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Mar 2017

Neuroendocrine Tumors

Reviewer(s): Dharam M. Ramnani, M.D.
Neuroendocrine tumors of the lung are subdivided into 4 major categories: 1) Small cell lung carcinoma (SCLC); 2) Large cell neuroendocrine carcinoma (LCNEC); 3) Atypical carcinoid (AC); and 4) Typical carcinoid (TC). SCLC and LCNEC are high-grade malignant tumors, AC is intermediate-grade, and TC is considered low-grade malignant tumor.

TC and AC are more closely related to each other than to SCLC or LCNEC. About 40% of patients with TC or AC are non-smokers. TC and AC can occur in patients with MEN type I syndrome and about 40% of sporadic cases carry MEN I mutations. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is considered to be a precursor lesion for both TC and AC.

SCLC and LCNEC are strongly linked with cigarette smoking and are rarely seen in non-smokers. There is no known precursor lesion. They are driven by inactivating mutations in TP53 (100% of cases) and RB genes (100% of cases) and have no association with MEN I syndrome. They carry the characteristic tobacco-smoking related carcinogenic signature large number of mutations and high fraction of G to T transversions in methylated CpG dinucleotides caused by polycyclic aromatic hydrocarbons in tobacco smoke.

Small Cell Carcinoma of Lung

Large Cell Neuroendocrine Carcinoma

Typical Carcinoid

Atypical Carcinoid

Diffuse Idiopathic NE Cell Hyperplasia