Dept. of Obstetrics and Gynecology, Clinical Center Novi Sad, Yugoslavia

Definition: Congenital cystic adenomatoid malformation (CCAM) is a pulmonary developmental anomaly arising from an overgrowth of the terminal respiratory bronchioles. The condition may be bilateral involving all lung tissue, but in the vast majority of cases it is confined to a single lung or lobe^[1]. The lesions are either macrocystic or microcystic. Congenital cystic adenomatoid malformation has been classified into three subgroups according to the size of the cysts^[2]

Classification and types of the disease^1,2,[3]:

Type I congenital cystic adenomatoid malformation

• single/multiple large cysts, 2- 7 cm in diameter

• smaller cysts can also be found

• alveolus-like structures, much larger than normal alveoli can be seen adjacent to or communicating with the larger cysts

Type II congenital cystic adenomatoid malformation

• smaller cysts, usually less than 1 cm

Type III congenital cystic adenomatoid malformation

• firm, bulky masses of lung tissue

• usually consisting of small cysts

The other classification is based on the size of the cysts^[4],^[5]:

a.       microcystic (cysts less than 5 mm in diameter)

b.      mixed

c.       macrocystic (cysts equal to or greater than 5 mm in diameter)

Embryology: The lower respiratory system begins its development approximately 26 days after conception. The development of the lungs can be divided into³:

During the alveolar period (late fetal period to 8 years of life), the lining of the terminal sacs attenuates to an extremely thin layer of squamous epithelium. Characteristic mature alveoli do not form for some time after birth³.

Pathogenesis: The disease almost always affects one lung - bilateral involvement is extremely rare. Furthermore, in the affected lung usually only one lobe is involved. If there is a bronchus leading to the affected lobe, it ends blindly¹.

Histological findings of congenital cystic adenomatoid malformation are^[6]:

1.      columnar and cuboidal epithelium lining the cysts

2.      elastic fibers and smooth muscle are found in the walls of larger cysts

3.      no cartilage surrounding the cysts

4.      presence of tall columnar epithelium resembling gastric mucosa

The essential problem in congenital cystic adenomatoid malformation is excessive overgrowth of the bronchioles, especially the terminal bronchioles, which causes the marked enlargement of the lobe, while the development of the alveoli is completely suppressed except at the periphery⁶.

There are two standpoints as on when the problem occurs – an older one, according to which it develops early in the pregnancy, the period ranging from early in embryogenesis to some 40 days after concepcion², and a newer one, that states that it probably occurs later in gestation (16 to 20 weeks)^[7]. The latter theory is based on the assumption that the presence of normal alveoli at the periphery of the lesion, with abnormal growth in the center of the lesion, implies the failure of canalization of terminal bronchioles and consequent inability to connect the conducting and respiratory elements⁷.

Inheritance: Sporadic⁵.

Teratogens: None⁵.

Prenatal diagnosis: The ultrasound diagnosis is based on the finding of a solid or cystic, non-pulsatile intrathoracic tumour⁵.

• Microcystic disease results in a striking hyperechogenicity of the affected lung tissue, which is thought to represent fluid accumulation in small cystic spaces.

• Macrocystic disease is characterized by the presence of single or multiple translucent cystic spaces within the thorax.

Common associated findings are polyhydramnios (65%), hydrops (common in microcystic form) and placentomegaly (in case of hydrops)⁵. Unilateral lesions are often associated with deviation of the mediastinum in the contralateral side. In bilateral disease, the heart may be severely compressed, and this is usually associated with ascites from venocaval obstruction or cardiac compression^[8].

In about 85% of cases CAM is unilateral and approximately half are microcystic and the other half macrocystic. During the third trimester in about 30% of cases there is polyhydramnios which is likely to be due to decreased fetal swallowing, the consequence of esophageal compression by the mass or decreased absorption of lung fluid by the hypoplastic, malformed lungs or there may be increased fetal lung fluid production by the abnormal tissue. It is speculated that the polyhydramnios often found in congenital cystic adenomatoid malformation is secondary to fluid production by the type 2 pneumocytes lining the cysts^2,7,[9],[10].

Differential diagnosis⁵:

• intralobar pulmonary sequestration

• bronchogenic cyst

• mediastinal lesions: enterogenous cyst, neurenteric cyst, or cystic teratoma

• diaphragmatic hernia

The use of duplex Doppler imaging has been described to establish the diagnosis of pulmonary sequestration and to distinguish between extralobar sequestration and intralobar sequestration^[11]. As extralobar and intralobar lung sequestration may mimic congenital cystic adenomatoid malformation in ultrasound appearance, it is important to search for an anomalous blood supply when attempting to make the diagnosis – typical of extralobar sequestration is arterial flow from the peritoneal cavity into the mass and venous flow in the opposite direction¹¹.

Associated anomalies: The condition is usually isolated. Unlike diaphragmatic hernia there is no association with chromosomal defects.

In about 10% of cases there are additional malformations^2,6 :

• Renal abnormalities (bilateral renal agenesis)

• abdominal wall abnormalities

• central nervous system defects (hydrocephalus)

• spinal deformities (cervical spine/thoracic spine)

• gastrointestinal defects (diaphragmatic hernia, jejunal atresia, tracheoesophageal fistula)

• cardiac anomalies and anomalies of the great vessels (ventricular septal defect, tetralogy of Fallot, truncus arteriosus)

• sirenomelia (including agenesis of ureters, bladder, urethra, uterus, cervix, vagina, gallbladder, descending colon, sigmoid colon and rectum, and imperforate anus)

There is no association with chromosomal abnormalities⁵.

CAM III has been reported in association with grossly elevated amniotic fluid alpha feto-protein^[12].

It is possible that cysts in CAM produce pulmonary fluid and that their communication with otherwise normal bronchial tree may mitigate the usual findings in bilateral renal agenesis (facial and limb positional defects), an often associated anomaly in the cases of CAM^[13].

Prognosis: