Development and Validation of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia (DIPNECH) Diagnostic Criteria

Abstract Background Diffuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH) is a rare condition that is likely underdiagnosed due to lack of established and validated diagnostic criteria. Current clinical guidelines are empirical and based on a limited number of studies. The present study was designed to validate the existing criteria and to identify new clinical parameters that can accurately diagnose DIPNECH. Methods DIPNECH patients were identified from a cohort who underwent surgical lung resection for pulmonary carcinoids. The study cohort included a total of 105 consecutive cases with neuroendocrine lesions. Initial diagnostic predictors of DIPNECH were selected from the literature. We employed univariate and multivariate models to examine the association of clinical, pathological, radiological variables on the likelihood of DIPNECH. Results Univariate analysis identified age, gender, COPD diagnosis, obstructive abnormalities, pulmonary nodules, mosaicism, absolute numbers of pulmonary neuroendocrine lesions (PNELs), number of tumorlets as significant DIPNECH predictors. After adjustment for sampling variations, the ratio of total number of PNELs to number of bronchioles was found to be significantly higher in DIPNECH category. Multivariate analysis identified total number of PNELs, multiple pulmonary nodules (>10) as independent predictors of DIPNECH. The performance of our criteria showed an accuracy of 76% to detect DIPNECH cases. Conclusion We proposed a set of diagnostic criteria for DIPNECH based on an expert-panel approach integrating pathology, radiology, clinical data. Our findings will help identify DIPNECH patients, without a pathology confirmation of a neuroendocrine lesion. Before the implementation of these criteria in clinical practice, they require further validation on multi-institutional cohorts.