Congenital Cystic Adenomatoid Malformation of the Lung

Introduction

Congenital cystic adenomatoid malformation of the lung (CCAM) is a developmental abnormality resulting from an overgrowth of the terminal respiratory bronchioles. The condition may be bilateral involving all the lobes of the lungs, but in the vast majority of cases it is confined not only to a single lung, but also to only one lobe of the lung¹. The lesion may be macrocystic (>5mm) or microcystic (<5mm), with a full spectrum of clinical presentations^2-4. Antenatal sonography may reveal an echogenic or multicystic mass with a mediastinal shift, hydrops fetalis and polyhydramnios. At times, the lesion may not be discovered until several weeks after birth when the neonate develops mild respiratory symptoms, or even discovered only in childhood when the child presents with recurrent respiratory tract infections. Clinical presentations and prognosis are dependant on the type of lesion and its resulting sequelae. The diagnosis is confirmed histologically.

A case of suspected CCAM seen recently at the Fetal Unit of King Edward VIII Hospital is presented, followed by an overview on the aetiology, embryology, natural history, prenatal diagnosis, management and prognosis. An algorithm for the management of CCAM is also presented. The pregnancy is still ongoing at the time of this writeup.

Case Report

A 29 year old lady in her 3rd pregnancy presented to our antenatal clinic at 27 weeks gestation for booking. Her previous pregnancies were uneventful and both children are well. The booking bloods, including screening for Diabetes, were normal. She was tested positive for HIV infection.  Routine antenatal ultrasound showed marked polyhydramnios. A 5x5x5 cm cystic mass was noted in the right thorax, compressing and displacing the heart to the left. The left lung and heart could not be adequately assessed. A small pleural effusion was noted on the right. The stomach, both kidneys and bladder appeared normal.

The patient was seen at the Fetal unit at 30 weeks gestation. Maternal respiratory discomfort was observed and this was attributed to the gross polyhydramnios. The amniotic fluid index (AFI) measured 50cm with a deepest pool of 18cm. A large cystic mass (7x7x5 cm) with incomplete septations occupied the right hemithorax, resulting in a mediastinal shift to the left. The left lung was collapsed and most probably hypoplastic. The heart was compressed and further deviated to the left, but appeared structurally normal. No normal lung tissue could be visualized. No obvious pleural effusions were noted on this scan and the surrounding skin appeared oedematous. (Figs 1 & 2).

Fig 1:  Longitudinal section of thorax showing a large cystic lesion

Fig 2: Cross-section view.The large cystic lesion is seen in the right hemithorax. The heart is compressed and deviated to the left (arrow). Skin oedema and polyhydramnios

A small stomach bubble, most probably due to oesophageal compression by the thoracic mass, was visualized below the diaphragm. Both kidneys and bladder were normal. The liver appeared slightly enlarged and there was moderate ascites present (Fig 3 & Video clip 3). There was no placentomegaly and a normal 3 vessel cord was seen. The UA Doppler showed a positive end diastolic frequency and the UV was pulsatile.

Fig 3: Illustration of ascites and a small stomach

bubble (arrow).

The most probable diagnosis was CCAM Type 1 (macrocystic) with fetal hydrops. In view of the large size of the lung cyst associated with a mediastinal shift and virtually no normal lung tissue, as well as fetal hydrops and polyhydramnios, the patient was informed of the poor prognosis for her fetus. After appropriate counseling and discussion with her family, she opted to continue with the pregnancy. The increased risk of vertical transmission of HIV infection with fetal invasive procedures was also discussed. She was offered and consented to karyotyping by fetal blood sample and a concomitant therapeutic amniodrainage of 1500mls of fluid was removed. This relieved her discomfort significantly. The post drainage AFI measured 30cm. The result of the karyotype was normal. Thoraco-amniotic shunting is not yet practiced at our unit, and the patient could not afford referral to an appropriate unit. She was made aware that in the worst case scenario, this fetus may demise in utero largely due to cardiac failure, or more likely to succumb in the early neonatal period with respiratory insufficiency. She was advised to have fortnightly followup scans with the possibility of repeat amniodrainage should she become symptomatic. The patient has been discussed at our regular Prenatal Meeting with a multidisciplinay team, and it has been decided that if the fetus remains hydropic, there will be no fetal cardiotocograph monitoring. This has been fully explained to the patient. She was referred back to the clinic to continue her antenatal care and followup scans.

Literature review of CCAM

Synonyms: Congenital lobar adenomatosis, adenomatoid hamartoma, congenital bronchiolar malformation.

Prevalence: CCAM is found in about 1: 4000 births.  M1.7 : F15

Aetiology: CCAM is caused by an overgrowth of the terminal respiratory bronchioles at the expense of the saccular tissue. There is failure of the endodermal bronchiolar epithelium to induce surrounding mesenchyme to form the bronchopulmonary segments. The arrest of development probably occurs at 6-8 weeks gestation, and may be caused by a maturation defect in lung embryogenesis6 or localized bronchial atresia7. The exact nature of this defect remains unclear.

