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Congenital lung malformations

Nature Reviews Disease Primers volume 9, Article number: 60 (2023) Cite this article

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Abstract

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.

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Fig. 1: Types of CLM.
Fig. 2: Histology of CPAM type 1 with mucinous cell clusters.
Fig. 3: Prenatal CLM diagnosis and management.
Fig. 4: Asymptomatic patient with CPAM becoming symptomatic.
Fig. 5: Algorithm of postnatal diagnosis and surgical management in asymptomatic and symptomatic CLM.

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Authors and Affiliations

  1. Paediatric Surgery, “F. Del Ponte” Hospital, ASST Settelaghi, Varese, Italy

    Federica Pederiva

  2. Department of Paediatric Surgery, Rocky Mountain Hospital for Children, Denver, CO, USA

    Steven S. Rothenberg

  3. University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton, UK

    Nigel Hall

  4. Department of Paediatric Surgery and Intensive Care, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

    Hanneke Ijsselstijn

  5. Department of Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong, China

    Kenneth K. Y. Wong

  6. Department of Pathology and Clinical Bioinformatics, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

    Jan von der Thüsen

  7. Departments of Radiology and Nuclear Medicine and Respiratory Medicine and Allergology, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

    Pierluigi Ciet

  8. Department of Radiology, University of Cagliari, Cagliari, Italy

    Pierluigi Ciet

  9. Department of Obstetrics and Gynecology, Fetal Medicine Unit, The Chaim Sheba Medical Center Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Reuven Achiron

  10. Laboratory of Medical Genetics, Institute for Maternal and Child Health — IRCCS “Burlo Garofolo”, Trieste, Italy

    Adamo Pio d’Adamo

  11. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

    Adamo Pio d’Adamo

  12. Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

    J. Marco Schnater

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Contributions

Introduction (F.P.); Epidemiology (F.P. and J.M.S.); Mechanism/pathophysiology (K.K.Y.W., A.P.D. and F.P.); Diagnosis, screening and prevention (R.A., P.C., F.P. and J.v.d.T.); Management (N.H., J.M.S., S.S.R. and F.P.); Quality of life (H.I.); Outlook (F.P.). All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Federica Pederiva.

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Nature Reviews Disease Primers thanks M. Davenport, A. W. Flake, S. Kunisaki, G. B. Mychaliska and N. Usui for their contribution to the peer review of this work.

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Glossary

Acinar dysplasia

A rare malformation characterized by growth arrest of the lower respiratory tract and complete absence of gas-exchanging units, resulting in critical respiratory insufficiency at birth.

Acinar-like tissue

A tissue composed of polarized epithelial cells rich in rough endoplasmic reticulum and characterized by an abundance of secretory zymogen granules.

Channels of Lambert

Microscopic collateral airways between the distal bronchiolar tree and adjacent alveoli.

Congenital anomalies

Structural or functional anomalies occurring during intrauterine life and affecting an estimated 6% of global live births (WHO definition).

Congenital diaphragmatic hernia

A defect in the diaphragm causing the herniation of abdominal contents into the thoracic cavity, resulting in lung hypoplasia and altered pulmonary vascular development.

Epithelial–mesenchymal interaction

A series of programmed, sequential and reciprocal communications between the epithelium and the mesenchyme, with its heterotypic cell population, that result in the differentiation of one or both cell populations.

EXIT-to-resection

In the EXIT-to-resection procedure, a hysterotomy is performed to exteriorize the fetal head and torso enabling orotracheal intubation and placement of peripheral IV; the lung malformation can be resected while the fetus is still on placental support34.

Foregut duplication cysts

Benign developmental anomalies that contain foregut derivatives.

Hydrops

Abnormal interstitial fluid collection in two or more compartments of the fetal body.

Lung compliance

A measure of the expansion of the lung.

Mediastinal shift

The deviation of mediastinal structures towards one side of the chest cavity.

Oesophageal duplication

Separate masses along or in continuity with the native oesophagus.

Polyhydramnios

A condition that occurs when too much amniotic fluid builds up during pregnancy.

Pores of Kohn

Small communications between adjacent pulmonary alveoli that provide a collateral pathway for aeration.

Thoraco-amniotic shunt

A shunt that drains fluid from the lung into the amniotic sac to treat pleural effusion, for example, in congenital pulmonary airway malformations.

Tidal volumes

The amount of air that moves in or out of the lungs with each respiratory cycle.

Tricuspid annular plane systole excursion

A scoring system used with non-invasive Doppler echocardiography to determine right ventricular function.

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Pederiva, F., Rothenberg, S.S., Hall, N. et al. Congenital lung malformations. Nat Rev Dis Primers 9, 60 (2023). https://doi.org/10.1038/s41572-023-00470-1

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