REVIEW URRENT C OPINION
Prenatal imaging and postnatal presentation, diagnosis and management of congenital lung malformations James Wall a and Anne Coates b
Purpose of review Congenital lung malformations (CLMs) vary in their clinical presentation and severity. Increases in prenatal diagnosis, observed regression of certain lesions, and prognostic uncertainty are driving an evolution in management. Recent findings There has been an increase in the early diagnosis of these malformations, a change that is attributable to the routine use of prenatal ultrasound. Although prenatal diagnosis of CLMs using ultrasound and MRI has increased, chest radiography and computed tomography still play important roles in diagnosis. The management of these lesions depends on the type of malformation and symptoms. The treatment of asymptomatic patients with lung malformations is controversial, because the prognosis of these lesions is largely unknown. Proponents of early intervention argue that the complications of CLM, which may include infection, pneumothorax, bleeding and malignant transformation, justify surgery. Advocates of conservative management note that some CLMs disappear postnatally, and that the long-term complication rate following surgery is unknown. There is a need to obtain natural history data regardless of the therapeutic recommendations. Summary This article reviews the prenatal radiographic features and postnatal clinical findings of various CLMs and the dilemmas regarding treatment. Keywords congenital lung malformation, infants, prenatal
INTRODUCTION Congenital lung malformations (CLMs) represent a heterogeneous group that spans a continuum of developmental disorders involving pulmonary parenchyma, bronchi, arterial supply, and venous drainage. No organizational structure or system of nomenclature exists to describe all lung abnormalities. The types of CLMs range from congenital lobar emphysema (CLE), which represents an abnormal lung supplied by normal vessels, to pulmonary arteriovenous malformations that consist of abnormal vessels within normal lung parenchyma. Thus, CLM includes almost all malformations with abnormal connections of one or more of the four major components of lung tissue: tracheobronchial tree, lung parenchyma, arterial supply, and venous drainage [1]. The pathogenesis of these malformations is poorly understood. According to one theory, many
of these lesions are because of defective foregut budding and differentiation [2]. Another theory of causation is that these lesions are related to airway obstruction with secondary pulmonary dysplastic changes. Variability in the timing and severity of airway obstruction may help explain the frequency of occurrence of hybrid or overlapping lesions [3,4].
a
Division of Pediatric Surgery, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, California and bPediatric Pulmonary Division, Department of Pediatrics, Tufts University School of Medicine, Boston, Massachusetts, USA Correspondence to James Wall, MD, MS, Assistant Professor of Pediatric Surgery, Lucile Packard Children’s Hospital, Stanford University, 777 Welch Road, Suite J, Palo Alto, CA 94304, USA. e-mail: [email protected] Curr Opin Pediatr 2014, 26:315–319 DOI:10.1097/MOP.0000000000000091
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KEY POINTS Congenital lung malformations are rare and vary widely in their clinical presentation and severity. Although prenatal diagnosis of CLMs using ultrasound and MRI has increased, chest radiography and computed tomography (CT) remain the gold standard for postnatal diagnosis. Surgical resection remains the treatment of choice for all symptomatic lesions. Asymptomatic CLE and ELS can generally be observed. Cystic lung lesions, including CPAM and bronchogenic cysts, should be resected between 3 and 12 months of age because of risks of infection, malignant transformation, and diagnostic uncertainty. Minimally invasive surgical approaches to CLMs are a well-tolerated and effective approach in experienced hands. Long-term prospective studies of CLMs are needed to enhance our understanding of their natural history and prognosis.
Although the prenatal diagnosis of CLMs has increased because of advances in imaging technology, such as ultrasound and MRI, chest radiography and computed tomography (CT) still have important diagnostic roles [1,5]. Understanding proper imaging techniques, characteristic imaging findings, and underlying gross and histopathological structures of congenital pulmonary malformation enhances the diagnostic accuracy and proper management of pediatric patients with these complex congenital pulmonary anomalies [6].
EPIDEMIOLOGY Enhanced prenatal and postnatal imaging has increased the frequency of congenital lung lesion diagnosis. These imaging techniques have increased the understanding of the onset, timing, natural history, and causative associations of congenital pulmonary malformations [6]. However, the epidemiology of these lesions remains largely unknown. The European Surveillance of Congenital Anomalies (EUROCAT) is the largest network of populationbased registries for the epidemiologic surveillance of congenital anomalies, including congenital thoracic malformations (CTMs). Data are collected from 43 European registries in 20 European countries, but still only capture less than 30% of Europe’s birth population. The incidence of CTM reported by EUROCAT in 2008 was 4.44/10 000 (which included live births, fetal deaths, and terminations of pregnancy) [7]. Additional literature reports an estimated 316
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annual incidence of CLMs ranging from 30 to 42 cases per 100 000 population [6,8,9]. Until further population-based studies are conducted, the precise incidence of CLM will remain unknown.
