Lung biopsy specimens in NEHI were originally described as normal or with minor nonspecific changes
Although the sensitivity of HRCT scanning for use in the diagnosis of NEHI is incomplete (78%), high specificity has been reported.
Lung biopsy specimens in NEHI were originally described as normal or with minor nonspecific changes. The only consistent abnormality seen in lung biopsy specimens is an increased proportion of neuroendocrine cells (NECs) within distal airways best demonstrated by bombesin and serotonin immunohistochemistry. There are no formal criteria for defining NEC excess in the lung, but it has been suggested that findings of NECs within >70% of bronchioles in the lung biopsy specimen and > 10% NECs in an individual airway are consistent with the diagnosis in the appropriate clinical setting.
Pulmonary NECs, which produce bioactive products, including bombesin-like peptide and serotonin, are specialized epithelial cells scattered throughout the conducting airways and as innervated clusters (neuroepithelial bodies [NEBs]). In the fetus, NECs are most abundant in the distal airways where they promote branching morphogenesis, epithelial and mesenchymal cell proliferation, and surfactant secre-tion. Postnatally, NECs function as oxygen chemosen-sors and degranulate in response to hypoxia. Although NECs decline rapidly in number after the neonatal period, NEC hyperplasia has been described in a number of conditions or disorders, including bronchopulmonary dysplasia (BPD), sudden infant death syndrome, pulmonary hypertension, cystic fibrosis, and mechanical ventilation. Increased NEC number with proliferation also has been observed in animal models of airway epithelial repair, imparting a progenitor cell role for NECs.
Increasing clinical experience with NEHI has resulted in the recognition of a wider range of pathologic features than the near-normal appearance previously described, most commonly, patchy airway inflammation or fibrosis. Although NECs have been shown to be increased in patients with NEHI compared with age-matched control subjects, there has been no systematic comparison with other pulmonary disorders associated with NEC hyperplasia.