Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis

Abstract

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF.

Methods: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death.

Results: The median age at autopsy was 71 years (range 47-86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections.

Conclusions: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.

Figure 1

A 78-year-old male with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). High resolution computed tomography (HRCT) images at the initial diagnosis of IPF showed subpleural-predominant interstitial fibrosis, traction bronchiectasis (arrow) and honeycombing (arrowhead) (A). HRCT images at the onset of acute exacerbation (12 months after the initial diagnosis) showed diffuse areas of ground glass attenuations superimposed on underlying fibrotic opacities (B). The underling fibrotic lesions were classified as the UIP pattern, including dense interstitial fibrosis with focal squamous or bronchial metaplasia (inset), alternating with only bland-looking alveolar walls (H&E, ×100) (C). DAD with hyaline membranes (inset) superimposed on a background fibrotic and edematous lung with several fibroblastic foci (H&E, ×100) (D).

Figure 2

The histopathological findings of the lung specimens obtained at autopsy. The microscopic findings of the lung showed diffuse alveolar hemorrhage (arrows) without any specific evidence of vasculitis (A) or pulmonary thromboembolism (B) (H&E, ×10). The macroscopic findings of the heart showed overt right ventricular hypertrophy, confirmed by an increased (≥5 mm) right ventricular wall thickness (double-headed arrows) (C). Immunohistochemical staining of an inflamed lung tissue specimen revealed a number of specific cytomegalovirus-positive cells (proliferating type II pneumocytes) (D).

Figure 3

A flow diagram showing the pathological findings of the patients with AE-IPF. *One patient showed pulmonary thromboembolism with alveolar hemorrhage.