COVID-19: Histopathological correlates of imaging patterns on chest computed tomography

Abstract

Background and objective: Patients with coronavirus disease 2019 (COVID-19) pneumonia present with typical findings on chest computed tomography (CT), but the underlying histopathological patterns are unknown. Through direct regional correlation of imaging findings to histopathological patterns, this study aimed to explain typical COVID-19 CT patterns at tissue level.

Methods: Eight autopsy cases were prospectively selected of patients with PCR-proven COVID-19 pneumonia with varying clinical manifestations and causes of death. All had been subjected to chest CT imaging 24-72 h prior to death. Twenty-seven lung areas with typical COVID-19 patterns and two radiologically unaffected pulmonary areas were correlated to histopathological findings in the same lung regions.

Results: Two dominant radiological patterns were observed: ground-glass opacity (GGO) (n = 11) and consolidation (n = 16). In seven of 11 sampled areas of GGO, diffuse alveolar damage (DAD) was observed. In four areas of GGO, the histological pattern was vascular damage and thrombosis, with (n = 2) or without DAD (n = 2). DAD was also observed in five of 16 samples derived from areas of radiological consolidation. Seven areas of consolidation were based on a combination of DAD, vascular damage and thrombosis. In four areas of consolidation, bronchopneumonia was found. Unexpectedly, in samples from radiologically unaffected lung parenchyma, evidence was found of vascular damage and thrombosis.

Conclusion: In COVID-19, radiological findings of GGO and consolidation are mostly explained by DAD or a combination of DAD and vascular damage plus thrombosis. However, the different typical CT patterns in COVID-19 are not related to specific histopathological patterns. Microvascular damage and thrombosis are even encountered in the radiologically normal lung.

Keywords: COVID-19; SARS-CoV-2, viral infection; acute respiratory distress syndrome; chest CT; coronavirus disease; histopathological and imaging.

FIGURE 1

Fresh resection specimen of right lung photographed from the lateral view (A). Distance from the lobar apex and fissure relevant to the CT‐pattern of interest is measured on the CT scan and subsequently in the specimen in order to reach exactly the same level (B,C). (D) Another example of the left lung photographed from the medial view which correlates with the premortem CT image (E,F) in order to correlate with the oblique fissure and bronchial branch (arrows)

FIGURE 2

(A) CT image of the right lung reveals areas of Patchy GGO (region 1 & 2) and Consolidation with surrounding GGO (region 3 and 4). (B) Corresponding histopathology of Patchy GGO (region 1 and 2) revealed prominent microthrombi (arrow) and (C) patchy stage DAD. (D) Corresponding histopathology of Consolidation with surrounding GGO (region 3 and 4) revealed exudative DAD (scale bars correspond to 50 μm)

FIGURE 3

(A) CT image of the right lung reveals sharply demarcated consolidation (region 1) and diffuse GGO (region 2 and 3) with thickened interlobular septa. (B) Corresponding histopathology of sharply (arrows) demarcated consolidation (region 1) revealed acute fibrinous and organizing pneumonia (AFOP, scale bar corresponds to 2 mm). Note the microscopical haemorrhages (asterix in the spared pulmonary parenchym, scale bar corresponds to 2 mm). (C) Diffuse GGO revealed exudative stage of DAD (region 2 and 3) with microscopic haemorrhages (asterix), segmental infarction (asterix) and (D) thickened interlobular septa which were venulitis with venous thrombosis (region 3, scale bar corresponds to 50 μm)

FIGURE 4

(A) CT image of the right lung reveals consolidation with traction bronchiectasis in the middle lobe (region 1) and consolidation with surrounding GGO in the right lower lobe (region 2). (B) Corresponding Histopathology of the consolidation with traction bronchiectasis in the middle lobe (region 1, scale bar corresponds to 2 mm) revealed proliferative stage of DAD. (C) EVG staining of proliferative DAD in region 1 lacking pink collagen deposition in the parenchyma indicating no fibrosis and possible reversibility of parenchymal remodelling. Note the pink collagen of normal vascular adventitia (green asterix, scale bar corresponds to 50 μm). (D) Consolidation with surrounding GGO (region 2) revealed large area of haemorrhage (arrows) with surrounding patchy microscopical haemorrhages (asterix) and exudative phase of DAD (arrowhead, scale bar corresponds to 1 mm)

FIGURE 5

(A) CT image of the left lung reveals radiologic unaffected pulmonary parenchyma (region 1), patchy GGO (region 2), peribronchovascular consolidation (region 3) and subpleural consolidation (region 4). b. Radiologic unaffected pulmonary parenchyma (region 1) revealed patchy endothelialitis (arrow). c. Corresponding histopathology of patchy GGO (region 2) revealed patchy haemorrhages d. Corresponding histopathology of the peribronchovascular and subpleural area (region 2 and 3) revealed acute exudative pneumonia (bronchopneumonia) with neutrophil granulocytes infiltration of alveolar spaces (arrow, scale bars corresponds to 50 μm). (B) a. CT image of the left lung reveals an early stage patient with areas of unaffected pulmonary parenchyma (region 1), peribronchovascular consolidation (region 2) and subpleural consolidation (region 3). b. Corresponding histopathology of the unaffected pulmonary parenchyma (region 1) reveals early stage microthrombi (arrow). c. Corresponding histopathology of peribronchovascular consolidation (region 2 and 3) revealed bronchopneumonia with bronchocentric distribution and vascular involvement d. with thrombi (scale bars correspond to 50 μm)