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NeoQuest February 2025: Cystic Lung Lesions in a Preterm Neonate

January 29, 2025

A 2-week-old extremely low-birth-weight female infant was born at 24 weeks’ gestation via vaginal delivery following premature rupture of membranes and now has respiratory failure. She was intubated in the delivery room and subsequently received two doses of surfactant. Her ventilation and oxygenation have worsened despite appropriate ventilation strategies and a dexamethasone course. Her most recent arterial blood gas showed the following results: pH of 7.18, pCO2 of 65 mm Hg, paO2 of 45 mm Hg, and base deficit of -2. A sepsis evaluation from admission was normal, and a repeat sepsis evaluation is pending. Figure 1 shows her most recent chest radiograph.


Figure 1: Frontal view of the chest radiograph of the neonate described in the vignette. Image from: Diamond SE, Perez S, Dumpa V, Jayappa S, et al. Multicystic lobar lung lesion in a preterm neonate. Neoreviews. 2025;26(2):e115-e118.1

What is the most common location of this type of pulmonary lesion?

  1. Extra-lobar with equal left- and right-sided distribution
  2. Left upper lobe of the lung
  3. Localized or diffuse with no predilection of any particular lobe
  4. Lower lobes with equal left- and right-sided distribution
  5. Right lung predominance

Answer: C. Localized or diffuse with no predilection of any particular lobe

Explanation:

The neonate described in the vignette has risk factors (extremely low birth weight, extreme prematurity, and surfactant administration) for the clinical progression of and characteristic radiologic findings of persistent pulmonary interstitial emphysema (PIE), which can be localized or diffuse in location with no predilection for any particular lobe (Option C).1 In PIE, air leaks from damaged alveoli into the interstitial space of the lung parenchyma, resulting in the finding of linear, oval, and spherical cystic air-containing lucencies on the chest radiograph (Figure 2).1,2 Additional risk factors associated with PIE include perinatal depression, sepsis, and late or asymmetric administration of surfactant.2 PIE commonly occurs in extremely premature infants with poor lung compliance, resulting in alveolar overdistention with invasive positive pressure ventilation.1-3 The pathological findings include thickening of the airway and basement membrane, mucus exudates in the airway lumen, alveolar and connective tissue tears, and parabronchial and perivascular widening (Figure 3).2


Figure 2: Frontal view of the chest radiograph demonstrating diffuse cystic lucencies (right side greater than left side – red arrow) with lung hyperinflation and mass effect.  Image from: Diamond SE, Perez S, Dumpa V, Jayappa S, et al. Multicystic lobar lung lesion in a preterm neonate. Neoreviews. 2025;26(2):e115-e118.1


Figure 3: Histopathology slide showing airspace enlargement (stars) compared to the surrounding lung parenchyma, alongside mild fibrotic changes (arrows), consistent with pulmonary interstitial emphysema. Image from: Diamond SE, Perez S, Dumpa V, Jayappa S, et al. Multicystic lobar lung lesion in a preterm neonate. Neoreviews. 2025;26(2):e115-e118.1

PIE can cause worsening oxygenation through the following mechanisms:1,2

  • Air trapping can lead to increased oxygen requirement and carbon dioxide retention.
  • Increased intrathoracic pressure from air trapping and high mean airway pressure requirement can decrease venous return to the heart, which can proceed to decreased right ventricular output and pulmonary hypertension, further worsening oxygenation
  • Severe PIE can compress the mediastinum and opposite lung and cause rapid hemodynamic decompensation

Permissive hypercapnia can be beneficial in the management of PIE by lowering ventilator settings to reduce volutrauma from hyperexpansion of the lungs. Selecting modes of ventilation, such as high-frequency jet ventilation or neurally adjusted ventilatory assist, can help decompress areas with significant air trapping.3 For localized, persistent PIE, selective intubation of the contralateral lung can be considered to prevent further lung injury to the affected lung.4 For infants with prolonged, severe PIE, despite appropriate ventilatory strategies and a dexamethasone course, a computed tomography scan (CT scan) or magnetic resonance imaging (MRI) may be required to evaluate for the potential presence of other cystic lesions, such as congenital pulmonary airway malformation, bronchogenic cyst, pulmonary sequestration, abscess, congenital lobar emphysema, or cysts resulting from thromboembolism or septic embolism.3 CT scan findings of PIE include multiple thin-walled, air-filled cystic structures and line-and-dot patterns in these cystic radiolucencies (Figure 4).1 Imaging can also further assist in delineating anatomical extension for percutaneous drainage or surgical resection, if needed.1

Figure 4: Computed tomography scan of the chest with a lung window. Axial (A) and coronal (B) images demonstrate multiple round, ovoid, and oblong-shaped cystic lucencies involving the right lower lobe that are consistent with pulmonary interstitial emphysema. In the coronal image, the right lower lobe bronchus is seen entering the hyperinflated multicystic lower lobe (white arrowhead). The left lung is well-expanded and shows some small focal atelectasis. The endotracheal tube tip is in the lower thoracic trachea (white arrow). A nasogastric tube is seen in the stomach (black arrow). Image from: Diamond SE, Perez S, Dumpa V, Jayappa S, et al. Multicystic lobar lung lesion in a preterm neonate. Neoreviews. 2025;26(2):e115-e118.1

The differential diagnosis of persistent cystic lesions in a neonate includes congenital lobar emphysema (CLE). CLE is a rare lung malformation with male predominance that develops when one or more lobes become overdistended from air entrapment secondary to a ball-valve effect. This entrapment can be from bronchomalacia, dysplastic cartilage formation, mucosal hyperinflation, or thick mucus. Unlike PIE, infants with CLE typically have radiographic findings of hyperlucent lungs, often featuring a single large focal cyst confined to one lobe, most commonly the left upper lobe (Option B) (Figure 5).5,6 In contrast, the chest radiograph of the infant in the vignette has a diffuse cystic appearance affecting both lungs, making CLE less likely.


