Prenatal diagnosis and management of congenital cystic adenomatoid malformation of the lung Gregory J. Duncombe, FRANZCOG, DDU,a,b,c Jan E. Dickinson, FRANZCOG, DDU, CMFM,a,b,c and Colin S. Kikiros, FRACSa,d Perth, Australia OBJECTIVE: Our purpose was to review the management and outcome of pregnancies with a prenatal diagnosis of fetal congenital cystic adenomatoid malformation of the lung (CCAM). STUDY DESIGN: A retrospective review was performed of all cases since 1995 with a prenatal diagnosis of fetal CCAM from the sole tertiary perinatal referral center in Western Australia. RESULTS: Twenty-one pregnancies with CCAM were identified. The gestational age at diagnosis was <22 weeks in 86% of cases. Macrocysts were seen in 76% of cases during ultrasound examination. Seventeen pregnancies continued until term. Regression of the sonographic appearances was observed in 19% of cases. Fetal hydrops complicated two cases. One neonate died within 24 hours of delivery because of pulmonary hypoplasia. Twelve children have required pulmonary lobectomies. No adverse sequelae are evident in surviving children. CONCLUSION: Most cases of prenatally diagnosed CCAM have had a good outcome. This review has positively influenced the counseling of women with this diagnosis. (Am J Obstet Gynecol 2002;187:950-4.) Key words: Congenital cystic adenomatoid malformation, prenatal diagnosis Congenital cystic adenomatoid malformation of the lung (CCAM) is an uncommon fetal anomaly with fewer than 1000 cases reported in the medical literature. The reported incidence of CCAM is approximately 1 in 25,000 pregnancies.1 This abnormality is believed to be the result of hamartomatous change in the tertiary bronchioles or an arrest in their embryologic development between 7 and 15 weeks’ gestation.1-6 CCAM is observed as a cystic mass occupying part or all of one fetal hemithorax, with up to 15% of cases having bilateral involvement. The cysts within the mass may be macrocystic (single or multiple cysts with diameters ≥5 mm) or microcystic (echodense homogeneous lung).7 The vascular supply for a CCAM arises from pulmonary vessels. Some communication may occur between the mass and surrounding normal lung tissue. The ultrasound differential diagnoses are related to the appearances of the cysts, the location of the lesion, the vas- From the King Edward Memorial Hospital for Women,a the Women and Infants Research Foundation,b the Department of Obstetrics and Gynaecology, University of Western Australia,c and the Department of Pediatric Surgery, Princess Margaret Hospital.d Presented at the Twenty-second Annual Meeting of the Society for Maternal-Fetal Medicine, New Orleans, La, January 14-19, 2002. Reprint requests: Greg Duncombe, FRANZCOG, DDU, Department of Obstetrics and Gynaecology, University of Western Ontario, Lawson Health Research Institute, 268 Grosvenor St, London, Ontario N6A 4V2, Canada. E-mail: gduncomb@uwo.ca © 2002, Mosby, Inc. All rights reserved. 0002-9378/2002 $35.00 + 0 6/6/127460 doi:10.1067/mob.2002.127460 950 cular supply as assessed by color Doppler analysis, and the lesion’s effects on dependent tissues and structures. These differential diagnoses include pulmonary sequestration, bronchogenic cyst, diaphragmatic hernia, mediastinal cystic teratoma, and congenital pulmonary emphysema.2,6-8 In 1949, Chin and Tang9 first reported a case of CCAM. The current descriptions are based on studies from Stocker et al10 and Adzick et al.11 The Stocker classification is founded on the histologic appearances of cyst size and the mixture of sizes within the specimen, whereas the Adzick classification is based on sonographic appearances and cyst dimensions. This review of the outcome of cases with a prenatal diagnosis of CCAM was stimulated by an apparent increase in the incidence of this diagnosis within our institution. The objectives of this study were to assess the accuracy of the prenatal diagnosis of CCAM of the lung and the potential prognostic features and to review perinatal outcomes in relation to the current management practices at our institution. Material and methods Twenty-one pregnancies with a prenatal diagnosis of CCAM were identified between 1995 and 2001 at the Fetal Medicine Service of King Edward Memorial Hospital for Women with follow-up at the Princess Margaret Hospital for Children in Perth, Australia. These two institutions are the sole tertiary referral centers for perinatal medicine and pediatric