- Email: [email protected]
Sequestrations, congenital cystic adenomatoid malformations, and congenital lobar emphysema
Sequestrations, Congenital Cystic Adenomatoid Malformations, and Congenital Lobar Emphysema Eric N. Mendeloff, MD The respiratory system begins to develop at 3 weeks gestation, and aberrations in developmental processes may give rise to a group of structural abnormalities collectively referred to as bronchopulmonary foregut malformations (BPFMs). These lesions or anomalies may subsequently present in the newborn period as pulmonary parenchymal abnormalities in association with significant respiratory compromise. This article briefly reviews fetal lung development and then proceeds to delineate the characteristics, presentation, and surgical treatment of 3 of the more common BPFMs, those being sequestrations, congenital cystic adenomatoid malformations, and infantile lobar emphysema. The various types of BPFMs may occur in conjunction with one another or in association with other congenital anomalies, and these lesions should be managed with a thoughtful and aggressive surgical approach. Semin Thorac Cardiovasc Surg 16:209-214 © 2004 Elsevier Inc. All rights reserved. KEYWORDS intralobar/extralobar sequestration, congenital cystic adenomatoid malformation, infantile lobar emphysema
A
spectrum of bronchopulmonary foregut malformations (BPFMs) may result from disordered embryologic interactions occurring during the course of fetal lung development. As their presentation may be life-threatening and may require urgent surgical intervention, clinical recognition of these relatively unusual anomalies is important. BPFMs may occur in conjunction with congenital diaphragmatic hernias. When they do, it presents a particularly lethal combination.1 A brief review of lung development will be followed by a more in depth discussion of three forms of BPFMs, those being sequestrations, congenital cystic adenomatoid malformations, and infantile or congenital lobar emphysema. Bronchogenic cysts, the most commonly diagnosed BPFM, will not be covered in this article.
Development of the Lung The lung begins differentiation in the third week of gestation when it develops as a ventral out pouching on the floor of the primitive foregut.2 The subsequent development of the lung is then generally broken down into 5 phases including the embryonic, pseudoglandular, acinar
Congenital Medical City Children’s Hospital, Dallas, TX 75230. Address reprint requests to Dr. Eric N. Mendeloff, Director, Congenital Heart Surgery, Medical City Children’s Hospital, 7777 Forest Lane, Suite B-115, Dallas, TX 75230. E-mail: [email protected]
1043-0679/04/$-see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2004.08.007
(or canalicular), saccular, and alveolar phases. During the embryonic phase (26 days to 6 weeks gestation), 2 lung buds ultimately give rise to 5 lobar bronchi that come to be associated with the developing pulmonary arteries and veins. The pseudoglandular phase (6 to 16 weeks gestation) encompasses development of the conducting airways and also includes the first appearance of cartilaginous tracheal rings, pseudostratified columnar epithelium, and cilia. The basic structure of the gas exchange units of the lung appear in the acinar phase (16 to 28 weeks gestation) including the initial differentiation of the Type I and Type II pneumocytes. The distal airspaces continue to multiply and differentiate into more complex gas exchange units during the saccular phase (28 to 34 weeks gestation), while the alveolar phase continues from 34 weeks of gestation to beyond birth and truly represents the time during which the majority of alveolar development occurs. Approximately 20 million thick walled air sacs exist at birth and these proliferate into 300 to 600 million alveoli by about 2 years of age after which lung growth occurs more in terms of volume and alveolar size. In this manner, the surface area for gas exchange in the lung increases from 3 to 4 m2 in the neonate to 75 m2 in the adult. Multiple publications have suggested a commonality or overlap in embryological pathogenesis of BPFMs as several different types of these lesions may coexist in the same patient.3,4,5 That said, separate theories do exist as to the etiol209
E.N. Mendeloff
210
Figure 1 (A) This is a thoracic aortogram of a patient with bilateral intralobar sequestrations deriving their blood supply from individual branches of the upper abdominal aorta. The arterial supply to the lesion in the left lung branches multiple times before entering the sequestration itself. (B) This is venous phase of the same angiogram in Fig. 1A. The lesion in the right lung has venous drainage to the pulmonary venous system and that in the left lung drains into the hemiazygous system. Both of these lesions proved to be intralobar sequestrations.
ogy of each of these lesions, and these will be delineated in each the forgoing sections.