CLINICAL PRESENTATION The clinical manifestation of these malformations varies from respiratory distress in the immediate postnatal period to an incidental finding on routine chest radiographs. In a small proportion, the larger lesions may adversely affect the contralateral developing fetal lung by causing mediastinal shift, polyhydramnios, hydrops, or even intrauterine death [10]. This review focuses on the following malformations: congenital pulmonary airway malformations (CPAMs), pulmonary sequestrations, bronchogenic cysts, and CLE. CPAMs are a heterogeneous group of cystic and noncystic lung lesions that largely result from early airway maldevelopment. The term ‘congenital pulmonary airway malformation’ has been recommended as preferable to the term ‘congenital cystic adenomatoid malformation’ (CCAM), as the lesions are cystic in only three of the five types of these lesions and adenomatoid in only one type (type 3) [11]. The pathogenesis of CPAM has been the subject of controversy [4]. CPAMs have been classified by Stocker [11] according to the cyst size and histologic resemblance to segments of the developing bronchial tree and airspaces. Langston [3] believes that the five types may represent different malformations with varying causes. Imaging can distinguish three types of CPAM: large cyst CPAM (type I) and small cyst CPAM (type II), which constitute macrocystic CPAMs, and microcystic or solid type (type III) lesions, which have cysts that are smaller than 5 mm in diameter. Fetal ultrasound and MRI reveal variable-sized masses, whose appearance depends on the cystic and solid components of the lesions [12]. Postnatally, the diagnosis may be suggested by chest X-ray (CXR); however, a thoracic high resolution CT scan is indicated to strengthen the diagnosis [13,14]. Indicators of poor prognosis include large lesions, bilateral lung involvement, and hydrops [4,15]. Quantitative measurement of mass size, such as CPAM volume ratio (CVR) over 1.6, has also been used to predict the development of hydrops [15]. In one study, 86% of patients who were asymptomatic at birth had become symptomatic by 13 years of age (median age of 2 years) [16,17]. Pneumonia with or without infected CPAM was reported in 43% of patients, whereas respiratory distress and spontaneous pneumothorax were reported in 14% [17]. Volume 26 Number 3 June 2014
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Pulmonary sequestration is characterized by a portion of lung that does not connect to the tracheobronchial tree and has a systemic arterial supply. It commonly occurs in the lower lobe, primarily in the left posterior basal segment [18]. Two types of sequestration have been described: extralobar sequestration (ELS) and intralobar sequestration (ILS). The ELS form has its own pleural investment and systemic venous drainage, whereas the ILS form shares the pleural investment with the normal lung and usually drains into the pulmonary venous system [15,19]. The ELS form is most commonly diagnosed in the prenatal–neonatal period, whereas the ILS form is usually diagnosed later in childhood or adulthood [4]. ILS lesions account for 80% of sequestrations [18]. Furthermore, ELS lesions may be associated with other congenital systemic anomalies, such as congenital diaphragmatic hernia, cardiac abnormalities, pulmonary hypoplasia, or foregut duplication cysts [2]. At fetal ultrasound, ELS is seen as a homogeneous hyperechoic mass in a paraspinal location, most often the left lower thorax. The feeding artery originating from the descending aorta may be seen at color Doppler ultrasound. Occasionally, these vessels may not be identified at Doppler ultrasound, making ELS indistinguishable from a microcystic CPAM. Large lesions can compress the esophagus and thoracic veins and subsequently cause hydrops, which is an indication for fetal intervention or early delivery [20]. Either ultrasound with Doppler imaging or thoracic CT with contrast may be used to define the lesion postnatally [13]. The age of presentation is variable in children with ELS. Symptoms may include cough, chest pain, dyspnea, and hemoptysis. In addition, recurrent lower lobe pneumonia unresponsive to antibiotic therapy may be suggestive of the diagnosis [17,18]. Bronchogenic cysts are part of the spectrum of foregut duplication cysts [4]. They are characterized by the presence of cartilage, smooth muscle, and glands in their wall. They are usually unilocular, filled with fluid or mucus, and generally do not communicate with the airway. The majority are located in the mediastinum, usually adjacent to the distal trachea or proximal mainstem bronchi, but they can also be found within the lung parenchyma, pleura, or diaphragm [21]. At fetal ultrasound, bronchogenic cysts may manifest as unilocular fluid-filled cysts in the middle or posterior mediastinum [4]. Similarly to the lesions mentioned above, postnatally, the diagnosis may be suggested by CXR; however, a thoracic high resolution computerized tomography scan is indicated to confirm the diagnosis [19].
