Download Congenital Malformations – Cystic lung lesions

Congenital Malformations – Cystic lung lesions
Dr Sandra Chuang Respiratory fellow Sydney Children’s Hospital, Randwick, Australia
Definition: Congenital cystic lung lesions encompass a wide spectrum of rare lung malformations
including congenital pulmonary airway malformation (CPAM) (previously termed congenital cystic
adenomatoid malformations (CCAMs)), bronchopulmonary sequestration (intralobar and extralobar),
bronchogenic cysts, and congenital lobar emphysema (CLE, also known as congenital lobar
overinflation). These congenital malformations of the developing lungs may be supplied by either or
both of the pulmonary or systemic arterial system, and drain to pulmonary or systemic veins.
Causes: No definite known cause although there is interest in the role of some genes such as fatty
acid binding protein-7 in the pathogenesis of CPAMs . The overlap and occasional coexistence of
these cystic lesions suggest a possible single common pathologic mechanism for their development.
Dr Claire Langston proposed that the development of these lesions can be attributed to in utero
airway obstruction. The level of the obstruction, the completeness of the obstruction, and the timing
of the obstructive events together produce the different patterns of lung malformations seen. The
exact mechanism by which obstruction or atresia bring about various final lesions have yet to be
elucidated. These diseases may result from compromised interaction between embryologic
mesodermal and ectodermal lung components during development.
Clinical presentations: A cystic lung lesion is the most commonly identified pulmonary lesion on
routine antenatal ultrasound. In most cases the baby is well after delivery. Postnatal presentation of
cystic lung lesions varies depending on the size, location, type of lesion, and whether a
communication with the airway or the gastrointestinal tract exists. Affected newborn infants can
present with severe respiratory failure requiring mechanical ventilation from birth. In less affected
infants, they may present later in life with complications such as pneumothorax, infections such as
pneumonia, haemoptysis, high output heart failure if the cystic lung lesions is supplied by a large
systemic artery, and malignancies in very rare cases. Other lesions may be detected as an incidental
finding on routine imaging. Most lesions are an isolated finding in an otherwise normal child and
only rarely associated with other anomalies. Extralobar sequestrations may be found in association
with cardiac and diaphragmatic anomalies. CPAMs may be associated with cardiac, renal, and other
coexistent lung lesions such as sequestrations.
Investigations: Once identified antenally, cystic lungs lesions can be monitored with serial antenatal
ultrasound scans or MRI in a unit where this is available. A plain radiograph at birth and thereafter
every 6 to 12 months (as long as the lesion is visible by this technique) is reasonable. A chest
Computer Tomography (CT) scan with intravenous contrast should be performed sometime after
birth even if the chest x-ray is normal. The timing of the CT is dependant on the practice of the
various tertiary centres. The blood supply to the cystic lung lesions should be defined by contrast CT
or magnetic resonance imaging (MRI) angiography to assist in diagnosis and management.
Treatment: The improvement in the diagnostic accuracy of antenatal ultrasound has meant a
significant proportion of congenital cystic lung lesions are detected in the presymptomatic phase.
There is evidence that up to 15% of antenatally diagnosed congenital lung lesions such as CPAM can
regress during gestation and even continue to regress in the first 12 months of life. Prenatal features
previously thought indicative of poor outcome such as mediastinal shift and polyhydramnios no
longer have sufficient discriminatory value in differentiating outcomes. The development of non
immune hydrop fetalis remains the single most useful predictor of poor fetal outcome. It is agreed
that infants and older children with symptomatic cystic lung lesions including those with respiratory
distress or infected lesions should have early surgery.
Those with lung lesions which are supplied by large systemic vessels may warrant early coil
embolisation or surgery. However, for patients with small asymptomatic lesions (<3 cm or less than
25% of ipsilateral lung involvement as assessed on CT scan), the benefit of surgery is unclear. Those
who favour elective surgery between 1 month and 12 months of age suggest that the risk of infections
and associated increase in operation complications, pneumothorax, and possibly malignancy such as
pleuropulmonary blastoma (PPB), outweighs the risk of the surgery. However the actual relationship
between cystic lung lesions and malignancy is not clear cut. Conflicting reports of malignancy arising
in the ipsilateral or contralateral lung after successful resection of lung lesions question the protective
effect of surgery.
More recent reports indicate the relationship between cystic lung lesions and malignancy may be one
of pathological misclassification. An expectant approach with serial imaging and specialist review
may be appropriate for small asymptomatic lesions after consultation with the parents of the affected
child. Many unanswered questions regarding congenital cystic lung lesions remain. These will be
resolved if the natural progression of these lung lesions is known. Long term follow up programs
such as the UK Long Term Outcome Study (LoTOS) and data registries for orphan lung disease will
help answer some of these questions. A recent success from the PPB registry is the discovery of the
relation of DICER1 gene to familial PPB which may be helpful in differentiating between CPAM and
PPB in the future. Future studies will help unravel the mysteries of congenital cystic lung lesions and
aid management decisions.
Useful links
British Paediatric Orphan Lung Disease Registry www.bpold.co.uk
Pleuropulmonary blastoma can be found at www.ppbregistry.org
References:
Stocker J. Congenital and developmental diseases. In: Dail DH, Tomashefski JF, Cagle P, Hammar
SP, Farver C, Colby TV, et al., editors. Dail and Hammar's Pulmonary Pathology. 3rd ed. New York:
Springer-Verlag; 2008. p. 132-5.
Langston C. New concepts in the pathology of congenital lung malformations. Semin Pediatr Surg.
2003;12(1):17-37
Laberge JM, Puligandla P, Flageole H. Asymptomatic congenital lung malformations. Semin Pediatr
Surg. 2005;14(1):16-33
Davenport M, Warne SA, Cacciaguerra S, Patel S, Greenough A, Nicolaides K. Current outcome of
antenally diagnosed cystic lung disease. J Pediatr Surg. 2004 ;39(4):549-56
Priest JR, Williams GM, Hill DA, Dehner LP, Jaffe A. Pulmonary cysts in early childhood and the
risk of malignancy. Pediatr Pulmonol. 2009;44(1):14-30
Shanti CM, Klein MD. Cystic lung disease. Semin Pediatr Surg. 2008;17(1):2-8
Stanton M, Njere I, Ade-Ajayi N, Patel S, Davenport M. Systematic review and meta-analysis of the
postnatal management of congenital cystic lung lesions. J Pediatr Surg. 2009;44(5):1027-33
Wagner AJ, Stumbaugh A, Tigue Z, Edmondson J, Paquet AC, Farmer DL, et al. Genetic analysis of
congenital cystic adenomatoid malformation reveals a novel pulmonary gene: fatty acid binding
protein-7 (brain type). Pediatr Res. 2008;64(1):11-6
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA,
Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y,
Goodfellow PJ. DICER1 Mutations in Familial Pleuropulmonary Blastoma. Science,2009; E Pub 25
June