Image Description
Pulmonary carcinoids show immunoreactivity for neuroendocrine markers, including synaptophysin (cytoplasmic), chromogranin (cytoplasmic), NCAM/CD56 (cell membrane staining; shown here), neuron-specific enolase, serotonin, and neurofilaments. Pancytokeratin is positive, whereas high molecular weight cytokeratin is generally negative. Pulmonary carcinoids are usually negative for TTF-1 (some peripherally-located pulm. carcinoids may be positive). Based on the active peptides produced by a given tumor, there may be positivity for somatostatin, calcitonin, ACTH, gastrin-releasing peptide/bombesin, GHRH, substance P and VIP. Ki-67 labeling index is lower in carcinoids (< 10-20%) as compared to small cell carcinoma and large cell neuroendocrine carcinoma (> 50%, often as high as 80%) and can be a useful adjunct in small biopsies with crush artifact.
About the Disease
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.