Elsevier

Medicina Clínica

Volume 152, Issue 3, 1 February 2019, Pages 104-106
Medicina Clínica

Clinical report
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two casesHiperplasia neuroendocrina difusa pulmonar idiopática: estudio de dos casos

https://doi.org/10.1016/j.medcli.2018.03.036Get rights and content

Abstract

Introduction

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern.

Patients and methods

We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea.

Results and discussion

The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions.

Resumen

Introducción

La hiperplasia neuroendocrina difusa pulmonar idiopática (HNDPI) es una patología poco frecuente que se caracteriza por la proliferación de células neuroendocrinas en el parénquima pulmonar. Se describe clásicamente como una enfermedad que afecta a mujeres de mediana edad no fumadoras y que presentan tos persistente, disnea y sibilancias. La TC muestra una imagen de patrón en mosaico como resultado del atrapamiento aéreo.

Pacientes y métodos

Presentamos dos casos de HNDPI que fueron enviados a nuestro servicio para realizar una biopsia pulmonar con la sospecha diagnóstica de enfermedad intersticial difusa. Ambos casos fueron mujeres con antecedentes de tos crónica y disnea de esfuerzo moderado.

Resultados y discusión

El objetivo de este documento es que los facultativos tengan en cuenta este diagnóstico antes de tratar como asmática a una paciente con estas características, no olvidando además que son lesiones preneoplásicas.

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.

Section snippets

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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