surgery within the state of Western Australia. Duncombe, Dickinson, Kikiros 951 Volume 187, Number 4 Am J Obstet Gynecol A Fig 2. Transverse ultrasound image of a 19-week fetus with a leftsided CCAM. The mass volume was >50% of the fetal thorax, and the fetal heart was compressed and deviated to the right. Other mass effects included tenting of the diaphragm and the production of gross ascites. B Fig 1. Examples of the ultrasound examination images of the different types of CCAM of the lung. A, Microcystic type. B, Mixed macrocystic and microcystic type. Table I. Obstetric and neonatal characteristics Maternal age (y) Parity Gestational age at diagnosis (wk) Period in utero after diagnosis (wk)* Gestational age at delivery (wk)* Birth weight (g)* Apgar score, 5 min 30.5 (28-33) 1 (0-2) 20 (19-22) 18 (6-20) 39 (36-40) 3150 (2805-3510) 9 (9-10) All data are displayed as median (interquartile range). *In cases that didn’t undergo therapeutic termination. Twelve cases had preliminary examinations at other centers before referral to our unit for evaluation and management. Data before 1999 was ascertained and assessed retrospectively through the Fetal Medicine Service database. On referral each fetus was evaluated sonographically, and a CCAM classification was provided on the basis of the ultrasound features evident. All ultrasound examinations were performed with an ATL 3000 or ATL 5000 machine (ATL, Philips Medical Systems, Bothell, Wash) equipped with multihertz 5 to 2, 7 to 4 curvilinear transducers and a 7 to 4 vector transducer. Amniocentesis for fetal karyotype was not performed routinely. In all but one case, antenatal, neonatal, and pediatric care was performed within our tertiary institution. Complete data ascertainment was achieved. Specific information collected included maternal age, parity, gestational age at diagnosis, gestational age at delivery, and indication for delivery. Ultrasound examination details included referral base, gestational age, biometry, appearance of lesion (side, laterality, size, type [Adzick criteria])(Fig 1), cardiac axis deviation, polyhydramnios, appearance of hydrops, color Doppler analysis, and presence or absence of lesion regression. Pediatric characteristics included birth weight, sex, Apgar scores, postnatal imaging results, time and type of surgery, surgical pathologic results, and general health. In all cases involving termination of pregnancy or neonatal death, pathologic examination results were available. Results This series involved 21 pregnancies with a prenatal diagnosis of CCAM made or confirmed by our department occurring over a 6-year period, 15 of which occurred in the last 3 years, consistent with our clinical impression of a sporadic change in the frequency of prenatal diagnosis. The median maternal age at diagnosis was 30.5 years (Table I). Most diagnoses were made before 22 weeks’ gestation and the fetal thoracic lesion was principally observed during the conduct of the second-trimester fetal morphologic examination. Referrals at later gestational ages were generated by smaller obstetric units and prompted by abnormal pregnancy symptoms and signs such as polyhydramnios. By use of the Adzick descriptive classification, the majority of fetal CCAM lesions contained macrocysts (Table II). This descriptive diagnosis was usually made on the 952 Duncombe, Dickinson, Kikiros October 2002 Am J Obstet Gynecol Table II. Prenatal features of the CCAM lesions (n = 20) Microcystic only Macrocysts present Right-sided lesion laterality Cardiac deviation Mass volume >50% of fetal thoracic volume Incidence of spontaneous regression Hydrops 5 (24%) 16 (76%) 13 (62%) 11 (52%) 5 (24%) 4 (19%) 2 (9%) Data displayed as number (%). Table III. Outcome of pregnancies and postnatal care Live births Termination of pregnancy Neonatal deaths Surgery (n = 16)* Observation only Pulmonary resection Presurgery 17 (81%) 4 (19%) 1 (5%) 2 (12.5%) 12 (75%) 2 (12.5%) Data displayed as number (%). *Median (interquartile range) age at time of surgery was 265 days (12,280). first ultrasound examination (primary or tertiary referral), although in a few cases a second examination was necessary. No case had a bilateral thoracic mass, although one large lesion initially gave that impression. The mass filled half or more of the thorax in 29% of cases. Cardiac axis deviation was observed in 52% of cases, virtually always at the time of initial diagnosis. In two cases hydrops was