Sequestrations Sequestration may defined as a portion of the lung isolated from the remainder of the lung such that it is not in continuity with the upper tracheo-bronchial tree and it receives arterial blood supply from an aberrant branch of the aorta rather than the pulmonary artery (Fig. 1A). This lesion is further broken down into 2 variants, extralobar sequestration (ELS) and intralobar sequestration (ILS) and given their very distinctive elements, these will be discussed in order. ELS is a discrete mass of pulmonary parenchyma existing outside the pleural investment of the lung; i.e., the sequestered lung is enclosed entirely by a separate pleural envelope.6 It is postulated that this develops when independent
collections of cells with respiratory potential arise from the primitive foregut (esophagus) caudal to the normal lung bud. Volpe and coworkers have demonstrated that homeobox gene Hoxb-5 is necessary for normal airway branching and development and have suggested that the developmental abnormalities seen with bronchopulmonary sequestration is related to abnormal expression of the homeobox genes.7 ELS are most commonly found on the left side (66%) adjacent to the esophagus and between the lower lobe and diaphragm.8 These independent collections of cells may arise so caudally that subdiaphragmatic and retroperitoneal locations of the various types of sequestrations do occur as often as 15% of the time and may be frequently misdiagnosed. An intraabdominal, extralobar pulmonary sequestration may present as a suprarenal mass electively resected using laparoscopic techniques.9 While 80% of the time the ELS derives its blood supply from the descending thoracic or abdominal aorta,
Sequestrations, congenital cystic adenomatoid malformations, and congenital lobar emphysema
211
Figure 1 (continued)
arterial supply of extralobar sequestrations may also be derived from the great vessels or branches thereof. Venous drainage is to the azygous or hemiazygous system 80% of the time, with the remainder either partially or completely draining by the pulmonary venous system (Fig. 1B). ELS is 3 to 4 times more common in males and more than half of patients with this anomaly present with respiratory distress (due to compression of normal lung parenchyma) in the first 6 months of life, frequently in the first several days of life. While these may be diagnosed by fetal ultrasound as early as 19 weeks of gestation, postnatally they are most commonly diagnosed by chest radiograph.10 Exciting new radiographic techniques have lent themselves nicely to the evaluation of sequestrations and other BPFMs. Both magnetic resonance angiography (MRA) and 3 dimensional computed tomography (CT) scan reconstructions have been used to delineate the vascular anatomy for sequestrations, and it is beyond the scope of this paper to determine either the indications for each of these modalities or the superiority of one over the other. Associated anomalies are common (⬎65%)
with ELS and include congenital diaphragmatic hernia (20 to 30%), other BPFMs, pericardial defects, and total anomalous pulmonary venous return. Treatment of these lesions is resection, taking great care to dissect, identify, and isolate the feeding artery so that it is not inadvertently transected and allowed to retract to the thoracic or abdominal aorta where the bleeding vessel could prove very difficult to control. Microscopic examination of these lesions frequently demonstrates dilated subpleural lymphatics, dilated bronchioles, alveolar ducts, and alveoli. ILS clearly deserves separate distinction as this entity is really distinguished by having characteristics very different than the extralobar counterpart. ILS rest within a lobe of the lung and have no separate pleural investment. They are localized to the lower lobe 98% of the time with 55% being on the left and 45% on the right. Arterial supply is by an anomalous branch of the descending thoracic aorta that almost 75% of the time traverses the pulmonary ligament. Arterial supply may also come from the abdominal aorta or celiac axis and there may be multiple feeding arteries approximately
212 15% of the time. In contrast to ELS, venous drainage is uniformly via the pulmonary veins (Fig. 1B). There are multiple characteristics of ILS that point to it being an acquired lesion. Usually presenting in the older child or young adult, ILS occurs in equal frequency between the sexes, and there is very often a history of recurrent respiratory infections (85%). Given this history of recurrent infections and older age at presentation, rather than the sequestration being the cause of the infections, in fact, the reverse may be true. Specifically, recurrent bronchial obstruction and distal infection may give way to scarring and fibrosis around the airway and ultimate isolation of the involved parenchyma. Microscopic examination of resected lobes containing ILS do, in fact, reveal bronchial remnants surrounded by chronic inflammation and fibrosis. In addition to acquired isolation of the involved lung parenchyma, recurrent bouts of inflammation may stimulate a neovascular response resulting in “parasitization” or development of collateral vessels in the pulmonary ligament. The recurrently inflamed and infected segment of lung gets sequestered from the adjacent, normal lung. Thus, evidence pointing to the acquired nature of ILS includes the fact that in children and adults, ILS is 3 to 6 times mores common than ELS. At the same time, a review of 42,000 infant autopsies uncovered 12 cases of ELS and no cases of ILS. Unlike ELS, ILS is rarely associated with other congenital anomalies and as delineated above, in addition to chronic inflammation almost always being present, there is a normal pulmonary venous drainage pattern and a predilection to the lower lobe that provides access to the naturally occurring pulmonary ligament as a source for developing collaterals. The complex nature of sequestrations and the care with which they should be approached is highlighted in the review by Bratu and coworkers from Quebec. Their study revealed that under half of their patients diagnosed with sequestration over a 17-year period presented with classic isolated extralobar or intralobar sequestration.11 That is, the majority of these lesions were atypical in that they did not fit the strict definition or were associated with other BPFMs. Lesions diagnosed antenatally predominantly remained asymptomatic while those diagnosed postnatally were uniformly symptomatic. In this latter group, infants presenting at 2 weeks of age or less usually had symptoms of respiratory distress, while patients presenting at greater than 2 weeks of age usually had symptoms consistent with a respiratory tract infection. As in the reported experience of others, sequestrations frequently presented as a spectrum of anomalies having overlap with other lung lesions. As a result, these authors recommended very thorough assessment and consideration of anatomical issues before deciding to pursue surgical intervention. They emphasized the importance of delineation of: (1) connection to the tracheobronchial tree, (2) presence or absence of visceral pleura, (3) arterial supply, (4) venous drainage, (5) foregut communication, (6) histology, (7) mixed or multiple lesions, and (8) whether or not there are associated anomalies.
E.N. Mendeloff
Congenital Cystic Adenomatoid Malformation (CCAM) Accounting for 25% of cases, behind infantile lobar emphysema (ILE), CCAM is the second most common entity in the differential diagnosis of newborn respiratory distress secondary to a structural lung lesion. Occurring in equal frequency in males and females, 50% of the time, this anomaly presents as lifethreatening respiratory distress in the newborn period2 (Fig. 2). The other half of the infants and children with this lesion escape crisis in the newborn period and present at a slightly older age with recurrent pneumonias. It is typically described as a hamartomatous, rubbery overgrowth of bronchioles that can enlarge rapidly due to air trapping. Felt to be due to a derangement occurring in the acinar phase of fetal lung development, it is postulated that there is abnormal signaling or conjugation between the developing terminal bronchioles and the alveolar mesenchyme into which these bronchioles are growing.12 The result is a developmental malformation secondary to uncontrolled overgrowth of the terminal bronchioles. It occurs with equal frequency in the right and left lungs and while it can occur in any lobe and is usually confined to one lobe, there is a predilection for this entity to occur in the lower lobes. Stocker, Madewell and Drake have correlated the pathologic appearance of CCAM with clinical outcome.13 Stocker’s Type I lesions account for nearly 75% of cases and consist predominantly of a relatively small number of large cysts (3 to 10 cm diameter) that compress the surrounding lung parenchyma. The Type II lesions have numerous, evenly spaced cysts usually less than 1 cm diameter and carry a worse prognosis due to the association of this type with other congenital anomalies. Type III lesions are the most rare and are more solid on gross examination and cysts, when present, are only a few millimeters in diameter. Intense pathologic scrutiny and evaluation of excised CCAM specimens does provide supportive evidence for a malignant potential for these lesions.14 Prenatal magnetic resonance imaging (MRI) has been successfully used to differentiate CCAM from other fetal chest masses such as sequestrations or diaphragmatic hernias.15 Postnatally, chest radiograph is highly suggestive of the diagnosis although computerized tomography of the chest is frequently obtained. In Bailey’s review, the mean age at diagnosis for 9 children with CCAM was 7 weeks, and associated anomalies may occur as frequently as 15 to 20% of the time.1,2 Surgical resection of the involved lobe for cure at the time of diagnosis is recommended.
Infantile Lobar Emphysema (ILE) ILE is the most common of the surgically extirpated lesions considered in the differential diagnosis of respiratory distress in the newborn, accounting for 50% of such structural lesions. Approximately twice as common in males, put simply, it is over distension of a pulmonary lobe due to partial or complete obstruction of the bronchus to that lobe. While the obstruction of the bronchus may be extrinsic or intrinsic in
Sequestrations, congenital cystic adenomatoid malformations, and congenital lobar emphysema
213
occurs distal to the obstruction results in breakdown of alveolar septae and over-expansion of the involved lung. Fifty percent of cases present in the first several days to first few months of life and, while there are exceptions, the majority of the remaining cases have presented by 6 months of age. As with the other BPFMs that present early in life, the initial symptoms are those of respiratory distress that may be rapidly progressive in nature with a physical examination that characteristically reveals hyperresonance to percussion and decreased breath sounds on the affected side. This lesion rarely involves the lower lobes (the upper lobes are involved in 90%) and is found on the left slightly more frequently than the right.2 Chest radiograph is diagnostic and reveals massive distension of the involved lobe with mediastinal shift and compression of the contralateral lung. There are two important caveats in caring for these infants so that tragic pitfalls can be avoided. First, it is important not to mistake the radiograph for a pneumothorax and subsequently place a chest tube into the hyperexpanded lobe. Second, the respiratory distress that exists may be severely exacerbated by intubation and positive pressure ventilation. Thus, the airway management of these patients must be anticipatory and well thought out by neonatologists and anesthesiologists participating in the care of these patients. Associated anomalies may be present 14 to 40% of the time the most common of which are cardiovascular in nature. As has been the case with the other entities discussed in this article, surgical resection of the involved lobe at the time of diagnosis is the treatment of choice.
