Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), a rare disease previously overlooked, is gradually being recognized as an important precursor state to pulmonary neuroendocrine tumors. The very insidious onset of symptom presentation makes early diagnosis of DIPNECH almost impossible in clinical settings. In this report, we present a case of persistent and worsening cough for over five years with waxing and waning lung nodules of varying sizes which were eventually diagnosed as DIPNECH on biopsy. However, due to the location and the multiplicity of these nodules, surgical resection was not an option in this case. The diagnostic workup including imaging and biopsy, management options, and possible prognosis of DIPNECH are discussed in detail. This report highlights the growing recognition of DIPNECH as a clinical entity to be aware of during the formulation of a differential diagnosis for patients presenting with chronic unrelenting cough and associated lung nodules.

Although incidental reactive pulmonary neuroendocrine cell hyperplasia (PNECH) is seen on biopsy specimens in adults with chronic lung disease, disorders characterized by marked PNECH are rare. Primary hyperplasia of neuroendocrine cells in the lung and obstructive lung disease related to remodeling or physiologic constriction of small airways define diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) in the adult and neuroendocrine cell hyperplasia of infancy (NEHI) in children. DIPENCH and NEHI share a similar physiology, typical imaging appearance, and increased neuroendocrine cells on biopsy. However, there are important differences related to the underlying disease mechanisms leading to disparate outcomes.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.