Management of asymptomatic neonatal cystic adenomatoid malformations

Management of Asymptomatic Neonatal Cystic Adenomatoid Malformations By Fr~d6rique Sauvat, Jean-Luc Michel, Alexandra Benachi, Sophie Emond, and Yann Revillon Paris, France

Background~Purpose: Although much is known about the prenatal course of cystic a d e n o m a t o i d m a l f o r m a t i o n s (CCAM), the postnatal course of a s y m p t o m a t i c lesion is less well documented. The authors studied the pre- and postnatal course and treatment of a s y m p t o m a t i c CCAM. Methods: The authors reviewed the files of all patients referred to Necker-Enfants Malades hospital with an antenatal diagnosis of CCAM and a s y m p t o m a t i c at birth. Results: Files of 29 patients were studied. The first x-ray film was considered normal in 12 cases (41.3%). Computed tom o g r a p h y was normal in 4 cases and s h o w e d cystic lung m a l f o r m a t i o n s in the other patients. Postnatally, clinical manifestations occurred in 3 patients (10.3%). CCAM vanished in 6 cases. Surgical resection of CCAM was performed in 17 cases (58.6%). All the patients currently are a s y m p t o m atic.

rITH THE INCREASING use of fetal sonography (US), a large number of cystic lung lesions, especially congenital cystic adenomatoid malformations (CCAM), are identified antenatally. Antenatally, the severity of CCAM ranges from life-threatening hydrops fetalis to complete regression in utero. The prognosis has been linked to the size of the tumor, the extent of involvement, the existence of a mediastinal shift, and, above all, the presence of hydrops fetalis. 1 Contrary to the antenatal course of CCAM, little is known of the postnatal outcome of asymptomatic patients. The treatment of patients whose malformation is only diagnosed by antenatal sonography has not been addressed in detail. We report the antenatal findings, postnatal outcome, and treatment of an asymptomatic population with CCAM, defined by patients entirely free of clinical signs, in particular, respiratory, at birth.

W

From the Departments of Pediatric Surgery, Obstetrics, and Pediatric Radiology, Hospital Necker-Enfants Malades, Paris Cedex, France. Address reprint requests to Y. Revillon, Department de Chirurgie Pddiatrique, H@ital Necker-Enfants Malades, 149 rue de Sdvres, 75015 Paris, France. Copyright 2003, Elsevier Science (USA). All rights reserved. 0022 -3468/03/3804-0005530. 00/0 doi: 10.1053/jpsu.2003.50119

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Conclusions: CCAM can shrink or vanish during pregnancy and antenatal ultrasound findings are not predictive of the postnatal course. Thus, all infants with prenatal diagnosis of CCAM require postnatal evaluation. Normal radiographic findings at birth do not rule out CCAM persistence on CT. The treatment of a s y m p t o m a t i c CCAM is controversial. Surgery m a y be advocated because of the l o w m o r b i d i t y and the prevention of late complications, above all, cancer. The surgical indications of small (<3 cm) and a s y m p t o m a t i c lesions should be discussed on a case-by-case basis with the parents. J Pediatr Surg 38:548-552. Copyright 2003, Elsevier Science (USA). All rights reserved.

INDEX WORDS: Cystic a d e n o m a t o i d m a l f o r m a t i o n , prenatal diagnosis, neonates.

MATERIALS AND METHODS From January 1990 to January 2000, we reviewed the files of all patients referred to the Pediatric Surgery Unit of Necker-Enfants Malades hospital in Paris for CCAM diagnosed either antenatally or during the first years of life. This analysis focuses only on patients with an antenatal diagnosis who were entirely free of clinical manifestations at birth. Diagnosis of CCAM was performed during one of the 3 obligatory antenatal US. After diagnosis, the fetuses were monitored by serial sonography to determine the morphologic aspect, size, and type of CCAM (macrocystic or microcystic, according to Stocker's classification), together with the presence of hydrops, a mediastinal shift, polyhydramnios, and other anomalies. The first postnatal assessment included a thorough physical examination (weight, respiratory function, and other potential clinical signs). In our experience, standard postnatal workup was an x-ray at birth or during the first days of life and always before hospital exist. All patients also underwent a CT examination during the first days of life, when clinical symptoms existed. If patients were totally free of symptoms, as in our series, it was proposed to delay CT up to 45 days of life. Because of the lack of difference between these 2 dates, the exit of maternity is earlier. Surgery was never an emergency in asymptomatic patients. Postnatal follow-up included clinical signs, radiologic changes, treatment (surgery or monitoring), and long-term outcome.