Conclusion
Figure 2 (A & B) This newborn was diagnosed antenatally with a large congenital cystic adenomatoid malformation. This occupied all of the left chest shifting the mediastinum to the right. It was resected emergently leaving a small single right lung which was insufficient for survival.
nature, 50% of the time no clear-cut cause of the obstruction can be elucidated.16 Examples of extrinsic obstruction include vascular anomalies or enlarged lymph nodes while examples of intrinsic obstruction include aspirated meconium, granulation tissue or bronchial torsion. The air trapping that
Bronchopulmonary foregut malformations represent a relatively rare group of potentially life-threatening congenital, structural lesions of the lung. If not life-threatening in the immediacy with which they can cause respiratory embarrassment, as referred to in the section on CCAM and in the author’s own experience, they may have unrecognized malignant potential. On performing an uneventful left upper lobectomy for what appeared to be a relatively typical presentation of ILE, review of the pathologic specimen revealed findings consistent with pulmonary pleuroblastoma. As is typical of this lesion, the patient, who was followed closely with follow-up serial CT scanning, subsequently returned with multiple, bilateral cystic lesions that are being aggressively treated by pediatric hematology/oncology. As BPFMs can be surgically resected at any age with minimal morbidity and mortality, an aggressive approach is appropriate. As put forth in the paper by Bailey and coworkers,1 in the absence of significant pulmonary hypoplasia or pulmonary hypertension such as would be seen in an infant with a concomitant congenital diaphragmatic hernia, symptomatic neonates should tolerate thoughtful operative intervention well.
References 1. Bailey PV, Tracy T, Connors RH, et al: Congenital bronchopulmonary foregut malformations: diagnostic and therapeutic considerations. J Thorac Cardiovasc Surg 99:597-603, 1990
214 2. Stocker JT: Textbook of Pediatric Pathology. The respiratory system. 1992, pp 505-532 3. Yasufuku M, Hatakeyama T, Maeda K, et al: Bronchopulmonary foregut malformation: A large bronchogenic cyst communicating with an esophageal duplication cyst. J Pediatr Surg 38:E2, 2003 4. Borsellino A, Alberti D, Vavassori D, et al: Communicating bronchopulmonary foregut malformation involving a mixed sequestration/cystic adenomatoid malformation: A case report. J Pediatr Surg 37:E38, 2002 5. Kim KW, Kim WS, Cheon JE, et al: Complex bronchopulmonary foregut malformation: Extralobar pulmonary sequestration associated with a duplication cyst of mixed bonchogenic and oesophageal type. Pediatr Radiol 31:265-268, 2001 6. Liejala M, Louhino I: Extralobar sequestration of the lung in children. Prog Ped Surg 21:98-106, 1987 7. Volpe MV, Archivachotikul K, Bhan I, et al: Association of bronchopulmonary sequestration with expression of the homeobox protein Hoxb-5. J Pediatr Surg 35:1817-1819, 2000 8. Stocker JT: Sequestrations of the lung. Sem Diag Path 3:106-121, 1986
E.N. Mendeloff 9. Danielson PD, Sherman NJ: Laparoscopic removal of an abdominal extralobar pulmonary sequestration. J Pediatr Surg 36:1653-1655, 2001 10. Sauerbrei E: Lung sequestration: Duplex doppler diagnosis at 19 weeks gestation. J Ultrasound Med 10:101-105, 1991 11. Bratu I, Flageole H, Chen MF, et al: The multiple facets of pulmonary sequestration. J Pediatr Surg 36:784-790, 2001 12. Becker MR, Schindeera F, Maier WA: Congenital cystic adenomatoid malformation of the lung. Prog Ped Surg 21:112-117, 1987 13. Stocker JT, Madewell JE, Drake RM: Congenital cystic adenomatoid malformation of the lung. Hum Pathol 8:155-171, 1977 14. Wang NS, Chen MF, Chen FF: The glandular component in congenital cystic adenomatoid malformation of the lung. Respirology 4:147-153, 1999 15. Hubbard AM, Adzick NS, Cromblehome TM, et al: Congenital chest lesions: Diagnosis and characterization with prenatal MR imaging. Radiology 212:43-48, 1999 16. Ferguson TB: Congenital lesions of the lung and emphysema. Surgery of the Chest 762-814, 1990
A
spectrum of bronchopulmonary foregut malformations (BPFMs) may result from disordered embryologic interactions occurring during the course of fetal lung development. As their presentation may be life-threatening and may require urgent surgical intervention, clinical recognition of these relatively unusual anomalies is important. BPFMs may occur in conjunction with congenital diaphragmatic hernias. When they do, it presents a particularly lethal combination.1 A brief review of lung development will be followed by a more in depth discussion of three forms of BPFMs, those being sequestrations, congenital cystic adenomatoid malformations, and infantile or congenital lobar emphysema. Bronchogenic cysts, the most commonly diagnosed BPFM, will not be covered in this article.
