Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with ectopic adrenocorticotropic hormone syndrome in Asia.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, preinvasive lung disorder characterized by multifocal neuroendocrine cell proliferation. Because it presents with chronic cough and wheezing, it is frequently misdiagnosed as asthma. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) arising from DIPNECH is exceptionally rare. We present a rare case of a 62-year-old woman with a long-standing history of presumed asthma who developed ACTH-dependent Cushing syndrome. Bilateral inferior petrosal sinus sampling confirmed ectopic ACTH secretion. Subsequently, comprehensive thoracic imaging revealed a potential ectopic source in a dominant right middle lobe nodule, accompanied by subtle micronodules and mosaic attenuation, which are characteristic of DIPNECH. Targeted lobectomy achieved complete remission, yielding a histopathological diagnosis of a neuroendocrine tumor within background DIPNECH that demonstrated marked immunohistochemical ACTH heterogeneity among hyperplastic cells and tumorlets. Consistent with previously reported cases, our findings highlight that even subtle pulmonary nodules can secrete ACTH and must be evaluated in unexplained EAS. Furthermore, because these subcentimeter nodules possess secretory potential and morphological progression risks, lifelong multidisciplinary surveillance is imperative.