RESULTS During the last 10 years, 75 patients were referred to our institution with CCAM, that had been diagnosed antenatally in 53 cases (70.6%). Of these latter cases, 29 (54.7%) were fully asymptomatic at birth and are the focus of this report. Only 29.4% of patients referred to

Journal of Pediatric Surgery, Vol 38, No 4 (April), 2003: pp 548-552

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Table 1. Prenatal Differences Between Symptomatic and Asymptomatic Population at Birth and Surgical Course Prenatal Diagnosis Age at diagnosis* Hydramnios Hydrops fetalis Mediastinal shift Amniotic punction Postnatal surgery

Asymptomatic Patients (n 29)

Symptomatic Patients (n 20)

23.2 2 (7%) 0 8 (27.5%) 2 (7%) 17 (58.6%)

9 3 13 10 19

23 (45%)l(15%)1(65%)1(50%)1(95%)1-

*Mean gestational age at diagnosis in weeks. l-Significantly different with P value less than .05, with statistical analysis of t test.

our institution with postnatal diagnosis of CCAM had normal antenatal US scan.

Antenatal Course Gestational age at diagnosis ranged from 18 to 38 weeks (mean, 23.2 _+ 3.73). Macrocystic (type I) CCAM was diagnosed in 26% of cases, microcystic (type II) CCAM in 31%, and a solid US scan aspect (type III CCAM) in 13%. Two fetuses had polyhydramnios, but none had hydrops or associated malformations. A mediastinal shift was present in 8 fetuses, 7 of which underwent surgical resection. Amniotic puncture was required for hydramnios in 2 cases. Table 1 compares the antenatal course in the overall population according to whether the neonates were symptomatic or asymptomatic. The size of the masses ranged from 17 × 13 mm to 40 × 30mm, with amean of 23.6 × 18.8 _+ 8.1 mm. The lesion was bilateral in one case and unilateral in the other 28 cases (right sided in 17 and left sided in 10). Fetal growth was always regular, and no signs of fetal distress were found. No spontaneous miscarriages occurred. The size of the lung lesion changed during fetal life in 14 cases (48.2%): two increased, 8 decreased, and 4 disappeared. Therefore, we considered as vanishing CCAM during prenatal life, lesions diagnosed during the early antenatal US scan, disappearing on US during pregnancy with a normal postnatal evaluation (x-ray and CT). Table 2 shows the antenatal course according to postnatal treatment. The karyotype was normal in all 22 fetuses tested. In the last 7 patients, karyotype was not realized because of the lack of association between CCAM and chromosomal abnormalities.

Postnatal Clinical and Radiologic Course The birth term ranged from 38 to 41 weeks, with a mean (_+ SD) of 40.1 _+ 1.02 weeks. Mean birth weight was 3,467 _+ 642 g. Only one cesarean delivery was performed for obstetric reasons. All the infants were delivered in the hospital, and 14 (48.2%) were hospital-

