Congenital pulmonary airway malformations
Key points
A range of pulmonary malformations during the foetal development and maturation of the lungs
Some are incompatible with life and result in spontaneous abortion
Some develop into intra uterine lung malformations which may still endanger intra uterine foetal life but usually progress to delivery. Some may cause post-natal complications.
Three major types of CPAM are identified:
1. Congenital Cystic Adenomatoid Malformations (CCAM)
2. Intra and Extra Lobar sequestrations
3. Congenital Lobar Emphysema (CLE)/Congenital Bronchial Atresia or Obstruction
CCAM: Likely arrest in Lung maturation
Sequestration: Likely a vascular event
CLE: Likely bronchomalacia
Incidence/Prevalence
Occurs in approximately 1 in 2,000 to 12,000 live births
Embryology
A ventral diverticulum arises from the foregut which bifurcates dichotomously to form the foetal lungs
It goes through stages of:
Embryonic
Pseudo glandular
Canicular
Saccular
Alveolar
Internal lining also differentiates from tall columnar cells to cuboidal to flat single layer of cells lining he alveoli
Many genetic and growth factors and chemicals interact for the lungs to development and mature.
One important factor is Platelet Derived Growth Factor B (PDGF-B) which normally peaks at 20-week gestation and then declines
Pathophysiology
Part of the lung arrests in the Canicular or Pseudo glandular phase while the rest of the lung progresses normally with maturation towards Saccular and Alveolar stages.
That part is termed CCAM. It is connected to the rest of the airway. Although it fails to mature further, it continues to grow with the rest of the lung, sometime even faster.
The growth of CCAM occurs antenally and postnatally
In foetuses with CCAM, the normal decline of PDGF B levels beyond 20 weeks does not occur and the levels persists
Can be seen in PDGF B stains of resected foetal CCAM lungs
CPAM
Cystic Congenital Cystic Adenomatoid Malformation (CCAM) is now referred to as Congenital Pulmonary Airway Malformation (CPAM)
CPAMs can be cystic (macroscopic) or adenomatoid (microscopic) in appearance
Macrocystic CPAMs have cysts larger than 5mm and can grow rapidly, often affecting the lower lobes
Microcystic or solid CPAMs generally grow slowly and predictably
Bronchopulmonary Sequestration (BPS)
80% of BPS cases are intralobar, 20% are extralobar
Most commonly found in the lower lobes, particularly the left lower lobe
Typically receives blood supply from the thoracic aorta (75% of cases), but other sources include the abdominal aorta (extralobar) and intercostal arteries
Hybrid lesions, such as CPAM with systemic blood supply, can occur
Congenital Lobar Emphysema (CLE)
Not common, characterised by large, inflated lobes
Fluid-filled antenatally, air-filled postnatally
Most cases require surgery around 1 year of age, unless the lesion is small and asymptomatic
Segmental emphysema can occur, often due to bronchial atresia, and may develop into mucocoele
The left upper lobe is most frequently affected, followed by the right middle lobe
Antenatal Features and Counselling
Adzick classification (antenatal)
(A) Macrocystic Group (75%):
Lesion characterised by single or multiple cysts with a size of 5 mm or larger
(B) Microcystic Group (25%:
Predominantly solid lesion with cysts smaller than 5 mm in size
Some are mixed macro and microcystic
Pressure effects:
Oesophagus: Polyhydramnios
Lungs: Hypoplasia
Mediastinum and IVC: Non-immune Hydrops
CCAM volume ratio in utero: Volume of CCAM X 0.52/ Head circumference
CPAM Volume Ratio (CVR) is calculated using ultrasound measurements; a CVR less than 1.6 indicates a low risk of hydrops (2%), while a CVR greater than 1.6 indicates a high risk (80%) - near 100% mortality.
10% of CCAMS become less obvious with pregnancy progression
10% Grow rapidly causing non-immune hydrops
80% Progress with normal deliver to term
If hydrops is present and the gestation is viable, delivery is indicated; if not, intervention may include steroids or procedures like thoraco-amniotic shunt for large cysts (70% survival) or open thoracotomy (50% mortality)
Laser ablation of the arterial supply in sequestrations is possible but lacks strong evidence
Antenatal assessment should include evaluation for hydrops, mediastinal shift, and lesion size, with polyhydramnios indicating oesophageal compression
90% of cases can go to term, and lesions generally do not regress
Associations
Approximately 6% of cases are associated with other anomalies
CPAM Type 4 is similar to Pleuropulmonary Blastoma (PPB) Type 1 and can develop even after lesion excision
CPAM Type 2 is associated with renal agenesis, cardiovascular defects, diaphragmatic hernia, skeletal defects, and oesophageal atresia/tracheoesophageal fistula (OA/TOF)
History and Examination
Can be asymptomatic
Symptomatic: Respiratory distress at birth
Respiratory insufficiency
Recurrent chest infections (more severe and more recalcitrant to therapy)
Reports of Malignant change
CPAMs are diagnosed in 30% of cases in later childhood, typically Types 1, 2, or 4, often smaller lesions
Extralobar BPS presents in the neonatal period with respiratory distress and infection, while intralobar BPS presents in childhood or early adulthood with recurrent pneumonia
Histology
CCAMs appear as hamartomas with pseudostratified epithelium
CPAMs are distinguished microscopically by polypoid mucosal projections, increased smooth muscle and elastic tissue, absence of cartilage, presence of mucus-secreting cells, and lack of inflammation
Mnemonic: CPAM
C Cartilage absence
P Polypoid projections of mucosa
A Absence of inflammation
M smooth Muscle increase
Modified Stocker classification (postnatal histological classification):
Type 0: Small, firm lungs with poor prognosis (2%) - Almost Incompatible with life
Type 1: Large cysts (>2cm) with pseudostratified epithelium (60-70%) Broncho alveolar carcinoma association
Type 2: Smaller cysts (<2cm) with solid tissue (BPS), originating in bronchiolar regions, poor prognosis (10-15%) No malignant potential
Type 3: Solid lesions with poor prognosis (5%) No malignant potential
Type 4: Large, multiloculated cysts lined by flat epithelium, originating in acinar structures, very rare (15%) - Pleuropulmonary blastoma association
Sequestrations are typically microcystic
Radiology
Chest X-ray in the first week of life, followed by a CT scan at 3-8 months of age
CLE appears radio-opaque and hyperechoic antenatally and immediately postnatally due to decreased fluid clearance
Operation
Symptomatic Lesions - Resection
Controversy exists surrounding whether CPAMs should be resected or observed for complications - see the Seminars in Pediatric Surgery articles in the references
Conservative Management -
Advantages: Avoids anaesthetic and Surgical risks and complications
Disadvantages: Prolonged follow up, infections making subsequent resection more difficult, malignant change, parental anxiety
Elective Surgery -
Usually performed between 1 and 2 years of age after CT scan of the chest.
