Radiologic and Histologic Correlates of Early Interstitial Lung Changes in Explanted Lungs

Abstract

Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants. Materials and Methods Explanted lungs or lobes from participants with radiologically documented ILAs were prospectively collected from 2010 to 2021. These specimens were air-inflated, frozen, and scanned with CT and micro-CT (spatial resolution of 0.7 mm and 90 μm, respectively). Subsequently, the lungs were cut and sampled with core biopsies. At least five samples per lung underwent micro-CT and subsequent histopathologic assessment with semiquantitative remodeling scorings. Based on area-specific radiologic scoring, the association between radiologic and histopathologic findings was assessed. Results Eight lung explants from six donors (median age at explantation, 71 years [range, 60-83 years]; four men) were included (unused donor lungs, n = 4; pre-emptive lobectomy for oncologic indications, n = 2). Ex vivo CT demonstrated ground-glass opacification, reticulation, and bronchiectasis. Micro-CT and histopathologic examination demonstrated that lung abnormalities were frequently paraseptal and associated with fibrosis and lymphocytic inflammation. The histopathologic results showed varying degrees of fibrosis in areas that appeared normal on CT scans. Regions of reticulation on CT scans generally had greater fibrosis at histopathologic analysis. Vasculopathy and bronchiectasis were also often present at histopathologic examination of lungs with ILAs. Fully developed fibroblastic foci were rarely observed. Conclusion This study demonstrated direct histologic correlates of CT-defined interstitial lung abnormalities. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Jeudy in this issue.

Graphical abstract

Figure 1:

Study design. (A) Photograph shows the explanted lung frozen solid in liquid nitrogen fumes. (B) Axial noncontrast ex vivo CT scan of the specimen is obtained while it is frozen. (C) Whole-lung micro-CT scan is obtained for better spatial resolution. (D) Photograph shows the lung sliced transversally in 2-cm slices. (E) Micro-CT scan of a core sample (indicated with the circle in B–D) is obtained. (F) Matched histologic image (hematoxylin-eosin stain; magnification, ×5) is shown at the same location as the micro-CT scan. (G) High-magnification histologic image (hematoxylin-eosin stain; magnification, ×20) shows paraseptal fibrosis.

Figure 2:

Flowchart of participant inclusion. ILA = interstitial lung abnormality.

Figure 3:

Illustrative examples of sampled lung areas with ex vivo CT, micro-CT, and histologic staining. (A) Axial noncontrast ex vivo CT scan shows highly abnormal (25% healthy, 55% reticulation, 20% ground-glass opacification) lung findings. (B–E) Micro-CT scan (B) and histopathologic images (hematoxylin-eosin [C, D] and trichrome [E] staining; magnification, ×5 for C and E, ×20 for D) of the area highlighted with the circle in A show paraseptal and interstitial fibrotic changes. (F) Axial noncontrast ex vivo CT scan shows lung considered healthy (80%), with mild ground-glass opacification (15%) and limited reticulation (5%). (G–J) Micro-CT scan (G) and histopathologic images (hematoxylin-eosin [H, I] and trichrome [J] staining; magnification, ×5 for H and J, ×20 for I) of the matched location (circle in F) show paraseptal and interstitial fibrosis. Awy = airway, BV = blood vessel.

Figure 4:

(A) Three-dimensional reconstruction of distal airway tree based on specimen micro-CT scans shows typical tortuous and distorted airways. (B) Cross-sectional micro-CT panel shows the absence of overt fibrosis in the vicinity of the airway, which is highlighted in red.