Development of the Lung The lung begins differentiation in the third week of gestation when it develops as a ventral out pouching on the floor of the primitive foregut.2 The subsequent development of the lung is then generally broken down into 5 phases including the embryonic, pseudoglandular, acinar
Congenital Medical City Children’s Hospital, Dallas, TX 75230. Address reprint requests to Dr. Eric N. Mendeloff, Director, Congenital Heart Surgery, Medical City Children’s Hospital, 7777 Forest Lane, Suite B-115, Dallas, TX 75230. E-mail: [email protected]
1043-0679/04/$-see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2004.08.007
(or canalicular), saccular, and alveolar phases. During the embryonic phase (26 days to 6 weeks gestation), 2 lung buds ultimately give rise to 5 lobar bronchi that come to be associated with the developing pulmonary arteries and veins. The pseudoglandular phase (6 to 16 weeks gestation) encompasses development of the conducting airways and also includes the first appearance of cartilaginous tracheal rings, pseudostratified columnar epithelium, and cilia. The basic structure of the gas exchange units of the lung appear in the acinar phase (16 to 28 weeks gestation) including the initial differentiation of the Type I and Type II pneumocytes. The distal airspaces continue to multiply and differentiate into more complex gas exchange units during the saccular phase (28 to 34 weeks gestation), while the alveolar phase continues from 34 weeks of gestation to beyond birth and truly represents the time during which the majority of alveolar development occurs. Approximately 20 million thick walled air sacs exist at birth and these proliferate into 300 to 600 million alveoli by about 2 years of age after which lung growth occurs more in terms of volume and alveolar size. In this manner, the surface area for gas exchange in the lung increases from 3 to 4 m2 in the neonate to 75 m2 in the adult. Multiple publications have suggested a commonality or overlap in embryological pathogenesis of BPFMs as several different types of these lesions may coexist in the same patient.3,4,5 That said, separate theories do exist as to the etiol209
E.N. Mendeloff
210
Figure 1 (A) This is a thoracic aortogram of a patient with bilateral intralobar sequestrations deriving their blood supply from individual branches of the upper abdominal aorta. The arterial supply to the lesion in the left lung branches multiple times before entering the sequestration itself. (B) This is venous phase of the same angiogram in Fig. 1A. The lesion in the right lung has venous drainage to the pulmonary venous system and that in the left lung drains into the hemiazygous system. Both of these lesions proved to be intralobar sequestrations.
ogy of each of these lesions, and these will be delineated in each the forgoing sections.
