RESULTS
Sixteen children (ages 8d to 3y4m at first CT: 9M,7F) with subpleural cysts were identified during the study period over 22 years. Of these 16 children, 7 children received only a single CT examination. The remaining 9 children underwent multiple CT studies (up to three CTs in 4 children and four CTs in 1 child) at variable intervals depending on the clinical need. Of the 9 children who underwent repeat CT chest examinations, 7 occurred> 5 months after the first scan, and 6 children went on to have a third CT after an average of 12 months. One child had a fourth follow-up CT, performed 10 years after their initial CT.
Considering the known association with Trisomy 21, we divided the cases into two groups based on their genetic profiles (Table 1). The first group had an underlying genetic defect identified (n=11) while the second group had no identifiable genetic defect (n=5).
Findings of the CT scans are provided in Table 2. Of note, only 2 children manifested unilateral cysts. In the first child (case 12), cysts were only present on the left side. This child had left lower pulmonary vein stenosis and a smaller left lung. In the second child, (case 13), only right sided cysts were seen. This child had an absent right pulmonary artery and a smaller right lung.
While Trisomy 21 was the most common underlying genetic association when a genetic disorder was discovered (n=6/11), the cysts were found in other rare disorders, including one case of Kabuki syndrome and one case of Cornelia-de-Lange syndrome. The other 4 genetic abnormalities are listed. The remaining 5 children listed had other clinical pathologies which did not warrant genetic evaluation.
The most common clinical pathology in all these children was some form of congenital heart disease (14/16), most associated with left to right physiology (VSD or AVSD in 6/14, ASD in 6/11, PDA in 2/11, allowing for children with multiple defects). Pulmonary artery hypertension was recorded to be present in 8 children.
Two children who had no defined genetic abnormality were discovered to have these cysts in their teens, one with microscopic polyangiitis and one with hepatoportal sclerosis at birth of unknown etiology requiring liver transplantation (Image 2). Of note, this latter case had secondary hepatopumonary syndrome before liver transplantation.
While only a small number of children underwent follow-up CT scans for assorted reasons, it is noteworthy that in most cases (n=5/9) the number and size of cysts increased with time. (Image 1). The child with hypoplastic left heart syndrome (case 12) had 2 CTs performed in the first year of life that had no peripheral cysts, with the cysts only appearing on the 3rd CT at 2 years of age.
We could not find any significant correlation with ventilatory requirements. 7 cases required mechanical ventilation, usually in association with surgery for the underlying CHD. All 7 cases had underlying CHD, of which 5 were premature as well.
Pulmonary function tests were only performed in 2 teens, with contradictory results.
Indications for CT chest examination included evaluation of lung parenchyma in moderate to severe PAH (6/16), pre-operative evaluation of an underlying congenital heart disease (2/16), post-operative follow-up for worsening hypoxemia (2/16), and evaluation of recurrent upper respiratory tract infections (3/16). Other indications included evaluation of antenatally diagnosed pulmonary lymphangiectasia (1/16), concern for right-to-left shunting (1/16), and evaluation of non-specific dry cough and respiratory difficulty (1/16).
Histopathology was correlative in only two cases, both with Trisomy 21. The first was performed at the time of cardiac surgery (case 1) which demonstrated focal enlargement and simplification of subpleural alveolar spaces (image 3). The second was at autopsy (case 9) A third biopsy was performed in the teen with ANCA (Anti Neutrophil Cytoplasmic Antibodies) positive MPO positive microscopic polyangiitis, revealing pulmonary hemosiderosis without capillaritis.
Long term outcomes seemed to be more related to the child’s underlying anomalies than to a pulmonary etiology. All 5 children who died had underlying CHD. Short term outcomes could not be associated with the presence of subpleural cysts due to the paucity of cases and to the complexity of confounding clinical variables including but not limited to prematurity, CHD, surgeries and intercurrent infections.