications linked primarily to external technical factors.

Radiofrequency ablation treatment of early-stage NSCLC seems to be a effective minimally invasive therapy even in the long-term period, particularly for stage Ia tumors.

As the European population ages, surgeons are regularly faced with octogenarians with resectable early stage non-small cell lung cancer (NSCLC). We compared our experience with those reported in the literature to comprehend the feasibility, outcomes and lessons learned regarding surgical treatment. We reviewed octogenarians who underwent lung resection for NSCLC in the past nine years in our Department. The purpose of this paper is to retrospectively analyse postoperative surgical and oncological outcomes of our series, trying to find possible correlations between mortality, morbidity, survival and preoperative oncological and functional assessment, surgical approach and extent of resection. Eighty-two patients (M/F = 63/19), with a mean age 81.0 years (range 80-87 years) underwent lung resection for NSCLC: 63 lobectomies, one inferior bilobectomy, three segmentectomies, and 15 wedge resections. There were two perioperative deaths (2.4%). The overall complication rate was 30.0%, with a major complication rate of 2.5%. Actuarial cancer-related survival rates at one, three and five years were 90%, 44% and 36%, respectively, with a statistically-significant correlation with pathological stage. Octogenarians may benefit from surgical treatment of NSCLC with an acceptable morbidity and mortality rate, if an accurate preoperative selection is pursued.

ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.