Sequestrations Sequestration may defined as a portion of the lung isolated from the remainder of the lung such that it is not in continuity with the upper tracheo-bronchial tree and it receives arterial blood supply from an aberrant branch of the aorta rather than the pulmonary artery (Fig. 1A). This lesion is further broken down into 2 variants, extralobar sequestration (ELS) and intralobar sequestration (ILS) and given their very distinctive elements, these will be discussed in order. ELS is a discrete mass of pulmonary parenchyma existing outside the pleural investment of the lung; i.e., the sequestered lung is enclosed entirely by a separate pleural envelope.6 It is postulated that this develops when independent
collections of cells with respiratory potential arise from the primitive foregut (esophagus) caudal to the normal lung bud. Volpe and coworkers have demonstrated that homeobox gene Hoxb-5 is necessary for normal airway branching and development and have suggested that the developmental abnormalities seen with bronchopulmonary sequestration is related to abnormal expression of the homeobox genes.7 ELS are most commonly found on the left side (66%) adjacent to the esophagus and between the lower lobe and diaphragm.8 These independent collections of cells may arise so caudally that subdiaphragmatic and retroperitoneal locations of the various types of sequestrations do occur as often as 15% of the time and may be frequently misdiagnosed. An intraabdominal, extralobar pulmonary sequestration may present as a suprarenal mass electively resected using laparoscopic techniques.9 While 80% of the time the ELS derives its blood supply from the descending thoracic or abdominal aorta,
Sequestrations, congenital cystic adenomatoid malformations, and congenital lobar emphysema
211
Figure 1 (continued)
arterial supply of extralobar sequestrations may also be derived from the great vessels or branches thereof. Venous drainage is to the azygous or hemiazygous system 80% of the time, with the remainder either partially or completely draining by the pulmonary venous system (Fig. 1B). ELS is 3 to 4 times more common in males and more than half of patients with this anomaly present with respiratory distress (due to compression of normal lung parenchyma) in the first 6 months of life, frequently in the first several days of life. While these may be diagnosed by fetal ultrasound as early as 19 weeks of gestation, postnatally they are most commonly diagnosed by chest radiograph.10 Exciting new radiographic techniques have lent themselves nicely to the evaluation of sequestrations and other BPFMs. Both magnetic resonance angiography (MRA) and 3 dimensional computed tomography (CT) scan reconstructions have been used to delineate the vascular anatomy for sequestrations, and it is beyond the scope of this paper to determine either the indications for each of these modalities or the superiority of one over the other. Associated anomalies are common (⬎65%)
with ELS and include congenital diaphragmatic hernia (20 to 30%), other BPFMs, pericardial defects, and total anomalous pulmonary venous return. Treatment of these lesions is resection, taking great care to dissect, identify, and isolate the feeding artery so that it is not inadvertently transected and allowed to retract to the thoracic or abdominal aorta where the bleeding vessel could prove very difficult to control. Microscopic examination of these lesions frequently demonstrates dilated subpleural lymphatics, dilated bronchioles, alveolar ducts, and alveoli. ILS clearly deserves separate distinction as this entity is really distinguished by having characteristics very different than the extralobar counterpart. ILS rest within a lobe of the lung and have no separate pleural investment. They are localized to the lower lobe 98% of the time with 55% being on the left and 45% on the right. Arterial supply is by an anomalous branch of the descending thoracic aorta that almost 75% of the time traverses the pulmonary ligament. Arterial supply may also come from the abdominal aorta or celiac axis and there may be multiple feeding arteries approximately
212 15% of the time. In contrast to ELS, venous drainage is uniformly via the pulmonary veins (Fig. 1B). There are multiple characteristics of ILS that point to it being an acquired lesion. Usually presenting in the older child or young adult, ILS occurs in equal frequency between the sexes, and there is very often a history of recurrent respiratory infections (85%). Given this history of recurrent infections and older age at presentation, rather than the sequestration being the cause of the infections, in fact, the reverse may be true. Specifically, recurrent bronchial obstruction and distal infection may give way to scarring and fibrosis around the airway and ultimate isolation of the involved parenchyma. Microscopic examination of resected lobes containing ILS do, in fact, reveal bronchial remnants surrounded by chronic inflammation and fibrosis. In addition to acquired isolation of the involved lung parenchyma, recurrent bouts of inflammation may stimulate a neovascular response resulting in “parasitization” or development of collateral vessels in the pulmonary ligament. The recurrently inflamed and infected segment of lung gets sequestered from the adjacent, normal lung. Thus, evidence pointing to the acquired nature of ILS includes the fact that in children and adults, ILS is 3 to 6 times mores common than ELS. At the same time, a review of 42,000 infant autopsies uncovered 12 cases of ELS and no cases of ILS. Unlike ELS, ILS is rarely associated with other congenital anomalies and as delineated above, in addition to chronic inflammation almost always being present, there is a normal pulmonary venous drainage pattern and a predilection to the lower lobe that provides access to the naturally occurring pulmonary ligament as a source for developing collaterals. The complex nature of sequestrations and the care with which they should be approached is highlighted in the review by Bratu and coworkers from Quebec. Their study revealed that under half of their patients diagnosed with sequestration over a 17-year period presented with classic isolated extralobar or intralobar sequestration.11 That is, the majority of these lesions were atypical in that they did not fit the strict definition or were associated with other BPFMs. Lesions diagnosed antenatally predominantly remained asymptomatic while those diagnosed postnatally were uniformly symptomatic. In this latter group, infants presenting at 2 weeks of age or less usually had symptoms of respiratory distress, while patients presenting at greater than 2 weeks of age usually had symptoms consistent with a respiratory tract infection. As in the reported experience of others, sequestrations frequently presented as a spectrum of anomalies having overlap with other lung lesions. As a result, these authors recommended very thorough assessment and consideration of anatomical issues before deciding to pursue surgical intervention. They emphasized the importance of delineation of: (1) connection to the tracheobronchial tree, (2) presence or absence of visceral pleura, (3) arterial supply, (4) venous drainage, (5) foregut communication, (6) histology, (7) mixed or multiple lesions, and (8) whether or not there are associated anomalies.