In infants, symptoms are generally caused by compression of the trachea or bronchi and esophagus, leading to wheezing, stridor, dyspnea, and dysphagia. Intraparenchymal cysts may manifest with recurrent infection [4]. CLE is a term used to describe a distended, hyperlucent lobe on plain radiographs, usually involving the left upper or the right middle lobe [22]. Pathologically, a distinction is made between a polyalveolar lobe, in which the number of alveoli is greatly increased, and congenital lobar overinflation (CLO), in which the alveoli are markedly distended [5]. CLO is thought to be caused by a partial bronchial obstruction creating a ball-valve effect. This obstruction may be intrinsic (bronchomalacia) or, less commonly, extrinsic (vascular, bronchogenic cyst), but in many instances an exact cause cannot be determined [5]. Fetal ultrasound may show a homogeneously hyperechoic mass [4]. Hyperlucency of the affected lobe(s) is the characteristic feature on CXR [21]. Like other CLMs, thoracic HRCT may confirm the diagnosis. Lesions may be asymptomatic or present with severe respiratory distress in the neonatal period, whereas older infants may experience dyspnea or recurrent respiratory infections [23]. Asymptomatic newborns with an antenatal diagnosis of a CLM should have an early CXR [24]. It will often be normal, but subsequent, more detailed imaging may reveal malformations; CXR was only 61% sensitive for malformations compared with the gold standard of HRCT, in which there were no false-positive diagnoses [25].
MANAGEMENT Prenatal management is evolving as more CLMs are being diagnosed. The development of hydrops in the second trimester because of a large mass or high-flow vascular lesions warrants fetal intervention. Intervention is limited to highly specialized fetal treatment centers and includes cyst aspiration, pleuroamniotic shunt, and open fetal lung resection. In 2009, an observation was made that maternal steroid administration may induce regression of cystic lung lesions [26]. Studies are ongoing and subsequent reports have shown a variable response to steroid therapy [27 ,28]. Postnatal management of symptomatic CLM is timely resection; however, much controversy remains around the management of asymptomatic lesions. Incomplete knowledge surrounding the natural history of CLM compromises our ability to better define the relative risks and benefits of early resection. Arguments for early resection of asymptomatic lesions are infection risk, malignant
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potential, uncertainty in radiographically distinguishing lesions, prevention of pneumothorax, decreasing radiation exposure associated with surveillance, and greater compensatory lung growth early in life. These risks vary among the various subsets of CLM. The risk of infection is most associated with aerated lesions, including CPAM and hybrid sequestrations. The risk of malignancy is two-fold. First, malignant transformation from CPAM to bronchioloalveolar carcinoma (BAC) is biologically established and estimated to occur in 1% of cases. Second, pleuropulmonary blastoma (PBB) is associated with cystic lung lesions in young children and probably represents missed diagnosis instead of malignant transformation. PBB is thought to evolve from cystic to solid over time. Up to 4% of cases thought to be CPAM with a cystic component may in fact represent misdiagnosed cases of PPB. On the basis of risk of infection and malignancy, current recommendations are resection of bronchogenic cysts, CPAM, and ILS. Asymptomatic CLE and ELS may be observed. The surgical approach to resection of CLMs was classically via thoracotomy. In the last decade, CLE, CPAM, sequestration, and bronchogenic cysts have all been successfully resected with minimally invasive thoracoscopic techniques [29,30]. A metaanalysis of six retrospective series of thoracoscopic versus open management of CLMs revealed no difference in complications or operative time between the two approaches. Thoracoscopy was associated with significantly shorter hospital stay and fewer days with a chest tube in place [31 ]. Thoracoscopy may be limited in young infants and symptomatic lesions if single-lung ventilation is not well tolerated. More recently, lung-sparing thoracoscopic segmental resections have been reported in infants [32 ]. Although it is conceptually appealing to remove only the affected segment(s) of the lobe, the gross intraoperative differentiation between normal and CPAM remains challenging. Timing of elective CLM resection in asymptomatic lesions is debated. It is unnecessary to operate in the immediate newborn period with a higher risk of anesthesia and poorer tolerance of single-lung ventilation. However, the incidence of infection in the first 6 months of life is reported from 10 to 30% and resection is preferable before an episode of pneumonia that may create peribronchial lymphadenopathy and scarring. A recent review of 49 thoracoscopic CLM cases reported complications, and conversion to thoracotomy was 2.5-fold higher in patients under 5 months of age [33]. However, complication rates have also been reported to increase in patients who are left to develop symptoms [34]. When balancing the risks around the &
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timing of resection, most surgeons elect to resect between 3 and 12 months of age.
