Pediatr Surg Int (2011) 27:11591164 DOI 10.

1007/s00383-011-2909-1

ORIGINAL ARTICLE

Prospective study of antenatally diagnosed congenital cystic adenomatoid malformations

P. Raychaudhuri A. Pasupati A. James B. Whitehead R. Kumar

Accepted: 6 April 2011 / Published online: 26 April 2011 Springer-Verlag 2011

Abstract Purpose Congenital cystic adenomatoid malformations (CCAMs) are increasingly diagnosed in recent years due to the routine usage of antenatal ultrasound. The aim of this study was to present the natural course and outcome of antenatally diagnosed cystic lung diseases, which were prospectively studied. Methods Between the period June 2004 and June 2010, 25 fetuses with suspected CCAMs were seen in a single tertiary maternal fetal unit. One child was excluded as the fetal MRI suggested congenital diaphragmatic hernia. Data were prospectively entered into a database including antenatal and postnatal ndings which were then analyzed. Results Mean gestational age at the time of diagnosis was 20.8 weeks (range 1729). Fetal interventions included amnioreduction (n = 2) and fetal thoracocentesis (n = 3) in one child. The mean gestational age at delivery was 38.5 weeks (range 31.640.6). None of the mothers underwent termination of pregnancy or spontaneous abortion. All patients underwent postnatal radiological assessment. Of the 24 cases, 5 children were symptomatic in the
P. Raychaudhuri A. Pasupati R. Kumar (&) Department of Paediatric Surgery, John Hunter Childrens Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia e-mail: Rajendra.Kumar@hnehealth.nsw.gov.au A. James Department of Cardio Thoracic Surgery, John Hunter Childrens Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia B. Whitehead Department of Paediatric Respiratory Medicine, John Hunter Childrens Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia

immediate neonatal period and 19 were asymptomatic. Anatomical surgical resection was undertaken in all symptomatic cases. There was one death in this group due to severe pre-existing pulmonary hypoplasia. Among the 19 asymptomatic cases, 5 children were managed conservatively as the lesions were not signicant and the remaining 14 (73%) underwent surgical resection. The mean age at surgery was 11.1 months (range 3.334 months). Postnatal pathology conrmed CCAM in all operated cases, except one who had pulmonary sequestration. Conclusion Antenatally diagnosed CCAMs have an excellent prognosis except in children with a large lesion and associated with lung hypoplasia. Postnatal investigations are required in all cases to conrm the diagnosis. Symptomatic CCAMs require immediate surgery in the neonatal period with a good outcome. Asymptomatic CCAMs can be safely operated between 9 and 12 months of age. Keywords Antenatal diagnosis Congenital cystic adenomatoid malformations

Introduction Antenatal diagnosis of lung lesions in children have increased in recent years with the widespread use of antenatal ultrasound and improved technology [1, 2]. Congenital cystic adenomatoid malformations (CCAM) is the most common antenatally diagnosed lung lesion accounting for the majority of congenital cystic lung lesions with bronchopulmonary sequestration (BPS) and hybrid lesions accounting for most of the remaining cases [3]. Other rare conditions include bronchogenic cysts and congenital lobar emphysema. Since CCAMs and BPS cannot be reliably

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distinguished antenatally without evidence of a feeding artery from the aorta to the lung lesion and pathologically has mixture of elements, some authors prefer the term congenital pulmonary airway malformations (CPAMs) to describe these lesions [4, 5]. It is possible that both CCAM and BPS are two entities in a single brochopulmonary developmental defect spectrum [6]. The incidence of CCAM has been estimated to range from 1 in 25,000 to 1 in 35,000 pregnancies, although some reports suggest a prevalence of 9 per 1,00,000 births [7]. The antenatal course of CCAM ranges from fetal hydrops and polyhydramnios to spontaneous regression in utero [8, 9]. Postnatally, the presentation varies from severe respiratory distress to complete lack of symptoms [10, 11]. Although surgical resection of symptomatic cases is a widely accepted practice, there is divergence of opinion regarding management of asymptomatic lesions. While some clinicians favor routine surgical resection, expectant management has been advocated by others [12]. However, CCAM may not remain asymptomatic throughout life with complications including pneumonia, hemoptysis, pneumothorax, hemothorax and rarely malignancies potentially developing [7, 13, 14]. The optimal timing of surgery and optimal operative procedure remains controversial in asymptomatic children with CCAM [15]. In this study, we aimed to prospectively analyze the natural course and outcome of antenatally diagnosed cystic lung diseases over a 6-year period, in terms of incidence, clinical course, postnatal imaging, optimal timing of surgery and outcome.

