Classification of lung neuroendocrine tumors: lights and shadows

Neuroendocrine tumors of the lung are classified into low-grade typical and intermediate-grade atypical carcinoids, and high-grade poorly differentiated neuroendocrine carcinomas of the large and small cell types. This scheme is strongly predictive of patients’ prognosis but relies on few and scarcely reproducible pathological parameters (namely mitotic count and assessment of the presence of necrosis), which have been demonstrated to affect the inter-observer agreement of the classification. Moreover, tumor and nodal staging schemes are not specific for lung carcinoids, at variance with neuroendocrine tumors of the gastro-entero-pancreatic system, despite these tumors have specific features that strongly differ from conventional lung cancer. Finally, there is no grading for lung neuroendocrine neoplasms and prognostication, as well as the definition of treatment modalities and clinical strategies, which are based on tumor histotypes, only. However, literature data indicate that the evaluation of Ki-67 proliferation index may be a reliable and useful tool to determine the biological and clinical behavior of neuroendocrine tumors, with special reference to carcinoids, both in pre-operative and surgical samples.