LONG-TERM FOLLOW UP There is a paucity of long-term prospective studies on children with CLMs, which makes it challenging to provide firm recommendations regarding treatment and management of these lesions during the prenatal and postnatal period, particularly in the asymptomatic patient. Thus, it is important to share the uncertainties in prognosis with families. Overall, there are several issues to consider, including the effects of lung resection and the needs of the child with a malformation that is being managed conservatively. In general, human and animal data suggest that it is the extent, not age, of resection that is important [35]. Long-term prospective studies of CLMs are needed to document their natural history and outcomes, which will help guide optimal prenatal counseling and postnatal management. In addition, there may be a valuable role for the multidisciplinary team approach, which includes neonatology, maternal fetal medicine, pediatric surgery, radiology, and pulmonary, in determination of the diagnosis and ideal management of these lesions as well as long-term follow up of these patients over time. While a limited registry of PPB, based out of Children’s Hospitals and Clinics of Minnesota, exists (www.ppbregistry.org), no large multicenter registry of CLMs has been established. Such a registry would enhance the understanding of the onset, timing, natural history, and prognosis of these lesions.
CONCLUSION CLMs comprise a broad spectrum of lesions that involve maldeveloped lung parenchyma, bronchi, and vasculature. They vary widely in their clinical presentation and severity. The management of these lesions depends on the type of malformation and symptoms. Understanding proper imaging techniques, characteristic imaging findings, and underlying gross and histopathological structures of congenital pulmonary malformation can enhance the accurate diagnosis and proper management of patients. Improved diagnostic modalities are needed to remove the uncertainty, and long-term studies of natural history are needed to enable accurate prognosis. Acknowledgements The authors would like to thank Dr John David Mark and Robert Wright for their review and contributions to this article. Volume 26 Number 3 June 2014
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Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Watarai F, Takahashi M, Hosoya T, Murata K. Congenital lung abnormalities: a pictorial review of imaging findings. Jpn J Radiol 2012; 30:787–797. 2. Newman B. Congenital bronchopulmonary foregut malformations: concepts and controversies. Pediatr Radiol 2006; 36:773–791. 3. Langston C. New concepts in the pathology of congenital lung malformations. Semin Pediatr Surg 2003; 12:17–37. 4. Biyyam DR, Chapman T, Ferguson MR, et al. Congenital lung abnormalities: embryologic features, prenatal diagnosis, and postnatal radiologic– pathologic correlation. Radiographics 2010; 30:1721–1738. 5. Laberge JM, Puligandla P, Flageole H. Asymptomatic congenital lung malformations. Semin Pediatr Surg 2005; 14:16–33. 6. Lee EY, Dorkin H, Vargas SO. Congenital pulmonary malformations in pediatric patients: review and update on etiology, classification, and imaging findings. Radiol Clin North Am 2011; 49:921–948. 7. Michael R, Bush A, Chitty L, et al. Respiratory disorders in the newborn. In: Wilmott R, Boat T, Bush A, et al., editors. Kendig and Chernick’s disorders of the respiratory tract in children. 8th ed. Amsterdam: Elsevier; 2012. p. 319. 8. Sylvester K, Albanese C. Bronchopulmonary malformations. In: Ashcraft K, Holcom G, Murphy J, editors. Ashcraft’s pediatric surgery. Philadelphia: Saunders Elsevier; 2005. pp. 276–289. 9. Costa Junior Ada S, Perfeito JA, Forte V. Surgical treatment of 60 patients with pulmonary malformations: what have we learned? J Bras Pneumol 2008; 34:661–666. 10. Crombleholme TM, Coleman B, Hedrick H, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg 2002; 37:331–338. 11. Stocker J. Congenital pulmonary airway malformation: a new name for and an expanded classification of congenital cystic adenomatoid malformation of the lung. Symposium 24. Histopathology 2002; 41 (Suppl. 2):424–430. 12. Daltro P, Werner H, Gasparetto TD, et al. Congenital chest malformations: a multimodality approach with emphasis on fetal MR imaging. Radiographics 2010; 30:385–395. 13. Lanza C, Bolli V, Galeazzi V, et al. Cystic adenomatoid malformation in children: CT histopathological correlation. Radiol Med 2007; 112:612–619. 14. Kim WS, Lee KS, Kim IO, et al. Congenital cystic adenomatoid malformation of the lung: CT-pathologic correlation. AJR Am J Roentgenol 1997; 168:47–53. 15. Winters WD, Effmann EL. Congenital masses of the lung: prenatal and postnatal imaging evaluation. J Thorac Imaging 2001; 16:196–206. 16. Nadeem M, Elnazir B, Greally P. Congenital pulmonary malformation in children. Scientifica 2012; 2012:209896. 17. Wong A, Vieten D, Singh S, et al. Long-term outcome of asymptomatic patients with congenital cystic adenomatoid malformation. Pediatr Surg Int 2009; 25:479–485.