Fig. 1 Antenatal MRI shows a large CCAM with mediastinal shift

Methods A cohort of 25 children were antenatally diagnosed with CCAM in our maternal fetal medicine unit between the periods January 2004 and July 2010. All the cases were seen antenatally by a single pediatric surgeon together with neonatologist and fetal maternal specialists and images reviewed. Selective fetal magnetic resonance imaging (MRI) was performed in equivocal cases (Fig. 1). All patients were prospectively entered into a database and the data analyzed retrospectively. Prospectively entered data included the following antenatal and postnatal features antenatal information (gender, gestational age at the time of diagnosis, ultrasound(US) features at the initial and subsequent follow-up US, changes in the size of CCAM during pregnancy, fetal interventions, termination of pregnancy or spontaneous abortion); postnatal information (gestational age at delivery, neonatal symptoms at delivery including respiratory distress at birth), associated anomalies, postnatal course including the need for respiratory

support, radiological imaging (chest X ray (CXR), US, computed tomography (CT) and MRI) and management (symptoms at follow-up clinic appointments, type of management undertaken, age at surgery, the type of surgery, length of stay, post-operative complications, outcomes and the location and histological type of the lesions). One child was excluded as the fetal MRI showed diaphragmatic hernia. Lung lesions were dened as asymptomatic in those neonates stable for discharge before subsequent elective surgical resection usually at 912 months of age. Ethical permission was not required for this study.

Results Antenatal Of the 24 fetuses, 12 were male and 12 female. Mean gestational age at the time of diagnosis was 20.8 weeks (range 1729 weeks). Lesions were found in the left lung in 10 cases and the right lung in 14 cases. There was one case of fetal intervention in a child with a macrocystic lesion with mediastinal shift and polyhydramnios. This required two amnioreductions and three fetal thoracocenteses. Follow-up scans revealed mediastinal shift in 13 patients and polyhydramnios in three. There were no cases with fetal hydrops. In utero regression was noted in two cases. One of them was treated conservatively and the other was one of twins being followed by CT scan.

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Postnatal The mean gestational age at delivery was 38.5(range 31.640.6 weeks). There were no cases of spontaneous abortion or termination of pregnancy. The mode of delivery was determined by obstetric factors. Associated anomalies were found in only one child with hydrocephalus, horseshoe kidney and vertebral anomaly. Postnatal imaging All children had postnatal CXR, which demonstrated 70% sensitivity. Immediate postnatal chest US was performed in 13 consecutive cases in the later part of the series, which revealed 75% sensitivity in detecting these lesions. All children underwent either CT scan or MRI with a sensitivity of 100%. Postnatal clinical course
Fig. 2 Large CCAM after air transportnote the expanding cyst

Respiratory distress was noted in 11 of the 24 cases (46%), most of which settled with minimal treatment. However, severe respiratory distress requiring immediate surgical intervention was noted in 5 (20%) of the 24 cases. Four of the ve children had antenatal large lesions with mediastinal shift and postnatal respiratory distress was not unexpected. One child with a large CCAM, but without any mediastinal shift and considered stable, developed respiratory distress as a result of air transport resulting in a pneumothorax. Urgent transthoracic needle puncture of the CCAM was required in this child as well as one of the other children with respiratory distress as a temporizing measure. This enabled surgery to be performed within 24 h after stabilization of the neonates (Figs. 2, 3). Anatomical surgical resection was undertaken in all of these cases. Residual CCAM was noted in two of these cases requiring further redo surgery. In this symptomatic group, there was one death due to severe pre-existing pulmonary hypoplasia. Nineteen children were asymptomatic at birth. Surgical resection was performed in 14 of these children (73%). Thoracotomy with anatomical lobar resection was performed in all these cases. Thoracoscopic resection was not considered as it is a procedure currently under evolution and we plan to incorporate once more experience has been gained. The remaining ve children (27%) were managed conservatively and at long term follow up, two lesions have vanished, two lesions were less than 1 cm and not considered for surgery and one child has been lost for follow-up. The mean age at surgery was 8.3 months (range 0.0134 months). All children had an excellent recovery with no post-operative complications. The mean length of stay in hospital was 7.2 days (range 130 days).

