Congenital cystic adenomatoid malformation

Synonym: congenital pulmonary airways malformations

What is a congenital cystic adenomatoid malformation?

Congenital cystic lesions of the lung present as a spectrum of anomalies, most commonly congenital cystic adenomatoid malformations (CCAMs), pulmonary sequestrations, congenital lobar emphysema and bronchogenic cysts.¹ These are now also called congenital pulmonary airways malformations (CPAMs).²

CCAM is a rare abnormality of lung development. There is an adenomatous overgrowth of the terminal bronchioles with a consequent reduction in alveolar growth. The cause of CCAM is not yet understood.

Large lesions may be associated with the development of hydrops fetalis in as many as 40% of cases. Hydrops fetalis is a poor prognostic sign.

The other main prenatal complication is impaired lung development causing pulmonary hypoplasia, which may lead to respiratory distress after birth.

Classification of congenital cystic adenomatoid malformation

CCAM has been described as a hamartoma (abnormal tissue with an excess of one or more tissue components). Stocker grossly classified CCAM into five subtypes based on where they arise in the bronchial tree:³

• Type 0: originates in the trachea or bronchi. Is incompatible with life.

• Type I: originates in the bronchi and is the most common type of CCAM (70% of CCAMs). It is associated with an excellent prognosis after resection.

• Type II: originates from the bronchiolar regions and is the second most common type. It consists of multiple small cysts. It has little malignant potential and has a good prognosis.

• Type III: this type also arises in the bronchioles but tends to be solid rather than cystic and to expand and fill the whole lobe. It is less common but also has a good prognosis.

• Type IV: originates from the acinar structures of the lung. It is very rare and has a strong association with pleuropulmonary blastoma.

Adzick also devised a simpler, group system of classification:⁴

• Microcystic lesions (cysts measuring <5 mm): usually associated with fetal hydrops and have a poor prognosis.

• Macrocystic lesions (ie cysts >5 mm): not usually associated with fetal hydrops and have a good prognosis.

How common are congenital cystic adenomatoid malformations? (Epidemiology)

No data are available regarding the frequency of this lesion but it is a rare condition. The estimated incidence is 1:11,000 to 1:35,000.⁵ There is a male preponderance.

Presentation^{3 5}

CCAM is a congenital condition, which is often identified prenatally by routine ultrasound screening.⁶ Polyhydramnios has been associated with CCAM. Prenatal regression and complete prenatal resolution may occur.⁴

Most postnatally identified cases present in the newborn period with respiratory distress, which may be due to pulmonary hypoplasia, mediastinal shift, spontaneous pneumothorax or air trapping within the cyst. Pleural effusions may also occur.

CCAM may occasionally remain undiagnosed until it is discovered later in life.⁷ Recurrent chest infections may be a feature later in life.

Presenting clinical features include:

• Respiratory distress: this is the presenting symptom in most newborns. It may range in severity from grunting, tachypnoea and a mild oxygen requirement to fulminant respiratory failure requiring aggressive ventilator support.

• Recurrent infection: children in whom the CCAM has not been resected are at risk of recurrent pulmonary infections due to bronchial compression, air trapping and inability to clear secretions.

• Haemoptysis occasionally occurs in an older child with CCAM.

• Dyspnoea and chest pain: dyspnoea may be a feature of pneumothorax.

• Other clinical features include cough and fever .

Signs of congenital cystic adenomatoid malformations

Physical signs seen in children with CCAM include:

• Tachypnoea: the most common sign encountered in the newborn period, reflecting respiratory distress.

• Pneumothorax/air trapping: signs may include tracheal deviation, shifted heart sounds and decreased air entry on the affected side.

• Cyanosis.

• Accessory muscle use.

• Grunting.

• Faltering growth.

Differential diagnoses⁵

• Congenital diaphragmatic hernia.

• Congenital pneumonia.

• Haemothorax.

• Pleural effusion.

• Pneumatocele.

• Pneumothorax.

Investigations²

Prenatal ultrasound

• There are no specific diagnostic features of CCAM.

• It may demonstrate evidence of hydrops - eg, ascites or pleural effusions.

• Type I lesions appear as multiple large cystic areas in the lung.

• Type II lesions appear as multiple small cysts.

• Type III lesions appear as a homogeneous mass because of the very small size of the cysts.

CXR

• This almost always identifies CCAM of sufficient size to cause clinical problems.

