Article Text

The natural history of prenatally diagnosed congenital cystic lung lesions: long-term follow-up of 119 cases
  1. James Cook1,
  2. Lyn S Chitty2,3,4,
  3. Paolo De Coppi5,6,
  4. Michael Ashworth7,
  5. Colin Wallis1
  1. 1 Department of Paediatric Respiratory Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  2. 2 Department of Fetal Medicine, University College Hospitals NHS Foundation Trust, London, UK
  3. 3 Genetics and Genomic Medicine Section, Institute of Child Health, University College London, London, UK
  4. 4 Department of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London
  5. 5 Department of Paediatric Surgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  6. 6 Stem Cells and Regenerative Medicine Section, Institute of Child Health, University College London, London
  7. 7 Department of Pathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  1. Correspondence to Dr Colin Wallis, Department of Paediatric Respiratory Medicine, Great Ormond StreetHospital for Children NHS Foundation Trust, London WC1N 3JH, UK; colin.wallis{at}


Background A paucity of evidence regarding the natural history of congenital pulmonary airway malformations (CPAMs) and pulmonary sequestration (PS) has resulted in a divergence in management strategy of asymptomatic cases.

Methods We describe the long-term clinical course of 119 children diagnosed with these lesions treated at Great Ormond Street Hospital (GOSH). Cases were identified via the GOSH patient database. Study entry required the identification of a cystic lung lesion on prenatal ultrasound and confirmation of CPAM/PS on postnatal CT imaging. Patients followed up for at least 5 years were included.

Results 51 (43%) patients were managed surgically; 8 (6.7%) as an emergency during the neonatal period, 6 (5.1%) electively due to concerning features on CT scan, 20 (17%) following medical advice, 1 (0.8%) following a severe respiratory infection and in 5 (4.2%) the indication was unclear. The indication in 11 (9.2%) was recurrent respiratory infection and median age at surgery was 1.6 years (range 0.4 to 4.6 years). No cases of malignancy were identified on histological examination of resected lesions. 68 (57%) patients were managed conservatively for a median period of 9.9 years (range 5.2 years to 18 years). Seven (10%) were discharged, one was followed-up elsewhere (1.5%) and eight (11%) were lost to follow-up. In four patients (5.9%), the lesion resolved spontaneously. 52 (76%) continue to be followed-up and remain asymptomatic.

Conclusions This is one of the largest case series documenting the natural history of CPAMs and PS following a prenatal diagnosis and demonstrates that conservative management is a reasonable option in selected cases.

  • congenital
  • lung
  • cystic

Statistics from

What is already known on this topic?

  • Incidental identification of cystic lung lesions on prenatal scans is increasingly common.

  • A paucity of evidence regarding the natural history of the lesions has contributed to divergent management strategies.

  • The majority of surgical centres worldwide resect all identified lesions.

What this study adds?

  • This is the first long-term follow-up of asymptomatic, conservatively managed lesions (median 9.9 years).

  • The risk of recurrent infection is less than 10% and decreases following the second year.

  • No cases of malignancy were identified.


Routine fetal anomaly scanning, together with advances in ultrasonographic technology have resulted in an increase in the prenatal detection of congenital lung malformations (CLMs), with current prevalence estimated at 4.15 per 10 000 births.1 The CLM complex represents a heterogeneous group of abnormalities that include cystic pulmonary airway malformations (CPAMs), pulmonary sequestrations (PS), bronchogenic cysts, bronchial atresias and hybrid forms of these lesions.

Congenital pulmonary airway malformations and PS are of particular clinical interest due to continued debate surrounding their postnatal management.2 3 Both lesions are most commonly detected during pregnancy, usually at the routine 20-week anomaly scan, with the prevalence of CPAM at birth between 1 in 11 000 and 1 in 35 000.4–6 Detailed anatomical characterisation of CPAMs and PS can be made during the postnatal period using high-resolution CT,7 with hybrid lesions containing both cystic and sequestered components a frequent finding. Definitive diagnosis of a cystic lesion, however, requires histological examination.8

Resection of symptomatic CPAMs and PS in the neonatal period is indicated and not debated further. For asymptomatic lesions the decision is less clear. Advocates of an expectant approach suggest that prior to the introduction of fetal anomaly scanning these lesions had rarely been identified as pathogenic, the risk of complication in the majority is low9 and postnatal spontaneous resolution is possible.10 However, doubt regarding the safety of this approach due to the potential for malignant transformation and recurrent infection has resulted in approximately 70% of lesions being resected worldwide.11

To date there have been no long-term studies to determine the natural history of these lesions to inform evidenced-based clinical decision making. We describe the clinical course of a cohort of children born between 1996 and 2009, who were referred to Great Ormond Street Hospital (GOSH), following a prenatal diagnosis of CPAM or PS, with follow-up of 5 to 18 years.


