Congenital pulmonary artery malformations (CPAMs), previously known as congenital cystic adenomatoid malformations (CCAMs), are the most common bronchopulmonary malformations, accounting for approximately half of all lesions. The estimated incidence is around 1 in 2000 live births. ^, CPAMs occur sporadically, with no specific demographic or genetic risk factors. CPAMs are typically unilateral, isolated to one lobe, and more common in the lower lobes. Most CPAMs are believed to originate from an abnormal proliferation of terminal respiratory bronchioles during the pseudoglandular phase, although CPAMs may occur within other segments of the respiratory system, including trachea and alveoli. CPAMs are classified into 5 subtypes (Type 0 to Type 4), primarily based on size and location of the malformation along the bronchial tree ( Table 20.2 ). The original Stocker classification stratified CPAM lesions into 3 types by Roman numerals (I–III).

The current pathology classification system, which was revised in 2002, divides CPAMs into 5 types by Arabic numerals (0–4) that differ based on central/peripheral airway location, cystic structure, and epithelial lining. Type 1 CPAM is the most common subtype and is believed to arise from the distal bronchi and proximal bronchioles with cysts lined with pseudostratified ciliated columnar epithelium. The Type 4 subtype, which features large cysts lined by flattened alveoli, has been associated with pleuropulmonary blastoma (PPB).

While the exact disease pathogenesis of CPAMs remains unclear, one theory is the obstruction hypothesis, in which there is a proximal airway obstruction that may serve as an inciting event, leading to an imbalance in cell proliferation. ^, Others have shown a two-fold increase in cell proliferation and a five-fold reduction in apoptotic bodies in CPAM tissue compared to that observed in normal neonatal lung tissue. The specific biomolecular pathways leading to CPAM formation have yet to be identified. Various pulmonary morphogens such as FGF10 have been implicated, but no alteration of FGF10 expression has been found in evaluated specimens.

Since the early days of fetal ultrasound (US) technology in the 1980s, it has been well appreciated that some CPAMs can grow substantially in size in utero, resulting in profound mass effect on the adjacent lung, diaphragm, and heart. This compression can lead to the subsequent development of pulmonary hypoplasia and hydrops and was the rationale for open fetal lobectomy as the only option for survival in these cases. In other fetuses, CPAM compression of the esophagus was found to cause polyhydramnios. Fortunately, contemporary studies have shown that most CPAMs are relatively small in size and therefore do not cause substantial mass effect on the developing organs. However, upon delivery air trapping within CPAMs can still compromise native lung ventilation, resulting in respiratory distress and the need for supportive therapies.

Prenatal US during the routine anatomic survey performed between 18- and 20-weeks’ gestation is now the most common scenario for the initial detection of CPAMs. The widespread adoption of and ongoing advances in fetal US imaging technology have permitted more reliable prenatal diagnosis, with 68%–94% of CPAMs now identified prior to birth in high-income countries. ^, The enhanced resolution of fetal US has also enabled the detection of smaller lesions that were previously undiagnosed until early childhood where they were often discovered either incidentally or in the setting of a CPAM-related complication on cross-sectional imaging. An overview of prenatal diagnosis and management by lesion is available in Table 20.3 .

On fetal US, a CPAM appears as a hyperechogenic lung mass, with or without hypoechoic cysts that vary in number and size ( Fig. 20.2 ). In pure CPAMs, no systemic arterial feeding vessel is visualized. Larger lesions can cause a mass effect on surrounding structures. This is usually seen by displacement of the heart toward the contralateral chest and/or ipsilateral diaphragmatic eversion. In the most severe cases, there may be hydrops fetalis from compression of venous return to the heart. The definition of hydrops is not clearly defined but includes abnormal fluid accumulation in at least two body cavities (e.g., ascites, pleural effusion, pericardium) in combination with skin edema, placentomegaly, and evidence of cardiac dysfunction in unequivocal cases.