Figure 5: Congenital lobar emphysema. Chest radiograph (left panel) shows left-sided hyperinflation (arrow) with mediastinal shift to the right side (star) that was corroborated on a computed tomography scan (right panel). Note the diffuse and hyperlucent appearance of the affected side (red arrow). Image from: McBride W. Congenital lesions of the lung. Neoreviews. 2016;17(5):e263–e270.6

Congenital pulmonary airway malformation (CPAM) is the most common lung malformation, which is caused by abnormal bronchial morphogenesis.6,7 Predominantly seen in males, CPAM has five clinically and histologically major subtypes based on the origin of malformation in the bronchial tree. This lesion is more commonly seen in the lower lobes with equal left- and right-lung distribution (Option D). On a chest radiograph, it appears as a localized lesion as one or two large air-filled cysts, multiple small air-filled cysts with a bubbly appearance, or a radio-opaque mass depending on the type of CPAM. (Figure 6)6,7 In contrast, the patient in the vignette has a diffuse multicystic lesion with multilobar involvement. These findings appeared after one week of invasive positive pressure ventilation, while patients with a clinically significant CPAM typically present with abnormal findings on prenatal ultrasound and on chest radiograph within the first few days after birth.


Figure 6: Congenital pulmonary airway malformation (CPAM) of the left upper lobe. Chest radiographic finding of left upper lobe hyperlucency (arrow) correlated with a computed tomography scan finding of complex multicystic CPAM of the left upper lobe (arrow). Image from: McBride W. Congenital lesions of the lung. Neoreviews. 2016;17(5):e263–e270.6

Scimitar syndrome is a rare form of partial anomalous pulmonary venous return that involves a hypoplastic right lung (Option E) with displacement of the heart to the right side of the thoracic cavity and a prominent, curved vein draining blood from the right lung into the inferior vena cava.8 In some adults, this syndrome may be diagnosed incidentally. However, affected infants can present within the first few days to weeks after birth with tachypnea, congestive heart failure, and signs of severe pulmonary hypertension. Radiographic imaging of affected patients demonstrates a hypoplastic right lung or opacification of the right lung rather than cystic lesions, which is not consistent with the patient in the vignette (Figure 7). Echocardiography, CT angiography, and cardiac gated MRI can assist in diagnosing this syndrome.8


Figure 7: Radiograph reveals opacification of the right lung (red star) in Scimitar syndrome. Image from: Alaina Kipps, Henry Lee, Norman Silverman. Newborn who has respiratory distress. Neoreviews. 2005;6 (1):e49–e52.8

Extralobar bronchopulmonary sequestrations develop equally on both sides of the lung (Option A).  They arise from the formation of an extra bud during the pseudoglandular phase of lung development. These lesions are not connected to the tracheobronchial tree, and thus, air is not present within the lesions, and the blood supply comes directly from the systemic circulation. On chest radiographs, they appear as a well-defined homogenous mass.1,9

Did you know?
CPAM occurs in the pseudoglandular stage of lung development. To further review the various stages of lung development and associated lung lesions, refer to McBride W. Congenital Lesions of the Lung. Neoreviews. 2016;17(5):e263-e270.6

What are some of the fetal interventions used in the management of congenital lung malformations? For details on various prenatal interventions for congenital lung malformations please see: King A, Olutoye OO, II, Lee TC, Keswani SG. Surgical management of congenital lung malformations. Neoreviews. 2023;24(2):e84-e96.10

NeoQuest February 2025 Authors:
Ambika Bhatnagar, MD, Yale School of Medicine, New Haven, CT
Srirupa Hari Gopal, MBBS, FAAP, SSM Health Cardinal Glennon Pediatrics/St Louis University, St louis, MO

References:

  1. Diamond SE, Perez S, Dumpa V, Jayappa S, et al. Multicystic lobar lung lesion in a preterm neonate. Neoreviews. 2025;26(2):e115-e118
  2. Jalota Sahota R, Anjum F. Pulmonary interstitial emphysema. In: StatPearls. Treasure Island, FL: StatPearls Publishing. 2024 Jan
  3. Rocha G. Pulmonary pneumatoceles in neonates. Pediatr Pulmonol. 2020;55(10):2532-2541
  4. Joseph LJ, Bromiker R, Toker O, Schimmel MS, Goldberg S, Picard E. Unilateral lung intubation for pulmonary air leak syndrome in neonates: a case series and a review of the literature. Am J Perinatol. 2011;28(2):151-156
  5. Asif H, Mitchell M, Elmekkawi A, Kukreti V. Persistent work of breathing in a term neonate. Neoreviews. 2023;24(9):e599-e602
  6. McBride W. Congenital Lesions of the Lung. Neoreviews. 2016;17(5):e263-e270
  7. Leblanc C, Baron M, Desselas E, et al. Congenital pulmonary airway malformations: state-of-the-art review for pediatrician's use. Eur J Pediatr. 2017;176(12):1559-1571
  8. Kipps A, Lee H, Silverman N. Newborn who has respiratory distress. Neoreviews. 2005;6(1):e49-e52
  9. Ibrahim J, Sher I, Coren C, Amrita N. Case 1: Secondary structural cause of tachypnea following congenital diaphragmatic hernia repair in a term neonate. Neoreviews 2016;17(11):e667–e670
  10. King A, Olutoye OO, II, Lee TC, Keswani SG. Surgical management of congenital lung malformations. Neoreviews. 2023;24(2):e84-e96
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