Case Report
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

https://doi.org/10.1016/j.anndiagpath.2005.12.008Get rights and content

Abstract

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is an extremely rare pulmonary lesion, with only 39 cases reported in the literature. We report an additional case and review the literature. The patient is a 41-year-old man with a 5-year history of progressive dyspnea, cough, and wheezing. He was initially diagnosed as having bronchial asthma but did not respond to treatment of bronchodilators and inhaled steroids. Pulmonary function tests showed airflow obstruction. Chest computed tomography revealed a mosaic pattern of air trapping and thickening of bronchial walls. Open lung biopsy showed diffuse proliferation of pulmonary neuroendocrine cells within the bronchiolar epithelium, often bulging into or obliterating the bronchiolar lumen. These cells also breached the basement membrane, forming tumorlets. There was prominent peribronchiolar fibrosis and obliterative bronchiolitis. The pathologic evaluation of lung tissue is currently the gold standard in making a definitive diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, and all the reported cases were diagnosed by either open lung biopsy or lobectomy.

Introduction

Pulmonary neuroendocrine cell (PNEC) hyperplasia has been conventionally considered as a reactive process associated with regeneration of chronically injured airways or alveoli, such as in lung abscess, bronchiectasis, cystic fibrosis, and chronic obstructive pulmonary disease. In 1992, Aguayo et al [1] described 6 nonsmoking patients who presented with diffuse PNEC hyperplasia without any known pulmonary diseases. The authors postulated that these patients might belong to a distinct new entity of diffuse hyperplasia of PNEC without primary causes. After the initial report, more than 30 additional cases have been described [2], [3], [4], [5], [6], [7], [8], and the term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) became widely accepted for this new entity. The World Health Organization recognized this condition in the 1999 classification [9] and considered it as a preinvasive lesion of pulmonary carcinoid tumor. We describe a patient who was treated for bronchial asthma for 5 years before he was diagnosed as DIPNECH by open lung biopsy. The previous reported cases of DIPNECH were analyzed along with the current case for the common features in clinical presentation, radiologic imaging, pulmonary function testing, and pathologic examination.

Section snippets

Report of a case

The patient is a 41-year-old white man with a 5-year history of insidious onset of exertional dyspnea, cough, and wheezing. He denied history of any chronic pulmonary disorders or major systemic diseases. He worked as a medical technician in an emergency department. For the last 15 years, he has not smoked, but he did have a history of smoking for 6 years (0.5 pack per day). He was initially diagnosed with bronchial asthma and received treatment for the past 2 years with bronchodilators and

Pathologic findings

The open lung biopsy yielded 2 fragments of pink-tan, soft lung tissue without nodules or remarkable gross lesions. A distinct histologic feature was diffuse proliferation of bland cells involving the bronchiolar epithelium (Fig. 2). Cytologically, these cells have typical neuroendocrine features, including uniform oval-to-round nuclei, fine-stippled chromatin granules, inconspicuous nucleoli, and a moderate amount of eosinophilic cytoplasm. The cells formed clusters in the epithelium,

Discussion

DIPNECH is an exceedingly rare lung lesion characterized by generalized proliferation of PNEC often confined to the epithelium of bronchioles. Careful review of the literature disclosed 39 cases [1], [2], [3], [4], [5], [6], [7], [8]; they are analyzed with the current case and are summarized in Table 1. Although the age distribution appeared relatively wide (22-79 years), most patients presented in their fifth or sixth decades (mean age, 58 years). Females distinctly predominated, with a male

References (13)

  • J.C. Willey et al.

    Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells

    Exp Cell Res

    (1984)
  • S.M. Aguayo et al.

    Brief report: idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airways disease

    N Engl J Med

    (1992)
  • R.R. Miller et al.

    Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumors

    Am J Surg Pathol

    (1995)
  • O.A. Armas et al.

    Diffuse idiopathic pulmonary neuroendocrine cell proliferation presenting as interstitial lung disease

    Am J Surg Pathol

    (1995)
  • M.J. Brown et al.

    Bronchiolitis obliterans due to neuroendocrine hyperplasia: high-resolution CT–pathologic correlation

    AJR Am J Roentgenol

    (1997)
  • A.J. Cohen et al.

    High expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells

    Am J Respir Crit Care Med

    (1998)
There are more references available in the full text version of this article.

Cited by (39)

  • DIPNECH: When to suggest this diagnosis on CT

    2015, Clinical Radiology
    Citation Excerpt :

    Pulmonary function test alteration is reported to be moderate to severe in 44% of cases.10 It has been suggested that normal pulmonary function tests may represent the early phase of the disease when the airway obstruction is not severe enough to be detected.16 DIPNECH is defined as a proliferation of pulmonary neuroendocrine cells that do not cross the basement membrane.7

View all citing articles on Scopus
View full text