E.N. Mendeloff
Congenital Cystic Adenomatoid Malformation (CCAM) Accounting for 25% of cases, behind infantile lobar emphysema (ILE), CCAM is the second most common entity in the differential diagnosis of newborn respiratory distress secondary to a structural lung lesion. Occurring in equal frequency in males and females, 50% of the time, this anomaly presents as lifethreatening respiratory distress in the newborn period2 (Fig. 2). The other half of the infants and children with this lesion escape crisis in the newborn period and present at a slightly older age with recurrent pneumonias. It is typically described as a hamartomatous, rubbery overgrowth of bronchioles that can enlarge rapidly due to air trapping. Felt to be due to a derangement occurring in the acinar phase of fetal lung development, it is postulated that there is abnormal signaling or conjugation between the developing terminal bronchioles and the alveolar mesenchyme into which these bronchioles are growing.12 The result is a developmental malformation secondary to uncontrolled overgrowth of the terminal bronchioles. It occurs with equal frequency in the right and left lungs and while it can occur in any lobe and is usually confined to one lobe, there is a predilection for this entity to occur in the lower lobes. Stocker, Madewell and Drake have correlated the pathologic appearance of CCAM with clinical outcome.13 Stocker’s Type I lesions account for nearly 75% of cases and consist predominantly of a relatively small number of large cysts (3 to 10 cm diameter) that compress the surrounding lung parenchyma. The Type II lesions have numerous, evenly spaced cysts usually less than 1 cm diameter and carry a worse prognosis due to the association of this type with other congenital anomalies. Type III lesions are the most rare and are more solid on gross examination and cysts, when present, are only a few millimeters in diameter. Intense pathologic scrutiny and evaluation of excised CCAM specimens does provide supportive evidence for a malignant potential for these lesions.14 Prenatal magnetic resonance imaging (MRI) has been successfully used to differentiate CCAM from other fetal chest masses such as sequestrations or diaphragmatic hernias.15 Postnatally, chest radiograph is highly suggestive of the diagnosis although computerized tomography of the chest is frequently obtained. In Bailey’s review, the mean age at diagnosis for 9 children with CCAM was 7 weeks, and associated anomalies may occur as frequently as 15 to 20% of the time.1,2 Surgical resection of the involved lobe for cure at the time of diagnosis is recommended.
Infantile Lobar Emphysema (ILE) ILE is the most common of the surgically extirpated lesions considered in the differential diagnosis of respiratory distress in the newborn, accounting for 50% of such structural lesions. Approximately twice as common in males, put simply, it is over distension of a pulmonary lobe due to partial or complete obstruction of the bronchus to that lobe. While the obstruction of the bronchus may be extrinsic or intrinsic in
Sequestrations, congenital cystic adenomatoid malformations, and congenital lobar emphysema
213
occurs distal to the obstruction results in breakdown of alveolar septae and over-expansion of the involved lung. Fifty percent of cases present in the first several days to first few months of life and, while there are exceptions, the majority of the remaining cases have presented by 6 months of age. As with the other BPFMs that present early in life, the initial symptoms are those of respiratory distress that may be rapidly progressive in nature with a physical examination that characteristically reveals hyperresonance to percussion and decreased breath sounds on the affected side. This lesion rarely involves the lower lobes (the upper lobes are involved in 90%) and is found on the left slightly more frequently than the right.2 Chest radiograph is diagnostic and reveals massive distension of the involved lobe with mediastinal shift and compression of the contralateral lung. There are two important caveats in caring for these infants so that tragic pitfalls can be avoided. First, it is important not to mistake the radiograph for a pneumothorax and subsequently place a chest tube into the hyperexpanded lobe. Second, the respiratory distress that exists may be severely exacerbated by intubation and positive pressure ventilation. Thus, the airway management of these patients must be anticipatory and well thought out by neonatologists and anesthesiologists participating in the care of these patients. Associated anomalies may be present 14 to 40% of the time the most common of which are cardiovascular in nature. As has been the case with the other entities discussed in this article, surgical resection of the involved lobe at the time of diagnosis is the treatment of choice.