18. Wei Y, Li F. Pulmonary sequestration: a retrospective analysis of 2625 cases in China. Eur J Cardiothorac Surg 2011; 40:e39–e42. 19. Gezer S, Tastepe I, Sirmali M, et al. Pulmonary sequestration: a singleinstitutional series composed of 27 cases. J Thorac Cardiovasc Surg 2007; 133:955–959. 20. Azizkhan RG, Crombleholme TM. Congenital cystic lung disease: contemporary antenatal and postnatal management. Pediatr Surg Int 2008; 24:643– 657. 21. McAdams HP, Kirejczyk WM, Rosado-de-Christenson ML, Matsumoto S. Bronchogenic cyst: imaging features with clinical and histopathologic correlation. Radiology 2000; 217:441–446. 22. Williams HJ, Johnson KJ. Imaging of congenital cystic lung lesions. Paediatr Respir Rev 2002; 3:120–127. 23. Karnak I, Senocak ME, Ciftci AO, Buyukpamukcu N. Congenital lobar emphysema: diagnostic and therapeutic considerations. J Pediatr Surg 1999; 34:1347–1351. 24. Bush A. Prenatal presentation and postnatal management of congenital thoracic malformations. Early Hum Dev 2009; 85:679–684. 25. Calvert JK, Lakhoo K. Antenatally suspected congenital cystic adenomatoid malformation of the lung: postnatal investigation and timing of surgery. J Pediatr Surg 2007; 42:411–414. 26. Tsao K, Hawgood S, Vu L, et al. Resolution of hydrops fetalis in congenital cystic adenomatoid malformation after prenatal steroid therapy. J Pediatr Surg 2003; 38:508–510. 27. Loh KC, Jelin E, Hirose S, et al. Microcystic congenital pulmonary airway && malformation with hydrops fetalis: steroids vs open fetal resection. J Pediatr Surg 2012; 47:36–39. Although small and nonrandomized, this series makes the strongest argument to date for the novel approach of steroid therapy in severe cases of prenatal CPAM with hydrops. 28. Morris LM, Lim FY, Livingston JC, et al. High-risk fetal congenital pulmonary airway malformations have a variable response to steroids. J Pediatr Surg 2009; 44:60–65. 29. Albanese CT, Sydorak RM, Tsao K, Lee H. Thoracoscopic lobectomy for prenatally diagnosed lung lesions. J Pediatr Surg 2003; 38:553– 555. 30. Rothenberg SS. First decade’s experience with thoracoscopic lobectomy in infants and children. J Pediatr Surg 2008; 43:40–44; discussion 45. 31. Nasr A, Bass J. Thoracoscopic vs open resection of congenital lung lesions: & a meta analysis. J Pediatr Surg 2012; 47:857–861. This meta-analysis of restrospective data establishes safety and benefits of thoracoscopic resection in experienced centers. 32. Rothenberg SS, Shipman K, Kay S, et al. Thoracoscopic segmentectomy for && congenital and acquired pulmonary disease: a case for lung-sparing surgery. J Laparoendosc Adv Surg Tech A 2014; 24:50–54. This is the first published series of lung-sparing segmentectomy in the pediatric population. This series establishes safety of this approach in the hands of expert thoracoscopic surgeons. Long-term results are needed to establish efficacy. 33. Kunisaki SM, Powelson IA, Haydar B, et al. Thoracoscopic vs open lobectomy in infants and young children with congenital lung malformations. J Am Coll Surg 2014; 218:261–270. 34. Beres A, Aspirot A, Paris C, et al. A contemporary evaluation of pulmonary function in children undergoing lung resection in infancy. J Pediatr Surg 2011; 46:829–832. 35. Michael R, Bush A, Chitty L, et al. Respiratory disorders in the newborn. In: Wilmott R, Boat T, Bush A, et al., editors. Kendig and Chernick’s disorders of the respiratory tract in children. 8th ed. Amsterdam: Elsevier; 2012. p. 357.
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Prenatal imaging and postnatal presentation, diagnosis and management of congenital lung malformations James Wall a and Anne Coates b
Purpose of review Congenital lung malformations (CLMs) vary in their clinical presentation and severity. Increases in prenatal diagnosis, observed regression of certain lesions, and prognostic uncertainty are driving an evolution in management. Recent findings There has been an increase in the early diagnosis of these malformations, a change that is attributable to the routine use of prenatal ultrasound. Although prenatal diagnosis of CLMs using ultrasound and MRI has increased, chest radiography and computed tomography still play important roles in diagnosis. The management of these lesions depends on the type of malformation and symptoms. The treatment of asymptomatic patients with lung malformations is controversial, because the prognosis of these lesions is largely unknown. Proponents of early intervention argue that the complications of CLM, which may include infection, pneumothorax, bleeding and malignant transformation, justify surgery. Advocates of conservative management note that some CLMs disappear postnatally, and that the long-term complication rate following surgery is unknown. There is a need to obtain natural history data regardless of the therapeutic recommendations. Summary This article reviews the prenatal radiographic features and postnatal clinical findings of various CLMs and the dilemmas regarding treatment. Keywords congenital lung malformation, infants, prenatal
INTRODUCTION Congenital lung malformations (CLMs) represent a heterogeneous group that spans a continuum of developmental disorders involving pulmonary parenchyma, bronchi, arterial supply, and venous drainage. No organizational structure or system of nomenclature exists to describe all lung abnormalities. The types of CLMs range from congenital lobar emphysema (CLE), which represents an abnormal lung supplied by normal vessels, to pulmonary arteriovenous malformations that consist of abnormal vessels within normal lung parenchyma. Thus, CLM includes almost all malformations with abnormal connections of one or more of the four major components of lung tissue: tracheobronchial tree, lung parenchyma, arterial supply, and venous drainage [1]. The pathogenesis of these malformations is poorly understood. According to one theory, many
of these lesions are because of defective foregut budding and differentiation [2]. Another theory of causation is that these lesions are related to airway obstruction with secondary pulmonary dysplastic changes. Variability in the timing and severity of airway obstruction may help explain the frequency of occurrence of hybrid or overlapping lesions [3,4].