Fetal ultrasound images of a large right microcystic lung mass showing transverse and sagittal measurements used to calculate the CVR.

Courtesy Dr. Mara Rosner, Johns Hopkins Center for Fetal Therapy.

In the hands of an experienced maternal-fetal medicine specialist, prenatal US is usually the only imaging modality necessary to make an accurate diagnosis. Fetal CPAMs have historically been divided into two major categories as described by Adzick and colleagues: (1) macrocystic lesions containing a dominant cyst or multiple cysts that are ≥5.0 mm in diameter, and (2) microcystic lesions in which there is a solid echogenic mass or cysts <5.0 mm in diameter. This distinction can be important given that larger lesions may require fetal intervention based on cyst characteristics and are less likely to respond to maternal steroid therapy. Moreover, spontaneous resolution is much less common among macrocystic lesions. Although Stocker has historically associated microcystic CPAMs with a worse prognosis, that observation has since been debunked in multiple large cohort studies. ^, The association of some CPAMs with other congenital anomalies, namely cardiac defects, has also commonly been espoused, but the contemporary literature suggests that associated major anomalies are uncommon (approximately 5%), with isolated lesions making up the vast majority of cases. Accordingly, routine amniocentesis to screen for karyotype abnormalities is not indicated. In larger lesions, a fetal echocardiogram is recommended to evaluate heart structure and function.

Studies have shown that the exact type of a prenatal bronchopulmonary malformation itself does not play a major role in the occurrence of neonatal respiratory distress or other adverse neonatal outcomes. Instead, the overall prognosis for fetal lung lesions, including CPAMs, is strongly associated with lesion size. ^, The CPAM volume ratio (CVR), which is calculated by estimating the volume of the lesion (length × height × depth × 0.52) divided by the head circumference, remains the most widely used US metric to risk stratify fetal CPAMs. In a quaternary care institutional cohort study done prior to the widespread use of maternal steroids, an initial CVR < 1.6 cm ² without a dominant cyst predicted a low risk of developing hydrops, whereas an initial CVR > 1.6 cm ² identified those who were at high risk of hydrops and mortality. The latter group of fetuses therefore warranted more frequent US surveillance and possibly fetal lung resection to avoid in utero demise. ^, However, the diagnostic accuracy of CVR > 1.6 cm ² for identifying hydropic fetuses with CPAMs has been debated and has never been validated in a multiinstitutional or controlled trial. Regardless, this cutoff value does serve as a useful threshold for recommending more frequent US surveillance (e.g., twice weekly) and as the basis for administering maternal steroids (betamethasone 12.5 mg intramuscular every 24 hours × 2 doses) as first-line fetal therapy for microcystic CPAMs before 26 weeks’ gestation. Numerous studies have shown that the maternal administration of betamethasone induces regression of CPAM size, improvement in fetal hydrops, and reduced mortality in 80%–90% of fetuses. A second course of maternal steroids may be helpful in selected cases. The mechanism of action of steroids on CPAM regression remains unknown. Because macrocystic CPAMs are generally not as responsive to steroid treatment, lesions associated with imminent or documented hydrops are best treated by fetal thoracoamniotic shunting of any dominant cyst(s) ( Fig. 20.3 ). ^, A double-pigtail catheter is used to minimize dislodgement. In the era of maternal steroids, very few open fetal resections have been performed worldwide.

Transverse fetal ultrasound images of a large lung mass with dominant macrocyst ( left ) and pleural effusion ( white arrow ) that was subsequently managed with a thoracoamniotic shunt ( right ). The yellow asterisk denotes pigtail end located within the cyst with extension of the catheter into the amniotic cavity ( yellow arrow ).

Courtesy Dr. Mara Rosner, Johns Hopkins Center for Fetal Therapy.

