• Congenital Cystic Adenomatoid Malformation

    Congenital Cystic Adenomatoid Malformation / CCAM (recently termed Congenital Pulmonary Airway Malformation / CPAM) is a rare pulmonary maldevelopment that is usually restricted to one lobe of the lung.

    Grossly, CCAM represents a multicystic mass of pulmonary tissue with proliferation of bronchial structures.

    These lesions may result from a failure of maturation of bronchiolar structures or focal pulmonary dysplasia arising in the fifth or sixth week of gestation.

    Histologic studies reveal rapid vascular and epithelial growth within the tumor.

    Recent findings of accelerated cellular proliferation and decreased apoptosis within resected CCAM specimens further suggest a benign neoplastic development.

    CCAM is a rare anomaly that occurs slightly more often in the male population than in the female population.

    These lesions are almost always unilateral (85 percent to 95 percent), but occasionally they arise bilaterally (2 percent).

    Associated anomalies include:

    It has been suggested that approximately 6 percent of prenatally diagnosed CCAMs "resolve." This may be due to CCAMs becoming isoechogenic with adjacent normal lung, rendering them sonographically invisible.

    In these cases fetal MRI demonstrates the presence of the CCAM even when ultrasound cannot.

    Stocker and coworkers proposed a histologic classification of CCAMs as types I through III, according to cyst size and relative number. A single cyst or a small number of large cysts between 3 and 10 cm is classified as a type I CCAM, which typifies 50 percent of postnatal cases.

    Multiple small cysts make up a type II lesion, occurring in approximately 40 percent of postnatal cases. Type III lesions are composed of relatively homogeneous microcystic tissue.

    Since 2004, the Cincinnati Fetal Center has evaluated more than 168 patients for fetal CPAM / CCAM.

  • The prenatal diagnosis of CCAM can be difficult and relies on a number of sonographic features. Usually, a mass is identified in the fetal chest. This mass may be solid, cystic or both, usually without evidence of systemic arterial blood flow by color Doppler ultrasonography.

    If present, cysts may be solitary or multiple. With large CCAMs, mediastinal shift may occur away from the lesion, and polyhydramnios owing to esophageal compression may be present.

    In the worst cases, evidence of cardiac compression and fetal hydrops may be found. Fetal hydrops is universally associated with ensuing fetal demise and relates to cardiac or caval compression from tumor expansion within the thoracic cavity.

    The differential diagnosis includes:

    Large microcystic CCAMs are highly echogenic and, thus, are distinguished easily from neuroblastoma. The absence of peristalsis helps distinguish CCAM from herniated bowel in a CDH.

    Using color and power Doppler imaging, the demonstration of a systemic blood supply emanating from the descending thoracic or abdominal aorta suggests the diagnosis of BPS or hybrid CCAM lesion.

    A systemic arterial feeding vessel to an echogenic lung mass was previously considered pathognomonic of BPS; however, Cass and associates have reported a series of "hybrid lesions," which histologically appear to be CCAMs but have a systemic arterial supply. The natural history of hybrid lesions appears to be more favorable than CCAM but less favorable than BPS.

    Sonographic criteria taken from studies correlating the Stocker classification, or microcystic versus macrocytic appearance, with fetal outcome have been unreliable in predicting the development of fetal hydrops.

    A more consistent correlation may exist between overall volume of the lesion at presentation and the likelihood of development of fetal hydrops. Timothy Crombleholme, MD, FACS, FAAP, et al, demonstrated in a small retrospective study that the development of hydrops correlated with the volume of the CCAM at the time of presentation.

    In order to follow patients and correct for fetal growth, the CAM volume was divided by the head circumference to yield the CAM volume ratio (CVR). Based on retrospective data, a CVR of 1.6 was determined from the mean of the CVR of the group of fetuses that did not develop hydrops plus 2 standard deviations of the mean in order to identify 95% of patients who would be at low risk for the development of hydrops.

    Fetuses with a CVR less than 1.6 at presentation were defined as being at low risk for hydrops and those fetuses with a CVR > 1.6 at presentation were defined as being at high risk for the development of hydrops.

    A prospective study was conducted with 55 patients using CVRs which confirmed that CVR <1.6 identified a group of fetuses at very low risk for the development of hydrops. Only one patient in this group developed hydrops and required fetal intervention. The exceptions to this rule were the CCAMs that had a dominant cyst comprising more than 1/3 the volume of the CCAM.

    These cysts can enlarge rapidly and have a prenatal natural history distinct from the solid tumor which grow more slowly. Serial measurements of CAM volumes and CVRs show that the growth of CCAMS is exponential between 20 and 25 weeks gestation after which the CCAM growth reaches a plateau.

    The mean gestational age at which this growth plateau is reached is 25 weeks gestation, but can range from 23 to 30 weeks. After the plateau is reached there is a slow decrease in the size of the CCAM. Subjectively this may appear to be a greater decease in the appearance of the CCAM as the fetus continues to grow around the CCAM.

    No fetus that we have followed by serial CVRs had developed hydrops once they have reached the growth plateau. This is an important milestone as the fetus is usually assured of a favorable outcome once the growth plateau is reached.

    The indication for treating a fetus with a CCAM is the development of non-immune hydrops. The form of treatment depends upon the type of CCAM. Those CCAMs with a dominant cyst may respond to cyst aspiration and if it recurs, to thoracoamniotic shunting.

    In contrast to the approach to type I CCAMs with a dominant cyst, solid type III CCAMs require open fetal surgery for resection of the CCAM.

