Different clinico-pathological associations of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
23 February 2017 (online)
As a rare pre-invasive lesion for pulmonary carcinoids, DIPNECH is characterized by scattered proliferates of pulmonary neuroendocrine cells (pNEC) that are confined to the bronchial/bronchiolar epithelium and may form extraluminal proliferates (tumorlets, < 5 mm). The histological diagnosis may pose difficulties and optimal therapeutic strategy is still controversial.
In this observational study, patients with first diagnosis of DIPNECH evaluated at the University Hospitals of Leipzig and Homburg/Saar (2011 – 2016) were analyzed for clinico-pathological features, treatment and survival.
All six patients were identified by surgical resection (median age 70.9 years; 4/6 female; 3/6 never-smokers). DIPNECH was incidentally found in two patients with longstanding history of undertreated alleged bronchial asthma during evaluation of pulmonary nodules. Four otherwise asymptomatic patients were evaluated for lung cancer. In three of them, DIPNECH was found in close proximity to pulmonary adenocarcinoma (pADC) and in one close to a typical carcinoid. In one female patient, DIPNECH was associated with a pADC, and additionally a pulmonary meningotheliosis.
Five DIPNECH samples were immunohistologically reactive for chromogranin A and CD56, 4/6 for synaptophysin, 2/6 for neuron-specific enolase, 6/6 showed a Ki67-proliferation index of < 5%. During follow-up two patients underwent 68Ga-DOTATOC-PET: One with symptomatic history of bronchial asthma showed an increased expression of somatostatin receptors suggesting a pronounced presence of pNEC even after surgery. All patients were alive at the time of submission.
DIPNECH presents with a variety of pulmonary signs and symptoms. Airway obstruction may be mistaken for bronchial asthma. DIPNECH lesions may slowly progress to carcinoid tumors (> 5 mm), may be associated with pADC, and very rarely additionally with pulmonary meningotheliosis. Regular long-term follow-up is therefore warranted.