Performed thoracoscopically: Lesionectomy or Segmentectomy or Lobectomy
Lobectomy is preferred over segmentectomy due to lower complication rates, but segmentectomy may be necessary for multiple lesions or respiratory compromise
Minimal complications, excellent outcome and compensatory lung growth
Lobectomy involves controlling the pulmonary vein first
CPAMs can involve multiple lobes
In general - Complicated CPAMs, all sequestration and all CLE should be resected
Sequestrations should be resected due to the risk of infection and 'steal syndrome' from their systemic vascular supply
CLE should be resected due to its propensity to expand and cause respiratory compromise, unless the lesion is very small
Complications
Risk of developing Pleuropulmonary Blastoma (PPB)
Other potential malignancies include myxosarcoma, embryonal rhabdomyosarcoma, and bronchioalveolar carcinoma
Outcome and Follow-Up
Follow-up for thoracotomies includes 10-year checks for chest wall deformities
Segmentectomies require follow-up CT scans to monitor for residual or recurrent disease
Standard scenario
Antenatal/postnatal lung lesion
Differentials:
1. CPAM (CCAM)
2. Sequestration
3. Congenital lobar emphysema (CLE)
4. CDH (if only shown CXR)
5. Pleuropulmonary blastoma
If antenatal presentation:
MRI to define lesion - feeding vessel, Adzick classification
Look for hydrops, mediastinal shift, size
Polyhydramnios if compressing oesophagus
90% can go to term
Deliver in tertiary unit
Calculate CPAM volume ratio
Antenatal management:
Foetal medicine MDT
Routine scans, antenatal counselling and progression to normal delivery.
For those developing hydrops:
Beyond 32 weeks: Premature delivery
Less than 32 weeks:
Macrocystic Lesions - Aspiration or Pleuro-peritoneal shunt
Microcystic Lesions - Steroids, Growth Factor Inhibitors
Foetal Surgery to remove the lesion - in utero open thoracotomy - 50% mortality so reserved for cases not responding to steroids
Sequestrations can have laser ablation of artery - but minimal evidence so far
If postnatal:
Ensure stable and resuscitated by NICU team
History:
Ask about above antenatal features
Examination:
Respiratory distress, oedema
Investigation:
Classify lesion (Stocker post resection if CPAM - more solid lesions have worse prognosis)
CXR
Echo/USS for feeding vessel
CT urgently if unstable
Management:
If neonatal respiratory distress - thoracotomy + lobectomy
If asymptomatic lesion:
CT at 8 months
Plan open or VATS resection depending on type of lesion
Justification for resection vs observation
1. Risk of infection - will be more difficult surgery if allowed to get infected
2. Removes need for lengthy follow up period
3. Risk of steal syndrome if sequestration
4. Risk of rupture/expansion if CLE
5. Unknown but possible risk of malignancy - CPAM type 4 is similar to Pleuropulmonary blastoma but can still develop after lesion is excised
Page edited by Prof. Ashok Daya Ram MBBS, FRCS, FRCPS, FEBPS, FRCS (Paed Surgery), Consultant Paediatric and Neonatal Surgeon, Norfolk and Norwich University Hospital, Norwich, UK. March 2025
Page edited by Mrs Charnjit Seehra BSc March 2025
References
Holcomb and Ashcraft’s Pediatric Surgery, 7th edition, 2020, Chapter 22 Congenital Bronchopulmonary malformations
Kunisaki, Shaun M, et al. "Congenital Pulmonary Airway Malformations." Pediatric Surgery NaT, American Pediatric Surgical Association, 2021. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829070/all/Congenital_Pulmonary_Airway_Malformations.
https://www.perinatology.com/calculators/CVR.htm
Singh R, Davenport M. The argument for operative approach to asymptomatic lung lesions. Semin Pediatr Surg. 2015 Aug;24(4):187-95. doi: 10.1053/j.sempedsurg.2015.02.003. Epub 2015 Feb 27. PMID: 26051052.
Stanton M. The argument for a non-operative approach to asymptomatic lung lesions. Semin Pediatr Surg. 2015 Aug;24(4):183-6. doi: 10.1053/j.sempedsurg.2015.01.014. Epub 2015 Feb 3. PMID: 26051051.