Clinical reportDiffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two casesHiperplasia neuroendocrina difusa pulmonar idiopática: estudio de dos casos
Introduction
The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder commonly misdiagnosed. Aguayo et al. described it for the first time more than 25 years ago, showing a hyperplasia confined to the respiratory epithelium layer without penetration of the basement membrane.1 This entity encompasses symptomatic patients with airway disease as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumorlets/carcinoids tumors. The World Health Organization (WHO) in the spectrum of pulmonary neuroendocrine tumors also considers DIPNECH as preneoplastic lesion, because it is commonly observed in patients with peripheral carcinoid tumours.2
In this paper, we analyze clinical, physiological, radiological and histological features of DIPNECH documenting two new cases.
A 71-year-old female patient was referred to our department to perform a lung biopsy because of the suspected diagnosis of a diffuse lung disease. She was a no smoker, suffered a Von Willebrand disease and was diagnosed years before of bronchial asthma and chronic cough. There were no alterations in the physical examination and pulmonary function test was: FEV1 61%, FVC 69% and DLCO 56%.
CT showed a bilateral mosaic pattern and subcentimeter nodules in right lower lobe, middle lobe, left lower lobe and left upper lobe. There was also a solid lesion in the anterior segment of right upper lobe. We decided to perform a PET because the lesion of the right upper lobe was larger than previous in the last radiological study. PET showed again an interstitial mosaic pattern and a solid lesion with spiculated rims of 1.6 × 1.2 × 0.8 cm in the anterior segment of the right upper lobe with a SUV of 5.7 g/ml. The rest of the subcentimeter nodules did not show glucose uptake. Bronchoscopy did not reveal any endobronchial finding.
We performed a right upper lobectomy with systematic lymph node dissection. The histological study of the specimen showed a necrotizing granulomatous inflammation with acid-alcohol resistant bacillus (BAAR) forming a nodular area of 1.6 × 1 cm in the lobe. In the rest of the tissue we only observed a mild focal dilatation of the bronchioles, and a minor peribronchiolar lymphocyte inflammation. We did not find parenchymal fibrosis but we observed three microscopic nodules lesser than 3 mm made up of low-grade neuroendocrine cells (3 tumorlets). Despite we did not identify morphological changes of interstitial lung disease, a diffuse neuroendocrine cell hyperplasia was observed in the mucosa of multiple bronchioles. This fact went unnoticed with hematoxylin and eosin staining technique but was clearly recognized in the immunohistochemical work-up (these cells were positive for CD56 and Cytokeratins) (Fig. 1a and b). Five peribronchial lymph nodes did not showed granulomas or neoplasm. Nevertheless, in the paratracheal and subcarinal lymph stations we observed two little microscopic nodules (1.5 mm and 2 mm respectively) of epithelial neuroendocrine cells that were positive for CD 56 and TTF1. We did not find pleomorphism, neither necrosis and nor significant mitotic activity was observed. Expression of Ki 67 was minor than 2% (Fig. 1c). Postoperative evolution elapsed without complications and the patient was discharged seven days after surgery.
A 56-year-old woman was admitted to our hospital to perform a lung biopsy in the context of an interstitial lung disease. Se was a smoker of 20 cigarettes per day and suffered epilepsy treated with Carbamazepine that was suspended because of the possible relation with the interstitial pattern. She presented moderate effort dyspnea and chronic cough since youth.
CT demonstrated a nodule in the middle lobe of 0.6 cm, a nodule in the left lower lobe of 1 cm and a bilateral mosaic pattern (Fig. 1d). It was performed a PET that demonstrated a lower hypermetabolism in both nodules. Pulmonary function test was: FEV1 44%, FVC 60% and KCO 69%. Bronchoscopy did not show any finding.
We performed biopsies of right upper lobe and right lower lobe and a wedge resection to treat the nodule of the middle lobe. The definitive pathology results showed a diffuse neuroendocrine cell hyperplasia with multiple tumorlets in the biopsies from right upper lobe and right lower lobe and a typical carcinoid of 0.7 cm in the nodule of the middle lobe. Postoperative progress was satisfactory. The patient was discharged 2 days after surgery.
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Discussion
Neuroendocrine cells in the adult lung are part of the normal epithelial layer of the respiratory tract comprising about 1% of all cells. These specialized cells receive neural impulses and secrete several hormonally substances, mainly under reduced oxygen tension.2 Since DIPNECH was reported in 1992,1 several authors have reviewed additional cases, some of them were associated with carcinoids.
Clinical symptoms and radiological findings of DIPNECH are indistinguishable from other diffuse lung
Contributions
(I) Conception and design: all authors; (II) Administrative support: none; (III) Provision of study materials or patients: all authors; (IV) Collection and assembly of data: E. García-Fontán and M Blanco; (V) Data analysis and interpretation: all authors; (VI) Manuscript writing: all authors; (VII) Final approval of manuscript: all authors.
Conflict of interests
The authors declare no conflict of interests.
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