Neuroendocrine Lung tumors
Paris A. Kosmidis,MD

Neuroendocrine tumours (NETs) are neoplasms mainly originating from the gastro-entero-pancreatic area (67.5%) and the bronchial tree (25.3%). According to the World Health Organization (WHO) criteria, lung tumours with neuroendocrine differentiation include four major categories of morphologically identifiable NETs from low-grade [typical carcinoid (TC)] and intermediate-grade [atypical carcinoid (AC)] to high-grade tumours [large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC)] that exhibit considerably different histological and clinical characteristics. TCs are generally benign tumours with an excellent prognosis after radical surgery (up to 98% of 5-year survival). Regional lymph node or distant metastases are detected or develop over time in ~10% of cases. ACs are histologically similar to TCs (though with a higher mitotic count and/or necrosis), but up to 48% of cases present lymph node or distant metastases at diagnosis; their prognosis has been related to several predictive factors. LCNEC and SCLC, both highly aggressive tumours, have overlapping histopathological features (except for the cell size) and clinical behaviour.
The molecular profile of NE tumours has been widely investigated to identify features helpful for the diagnosis, prognosis and even therapy for this special lung tumour category. Specific chromosomal alterations, oncogene mutations and cell cycle molecule disregulation has been documented in NE tumours of the lung, as well as the expression of specific receptors or enzymes implicated in the response to biotherapies or to chemotherapeutic agents.
Several neuroendocrine markers and hormonal receptors have been described in NETs having diagnostic, prognostic and also therapeutic implications. Among the latter, somatostatin receptors (SSTRs) are a family of five widely distributed G-protein-coupled receptors that mediate different intracellular signalling pathways involved in cell proliferation, differentiation and angiogenesis.
The clinical presentation includes cough, hemoptysis, and obstructive pneumonia but varies depending on site, size, and growth pattern. Less than 5% of BP-NETs exhibit hormonally related symptoms such as carcinoid syndrome, Cushing, acromegaly, and SIADH.
Differently from gastro-entero-pancreatic NETs, the management of pulmonary NET-affected patients is less standardised apart from surgical resection, chemoradiotherapy or liver metastasis embolisation. Synthetic somatostatin analogues have been produced, being the most widely employed in the clinical practice. Their higher receptor-binding affinity (especially for SSTR2, SSTR3 and SSTR5) is the basis for both diagnostic (i.e. scintigraphy or positron emission tomography scans) and therapeutic procedure (mostly palliation).
Interferons, m-tor inhibitors, sunitinib are novel agents useful or under investigation for the treatment of advanced disease.  
No curative treatment except for radical surgery exists. The slow-growing TC exhibit a fairly good prognosis (88%, 5-year survival), whereas AC demonstrate a 5-year survival of 50%, and the highly malignant LCNEC and SCLC 5-year survival of 15% to 57% and <5%, respectively.