Severe cryptogenic bronchiolitis: Case report

Abstract

Bronchiolitis obliterans (BO) is a progressive fibrotic process that predominantly affects the small airways and is identified as constrictive bronchiolitis by pathologists. It is commonly associated with allogeneic hematopoietic stem cell transplant (HSCT), lung transplant, exposure to inhaled toxins, post-infectious processes, autoimmune diseases, and sometimes, no known cause. In the latter case, it is referred to as cryptogenic bronchiolitis obliterans. A 52-year-old Hispanic man with a medical history of hypertension, diabetes mellitus, and coronary artery disease was referred to the pulmonary department due to experiencing dyspnea on exertion, intermittent dry cough, and progressive limitation of activities of daily living. Spirometry revealed severe obstructive changes, and chest high-resolution computed tomography showed ground-glass opacities with nodular infiltrates in the upper lobes, leading to a presumptive diagnosis of hypersensitivity pneumonitis. The patient underwent a lung surgical biopsy of the right upper and lower lobes, which revealed extensive constrictive bronchiolitis. Due to the patient's worsening general condition, bilateral lung transplantation succeeded without any further complications. Following the transplantation, the patient showed good recovery and functional improvement. Bronchiolitis obliterans, or constrictive bronchiolitis, has a variable natural history. It is associated with a higher risk of mortality in allogenic HSCT. When BO is secondary to inhalation of toxic gases, it is usually nonprogressive and limited to toxin exposure. Autoimmune diseases or cryptogenic bronchiolitis are rare and have a heterogeneous clinical course. To make a proper diagnosis, clinical history, radiologic and histologic findings must be considered.

Keywords: Bronchiolitis; Constrictive bronchiolitis; Lung transplant; Obstructive pulmonary disease; Small airway.

Fig. 1

The high-resolution chest CT shows heterogeneity of the attenuation coefficient in both lungs (blue arrow). Ground-glass opacities with a perihilar predominance and prebronchial distribution (green arrow) are also present, along with subpleural nodular thickening in both upper lungs (red arrow) and interlobular interstitial thickening. No areas of consolidation are noted, and the hilum appears unremarkable. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

The thoracoscopic biopsy sample (A) was analyzed using H&E staining at 40x magnification. It showed a dense fibrotic pulmonary interstitium with a small lumen in the obstructed bronchus (blue arrow). (B, C) Another analysis was performed using the Movat stain at 4x magnification, revealing obvious bronchiole occlusion within the peribronchovascular interstitium (red arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

(A) The lung explant specimen reveals numerous bronchi and bronchioles that are dilated with thickened walls and mucoid material in the lumen. Subpleural fibrosis areas and congested vessels are present in all lobules, but no masses or cavitary lesions are identified. In the scarred areas, there are occluded bronchi and bronchioles along with vascular walls (blue arrow). (B) H&E staining of the lung parenchyma shows abnormal tissue due to the progression of the fibrotic process at 4x magnification (C) and complete fibrotic areas due to pulmonary parenchymal destruction at 40× magnification. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

(A, B) At 10x magnification with Movat stain, muscular hyperplasia, mucus production, and acute inflammation with subsequent fibrosis and occlusion of a bronchiole are evident (blue arrow). (C, D) At 40x magnification with Movat stain, the occlusion of the bronchiolar lumen is apparent, caused by the secretion of proteoglycan by young fibroblasts and ongoing fibrotic process (blue arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

(A, B, C, D) Immunohistochemistry was performed using CK7 marker at 10x magnification. The respiratory epithelium in the areas of bronchiole occlusion showed positive staining for the CK7 marker (blue arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6

The video bronchoscopy revealed the following findings: (A) The distal trachea and carina showed a normal appearance. (B) The right anastomosis showed no stenosis, dehiscence, or granulomas. (C) In the area prior to the anastomosis, the left main bronchus showed moderate to severe stenosis of the bronchial lumen. (D) A bronchial dilation balloon was seen in the image. (E, F) After dilation, the area of the left anastomosis showed the lumen of the left main bronchus and segmental bronchi with a normal appearance in the background.