ized in the neonatal intensive care unit because of the respiratory risks according to the prenatal diagnosis of CCAM, even if they were entirely asymptomatic at birth. The first standard chest radiograph, obtained during the first days of life, was considered normal in 12 cases (41.3%) and showed cystic lung malformation in the other cases. The lesion was right sided in 7 cases 5 in the inferior lobe), left-sided in 5, and bilateral in one. A mediastinal shift was found in 4 cases. The first CT examination was sometimes done during the first days of life, but usually at 45 days of life because of the lack of clinical manifestations. Findings from 4 CT examinations (13.8%) were normal, with no signs of CCAM (neonatal standard radiography had been considered normal in only one of these cases). CT scan showed cystic lung malformations in the other patients, on the right side in 13 cases (46.4%, inferior lobe in 12, and median lobe in one), on the left in 10 cases (superior lobe in 7, and on both sides in one case. During the first weeks of life, 3 patients (10.3%), entirely asymptomatic at birth, had clinical signs regarding CCAM. These clinical manifestations consisted of polypnea in a patient with a left lower lesion and a mediastinal shift; nocturnal cough in a patient with a right inferior lobe lesion; and malaise on day 7 of life in a patient with a left lower lesion and a mediastinal shift. CCAM vanished from standard radiographs and CT images in 6 cases: once antenatally, 3 times at birth, once during the first months of life, and once during the first years of life. The lesion shrank in 4 cases and did not change after birth in 2 patients. All 12 patients were monitored radiologically and clinically, whereas the other 17 patients (58.6%) underwent surgical resection. Age at surgery ranged from 5 to 240 days, with mean of 79 _+ 71 days. Surgical resection always was indicated by the onset of clinical signs in the neonatal period (3 cases in this series). In the remaining asymptomatic patients, surgery was proposed for voluminous (more than 3 cm) or liquid-filled CCAM (according to the infectious risks). The date for surgery depended on timing for postnatal radiologic evaluation (at birth or at 45 days of life), the weight of patient, and family wishes. Lobectomy was performed in 6 cases, including biTable 2. Prenatal Ultrasound Scan Changes in an Asymptomatic Population at Birth and Surgical Management Prenatal US Course No change Decrease Increase Disappearance Total

No. of Patients

Surgical Resection

15 (52%) 2 (7%) 8 (27%) 4 (14%) 29

7 (46.5%) 0 7 (46.5%) 3 (2%) 17 (58.5%)

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lobectomy in one case and lobectomy plus segmentectomy in one case. Segmentectomy was performed in 11 cases (64.7%), including one case of bisegmentectomy. Drains were removed 2 to 12 days after surgery (mean, 3.9 _+ 2.8 days). The only postoperative complication was a case of pneumothorax on postoperative day 4 (the day after drain removal); it was successfully treated by drainage for 4 days. The patients were discharged from the hospital between 4 and 15 days after surgery (mean, 6.8 _+ 3 days).

Long-Term Outcome At the first postoperative visit (one month postoperatively), all the patients were free of clinical signs. Standard chest radiography was normal after one month in 16 cases and after 2 months in the other case. One patient had asthma 2 years after surgical resection. All the other patients (with and without surgical resection) were asymptomatic after a mean follow-up of 15.5 _+ 14 months (range, 2 to 72 months). DISCUSSION

With the increasing use of antenatal US scan, 2 more cases of CCAM are being diagnosed during the second trimester of pregnancy. Antenatal follow-up focuses on factors of poor prognosis such as fetal h y d r o p s , 3 polyhydramnios, mediastinal shift, histological type III,4 and lesion size (particularly the lung-thorax transverse area ratio). 5 Some investigators consider that polyhydramnios and mediastinal shift are not significantly associated with poor outcome. 6 Two patients (6.8%) in this series of asymptomatic neonates had hydramnios requiring antenatal puncture, and 8 (27%) had a mediastinal shift. None had fetal hydrops. In contrast, in the same population, 45% of patients who were symptomatic at birth, had hydramnios, and 65% had a mediastinal shift (Table 1). Hydrops seems to be the most important factor of poor prognosis, being almost invariably fatal; hydrops may be an indication for surgical resection in utero 7 or cystico-amniotic shunt. CCAM lesions can shrink or even vanish during pregnancy, 8 as in 12 of our patients (8 lesions shrank and 4 vanished). Antenatal US scan findings were not predictive of the postnatal course; surgical resection was performed in 3 of the 4 patients whose lesions vanished and on 7 of the 8 patients whose lesions shrank. The value of magnetic resonance imaging in predicting postnatal outcome appears to be limited, 9 although it can be used to evaluate pulmonary hypoplasia in severe cases. Antenatal diagnosis of CCAM did not influence the mode of delivery, and intensive care seemed to be necessary only for cases in which poor prognosis factors had been