a
Division of Pediatric Surgery, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, California and bPediatric Pulmonary Division, Department of Pediatrics, Tufts University School of Medicine, Boston, Massachusetts, USA Correspondence to James Wall, MD, MS, Assistant Professor of Pediatric Surgery, Lucile Packard Children’s Hospital, Stanford University, 777 Welch Road, Suite J, Palo Alto, CA 94304, USA. e-mail: [email protected] Curr Opin Pediatr 2014, 26:315–319 DOI:10.1097/MOP.0000000000000091
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Pulmonology
KEY POINTS Congenital lung malformations are rare and vary widely in their clinical presentation and severity. Although prenatal diagnosis of CLMs using ultrasound and MRI has increased, chest radiography and computed tomography (CT) remain the gold standard for postnatal diagnosis. Surgical resection remains the treatment of choice for all symptomatic lesions. Asymptomatic CLE and ELS can generally be observed. Cystic lung lesions, including CPAM and bronchogenic cysts, should be resected between 3 and 12 months of age because of risks of infection, malignant transformation, and diagnostic uncertainty. Minimally invasive surgical approaches to CLMs are a well-tolerated and effective approach in experienced hands. Long-term prospective studies of CLMs are needed to enhance our understanding of their natural history and prognosis.
Although the prenatal diagnosis of CLMs has increased because of advances in imaging technology, such as ultrasound and MRI, chest radiography and computed tomography (CT) still have important diagnostic roles [1,5]. Understanding proper imaging techniques, characteristic imaging findings, and underlying gross and histopathological structures of congenital pulmonary malformation enhances the diagnostic accuracy and proper management of pediatric patients with these complex congenital pulmonary anomalies [6].
EPIDEMIOLOGY Enhanced prenatal and postnatal imaging has increased the frequency of congenital lung lesion diagnosis. These imaging techniques have increased the understanding of the onset, timing, natural history, and causative associations of congenital pulmonary malformations [6]. However, the epidemiology of these lesions remains largely unknown. The European Surveillance of Congenital Anomalies (EUROCAT) is the largest network of populationbased registries for the epidemiologic surveillance of congenital anomalies, including congenital thoracic malformations (CTMs). Data are collected from 43 European registries in 20 European countries, but still only capture less than 30% of Europe’s birth population. The incidence of CTM reported by EUROCAT in 2008 was 4.44/10 000 (which included live births, fetal deaths, and terminations of pregnancy) [7]. Additional literature reports an estimated 316
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annual incidence of CLMs ranging from 30 to 42 cases per 100 000 population [6,8,9]. Until further population-based studies are conducted, the precise incidence of CLM will remain unknown.