Embryology: The lower respiratory tract begins its development approximately 26 days after conception. The development of the lung8 can be divided as shown in the table below:

Recurrence risk: None. Usually sporadic

Natural history: The lesion is usually unilateral (85%) with equal incidence of microcystic or macrocystic disease, although bilateral cases have been reported. It generally affects one lobe of the lung, but the large size of the lesion may lead to compression of the other lobe and other side lung. Increasing size of the lesion results in mediastinal shift, with cardiac and pulmonary compression. Oesophageal and vena caval compression can also results in polyhydramnios and fetal hydrops. CCAM may undergo spontaneous resolution in 30 - 40%9 of the cases. In half of the cases there is no change in the size of the lesion, while it may enlarge in 10% of the cases2.

Classification and Types: Stocker2 proposed a classification of CCAM into 3 groups according to the size of the cysts:

Type 1: single / multiple large cysts (2-7cm diameter)

Type 2: multiple smaller cysts, up to 1.2cm diameter

Type 3: firm bulky mass of lung tissue, non-cystic appearance on ultrasound

An alternative classification include macrocystic (>5mm) and microcystic (<5mm) lesions3,4.

Prenatal Diagnosis:  The ultrasound diagnosis is based on the finding of a solid or cystic non-pulsatile intrathoracic tumour4. Although the lesion must exist in the 1st trimester, diagnosis at this time has not been reported. The diagnosis is usually made in the 2nd trimester, but sometimes in the 3rd trimester when referred for investigation of polyhydramnios.

Macrocystic lesion: This is characterised by single / multiple cysts occupying one side of the chest. It is usually difficult to identify normal lung tissue in the same side of the chest. May be associated with mediastinal shift and compression of the contralateral lung.

Microcystic lesion: There is uniform echogenic appearance of the affected lung on ultrasound. This is thought to be due to fluid accumulation in the small cystic spaces, comparable to that of polycystic kidneys. Commonly associated with polyhydramnios and hydrops.

Differential diagnosis: This includes congenital diaphragmatic hernia, bronchogenic cysts, pulmonary sequestration, mediastinal cystic terratoma, larangeal and bronchial atresia4,10.

Associated anomalies: Rare. This condition is usually isolated2 and rarely associated with chromosomal defects4. Associated anomalies include renal, cardiac, CNS & spinal defects and abdominal wall defects. Type II CCAM is more commonly associated with other anomalies11. Elevated alpha-feto protein has been reported with type III CCAM12.

Management: Once the diagnosis has been made, a careful search for other anomalies should be carried out, and consideration given to checking the karyotype13-14. Counseling should include the paediatrician and a paediatric surgeon experienced in the postnatal management of this condition. Such patients should be managed at a tertiary centre.

Atleast 3 weekly follow up scans should be performed, to identify the development of hydrops and polyhydramnios, since this is associated with a poor prognosis. Some cysts may resolve spontaneously. In the presence of large cysts and hydrops, consideration can be given to drainage of the cysts by thoraco-amniotic shunting. Nicolaides et al15 reported the first case of successful drainage of large pulmonary cysts by the use of a “double-pigtail” catheter which allows for continuous drainage. Successful shunt placement has also been reported in fetuses with unilocular CCAM lesions16-17. Multicystic or predominantly solid CCAM are not suitable for catheter decompression and require resection.  Fetal thoracocentesis alone is ineffective because of the rapid reaccumulation of cyst fluid. The relief of associated polyhydramnios by serial amniocentesis has also shown to be of value18. There has been reported successes for intrauterine surgery19-21. This is certainly not yet an option in our developing country.

A proposed algorithm for the management of CCAM (modified from Adzick et al21), that may be applicable for our setting is presented below:

Prognosis: There is a spectrum of severity of CCAM and this is important for prenatal counseling for CCAM. The lesion can either regress and be asymptomatic at birth or progress to cause either fetal death from hydrops or neonatal death from associated pulmonary hypoplasia22.

The following features are suggestive of poorer prognosis in unilateral lesions:-

1. large size cysts

2. mediastinal shift

3. fetal hydrops

4. polyhydramnios

5. associated anomalies

The prognosis is worst in type III lesions due to the earlier development of hydrops and polyhydramnios. Bilateral CCAM is lethal. Unilateral type I CCAM (macrocystic lesion) in the absence of hydrops and polyhydramnios  is associated with a good prognosis23. In symptomatic neonates the survival following postnatal thoracotomy and lobectomy is about 90%.

Conclusion: CCAM is a lesion that is well characterized pathologically. With the advances in ultrasound came the ability to classify the type of lesion and predict the most-likely outcome. Whether our patient will benefit from in-utero therapy such as chronic drainage of the cyst, in the background of maternal HIV infection, for which we cannot as yet offer antiretroviral therapy during fetal invasive procedures, is uncertain.