For large microcystic lesions with hydrops or severe cardiac compression that do not respond to maternal steroids, various fetal and perinatal operative approaches [e.g., fetal resection, ex utero intrapartum treatment (EXIT)] have been described to avoid imminent demise. Referral to a major tertiary or quaternary fetal care center is recommended given that the various options should be individualized based on anatomy, gestational age, and institutional expertise. In a recent study from the Children’s Hospital of Philadelphia, cesarean section with immediate neonatal resection in an adjacent operating room (section-to-resection) was the most widely employed strategy for these challenging cases. Extracorporeal life support may be required as an adjunct to successfully manage these children postoperatively.

More recently, the dynamic nature of the CVR in a given patient and its implications on perinatal outcomes has been appreciated. Rather than the CVR being a fixed measurement, the CVR of a lesion often follows a specific pattern that is likely related to the transition between canalicular and saccular lung development. In some cases, the CVR tends to peak in size between 25 and 27 weeks’ gestation, at which time a slow CVR decline continues until term. ^, Overall, larger CVRs tend to be better tolerated later in gestation since the thoracic cavity grows at a faster pace compared to the head. Conversely, many CVR measurements simply decrease over time. In almost 10% of cases late in gestation, smaller microcystic CPAMs will often become isoechoic with the adjacent lung by US, giving the false impression that they “disappeared.”

Since 2013, multiple groups worldwide have shown a significant association between serial CVR measurements and neonatal outcomes (e.g., respiratory distress, neonatal lung resection), even after adjusting for more traditional prenatal factors such as mediastinal shift. These data are useful in prenatal counseling and delivery planning with families given that most patients with CPAMs are asymptomatic at birth ( Fig. 20.4 ). Although the exact cutoff for predicting adverse neonatal outcomes remains controversial, multiinstitutional studies from the Midwest Pediatric Surgery Consortium, among others, suggest that a maximum CVR < 0.8–1.0 cm ² correlates with asymptomatic disease in more than 90%–95% of cases. ^{, ,} Vaginal delivery, if an option from an obstetrical perspective, is safe at a local birthing center for these smaller lesions. Those requiring neonatal surgery tend to have a CVR > 1.3 cm ² late in gestation. ^, Fetuses with elevated CVR cases should be delivered at a major birthing center with experienced surgical and neonatal intensive care teams readily available. A suggested CVR-based algorithm for the prenatal management of CPAMs is shown in Fig. 20.5 .

Serial CVR measurements correlate with the likelihood of symptomatic respiratory disease at birth. (A) Average CVR measurements throughout gestation in symptomatic and asymptomatic neonates. (B) Comparison of the initial, maximum, and final CVR in symptomatic (Sx) and asymptomatic (No Sx) neonates. The asterisk indicates significance ( P < .05).

From Ehrenberg-Buchner, AJOG paper.

Risk stratification algorithm for fetal bronchopulmonary malformations based on the congenital pulmonary airway malformation volume ratio (CVR). High neonatal risk cases may require fetal therapy and are at risk for neonatal lung resection. Low neonatal risk cases can be delivered at the birthing center of choice and are likely to be asymptomatic.

From Penikis et al., AJOG MFM, 2023.

The role of fetal ultrafast magnetic resonance imaging (MRI) as an adjunct to US in the workup of CPAMs is controversial. Although routine MRI use for all prenatal CPAMs has not been shown to have additional benefit, this imaging modality can be useful given that it is not limited by large maternal body habitus and can provide more detailed anatomic information that may be helpful in selected cases ( Fig. 20.6 ). For example, MRI can also be used to calculate mass size and total lung volumes and to clarify other anomalies suspected on US (e.g., congenital diaphragmatic hernia, lung agenesis). However, the optimal gestational age to obtain a fetal MRI remains unknown. MRI also adds additional cost, usually does not change prenatal management in most cases, and is not considered to be as accurate for characterizing the lung parenchyma when compared to postnatal computed tomography (CT).

