March 2021 — Pulmonary Pathology
A middle-aged woman underwent a left lung surgical wedge biopsy.
What is the likely diagnosis?
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
- Constrictive bronchiolitis
- Organizing pneumonia (OP)
- Respiratory bronchiolitis (RB)
The correct answer is ...
The diagnosis in this case is: Constrictive bronchiolitis.
This is a case of constrictive bronchiolitis, which is an uncommon fibrosing small airway disease with a poor prognosis. Patients usually present with an insidious onset of dyspnea and cough over weeks to months. A combination of a pulmonary function test and imaging findings can be helpful in making a diagnosis. A pulmonary function test (PFT) maybe normal or show an obstructive pattern with hyperinflation, which cannot be reversed with bronchodilators. Plain chest radiograph are usually normal. The most consistent imaging abnormality is bronchial wall thickening and expiratory air trapping (mosaic attenuation) seen on inspiratory and expiratory high-resolution computed tomography (HRCT). The etiology of constrictive bronchiolitis varies and includes infection, toxic fumes, drug toxicity, ingestion of Sauropus androgynous juice (used for weight loss), collagen vascular disease and idiopathic.
At a cursory glance the histological findings of constrictive bronchiolitis may not be readily observed. The defining feature is bronchial wall thickening by subepithelial concentric fibrosis leading to narrowing of the bronchial lumen and in some instances the fibrosis progresses to complete obliteration of the bronchioles. The fibrosis ranges from immature loose collagen mixed with a fibroblastic proliferation or more mature dense acellular collagen. A bronchial and the accompanying pulmonary artery should be similar in size and noticing a significantly smaller bronchial can be a clue to the diagnosis. A Verhoeff-Van Gieson (VVG) stain, pictured above, can highlight expansion between the bronchial lumen and the smooth muscle and in late stage disease highlight the elastic fiber remnants in a completely obliterated bronchial.
OP is a nonspecific pattern of acute lung injury that can be identified on low power by the characteristic mucopolysaccharide-rich intraluminal fibroblastic plugs within intact alveolar and distal bronchioles. Unlike constrictive bronchiolitis, OP is often associated with accumulation of microvesicle foamy macrophages in the alveolar sacs. OP can be the result of many etiologies that are often inferred based on the clinical setting.
DIPNECH is a clinical diagnosis and the presenting symptoms are similar to constrictive bronchiolitis. The widespread neuroendocrine hyperplasia and carcinoid tumorlets associated with DIPNECH can lead to fibrotic destruction of the bronchioles. Fibrotic stroma with nests of uniform neuroendocrine cells in most cases is easily identified upon microscopic examination. RB is usually an incidental finding present in most current smokers. RB has also been reported in individuals with a remote history of smoking and non-smokers with exposure to second hand smoke. Scattered pigmented macrophages within respiratory bronchioles and the adjacent alveolar parenchyma associated with minimal chronic inflammation and fibrosis is the histologic hallmark of RB.
- Churg, Andrew and Muller, Nestor. (2020) Atlas of Interstitial Lung Disease Pathology (2nd ed.) Philadelphia, PA: Wolters Kluwer.
- Katzenstein, Anna-Luise. (2016) Diagnostic Atlas of Non-Neoplastic Lung Disease. New York, NY: Sringer Publishing Company.
Lacey Schrader, M.D.
Fellow, Pulmonary Pathology
Joanne Yi, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science