Fig. 3 Patient after needle puncture and chest tube insertion

Histopathology revealed isolated CCAM in 16 cases (macrocystic n = 8, microcystic n = 8) and hybrid lesions (CCAM with BPS) in two cases and isolated BPS in the remaining one.

Discussion Antenatal diagnosis of lung lesions in children has increased in the last decade with rapid advances in imaging technology and increasing use of fetal sonography. The

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reported incidence of CCAM is 1 in 25,000 to 1 in 35,000 pregnancies [7]. The incidence seems to be increasing in recent years with a reported incidence of 1 in 10,000 from Western Australia [16] and 1 in 16,000 from Hong Kong [17]. The incidence in our series supports this view with 4.2 per 10,000 births, which is larger than all previously documented series. Possible reasons for this include increased incidence of the disease, increased antenatal ultrasound screening and improvements in ultrasound technology. Cystic lung lesions are the most commonly identied pulmonary lesion on routine antenatal ultrasonography [18]. The differential diagnoses of antenatally diagnosed congenital cystic lesions include CCAM, BPS, brochogenic cysts and congenital lobar emphysema [19]. CCAM was rst described by Chin and Tang in 1949 [20] and accounts for 95% of all cystic lung lesions [21]. CCAMs are congenital lung malformations characterized by an overgrowth of terminal respiratory bronchioles resulting in the formation of cysts of variable sizes within the lung. The reported accuracy of antenatal diagnosis has ranged from 65 to 91% [1, 3]. Results from our prospective study show an antenatal diagnostic accuracy of 96%. One child in this series, who was excluded from this study, was wrongly diagnosed with CCAM on antenatal scans, and subsequently found to be a congenital diaphragmatic hernia on a fetal MRI. Although CCAMs can be currently diagnosed with a greater accuracy, the diagnosis of underlying pathology can be difcult. CCAM can be differentiated from BPS if there is a denite feeding vessel arising from the aorta as seen in one of our patients, which was conrmed by histopathology. The mixture of CCAM with BPS, the so called Hybrid lesions, have been reported in

up to 25% of antenatally diagnosed cases and seen in two of the patients in this series [22]. Antenatal diagnosis of hybrid lesions is currently not possible. Roggin et al. found discrepancy between clinical and histopathologic diagnoses in 67% of their patients [23]. Kuroda et al. [24] found that histologic diagnosis matched with clinical diagnosis in less than half of their cases and concluded that prenatal diagnosis of CCAM was not always accurate in spite of modern imaging technology. Increasing detection of hybrid lesions has blurred the distinction between CCAM and BPS, suggesting that these lesions arise from common embryological bronchopulmonary disorder and that nding one of these lesions does not exclude the simultaneous presence of the other [15, 24, 25]. Once a diagnosis of CCAM is suspected, the child needs to be referred to a tertiary fetomaternal unit where further imaging can be performed accurately and counseling can be delivered. Serial imaging is necessary to look for hydrops and other complications. Hydrops was not seen in any children in this study, although reported in up to 1243% in some series from tertiary referral centers with a poor prognosis [7, 8]. The role of prenatal intervention seems to be minimal, as we had only one child in this series requiring thoracocentesis whereas some of the tertiary centers report high rates of antenatal interventions. Although some of the CCAMs seem to disappear in the later parts of the pregnancy, postnatal imaging is necessary in all patients as we have demonstrated persistent CCAM in 92% of cases in this series. Spontaneous resolution occurred in two cases in this series. Both cases had a small suspected CCAM antenatally, which was not seen in postnatal scans. Documentation of true resolution has to be