Conclusion
Figure 2 (A & B) This newborn was diagnosed antenatally with a large congenital cystic adenomatoid malformation. This occupied all of the left chest shifting the mediastinum to the right. It was resected emergently leaving a small single right lung which was insufficient for survival.
nature, 50% of the time no clear-cut cause of the obstruction can be elucidated.16 Examples of extrinsic obstruction include vascular anomalies or enlarged lymph nodes while examples of intrinsic obstruction include aspirated meconium, granulation tissue or bronchial torsion. The air trapping that
Bronchopulmonary foregut malformations represent a relatively rare group of potentially life-threatening congenital, structural lesions of the lung. If not life-threatening in the immediacy with which they can cause respiratory embarrassment, as referred to in the section on CCAM and in the author’s own experience, they may have unrecognized malignant potential. On performing an uneventful left upper lobectomy for what appeared to be a relatively typical presentation of ILE, review of the pathologic specimen revealed findings consistent with pulmonary pleuroblastoma. As is typical of this lesion, the patient, who was followed closely with follow-up serial CT scanning, subsequently returned with multiple, bilateral cystic lesions that are being aggressively treated by pediatric hematology/oncology. As BPFMs can be surgically resected at any age with minimal morbidity and mortality, an aggressive approach is appropriate. As put forth in the paper by Bailey and coworkers,1 in the absence of significant pulmonary hypoplasia or pulmonary hypertension such as would be seen in an infant with a concomitant congenital diaphragmatic hernia, symptomatic neonates should tolerate thoughtful operative intervention well.
References 1. Bailey PV, Tracy T, Connors RH, et al: Congenital bronchopulmonary foregut malformations: diagnostic and therapeutic considerations. J Thorac Cardiovasc Surg 99:597-603, 1990
214 2. Stocker JT: Textbook of Pediatric Pathology. The respiratory system. 1992, pp 505-532 3. Yasufuku M, Hatakeyama T, Maeda K, et al: Bronchopulmonary foregut malformation: A large bronchogenic cyst communicating with an esophageal duplication cyst. J Pediatr Surg 38:E2, 2003 4. Borsellino A, Alberti D, Vavassori D, et al: Communicating bronchopulmonary foregut malformation involving a mixed sequestration/cystic adenomatoid malformation: A case report. J Pediatr Surg 37:E38, 2002 5. Kim KW, Kim WS, Cheon JE, et al: Complex bronchopulmonary foregut malformation: Extralobar pulmonary sequestration associated with a duplication cyst of mixed bonchogenic and oesophageal type. Pediatr Radiol 31:265-268, 2001 6. Liejala M, Louhino I: Extralobar sequestration of the lung in children. Prog Ped Surg 21:98-106, 1987 7. Volpe MV, Archivachotikul K, Bhan I, et al: Association of bronchopulmonary sequestration with expression of the homeobox protein Hoxb-5. J Pediatr Surg 35:1817-1819, 2000 8. Stocker JT: Sequestrations of the lung. Sem Diag Path 3:106-121, 1986
E.N. Mendeloff 9. Danielson PD, Sherman NJ: Laparoscopic removal of an abdominal extralobar pulmonary sequestration. J Pediatr Surg 36:1653-1655, 2001 10. Sauerbrei E: Lung sequestration: Duplex doppler diagnosis at 19 weeks gestation. J Ultrasound Med 10:101-105, 1991 11. Bratu I, Flageole H, Chen MF, et al: The multiple facets of pulmonary sequestration. J Pediatr Surg 36:784-790, 2001 12. Becker MR, Schindeera F, Maier WA: Congenital cystic adenomatoid malformation of the lung. Prog Ped Surg 21:112-117, 1987 13. Stocker JT, Madewell JE, Drake RM: Congenital cystic adenomatoid malformation of the lung. Hum Pathol 8:155-171, 1977 14. Wang NS, Chen MF, Chen FF: The glandular component in congenital cystic adenomatoid malformation of the lung. Respirology 4:147-153, 1999 15. Hubbard AM, Adzick NS, Cromblehome TM, et al: Congenital chest lesions: Diagnosis and characterization with prenatal MR imaging. Radiology 212:43-48, 1999 16. Ferguson TB: Congenital lesions of the lung and emphysema. Surgery of the Chest 762-814, 1990