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Background  Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by multifocal proliferation of pulmonary neuroendocrine cells. On chest CT, DIPNECH exhibits bilateral pulmonary nodules and mosaic attenuation in most patients. We sought to: (1) assess the specificity of this pattern (i.e., bilateral pulmonary nodules together with mosaic attenuation) for DIPNECH; (2) describe its differential diagnosis; and (3) identify the clinico-radiologic features that may help prioritize DIPNECH over other diagnostic considerations.    Methods  We searched the Mayo Clinic records from 2015 to 2019 for patients with bilateral pulmonary nodules and mosaic attenuation on CT who had a diagnostic lung biopsy. A thoracic radiologist reviewed all CT scans. Chi-square test was used for categorical variables, and odds ratios were utilized to measure the association between certain variables and DIPNECH.    Results  Fifty-one patients met our inclusion criteria; 40 (78%) were females and 34 (67%) were never-smokers. Median age was 65 (interquartile range 55–73) years. Lung biopsy was surgical in 21 patients (41%), transbronchial in 17 (33%), and transthoracic in 12 (24%); explanted lungs were examined in 1 (2%). Metastatic/multifocal cancer was the most common diagnosis, and was found in 17 (33%) cases. Bronchiolitis was diagnosed in 12 patients (24%), interstitial lung disease in 10 (20%), and DIPNECH in 5 (10%). Previous diagnosis of an obstructive lung disease (odds ratio 15.8;  P  = 0.002), and peribronchial nodular distribution on CT (odds ratio 14.4;  P  = 0.006) were significantly correlated with DIPNECH. Although statistical significance was not reached, DIPNECH nodules were more likely to display solid attenuations (80% vs. 67%,  P  = 0.45), and were more numerous; > 10 nodules were seen in 80% of DIPNECH cases vs. 52% in others ( P  = 0.23). Because DIPNECH primarily affects women, we analyzed the women-only cohort and found similar results.    Conclusions  Various disorders can manifest the CT pattern of bilateral pulmonary nodules together with mosaic attenuation, and this combination is nonspecific for DIPNECH, which was found in only 10% of our cohort. Previous diagnosis of an obstructive lung disease, and peribronchial distribution of the nodules on CT increased the likelihood of DIPNECH vs. other diagnoses.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13023-021-02103-w.

Is the combination of bilateral pulmonary nodules and mosaic attenuation on chest CT specific for DIPNECH?