Coronal ( left ) and transverse ( right ) views of T2-weighted fetal magnetic resonance imaging demonstrating a large right upper lobe mass with dominant macrocyst ( black asterisk ).

Courtesy Dr. Patrick Tivnan, Division of Pediatric Radiology, Johns Hopkins Medicine.

Up to 25% of newborns with a CPAM do exhibit some abnormal breathing at birth, with 13% requiring supplemental oxygen or ventilator support. Surgical resection is indicated in this subset of symptomatic neonates, with lobectomy generally preferred over lung-preserving techniques such as segmentectomy or wedge resection ( Table 20.4 ). Since it is usually not possible to accurately determine the extent of a CPAM intraoperatively, performing a lobectomy avoids the risk of positive margins and postoperative parenchymal air leaks. Only when multiple lobes are involved (1%–2% of all CPAMs) should segmentectomy or wedge resection be considered when anatomically feasible. Thoracotomy is the preferred operative approach in neonates given the small working space and inability to tolerate single-lung ventilation. Many of these symptomatic patients can have prolonged respiratory morbidity for months to years after surgery.

Over 75% of newborns with a CPAM are asymptomatic at birth, and most of these lesions will be undetectable on plain-film radiographs. Many of these patients are initially observed in an intensive care unit, although this practice does not appear to be justified based on prenatal CVR measurements. A chest radiograph should never be used to rule out a bronchopulmonary malformation. An outpatient preoperative chest CT scan with IV contrast in asymptomatic infants remains the gold standard for imaging. The study is helpful for preoperative planning and is well tolerated without anesthesia, especially when performed at 2 or 3 months of age ( Fig. 20.7 ). The CT protocol should be tailored to the patient weight in accordance with As Low As Reasonably Achievable (ALARA) principles. Pure CPAMs, by definition, have a pulmonary arterial and venous blood supply without systemic vessels. It is imperative that a chest CT be performed even in those in whose lesions “disappeared” late in gestation by fetal US and in those with normal newborn chest radiographs. Spontaneous resolution of CPAMs once documented postnatally by CT is extremely unlikely. Postnatal lung US is of no value in the diagnostic workup since ultrasound waves cannot penetrate normally aerated lungs.

Anteroposterior chest radiograph ( left ) in the newborn period suggesting a right lower cystic area with mediastinal shift. Subsequent confirmation of a right lower lobe macrocystic congenital pulmonary airway malformation was shown by chest computed tomography (CT) with intravenous contrast ( right ).

CPAM lesions are known to be a risk factor for the development of pulmonary symptoms in later childhood and adulthood, including air trapping, pneumothorax, chronic cough, and/or pneumonias. The relationship between infection and CPAMs is well documented, particularly before the era of widespread prenatal diagnosis. These infections can be severe and life threatening, difficult to clear with antibiotics, and are known to make the subsequent lobectomy a much more difficult operation. In one study, over 80% of patients who were initially asymptomatic developed symptoms, including pneumonia with or without an infected CPAM (43%), respiratory distress (14%), and spontaneous pneumothorax (14%), at a mean of 2 years of age. In cases of prior pneumonia, lobectomy should be performed in these patients after clinical improvement with antibiotic therapy. These children may still be candidates for thoracoscopic lobectomy, although conversion to open thoracotomy is more common due to the chronic inflammation and tenacious adhesions that have occurred within the hilum and fissure.

