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O R I G I N A L A R T I C L E

Prospective study of antenatally diagnosed congenital cysticadenomatoid 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 findings 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 abor-

tion. All patients underwent postnatal radiological assess-

ment. Of the 24 cases, 5 children were symptomatic in the

immediate neonatal period and 19 were asymptomatic.

Anatomical surgical resection was undertaken in allsymptomatic cases. There was one death in this group due

to severe pre-existing pulmonary hypoplasia. Among the 19

asymptomatic cases, 5 children were managed conserva-

tively as the lesions were not significant and the remaining

14 (73%) underwent surgical resection. The mean age at

surgery was 11.1 months (range 3.334 months). Postnatal

pathology confirmed 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 investiga-

tions are required in all cases to confirm 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 ante-

natal ultrasound and improved technology [1, 2]. Congen-

ital cystic adenomatoid malformations (CCAM) is the most

common antenatally diagnosed lung lesion accounting for

the majority of congenital cystic lung lesions with bron-

chopulmonary 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

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

123

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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 rangefrom 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 withcomplications including pneumonia, hemoptysis, pneumo-

thorax, 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 sur-

gery and outcome.

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 anoma-

lies, 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 sur-

gery, length of stay, post-operative complications, out-

comes and the location and histological type of the

lesions). One child was excluded as the fetal MRI showed

diaphragmatic hernia. Lung lesions were defined 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 thoracocent-

eses. 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.

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

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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, horse-

shoe 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 sensi-

tivity of 100%.

Postnatal clinical course

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 five children had antenatal large lesions with medias-

tinal shift and postnatal respiratory distress was not

unexpected.

One child with a large CCAM, but without any medi-

astinal shift and considered stable, developed respiratory

distress as a result of air transport resulting in a pneumo-

thorax. 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 stabil-

ization 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 re-

do 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 pro-

cedure currently under evolution and we plan to incorporate

once more experience has been gained. The remaining five

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).

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

Fig. 2 Large CCAM after air transportnote the expanding cyst

Fig. 3 Patient after needle puncture and chest tube insertion

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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 antenatalultrasound screening and improvements in ultrasound

technology. Cystic lung lesions are the most commonly

identified pulmonary lesion on routine antenatal ultraso-

nography [18]. The differential diagnoses of antenatally

diagnosed congenital cystic lesions include CCAM, BPS,

brochogenic cysts and congenital lobar emphysema [19].

CCAM was first 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 hasranged 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 diag-

nosed with a greater accuracy, the diagnosis of underlying

pathology can be difficult. CCAM can be differentiated

from BPS if there is a definite feeding vessel arising from

the aorta as seen in one of our patients, which was con-

firmed 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 diag-

nosis of CCAM was not always accurate in spite of modernimaging technology. Increasing detection of hybrid lesions

has blurred the distinction between CCAM and BPS, sug-

gesting that these lesions arise from common embryolog-

ical bronchopulmonary disorder and that finding 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 to1243% 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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confirmed 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 confirm 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 hyperin-flation, left to right shunting or due to pulmonary hypo-

plasia as found in the only death in this series. One child

had an unusual complication of hyperinflation 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 nonop-

erative 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 demon-

strated 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 long-

term risks of infection, pneumothorax and, rarely, malig-

nancy. 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. Nonopera-

tive 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 sur-

gery due to varying complications with morbidity of

resection in those with complications being higher [15].

Nasr et al. [13] from Toronto recently reported 4% inci-

dence 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 dis-

tress due to air travel from this series stresses the impor-

tance of close monitoring of these cases. The concerns

related to operative morbidity and mortality of asymp-

tomatic 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 confirmed that antenatally diagnosed CCAMs

have an excellent prognosis except in children with a large

lesion and associated lung hypoplasia. Postnatal investi-gations are required in all cases to confirm 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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