Cases were identified from a prospectively maintained database of fetuses with a diagnosis of CLM made on prenatal ultrasound scan at University College Hospital, London and referred to GOSH. Detailed fetal sonographic findings and early postnatal course for many cases in this cohort have been reported previously.12 Additional cases from other referral centres were identified via the GOSH patient database. Entry into the study required radiological confirmation of CPAM or PS on postnatal CT imaging. To provide an adequate follow-up period, only patients followed up for at least 5 years were included in the study.

All patients had demographic details and results of postnatal CT imaging recorded. Additional data recorded for the conservatively managed cohort included the date of the last clinic attended and follow-up status: continued follow-up, lost to follow-up or discharged with reasons recorded. Data recorded for the surgically managed cohort of patients included the indication for surgery, age at surgery and the histological features of the resected lesion.

This project was registered as a service evaluation within the clinical audit department at GOSH.


One hundred and nineteen cases referred to GOSH were identified (62 (52%) girls, 57 (48%) boys). All patients had a diagnosis of a CLM following prenatal ultrasound imaging and a radiological diagnosis of CPAM and/or PS confirmed on postnatal CT imaging.

Sixty-eight (57%) patients were followed up conservatively. The median length of follow-up was 9.9 years (range 5.2 years to 18 years). Of this group, CPAM was diagnosed on CT imaging in 36 (53%) patients, PS in 27 (39%) patients and a hybrid lesion in 5 (7.4%) patients. Seven (10%) patients were discharged, four (5.9%) following spontaneous resolution as demonstrated on CT scan. Eight (11%) patients were lost to follow-up and one (1.5%) patient was followed up elsewhere after the family moved away. Of the 52 (76%) patients who continue to be followed-up at GOSH all remain asymptomatic and none have been referred for surgical intervention due to recurrent infection or concerns regarding malignant transformation.

Fifty-one (43%) patients underwent surgical resection of the identified lesion (table 1). Eight (6.7%) had emergency surgery during the neonatal period. In each of these cases, there was evidence of respiratory compromise, and in two (1.7%) cases this was also associated with mediastinal shift. Of the remaining 43 (36%) patients who underwent surgery, the median age at surgery was 1.2 years (range 0.2 to 5.1 years). The indication for resection in four (3.4%) patients were concerning features on initial CT scan, including: large size associated with mediastinal shift in two (1.7%) patients, large size and compression of healthy lung in one (0.8%) patient and a fluid filled cyst in one (0.8%) patient. Resection was performed in two (1.7%) patients due to a concerning change in appearance of the lesion on surveillance CT scan: a more solid appearance in one (0.8%) patient and an increase in size in one (0.8%) patient. Twenty (17%) patients underwent elective surgery following medical counselling (table 1, figure 1). Eleven (9.2%) patients underwent surgery due to a history of recurrent respiratory infection (table 2). Of this group, three (2.5%) patients were referred from other centres specifically for surgery following recurrent infection during local follow-up. The median age at surgery of patients with recurrent respiratory infection was 1.6 years (range 0.4 to 4.6 years). The number of patients who underwent resection decreased following the second year and no patients required surgical intervention beyond the age of 5 years (table 2, figure 2). One (0.8%) patient underwent surgery following a single severe respiratory infection requiring ventilation. There were no other recorded complications such as pneumothorax, haemothorax, abscess or empyema. In five (4.2%) patients, the indication for resection is unclear from correspondence. There were no deaths following elective surgical intervention. Details of other surgical complications were not recorded for this study.

Figure 1

Indication for surgery beyond the neonatal period as a percentage of all cases. RI, respiratory infection.

Figure 2

Age at surgery for recurrent respiratory infection as a percentage of all cases. m, month; y, year.