CLINICAL PRESENTATION The clinical manifestation of these malformations varies from respiratory distress in the immediate postnatal period to an incidental finding on routine chest radiographs. In a small proportion, the larger lesions may adversely affect the contralateral developing fetal lung by causing mediastinal shift, polyhydramnios, hydrops, or even intrauterine death [10]. This review focuses on the following malformations: congenital pulmonary airway malformations (CPAMs), pulmonary sequestrations, bronchogenic cysts, and CLE. CPAMs are a heterogeneous group of cystic and noncystic lung lesions that largely result from early airway maldevelopment. The term ‘congenital pulmonary airway malformation’ has been recommended as preferable to the term ‘congenital cystic adenomatoid malformation’ (CCAM), as the lesions are cystic in only three of the five types of these lesions and adenomatoid in only one type (type 3) [11]. The pathogenesis of CPAM has been the subject of controversy [4]. CPAMs have been classified by Stocker [11] according to the cyst size and histologic resemblance to segments of the developing bronchial tree and airspaces. Langston [3] believes that the five types may represent different malformations with varying causes. Imaging can distinguish three types of CPAM: large cyst CPAM (type I) and small cyst CPAM (type II), which constitute macrocystic CPAMs, and microcystic or solid type (type III) lesions, which have cysts that are smaller than 5 mm in diameter. Fetal ultrasound and MRI reveal variable-sized masses, whose appearance depends on the cystic and solid components of the lesions [12]. Postnatally, the diagnosis may be suggested by chest X-ray (CXR); however, a thoracic high resolution CT scan is indicated to strengthen the diagnosis [13,14]. Indicators of poor prognosis include large lesions, bilateral lung involvement, and hydrops [4,15]. Quantitative measurement of mass size, such as CPAM volume ratio (CVR) over 1.6, has also been used to predict the development of hydrops [15]. In one study, 86% of patients who were asymptomatic at birth had become symptomatic by 13 years of age (median age of 2 years) [16,17]. Pneumonia with or without infected CPAM was reported in 43% of patients, whereas respiratory distress and spontaneous pneumothorax were reported in 14% [17]. Volume 26 Number 3 June 2014
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Congenital lung malformations Wall and Coates
Pulmonary sequestration is characterized by a portion of lung that does not connect to the tracheobronchial tree and has a systemic arterial supply. It commonly occurs in the lower lobe, primarily in the left posterior basal segment [18]. Two types of sequestration have been described: extralobar sequestration (ELS) and intralobar sequestration (ILS). The ELS form has its own pleural investment and systemic venous drainage, whereas the ILS form shares the pleural investment with the normal lung and usually drains into the pulmonary venous system [15,19]. The ELS form is most commonly diagnosed in the prenatal–neonatal period, whereas the ILS form is usually diagnosed later in childhood or adulthood [4]. ILS lesions account for 80% of sequestrations [18]. Furthermore, ELS lesions may be associated with other congenital systemic anomalies, such as congenital diaphragmatic hernia, cardiac abnormalities, pulmonary hypoplasia, or foregut duplication cysts [2]. At fetal ultrasound, ELS is seen as a homogeneous hyperechoic mass in a paraspinal location, most often the left lower thorax. The feeding artery originating from the descending aorta may be seen at color Doppler ultrasound. Occasionally, these vessels may not be identified at Doppler ultrasound, making ELS indistinguishable from a microcystic CPAM. Large lesions can compress the esophagus and thoracic veins and subsequently cause hydrops, which is an indication for fetal intervention or early delivery [20]. Either ultrasound with Doppler imaging or thoracic CT with contrast may be used to define the lesion postnatally [13]. The age of presentation is variable in children with ELS. Symptoms may include cough, chest pain, dyspnea, and hemoptysis. In addition, recurrent lower lobe pneumonia unresponsive to antibiotic therapy may be suggestive of the diagnosis [17,18]. Bronchogenic cysts are part of the spectrum of foregut duplication cysts [4]. They are characterized by the presence of cartilage, smooth muscle, and glands in their wall. They are usually unilocular, filled with fluid or mucus, and generally do not communicate with the airway. The majority are located in the mediastinum, usually adjacent to the distal trachea or proximal mainstem bronchi, but they can also be found within the lung parenchyma, pleura, or diaphragm [21]. At fetal ultrasound, bronchogenic cysts may manifest as unilocular fluid-filled cysts in the middle or posterior mediastinum [4]. Similarly to the lesions mentioned above, postnatally, the diagnosis may be suggested by CXR; however, a thoracic high resolution computerized tomography scan is indicated to confirm the diagnosis [19].
In infants, symptoms are generally caused by compression of the trachea or bronchi and esophagus, leading to wheezing, stridor, dyspnea, and dysphagia. Intraparenchymal cysts may manifest with recurrent infection [4]. CLE is a term used to describe a distended, hyperlucent lobe on plain radiographs, usually involving the left upper or the right middle lobe [22]. Pathologically, a distinction is made between a polyalveolar lobe, in which the number of alveoli is greatly increased, and congenital lobar overinflation (CLO), in which the alveoli are markedly distended [5]. CLO is thought to be caused by a partial bronchial obstruction creating a ball-valve effect. This obstruction may be intrinsic (bronchomalacia) or, less commonly, extrinsic (vascular, bronchogenic cyst), but in many instances an exact cause cannot be determined [5]. Fetal ultrasound may show a homogeneously hyperechoic mass [4]. Hyperlucency of the affected lobe(s) is the characteristic feature on CXR [21]. Like other CLMs, thoracic HRCT may confirm the diagnosis. Lesions may be asymptomatic or present with severe respiratory distress in the neonatal period, whereas older infants may experience dyspnea or recurrent respiratory infections [23]. Asymptomatic newborns with an antenatal diagnosis of a CLM should have an early CXR [24]. It will often be normal, but subsequent, more detailed imaging may reveal malformations; CXR was only 61% sensitive for malformations compared with the gold standard of HRCT, in which there were no false-positive diagnoses [25].
