Morphogenesis, Malformations, and Natural Course of CCAM

I. Steps in Morphogenesis of Respiratory System (3 Marks)

Lung development occurs in 5 overlapping stages.

1. Embryonic Stage (Weeks 4–7):
   • Lung bud (respiratory diverticulum) arises from the ventral foregut.
   • Tracheoesophageal septum separates trachea from esophagus.
   • Branching into lobar and segmental bronchi.
2. Pseudoglandular Stage (Weeks 5–17):
   • Conducting airways form up to terminal bronchioles.
   • Appearance resembles a gland.
   • Key: No gas exchange is possible; respiration is impossible if born now.
3. Canalicular Stage (Weeks 16–26):
   • Formation of respiratory bronchioles and alveolar ducts.
   • Vascularization: Capillaries invade the mesenchyme.
   • Viability: Survival becomes possible towards the end (24-26 weeks) as the blood-gas barrier forms.
4. Saccular Stage (Weeks 24–36):
   • Formation of Terminal Sacs (primitive alveoli).
   • Surfactant: Type II pneumocytes begin secretion (significant by 28-32 weeks).
5. Alveolar Stage (Week 36 – 8 Years):
   • Development of true alveoli.
   • Septation: Secondary septation increases surface area.
   • Note: 85-90% of alveoli form postnatally.

II. Enumeration of Congenital Lung Malformations (3 Marks)

These are often grouped as Congenital Thoracic Malformations (CTMs).

A. Bronchopulmonary Anomalies

1. Congenital Pulmonary Airway Malformation (CPAM/CCAM): Hamartomatous cystic lesions.
2. Congenital Lobar Emphysema (CLE): Overdistension of a lobe (usually LUL/RML).
3. Bronchogenic Cyst: Foregut duplication cyst.
4. Pulmonary Agenesis / Aplasia / Hypoplasia: Failure of development.
5. Bronchial Atresia: Proximal obliteration with distal mucous impaction.

B. Vascular/Combined Anomalies

1. Pulmonary Sequestration: Non-functioning lung tissue with anomalous systemic blood supply.
   • Intralobar: Within normal pleural cover.
   • Extralobar: Separate pleural cover.
2. Scimitar Syndrome: Hypoplastic right lung + Partial anomalous pulmonary venous drainage (to IVC).
3. Pulmonary AV Malformation.

III. Natural Course of Congenital Cystic Adenomatous Malformations (CCAM) (4 Marks)

The natural history varies significantly from fetal life to childhood.

1. Prenatal Course (Fetal Life)

• Growth Phase: Lesions typically grow rapidly between 20–25 weeks of gestation.
• Plateau/Regression: Growth usually plateaus after 26 weeks, and many lesions appear to shrink relative to the growing fetus.
• Complications:
  • Mediastinal Shift: Large lesions compress the heart and contralateral lung.
  • Hydrops Fetalis: Esophageal compression (polyhydramnios) and cardiac compression (venous obstruction) can lead to hydrops. CPAM Volume Ratio (CVR) > 1.6 predicts high risk of hydrops and fetal demise.
• Spontaneous Resolution: Some lesions become "isoechoic" or invisible on prenatal USG, but true histological disappearance is rare (persisting as small cysts/abnormalities on postnatal CT).

2. Postnatal Symptomatic Course

• Neonatal Respiratory Distress: ~25% of neonates present at birth with distress due to air trapping/mass effect (requires emergency surgery).
• Recurrent Infection: If untreated, the cyst acts as a reservoir for infection, leading to recurrent pneumonia or lung abscess in infancy/childhood.

3. Malignant Potential (The Critical Concern)

There is a small but definite risk of malignant transformation within the CPAM, typically in Type 1 (large cyst) or Type 4 lesions.

• Pleuropulmonary Blastoma (PPB): Strongly associated with Type 4 CPAM (often indistinguishable).
• Bronchioloalveolar Carcinoma (BAC): Late complication (adulthood) in Type 1 CPAM.
• Management implication: This risk drives the recommendation for elective resection of asymptomatic CPAMs.

4. Overall Prognosis

• Hydrops: Poor prognosis (survival <50% without intervention).
• Non-Hydrops: Excellent survival (>95%).
• Post-Resection: Excellent long-term lung function due to compensatory growth of remaining lung.