identified during pregnancy (hydrops, severe mediastinal shift, antenatal surgery). The delivery of these patients at risk must take place near a pediatric surgical center. This guarantees an immediate postnatal evaluation and, if necessary, immediate surgery or "a wait and see" approach. Other infants, without antenatal poor prognosis factors, can be delivered in a standard maternity unit, provided a pediatrician with experience in this disorder is present, and respiratory distress can be adequately managed. As during pregnancy, neonatal manifestations of CCAM vary widely, ranging from acute respiratory distress requiring intubation to dyspnea and cyanosis. Patients who are completely asymptomatic at birth (55% in our series, to 7 2 % 1°-12) c a n experience clinical manifestations during the first months of life, like patients with other lung malformations (sequestration, lobar emphysema 13). In our series, 10% of asymptomatic infants had clinical signs during the first weeks of life, consisting of polypnea, malaise, and nocturnal cough. Thus, all infants with an antenatal diagnosis of CCAM require postnatal evaluation based on chest radiography and computed tomography, even if the lesions disappear during pregnancy or if clinical manifestations are absent at birth. Note that normal standard radiographic findings at birth do not rule out CCAM persistence on CT. In this study, only one of the 12 neonates with a normal standard chest x-ray had normal CT findings; likewise, some investigators 14 have observed persistent CT abnormalities in all children with disappearing fetal lung masses and normal standard radiography. Conversely, identification of a cystic mass by standard radiography may be predictive of clinical manifestations and the need for surgery in the neonatal period. 15 In our series, 75% of asymptomatic neonates with abnormal x-ray findings underwent surgery, compared with only 38% if x-ray had been considered normal (with pulmonary lesion on CT). Thus, CT is essential for postnatal evaluation of CCAM but can be postponed until day 45 of life if the patient is asymptomatic. If CCAM is voluminous (>3 cm) or liquid filled (risk of infection) on the first CT scan, surgery may be indicated during the first months of life. For smaller lesions, simple monitoring may suffice, with repeat CT after 6 to 12 months. The treatment of asymptomatic CCAM (monitoring or resection) is controversial. Some cases of completely asymptomatic CCAM may qualify for simple monitoring, given the risks of surgery and anesthesia in young children 1~ and the possibility of spontaneous postnatal resolution. 17 In this series, cystic lesions disappeared completely during the first months of life in 2 patients (7%). Routine surgery for all cases of CCAM that are apparent at birth (even if only radiologically) is advo-

ASYMPTOMATIC CCAM

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cared by some investigators 18 because of the low morbidity of pulmonary resection during infancy and the prevention of late complications. Pulmonary resection is very well tolerated by children 19 with a generally uneventful postoperative course and no long-term respiratory complications, as borne out in this series. Even when CCAM is associated with severe pulmonary hypoplasia or persistent pulmonary hypertension, 2° the longterm prognosis seems to be very good. Animal studies suggest that some compensatory lung growth occurs after lung resection, in terms of both volume and pulmonary weight, and seems to be more effective and extensive in infants and young children than in older subjects. 21 Moreover, lobectomy or segmentectomy can be done with a thoracoscopic approach. 22 Complications of CCAM in childhood and adulthood include recurrent pulmonary infections, 23 hemopneumothorax, 24 and, above all, cancer. 25 In the literature, 13 epithelial and mesenchymal malignancies (bronchoalveolar carcinoma and rhabdomyosarcoma) have been

Table 3. Pulmonary Tumors and CCAM: Review of Literature Studies

Bronchoalveolar Carcinoma

Granata et al, 27 1998

8

5

1 in child

All in child (18-42 months) 1 child (15 months) 1 child (13 months)

8

7

Roggin et al, 8 2000 Shariff et al, 28 1998 Ozcan et al, 2a 2001 Total

Rhabdomyosarcom a

reported in patients with a history of CCAM (Table 3). Rhabdomyosarcoma arises from the well-differentiated but poorly organized muscle fibers present in some CCAM, but cases associated with cystic lesions seem to be more favorable. 26 Surgical indications of small (<3 cm) and asymptomatic lesions should be discussed on a case-by-case basis with the parents. The long-term outcome of all patients (with or without surgical resection of CCAM) seems to be excellent, although long-term complications, including cancer, have been described in patients aged 30 to 40 years.

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