    The survival of the fetus undergoing fetal surgery for CCAM resection is clearly influenced by fetal hemodynamic status. Many of the fetuses referred for fetal surgery for CCAMs are in advanced hydrops and are almost moribund at the time of surgery.

    A significant improvement in the outcome of fetal surgery has been achieved by the combination of close serial observation allowing fetal surgery in the earliest stages of hydrops and by the use of intraoperative echocardiography.

    The intraoperative management of these patients has changed to include obtaining intravenous access in all patients for the administration of crystalloid or blood products to address volume status and inotropic agents to improve contractility.

    The need for either of these interventions is assessed by echocardiography to determine the adequacy of ventricular filling, the contractility of the heart and the competence of the atrioventricular valves during the procedure.

    In a recent retrospective study comparing the survival following fetal surgery for fetuses with conditions associated with hydrops managed before or after routine intraoperative echocardiographic monitoring found an increase from 42% before to 78% afterward.

    In some instances in which fetal surgery may not be an option, the use of maternal steroids had been reported to arrest the growth of fetal CCAMs. Although the mechanism is unknown, it is thought that steroids may induce the plateau in CCAM growth to occur earlier in gestation.

    The fact that CCAMs do plateau in growth makes it difficult without prospective data to be certain that the steroids induced the growth plateau verses the plateau would have occurred anyway.

    Fetal surgery for CCAM is performed with maternal laparotomy with exposure of the uterus and ultrasound to determine the orientation of the fetus and the placenta to plan the hysterotomy in the upper uterine segment overlying the fetal chest. The hysterotomy is made and the fetal arm and chest are exposed, leaving the head and remainder of the body within the amniotic sac. A fetal thoracotomy exposes the lobe containing the CCAM. The mass is exteriorized, and any systemic feeding vessels and the pulmonary vein draining the CCAM are ligated.

    An attempt is made to preserve normal adjacent lobe or lobes is preserved and dissected from the CCAM using electrocautery. The lobar hilum is divided using a surgical stapler. The thoracotomy is then closed. The fetus is returned to the amniotic cavity and the hysterotomy closed. Ultrasound examinations should be performed to confirm the resolution of placentomegaly and fetal hydrops, which usually takes 1 to 2 weeks.

    In addition, ultrasonography is helpful in assessing chorioamniotic separation or low amniotic fluid volume. Similarly, daily fetal echocardiography in the early postoperative period is needed to detect the presence of constriction of the ductus arteriosus and tricuspid regurgitation while the patient is on postoperative indomethacin therapy.

    Later, weekly ultrasound studies should be performed to confirm compensatory fetal lung growth. Cesarean section is planned just before term or earlier for uncontrolled premature labor. In survivors of fetal surgery for CCAM the outcome has been excellent, with minimal or no need for postnatal ventilatory support.

    The cause of Congenital Cystic Adenomatoid Malformation (CCAM / CPAM) is unknown.

    One theory holds that it is the result of bronchial structures failing to mature properly at approximately the fifth or sixth week of gestation, about the time the lungs begin to form.

    Another theory holds that CCAM / CPAM is due to an abnormal growth pattern of lung tissue due to bronchial obstruction.

    There is no known genetic cause for CCAM / CPAM, and no cases of recurrence in a sibling or offspring have been reported.

    Several classification systems have been used to describe the sonographic appearance of these malformations. Among the most commonly used is an adaptation of Stocker’s histologic classification.

    Type I

    Approximately 50 percent of postnatal Congenital Cystic Adenomatoid Malformation cases. The lesions consist of single or multiple cysts that are usually large in size (approximately three to 10 cm in diameter) and few in number (one to four).

    Prognosis: In general, typically favorable, but dominant cysts (cysts comprising 1/3 of the volume) can grow rapidly and unpredictably.

    Type II

    Approximately 40 percent of postnatal cases. These lesions have cysts that are smaller in size (less than one cm in diameter) and larger in number.

    Prognosis: In general, a higher frequency of associated congenital anomalies.

    Type III

    Only 10 percent of postnatal cases. The lesions are composed of very small cysts and appear solid sonographically. These malformations can grow exponentially, between 20 and 26 weeks gestation. The large size can cause mediastinal shift (a change in the space in the chest between the lungs).

    The large masses compress the lungs and depress the diaphragm, impairing the flow of blood to the heart. This can cause pulmonary hypoplasia (arrested or underdeveloped lungs) and hydrops (in utero heart failure).

    Prognosis: In general, poor when associated with hydrops and when associated with pulmonary hypoplasia leading to respiratory problems in the newborn.

    The long-term outcome of infants with CCAM / CPAM following resection is excellent. However, if the mass is not fully removed, the child can be at risk for complications, such as air trapped in the residual CCAM / CPAM, which causes gradual enlargement over time, infection and other problems.

    Once the mass is removed, the remaining lung tissue will undergo compensatory lung growth to make up for the lung tissue lost to resection. These children live life without any apparent limitations on their activities and with no increased risk of respiratory infections.

    Children who survived open fetal surgery for CCAM / CPAM associated with hydrops are still doing well from one to eight years after their procedure.

    The number of procedures performed at the Cincinnati Fetal Center:

    Fetal Therapy for CCAM / CPAM Volume*
    Open fetal surgery 7
    EXIT-to-resection 7
    Thoracoamniotic shunt 29

    *Feb. 1, 2004, through Sept. 30, 2013