Spread through air spaces (
STAS) have been recently recognized as a prognostic factor for
adenocarcinoma and
squamous cell carcinoma of the lung. Pulmonary neuroendocrine
neoplasms (NENs) include
tumors with different morphology and a heterogeneous clinical behavior. Among atypical
carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical
carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine
carcinomas, to assess the presence and potential prognostic role of
STAS.
STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the
tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses.
STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and
small-cell carcinomas in the control group. In the
carcinoid group, presence of
STAS was significantly correlated with unfavorable parameters, such as high
tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of
STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.