present at the time of diagnosis. In the first case, the initial presentation was at 19 weeks’ gestation and the parents selected termination of pregnancy after counseling (Figs 2 and 3). The second case complicated by hydrops was a late referral at 30 weeks’ gestation, the ultrasound examination prompted by severe polyhydramnios. Two therapeutic amnioreductions, each of 2-L volume, were performed on consecutive days. After these procedures the fetal hydrops completely resolved and the pregnancy progressed until term. Four women elected therapeutic termination of pregnancy. In one case cyst aspiration was performed, but rapid reaccumulation of fluid within the major cyst occurred and the pregnancy was interrupted. The second case exhibited extensive microcystic change with the impression of bilateral thoracic involvement. The third case involved earlyonset hydrops, as previously described. The fourth case chose termination after diagnosis and counseling. Seventeen women continued their pregnancies after the diagnosis of fetal CCAM. Our prenatal management strategy was based on serial sonographic assessment of the fetus, with a median of four examinations until delivery. In four cases there was ultrasound evidence of partial or complete resolution of the thoracic mass before delivery. All unterminated pregnancies reached term or near term. Delivery timing was related to the individual obstet- Fig 3. Fixed gross pathologic specimen of the CCAM, as shown in Fig 2, demonstrating the macrocystic and microcystic changes. This mass measured 5.9 ⫻ 3.8 ⫻ 2.9 cm. Both fetal lungs were severely hypoplastic for this gestational age. ric indications. Each fetus was born in good condition (Table I). In all cases postnatal imaging techniques concurred with the prenatal diagnosis. In two cases the neonatal condition deteriorated within hours of delivery. Severe neonatal respiratory distress necessitating surgery on day 2 occurred in the case in which amnioreduction was required antenatally. This child has subsequently done well. Another neonate had respiratory distress and cardiac failure and died on day 1 after delivery. Autopsy revealed a CCAM within a pulmonary sequestration; this diagnosis was suspected antenatally because of the presence of a large feeding vessel from the descending thoracic aorta. Pregnancy outcomes are described in Table III. Twelve children have had elective pulmonary resections (because of a small risk of malignant change12,13 or infection within the mass). The timing of surgery has been primarily related to the pediatric surgical opinion of the time. Initially performed in the first 2 weeks of life, in the last 2 years a more conservative management strategy has been developed with surgery delayed for months or not performed at all. In all but one case with a pathology specimen available for assessment, our diagnoses were correct. Four cases are currently under observation, with the oldest child being 7 years old (complete regression on prenatal and postnatal imaging examinations). At the time of writing, no long-term adverse sequelae were evident in the surviving children. Comment The prenatal diagnosis of CCAM is uncommon. With use of data obtained from the Western Australian Birth Defects Registry, the incidence of CCAM in the state of Western Australia during the period of our review was around 1.2 per 10,000 births (a total of 28 cases with this diagnosis, 2-6 per year). There were seven cases not in Duncombe, Dickinson, Kikiros 953 Volume 187, Number 4 Am J Obstet Gynecol our series with a notification made to the state registry. Two cases had terminations for multiple congenital anomalies with a CCAM lesion found on autopsy. One live birth at our institution (not examined in our department) and four other live births in other parts of the state had the diagnosis made after delivery. Before the advent of prenatal ultrasound imaging, the diagnosis of CCAM had been made at autopsy or during investigation of respiratory disease in childhood. The earliest recorded ultrasound imaging diagnosis of CCAM was made in 1975.14 As with many types of congenital anomalies, improvements in ultrasound technology have led to an increase in the number of cases of CCAM diagnosed prenatally. In addition, the diagnoses are occurring at earlier gestational ages. The majority of cases within our cohort were detected at the 18- to 20-week fetal morphologic examination. Reported prenatal prognostic