DIPNECH is a rare condition. Forty-six cases have so far been reported in the literature.1 2 3
The majority have airways disease symptoms. It is known that reactive hyperplasia of neuroendocrine cells can occur in the setting of airways fibrosis and inflammation or as an adaptive response to hypoxia.4 5
In DIPNECH there is the presence of neuroendocrine cell hyperplasia with physiological evidence of airflow obstruction that is otherwise unexplained. In the 1999 WHO classification of lung tumours, DIPNECH was included as a pre-neoplastic lung lesion. In DIPNECH there is hyperplasia of neuroendocrine cells in the airways without invasion beyond the basement membrane. If the cells extend into the interstitium and are <5 mm, the lesion is classified as a carcinoid tumourlet. If >5 mm it is a carcinoid tumour.6
A retrospective study of surgical specimens undertaken in 2007 found that 28 of 294 patients with a carcinoid tumour or tumourlet had two or more lesions. In total, 93% of cases were women with a mean age of 65 years. Half of those with multiple nodules had respiratory symptoms. Only one patient had a clinical syndrome resembling DIPNECH.
Several theories exist as to the pathophysiology of DIPNECH. It has been suggested that the neuroendocrine cells release gastrin-releasing peptide and fibroblast growth factors causing pulmonary fibrosis.4
Alternatively, epidermal growth factor receptor over expression may play a significant role in producing fibrosis providing a potential target for treatment strategies in the future.7
Others propose that hyperplasic neuroendocrine cells secrete bombesin, which leads to fibroblast and smooth muscle proliferation.8
Most patients have persistent but stable disease. There is no specific treatment. Most patients receive conventional treatment for airways disease including inhaled and oral steroids.9
A minority present with interstitial lung disease and are treated with oral corticosteroids.8
There is no agreed method or timescale for surveillance regarding the possible development of carcinoid tumours.
- DIPNECH can present with evidence of obstructive or restrictive lung disease.
- Consider DIPNECH in the differential diagnosis of bilateral pulmonary nodules.
- DIPNECH can only be diagnosed by lung biopsy.