Fig. 4 CXR and US of large CCAM with mediastinal shift

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conrmed by either postnatal CT or MRI, as only 70% of the lesions in this series were visible in postnatal CXR. We could not demonstrate the disappearance of any large macrocystic CCAMs. We conrm the view of Chow et al. [17] that in utero resolution of CCAM on antenatal US does not represent genuine resolution. In contrast to the in utero resolution of CCAMs, very little information is available on postnatal spontaneous resolution of CCAMs. Sauvat et al. [2] have reported this phenomenon in 4 out of 29 children (14%) with CCAM and Butterworth et al. [9] in 4% of their cases. Disappearing CCAMs, especially of the macrocytic type, should be viewed with caution. Postnatally, as seen in 80% of our cases, the majority of CCAMs are asymptomatic. Although variable degrees of postnatal respiratory distress was seen in 46% in this study, severe respiratory distress requiring urgent surgery was present in only 20% of our cases. Symptoms at birth were reported in around 2544% in other reports [2628]. Respiratory distress can be related to the effects of a large lung mass (Fig. 3) causing mediastinal shift with hyperination, left to right shunting or due to pulmonary hypoplasia as found in the only death in this series. One child had an unusual complication of hyperination of CCAM caused due to sudden cyst expansion (Fig. 4) during air transport and needed urgent transthoracic puncture and intercostal drain insertion. Although transthoracic puncture of the expanding cysts in CCAM has been reported by others [29], to the best of our knowledge, needle puncture under these unusual circumstances has not been previously reported in literature and must be kept in mind if nonoperative treatment of CCAM is considered in this modern era of frequent air travel and air transport of patients. Analysis of imaging techniques in this study demonstrated that CXR had a sensitivity of 70%, while US had a sensitivity of 75%. CT and MRI were found to be very reliable with a sensitivity of 100% for both diagnostic modalities. From the results, it is recommended that CXR followed by CT or MRI should be performed at 46 months. CT can be performed in the neonatal period with minimal sedation, whereas MRI requires general anesthesia. Recently, concern has been raised about the increased risk of cancer resulting from CT scans in infant and children [30]. The optimal postnatal imaging is still not clear. In this study, all symptomatic patients with CCAM received operative management. Elective surgery was recommended in asymptomatic cases because of the longterm risks of infection, pneumothorax and, rarely, malignancy. If asymptomatic, surgery at 9 months has been shown to be widely successful with a short length of stay and no post-operative complications recorded. Nonoperative management of asymptomatic lesions has to be viewed with caution. Wong et al. found that 81% of asymptomatic

CCAMs developed symptoms on follow-up requiring surgery due to varying complications with morbidity of resection in those with complications being higher [15]. Nasr et al. [13] from Toronto recently reported 4% incidence of pleuropulmonary blastoma in asymptomatic lung lesions. MacSweeney et al. [31] report histologic overlap of type 4 CCAM with grade 1 pleuropulmonary blastomas and occasional carcinomatous change in type 1 CCAM. Rhabdomyosarcomas have also been found to originate from CCAM [32]. The rare occurrence of respiratory distress due to air travel from this series stresses the importance of close monitoring of these cases. The concerns related to operative morbidity and mortality of asymptomatic cases is unfounded, as timed surgery in this series and others have found that the procedure is tolerated well by children with minimal morbidity [33, 34]. Thus, results from this prospective study over a 5-year period has conrmed that antenatally diagnosed CCAMs have an excellent prognosis except in children with a large lesion and associated lung hypoplasia. Postnatal investigations are required in all cases to conrm the diagnosis. Symptomatic CCAMs require immediate surgery in the neonatal period with a good outcome. Asymptomatic CCAMs can be safely operated between 9 and 12 months of age. Increasing evidence of complication of CCAMs including rapid expansion of CCAM during air travels supports the role of surgery in asymptomatic CCAMs. Further, lung resection in infancy allows compensatory lung growth. Psychological stress to the family during prolonged observation and radiation risk due to repeated follow-up CT scan of the chest can be minimized. We acknowledge the limitation of this study as this shares an experience from a single institution and results may be affected by the referral pattern, local population and absence of hydrops in our population. The referral pattern seen in our institution is a general referral pattern unlike those reported by Aldzick et al. [35] who have a special interest in CCAMS and foetal interventions.

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