• The usual appearance is of a mass containing air-filled cysts. Other features may include mediastinal shift, pleural and pericardial effusions and pneumothoraces.

• The diagnosis may not be clear from CXR and CT or MRI scans are required.

CT scan

• Defines the extent of CCAM in all age groups.

• Air fluid levels may be evident.

• May outline additional co-existing lesions.

• High-resolution CT (HRCT) allows differentiation between microcystic and macrocystic lesions.

MRI

• Allows increased definition of a particular lesion.

• It may be useful particularly in distinguishing CCAM from a congenital diaphragmatic hernia.

• No maternal or fetal exposure to ionising radiation occurs (in contrast to the use of CT scanning).

Other imaging studies

• Renal and cerebral ultrasonography should be performed in all newborns with CCAM, to exclude co-existing renal and central nervous system anomalies.

• Echocardiography is required in all newborns with CCAM, to rule out any co-existing cardiac lesions. It may also provide evidence of persistent pulmonary hypertension.

Amniocentesis or sending samples of amniotic fluid obtained after birth may be indicated to obtain amniotic fluid for karyotyping. However, the incidence of chromosomal anomalies associated with CCAM is very low.

Management of congenital cystic adenomatoid malformation²

• There is no specific medical treatment for CCAM apart from maternal steroids and antibiotics for affected children with pneumonia.

• Supportive care, with oxygen supplementation or even mechanical ventilation may be required for children with respiratory distress.

• Although surgery has been the mainstay of treatment, spontaneous improvement and even resolution of CCAM occurs over months or years with many lesions. Therefore, a more conservative approach has been advocated for many minimally symptomatic or asymptomatic infants in the early months of life.⁴

• Activity is not limited but children with an unresected CCAM should avoid any activity which may cause a pneumothorax (eg, diving, unpressurised air travel).

Surgical

Any surgical intervention for CCAM may be required antenatally or delayed until after birth.

Fetal intervention

• Fetal surgery should be considered in patients with large CCAMs and in cases complicated by hydrops.⁸

• Thoracocentesis allows drainage of a large cyst with immediate decompression of the CCAM. However, fluid usually rapidly reaccumulates.

• A thoraco-amniotic shunt may be considered in order to maintain drainage of fluid from the CCAM to the amniotic space.⁹

• Resection of the affected lobe (lobectomy) may be considered when there is no dominant cyst available for draining.

Older patients: in one third of cases, the presence of pneumonia may indicate the need for more extensive pulmonary resection.

Complications⁵

• Fetal death caused by hydrops, fetal surgery, prematurity, or associated malformations.

• Premature delivery due to polyhydramnios.

• Respiratory distress due to hydrops, pulmonary hypoplasia, pulmonary hypertension, pneumothorax, or prematurity.

• Postnatal death due to respiratory distress, untreated hydrops, or pulmonary hypertension.

• Recurrent pneumonia.

• Pneumothorax.

• Haemothorax.

• Malignant change has been described.

Malignancy and CCAM⁴

• There is some disagreement about the risk of a malignancy occurring in children with CCAM and the risk may be very small. Two large reviews of childhood lung tumours have reported an association between CCAMs and tumours in 4% and 9% of cases of lung tumours.

• The associated malignancies include pleuropulmonary blastomas in infants and young children and bronchoalveolar carcinoma in older children and adults.

• There are some reports suggesting a link between CCAMs and rhabdomyosarcoma. Bronchiolar carcinoma has been reported in older children and adults with previously unrecognised CCAMs or following incomplete resection of a CCAM.

• The greatest risk of malignancy may be in those with bilateral CCAMs.

• Although surgical removal of all CCAMs continues to be recommended by some experts because of the possible increased risk of a malignancy, a more conservative approach has been recommended that includes regular follow-up with serial chest CT scans.

Prognosis⁵

CCAM is a rare fetal lung disease with an excellent prognosis in the absence of fetal hydrops. Resection of the CCAM generally leads to full recovery.

Risk factors for a poor outcome include hydrops fetalis, microcystic CCAM and a large lesion. Other possible factors associated with a poorer outcome include bilateral lesions and polyhydramnios.

CCAM associated with fetal hydrops carries a grave prognosis but survival rates of 70% can be achieved by thoraco-amniotic drainage in those with macrocystic lesions.¹⁰

The reported perinatal mortality of antenatally diagnosed CCAMs has varied greatly, ranging from 9% to as high as 49%.⁴