features for CCAM include the size and type of the mass, laterality, progression or regression of the mass, cardiac axis deviation, presentation with or development of hydrops, and the finding of other anomalies.1,6,12,15 The larger the thoracic mass, the worse the prognosis tends to be. The microcystic type tends to have a more adverse prognosis. Lesions that regress behave in a more benign fashion.1,16 Interestingly, these reported characteristics seemed to have had a lesser impact on the final outcomes within our cohort. This may be due to the small number of cases in our series and the option of termination taken in four cases. The finding of other structural anomalies is considered an indication for a karyotyping procedure. No fetuses in this series had other structural anomalies detected on ultrasound examination, and amniocentesis was not required in any case. No child was born with other structural anomalies. The development of fetal hydrops, as in most fetal disease states, is a poor prognostic feature.1,7,11,15,17,18 Fetal hydrops is thought to be the result of a mass effect by the volume of the CCAM on fetal swallowing or of cardiac compromise produced by compression of the heart or major blood vessels. In this series there were two cases of fetal hydrops with two opposing outcomes, as previously described. Gestational age appeared the primary factor dictating management. We observed several cases of partial or complete regression of the pulmonary lesion during serial sonographic review. Resolution of CCAM is supported in the literature.1,4,15,16,19 One difficulty with these cases was a lack of confirmation of diagnosis as a result of there being no pathologic specimen for analysis. In cases where partial resolution has occurred antenatally, no further resolution was evident in the neonatal period.4 Similar to other recent publications, unless fetal hydrops persisted, most pregnancies continued to term. In three pregnancies, the volume of the lesion as a proportion of the chest volume appeared to stabilize or decrease. In these cases, the changes resulting from mass effect such as cardiac axis deviation tended to revert to be within normal limitations. This is suggestive of a plateau or peaking of the mass’s growth velocity and a catch up in growth of surrounding structures. Current neonatal and pediatric management at our institution involves stabilization and observation within the neonatal nursery. In the presence of respiratory distress, a computed tomographic examination is performed and surgery is undertaken immediately. If otherwise well, the computed tomographic examination is performed with the patient under general anaesthesia at 4 to 6 months of age, and surgery is arranged when the patient is between 6 and 12 months old. In some circumstances, typically in an asymptomatic infant, surgery may be even further delayed to optimize surgical access (for example, in lesions near the hilum). The longest delay from delivery to surgery in our cohort has been just under 4 years. The surgery usually consists of thoracotomy and lobectomy. If the mass is more extensive, further limited partial resection is performed to avoid chest wall deformation. Currently, on regular pediatric review no long-term adverse sequelae are evident in our survivors. Summary Fetal CCAM is a rare anomaly. An accurate diagnosis may be made at 18 to 20 weeks’ gestation. Partial or complete regression was demonstrated on serial ultrasound examinations in 19% of cases in our series. In the majority of cases in our series, delivery occurred at term and the outcome was satisfactory. Current pediatric surgical practice suggests surgical excision of the lesion within the first year of life. We thank Karen Reid, Fetal Medicine Co-coordinator at King Edward Memorial Hospital, Dr Adrian Charles, Perinatal Pathologist for King Edward and Princess Margaret Hospitals, and Dr Caroline Bower, Director of the Western Australian Birth Defects Registry, for their assistance in ascertainment of case details. REFERENCES 1. Laberge JM, Flageole H, Pugash D, Khalife S, Blair S, Filiatraut D, et al. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther 2001;16:178-86. 2. Sakala EP, Perrott WS, Grube GL. Sonographic characteristics of antenatally diagnosed extralobar pulmonary sequestration and congenital cystic adenomatoid malformation. Obstet Gynecol Surv 1994;49:647-55. 3. 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