Logie Govender

Senior Specialist and Lecturer

Nelson R Mandela School of Medicine & King Edward VIII Hospital

Durban, KwaZulu-Natal

References:

1.        Rempen A, Feige A, Wunsch P. Prenatal Diagnosis of Bilateral Cystic Adenomatoid Malformation of the Lung. JCU  15: 3-8, 1987

2.        Stocker JT, Madewell JE, Drake RN. Congenital Adenomatoid Malformation of the Lung. Classification and Morphological Spectrum. Human Pathol  8: 155-171, 1977.

3.        Adzick NS, Harrison MR, Glick PL, et al. Fetal Cystic Adenomatoid Malformation: Prenatal diagnosis and natural history. Pediatr Surg 20 (5): 483-488 , 1985.

4.        Sanders RC, Blackmon LR, Allen Hogge W, Wulfsberg EA. Structural fetal abnormalities - The Total Picture. Mosby. St Lois-Baltimore-Boston, 122-126, 1996.

5.        Gary M. Joffe, Luis A. Izquierdo, Gerardo O. Del Valle, et al. Congenital lobar adenomatosis, type I © Joffe www.TheFetus.net. 1991.

6.        Congiarella J, Greco MA, Askin F, Perlma E, Goswami S, Jagirdar J.  Congenital cystic adenomatoid malformation of the lung: Insights into the pathogenesis utilizing qualitative analysis of vascular marker CD 34 (QBEND-10) and cell proliferation marker MIB-1. Mod Pathol  8: 913-918, 1995.

7.        Moerman P, Frynns JP, Vandenberghe K, Devlieger H, Lauweryns JM. Pathogenesis of  congenital cystic adenomatoid malformation of the lung. Histopathology 21: 315-321, 1992.

8.        Moore KL. The developing Human: Clinically Orientated Embryology, 4th ed. Philadelphia; 1988.

9.        Barret J, Chitayat D, Sermer M, et al. The prognostic factors in the prenatal diagnosis of the echogenic fetal lung. Prenat Diagn 15: 849-853, 1995.

10.     King SJ, Pilling DW, Walkinshaw S. Fetal echogenic lungs: prenatal diagnosis and outcome. Paediatr Radiol 25: 208-210, 1995.

11.     Bromley B, Parad R, Estroff JA, Benacerraf BR. Fetal lung masses: Prenatal course and outcome. J Ultrasound Med 14: 927-936, 1995.

12.     Petit P, Bossens M, Thomas D, Moerman P, Fryns JP, Van den Berghe H. Type III Congenital Czstic Adenomatoid Malformation of the Lung: Another Cause of Elevated Alpha Feto Protein? Clin Genet 32: 172-174, 1987.

13.     Johnson P. Thoracic malformations: In Fetal Medicine basic science and clinical practise. 1st ed: Churchill Livingstone, 651-663, 1999.

14.     Roberts D, Sweeney E, Walkinshaw S. Congenital cystic adenomatoid malformation of the lung coexisting with recombinant chromosome 18. A case report. Fetal Diagn Ther 16(2): 65-67, 2001.

15.     Nicolaides KH, Blott M, Greenough A. Chronic drainage of fetal pulmonary cyst. Lancet 1618, 1987.

16.     Clark SL, Vitale DJ, Minton SD, et al. Successful fetal therapy for cystic adenomatoid malformation associated with second trimester hydrops. Amer J of Obstet  and Gynecol, 157, 294-297, 1987.

17.     Sugiyama M, Honna T, Kamii Y, et al. Management of prenatally diagnosed congenital cystic adenomatoid malformation of the lung. Eur J Pediatr Surg 9(1): 53-57, 1999.

18.     Meagher SE, Simon DR, Hodges MJ, et al. Successful outcome with serial amniocentesis for polyhydramnios complicating cystic adenomatoid malformation of the lung. Aust N Z J Obstet Gynaecol 35: 326-328, 1995.

19.     Adzick NS. Fetal thoracic lesions. Sem Pediatr Surg 2: 103-108, 1993.

20.     Bullard KM, Harrison MR. Before the horse is out of the barn: fetal surgery for hydrops. Semin Perinatol 19: 462-473, 1995.

21. Adzick NS, Harrison MR, Flake AW, et al. Fetal surgery for cystic adenomatoid malformation of the lung. J Pediatr Surg 28(6): 806-812, 1993.

22. Neilson IR, Russo P, Laberge JM, et al. Congeniatal adenomatoid malformation of the lung: current management and prognosis. J Pediatr Surg 26(8): 975-980, 1991.

23. Thorpe-Beeston JG, Nicolaides KH. Cystic adenomatoid malformation of the lung: prenatal diagnosis and outcome. Prenat Diagn 14(8): 677-688, 1994.