Pediatric Diffuse Lung Disease in Infants: Imaging Findings and Histopathologic Correlation

Abstract

Childhood interstitial lung disease (chILD) encompasses a diverse group of genetic, infectious, and inflammatory conditions affecting infants and children. The recognition and understanding of these entities have highlighted the necessity for more accurate classification. This group of rare heterogeneous diseases comprises more than 200 different conditions and has a combined estimated prevalence of less than one patient per 100 000 children. Hence, a systematic diagnostic approach is crucial. This article describes a diagnostic approach for pediatric diffuse lung diseases in infancy, including an analysis of clinical presentations and imaging and histologic features to effectively distinguish among various chILD entities. Although they often have overlapping and nonspecific radiologic features, some chILD entities may exhibit typical imaging findings, resulting in a CT diagnosis or aiding in narrowing the differential diagnosis, thus guiding the clinician to the appropriate genetic tests, potentially limiting unnecessary biopsies. This approach aims to enhance the understanding and diagnosis of chILD in infants, thereby facilitating improved patient care.

Graphical abstract

Figure 1.

Illustration shows the histologic phases of lung development, highlighting instances of lung growth arrest at specific times in particular disorders (5,6).

Figure 2.

Illustration shows the normal anatomy of a secondary pulmonary lobule and its corresponding representation at CT.

Figure 3.

Illustration shows the diagnostic workup for chILD (17).

Figure 4.

Proposed flowchart for the investigation of chILD. BAL = bronchoalveolar lavage, CHD = coronary heart disease, CXR = chest radiography, DLD =diffuse lung disease, Echo = echocardiography, EKG = electrocardiography, NEHI =neuroendocrine cell hyperplasia of infancy, PFT = pulmonary function tests.

Figure 5.

Alveolar capillary dysplasia and pulmonary hypertension in an 8-month-old infant. (A, B) Coronal (A) and axial (B) CT images (lung windows) show bilateral diffuse hazy ground-glass opacities (arrow), with preferential involvement of the perihilar regions and lower lobes. There is relative sparing of the upper lobes and the most peripheral regions of the lungs (arrowheads) and dependent atelectasis in B. (C) Photomicrograph of specimen shows slightly widened alveoli. The pulmonary artery (blue arrows) shows medial hypertrophy, and there are abnormal thin-walled muscular veins (green arrows) in the bronchovascular bundle. (Hematoxylin-eosin [H-E] stain; original magnification, ×10.) (D) Higher-power photomicrograph shows widened septa, with capillaries that are centrally located away from the epithelial interface (arrows). (H-E stain; original magnification, ×20.) (E) Illustration shows abnormal positioning of pulmonary veins and thickening of the interlobular septum.

Figure 6.

CLD of prematurity and pulmonary hypertension in a 2-month-old female infant. (A) Chest radiograph shows bilateral diffuse coarse interstitial lung markings with marked overinflation of the lungs and bilateral air-filled cystic spaces (right more than left). (B) Axial chest CT image (lung window) shows bilateral cystic changes with intercostal bulging (white arrows), subpleural triangles, and septal fibrosis (black arrows).

Figure 7.

Subpleural cysts in in a 5-year-old child with trisomy 21 and ventricular septal defect. Axial (A) and coronal (B) CT images of the chest (lung window) show diffuse subpleural cysts of various sizes extending along the periphery (arrowhead in A) and into the fissures (arrow in B).

Figure 8.

Severe pulmonary hypertension secondary to pathogenic FLNA mutation in a 3-month-old infant. (A, B) Axial CT images (lung window) during inspiration show bilateral interlobular septal thickening (arrow) and perihilar-predominant consolidation (arrowhead). (C) Coronal CT image (lung window) shows mosaic attenuation of the lung parenchyma on expiration, which is suggestive of airtrapping. Patchy airspace opacification at the posterior bases of both lungs likely represents dependent atelectasis. (D) Photomicrograph of specimen shows the alveoli markedly enlarged, with mild thickening of some alveolar septa. The pulmonary artery (arrow) shows severe intimal fibrosis with a small residual lumen. (H-E stain; original magnification, ×4 on a digital scale.) (E) Axial T2-weighted MR image through the lateral ventricles shows gray matter heterotopia lining both ventricles (arrows), which are also notably dilated.

Figure 9.

Pulmonary interstitial glycogenosis in a 2-month-old full-term infant. (A, B) Coronal (A) and axial (B) CT images (lung windows) show bilateral patchy ground-glass airspace opacities (arrows) and centrilobular nodules in the dependent upper and lower lobes. (C) Photomicrograph of specimen shows mildly enlarged alveoli, but the septa are widened by bland mononuclear cells with clear cytoplasms. There is minimal intra-alveolar material, and type 2 pneumocytes are not prominent. (Hematoxylin-eosin stain; original magnification, ×200 [objective, ×20].)

Figure 10.

NEHI in a 2-year-old child. (A–D) Axial inspiratory (A, B) and expiratory (C, D) CT images show central paramediastinal ground-glass opacities in both upper lobes (arrows in A and C), and geometric areas of ground-glass opacities are seen in the right middle lobe and lingula (arrows in B and D). Note that in inspiration and expiration, there are similar findings of the remaining lung parenchyma, consistent with air trapping on expiration. (E, F) Axial CT images acquired when the patient was 4 months old show more diffuse ground-glass opacities, findings less classic for NEHI than those on previous images.

Figure 11.

ILD due to biallelic ABCA3 mutations in a 2-week-old neonate. (A, B) Coronal (A) and axial (B) CT images (lung windows) show diffuse ground-glass opacities with mild interlobular septal thickening (arrow). (C) Photomicrograph of specimen shows widened alveolar septa with a combination of smooth muscle, inflammatory cells, and fibroblasts. Most septa are lined with reactive type 2 pneumocytes, and there are foci of intra-alveolar macrophages. Intra-alveolar surfactant material is not present in this field. Note that lung biopsy was performed before the availability of genetic results because of clinical concern for ACDMPV. (Hematoxylin-eosin stain; original magnification, ×100 [×10 objective].)

Figure 12.

SFTPC mutation in a 3-month-old infant. (A) Chest radiograph shows early findings of diffuse hazy opacities and hyperinflation. (B) Axial CT image shows patchy ground-glass opacities (arrow). (C) Axial CT image acquired when the patient was 8 years old shows chronic findings that include diffuse ground-glass opacity as well as cystic changes (arrowhead).