Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung
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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.
KeywordsLung Atypical carcinoid Neuroendocrine neoplasm Spread through air spaces (STAS) Prognosis
Study conception and design: MP. Data collection: SA, JM, FM, GG, PC, GVS, MV, MP. Analysis and interpretation of data: MP, MV, SA, JM, MV. Drafting of manuscript: MP, MV, SA, JM. Critical revision: SA, JM, FM, GG, PC, GVS, MV, MP. All the authors gave final approval for publication. The author MV takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.
This study was partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, Milan), grant #IG19238 to MV. JM is a PhD fellow at the University of Turin.
Compliance with ethical standards
The study was approved by the local ethical committee (Department of Oncology at San Luigi Hospital, number 17975/2015).
Conflict of interest
The authors declare that they have no conflict of interest.
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