Typical Versus Atypical Carcinoid and Diffuse Idiopathic Neuroendocrine Cell Hyperplasia Versus Carcinoid Tumorlets

Abstract

Carcinoid tumors of the lung are primary pulmonary neoplasms which typically occur in middle-aged individuals. The most common presentations are persistent cough, possibly with hemoptysis, or recurrent episodes of pneumonia. Pulmonary carcinoid tumors occur as either low-grade typical carcinoid (TC) or more aggressive intermediate-grade atypical carcinoid (AC). Histologically, both are characterized by nests of neuroendocrine cells arising from neuroendocrine cells of the airway epithelium. The atypical form is defined by the presence of either punctate necrosis or a mitotic rate from 2 to 10 mitotic figures/2 mm²; they are associated with more aggressive behavior and lower overall rates of survival when compared to TC.

Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) and carcinoid tumorlets are two forms of neuroendocrine cell hyperplasia that affect predominantly women in their 50s and 60s. Both entities will present with multiple pulmonary nodules. In DIPNECH, multiple small nodules are seen bilaterally, commonly showing a linear pattern along bronchi and bronchioles on radiographic imaging, whereas tumorlets are small (≤5 mm) localized lesions associated with underlying primary lung disease.

All these entities demonstrate similar immunohistochemical profiles, with positivity for neuroendocrine markers and variable expression of TTF-1. As such, their differentiation is based largely on their morphologic features in conjunction with both clinical and radiographic correlation. This is particularly true in making the diagnosis of DIPNECH.