Table 1

Surgically managed cases

Table 2

Surgically managed cases following recurrent respiratory infection

Histological examination of the 51 resected specimens revealed CPAM (type 1) in 23 (45%), CPAM (type 2) in 9 (18%), CPAM (not typed) in 4 (7.8%), PS in 7 (13%), a hybrid lesion in 1 (2.0%), bronchial atresia in 3 (5.9%), lobar emphysema in 1 (2.0%), bronchogenic cyst in 2 (3.9%) and tracheal diverticulum in 1 (2.0%) (table 1). There was no evidence of inflammatory change in 27 (53%), acute inflammatory change in 20 (39%) and chronic inflammatory change in 4 (7.8%) (table 1). Of the 11 lesions resected due to recurrent infection there was evidence of acute inflammatory change in 8 (72%) and no inflammatory change in 3 (27%) (table 2).

There were no features of malignancy in any of the resected specimens. Within one type 1 CPAM an area of well circumscribed mucinous proliferation was identified.


Main findings

This study represents one of the largest case series documenting the natural history of CPAMs and PS following a prenatal diagnosis. The median length of follow-up of the conservatively managed group is the longest yet published. We have demonstrated an absence of any cases of malignancy, confirmed that spontaneous resolution is possible, and established that the incidence of recurrent respiratory infection leading to surgical intervention diminishes after the second year.


There are four arguments used to justify a surgical approach in the management of all asymptomatic CPAM/PS13:

  • The risk of malignancy.

  • The risk of complications including infection and pneumothorax.

  • The potential for compensatory lung regrowth following early resection.

  • A reduction in postoperative complications following elective surgery.

The risk of malignancy

We did not find evidence of malignancy in any of the resected lesions and do not suspect malignancy in any of our conservatively managed cohort. These findings are in keeping with previous studies and augment the evidence that the risk of malignant transformation appears rare in early life.9 11 We cannot rule out a possible risk of approximately 1% within this cohort or an increase in malignancy risk as patients enter later adolescence and adulthood.

The two types of malignancy that have been reported as associated with cystic lung lesions are pleuropulmonary blastoma (PPB) and bronchioloalveolar carcinoma (BAC).

Pleuropulmonary blastomas are a distinct pathological entity and do not represent the malignant transformation of CPAM/PS. Ninety-eight per cent of PPBs are diagnosed before the age of 6.8 years.14 Importantly, a type 1 PPB is indistinguishable radiologically from a benign cystic lung lesion such as a CPAM. The risk, however, of a prenatally diagnosed CPAM or PS in fact representing a PPB is slight. A total of 350 pathology-confirmed PPB cases have been identified to date by the International PPB Registry,14 of which only nine were identified on prenatal ultrasound scan. Accurate identification of PPB may be improved by ascertaining a family history of PPB associated tumours (eg, ovarian, renal and thyroid) and detecting mutations within the DICER1 gene, demonstrated to be associated with 66% of cases.14 15 In addition, clinical features such pneumothorax and pleural effusion, commonly associated with PPB but rarely documented in cases of CPAM/PS, may be a sensitive clinical marker.14 16

Bronchioloalveolar carcinomas occur following the transformation of cells within type 1 CPAMs only. Mucinous cells have the potential to develop into areas of atypical adenomatous hyperplasia, transform into BAC (non-invasive) and subsequently adenocarcinoma (invasive).17 18 Both types of tumour, however, are exceptionally rare with only 24 cases described in total.17 19–35 Of these, the diagnosis was made incidentally in the majority of cases following resection of a cystic lesion for indications such as recurrent infection, cough, chest pain and haemoptysis.

Prophylactic resection of cystic lung lesions does not eliminate the risk of malignancy. Adenocarcinoma has been described following previous resection of CPAM in early life21 and a PPB described following prior resection of a cystic lesion from an anatomically distinct area of the lung.36

The risk of complications including infection and pneumothorax

Previous estimates of the incidence of respiratory infection in children with CPAM or PS range between 3% and 5%. A systematic review conducted by Stanton et al 11 described 505 expectantly managed infants, of which 3.2% became symptomatic in the first year. Ng et al 9 reported a case series of 74 patients in which 5% of children developed symptoms over a median follow-up period of 5 years. Chetcuti et al 37 reported a cohort of over 100 children of which approximately 5% developed symptoms of lower respiratory tract infection and subsequently underwent surgery during early childhood. It was unknown whether these figures underestimate the lifetime risk due to the short follow-up.