MANAGEMENT Prenatal management is evolving as more CLMs are being diagnosed. The development of hydrops in the second trimester because of a large mass or high-flow vascular lesions warrants fetal intervention. Intervention is limited to highly specialized fetal treatment centers and includes cyst aspiration, pleuroamniotic shunt, and open fetal lung resection. In 2009, an observation was made that maternal steroid administration may induce regression of cystic lung lesions [26]. Studies are ongoing and subsequent reports have shown a variable response to steroid therapy [27 ,28]. Postnatal management of symptomatic CLM is timely resection; however, much controversy remains around the management of asymptomatic lesions. Incomplete knowledge surrounding the natural history of CLM compromises our ability to better define the relative risks and benefits of early resection. Arguments for early resection of asymptomatic lesions are infection risk, malignant
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Pulmonology
potential, uncertainty in radiographically distinguishing lesions, prevention of pneumothorax, decreasing radiation exposure associated with surveillance, and greater compensatory lung growth early in life. These risks vary among the various subsets of CLM. The risk of infection is most associated with aerated lesions, including CPAM and hybrid sequestrations. The risk of malignancy is two-fold. First, malignant transformation from CPAM to bronchioloalveolar carcinoma (BAC) is biologically established and estimated to occur in 1% of cases. Second, pleuropulmonary blastoma (PBB) is associated with cystic lung lesions in young children and probably represents missed diagnosis instead of malignant transformation. PBB is thought to evolve from cystic to solid over time. Up to 4% of cases thought to be CPAM with a cystic component may in fact represent misdiagnosed cases of PPB. On the basis of risk of infection and malignancy, current recommendations are resection of bronchogenic cysts, CPAM, and ILS. Asymptomatic CLE and ELS may be observed. The surgical approach to resection of CLMs was classically via thoracotomy. In the last decade, CLE, CPAM, sequestration, and bronchogenic cysts have all been successfully resected with minimally invasive thoracoscopic techniques [29,30]. A metaanalysis of six retrospective series of thoracoscopic versus open management of CLMs revealed no difference in complications or operative time between the two approaches. Thoracoscopy was associated with significantly shorter hospital stay and fewer days with a chest tube in place [31 ]. Thoracoscopy may be limited in young infants and symptomatic lesions if single-lung ventilation is not well tolerated. More recently, lung-sparing thoracoscopic segmental resections have been reported in infants [32 ]. Although it is conceptually appealing to remove only the affected segment(s) of the lobe, the gross intraoperative differentiation between normal and CPAM remains challenging. Timing of elective CLM resection in asymptomatic lesions is debated. It is unnecessary to operate in the immediate newborn period with a higher risk of anesthesia and poorer tolerance of single-lung ventilation. However, the incidence of infection in the first 6 months of life is reported from 10 to 30% and resection is preferable before an episode of pneumonia that may create peribronchial lymphadenopathy and scarring. A recent review of 49 thoracoscopic CLM cases reported complications, and conversion to thoracotomy was 2.5-fold higher in patients under 5 months of age [33]. However, complication rates have also been reported to increase in patients who are left to develop symptoms [34]. When balancing the risks around the &
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timing of resection, most surgeons elect to resect between 3 and 12 months of age.
LONG-TERM FOLLOW UP There is a paucity of long-term prospective studies on children with CLMs, which makes it challenging to provide firm recommendations regarding treatment and management of these lesions during the prenatal and postnatal period, particularly in the asymptomatic patient. Thus, it is important to share the uncertainties in prognosis with families. Overall, there are several issues to consider, including the effects of lung resection and the needs of the child with a malformation that is being managed conservatively. In general, human and animal data suggest that it is the extent, not age, of resection that is important [35]. Long-term prospective studies of CLMs are needed to document their natural history and outcomes, which will help guide optimal prenatal counseling and postnatal management. In addition, there may be a valuable role for the multidisciplinary team approach, which includes neonatology, maternal fetal medicine, pediatric surgery, radiology, and pulmonary, in determination of the diagnosis and ideal management of these lesions as well as long-term follow up of these patients over time. While a limited registry of PPB, based out of Children’s Hospitals and Clinics of Minnesota, exists (www.ppbregistry.org), no large multicenter registry of CLMs has been established. Such a registry would enhance the understanding of the onset, timing, natural history, and prognosis of these lesions.
CONCLUSION CLMs comprise a broad spectrum of lesions that involve maldeveloped lung parenchyma, bronchi, and vasculature. They vary widely in their clinical presentation and severity. The management of these lesions depends on the type of malformation and symptoms. Understanding proper imaging techniques, characteristic imaging findings, and underlying gross and histopathological structures of congenital pulmonary malformation can enhance the accurate diagnosis and proper management of patients. Improved diagnostic modalities are needed to remove the uncertainty, and long-term studies of natural history are needed to enable accurate prognosis. Acknowledgements The authors would like to thank Dr John David Mark and Robert Wright for their review and contributions to this article. Volume 26 Number 3 June 2014
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Congenital lung malformations Wall and Coates
Conflicts of interest There are no conflicts of interest.
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