Surgical resection was undertaken in 9.2% of our cohort due to recurrent respiratory infection and the majority of resected specimens exhibited histological evidence of inflammation. The higher proportion of patients presenting with symptoms of recurrent infection than in previous studies may reflect the impact of a longer follow-up period and the selective referral of symptomatic cases from other centres. In addition, the definition of respiratory infection for this study was based on doctor diagnosed infection. The inherent subjectivity in this diagnosis has likely resulted in an overestimate of the occurrence of genuine recurrent lower respiratory tract infection in this cohort. This study has established that following the second year the rate of resection for recurrent infection diminishes, and there were no resections in those over the age of 5 years. Our results suggest that the figures previously described do not represent a cumulative risk of 3% to 5% per year.

We report one case of severe respiratory infection requiring ventilation. Severe infection is a complication that has been reported in other cohorts.38 There were no cases of pneumothorax within our cohort in keeping with previous data suggesting that pneumothorax is a rarely reported clinical feature of CPAM/PS.16

The potential for compensatory lung growth following early resection

The prospect of improved compensatory lung growth in patients if resection is completed in early life is proposed as an indication for elective resection. Traditionally alveolar regeneration was thought to be more likely to occur in early life during the alveolar stage of lung growth. Evidence for this phenomenon is lacking39–44 and indeed genuine new alveolar growth is likely to occur into adolescence.41 ,44 A further argument against this motivation for resection is that the majority of lesions identified are small and appear to reduce in size as the lung grows in early life. Indeed, we identified that 5.9% of lesions disappeared on CT imaging during the postnatal period, which is a similar proportion to that reported previously.10

The risk of surgery

It was beyond the scope of this study to report surgical complications. In their systematic review, Stanton et al 11 performed a meta-analysis of nine case series and calculated a greater than twofold increase in risk of postoperative complications in symptomatic compared with asymptomatic patients, suggesting a role for elective surgery. The majority of symptomatic cases, however, were neonates possibly influencing this result. Elective surgery is not without risk and postoperative complications occurred in 5% of asymptomatic infants, including air leak, infection, effusion and death in one case.11 Hall et al 44 ,45 recently reported a complication rate of 23% in a case series of 60 patients with asymptomatic CPAM who underwent surgery. This included complications in three cases defined as major: tension pneumothorax, aggressive chest wall fibromatosis and near fatal haemorrhage.

Further limitations

Over the long course of the study period, patients and families have been counselled by a variety of physicians and surgeons whose approach to the management of these lesions has varied. This is likely reflected in aspects of our results. A large proportion of our cohort opted for elective resection following medical advice. This group consisted of parents who decided that this was their preferred option when also given the option of a conservative approach, and also those who were counselled that the surgical option was preferable. In addition, variation in approach to management appears to be reflected in decisions to discharge patients from clinic. Figure 3 represents a summary of the current GOSH approach to assessment and follow-up of patients with asymptomatic CPAM/PS during the paediatric period with features at each stage that may trigger intervention.

Figure 3

GOSH approach to assessment and follow-up of asymptomatic CPAM/PS during the paediatric period and features that may trigger intervention. *DICER1 mutation analysis is not offered as a routine screening test. CLM, congenital lung malformation; CPAM, congenital pulmonary airway malformations; GOSH, Great Ormond Street Hospital; PS, pulmonary sequestration.


This report demonstrates that the conservative approach to prenatally diagnosed asymptomatic CLMs of the CPAM/PS type is a reasonable option in selected cases. Careful explanation to parents and antenatal counselling regarding these lesions is recommended. The evidence presented establishes for the first time that the need for surgical resection as a result of recurrent respiratory infection is reduced following the second year, has confirmed that spontaneous resolution may be expected in some cases and has demonstrated that malignancy associated with these lesions is a rare phenomenon during the paediatric period. Unfortunately, there remains no prospect of a randomised trial to assist with decision making in these difficult cases and clinical judgement is required. Continued long-term follow-up of cases will assist in further definition of their natural history.


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  • Contributors CW, LSC, PDC and JC contributed to study conception and design. JC, LSC and MA contributed to data acquisition. JC and CW drafted the manuscript. LSC, PDC and CW provided editing of the manuscript.

  • Funding LSC and PDC are partially funded by the NIHR Biomedical Research Centre at Great Ormond Street NHS Foundation Trust.

  • Competing interests None declared.

  • Ethics approval Clinical Audit Department, Great Ormond Street Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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