In contrast to the risk of pneumonia, the relationship between CPAM and long-term malignant transformation is less clear. One study found that 26% of asymptomatic prenatally diagnosed detected lesions demonstrated subclinical infection or malignancy. An adult study from the Mayo Clinic has not identified more than a handful of cases in which a CPAM was associated with malignancy. However, other investigators have argued in favor of their prophylactic removal on the basis of elevated cancer risk. In one such study of pediatric patients with lung neoplasms, 9% had a history of CPAM. Others have suggested premalignant features (e.g., gastric mucins within type 1 CPAMs) that are important in the pathogenesis of bronchioloalveolar carcinoma, and some CPAMs have been shown to harbor mucinous cell clusters and/or KRAS mutations. Perhaps the most compelling concern related to cancer has been the difficulty in distinguishing macrocystic CPAMs from cystic pleuropulmonary blastoma (PPB), a rare primary embryonal tumor of the lung that arises in infants and young children and is associated with the DICER1 mutation ( Fig. 20.8 ). ^, Those carrying the DICER1 mutation are predisposed to the development of malignant tumors of the lung, kidney, ovary, and thyroid. PPB cases are rarely detected prenatally, with the majority of lesions being incidentally discovered upon histopathologic review of a presumed CPAM. A radiology-pathology study from the Midwest Pediatric Surgery Consortium has suggested that any macrocystic lung lesion in a young child without an antenatal diagnosis should raise suspicion for PPB, regardless of symptomatology or DICER1 status. Delays in surgery and chemotherapy for cystic PPB are associated with disease progression and increased mortality.

Examples of CT images of CPAM and pleuropulmonary blastoma (PPB). Representative coronal (A) and axial (B) lung window images in a 2-month-old girl show a cystic lung lesion located in the medial right lower lobe with thin internal septations. The pathologic diagnosis was PPB but was interpreted as a benign macrocystic CPAM. Representative coronal (C) and axial (D) lung window images in a 5-month-old boy with a posterior left lower lobe solid lung lesion with an internal cyst. The pathologic diagnosis was CPAM but was given the radiologic diagnosis of PPB.

From Engwall-Gill et al., JAMA Network Open, 2023.

Given the natural history of postnatal CPAMs during childhood, most pediatric surgeons in the United States and elsewhere advocate that patients with asymptomatic CPAMs undergo prophylactic lobectomy during infancy. ^, This approach allows for compensatory alveolar lung growth in the remaining ipsilateral lobe(s) and has been associated with excellent long-term pulmonary outcomes. Elective thoracoscopic or open lobectomy in asymptomatic patients is commonly performed between 2 and 6 months of age before clinical or subclinical inflammation occurs. Several investigators have shown there is no difference in surgical outcomes based on timing, although earlier resection has been shown to be associated with decreased operative time and a trend toward lower postoperative complications among high-volume surgeons. The widespread adoption of thoracoscopic techniques, resulting in less morbidity in some but not all studies, has lowered the threshold for resection and is now associated with a 2- to 3-day hospitalization in most patients. Among macrocystic lesions without an antenatal history of diagnosis, open resection would be advised should there be a concern for an occult PPB regardless of CT diagnosis.

For prenatally diagnosed, asymptomatic CPAMs that are found to be small by CT imaging, a nonoperative approach may be justified as an alternative management strategy depending on the clinical scenario. Surgical resection would be advised only for those who developed subsequent symptoms or complications. This more nuanced practice has been reflected by international survey data, and prospective global registries have recently been established to clarify the role of nonoperative management. Studies from the United Kingdom have suggested an avoidance of unnecessary morbidity with failure rates associated with expectant management, which may be as low as 5% in carefully selected patients. Others have cited the potential life-threatening complications of lobectomy, continued pulmonary morbidities despite lung resection, and/or the belief that the risk-benefit ratio favors nonoperative management due to the potential neurotoxicity of anesthesia as well as lack of strong data on compensatory lung growth and avoidance of malignant transformation. Failure of nonoperative management may be related to the initial lesion size by CT. However, serial surveillance protocols associated with nonoperative management are not well defined. Long-term surveillance is also challenging due to poor patient compliance over time. Since a chest radiograph is not a sensitive imaging modality, most patients managed expectantly require serial CT scans, an approach that exposes the patient to the potential long-term risks of increased ionizing radiation. MRI represents an alternative to CT scan but is currently hampered by inferior resolution of the lung parenchyma and poor tolerance of the exam in younger children without sedation.

Since the mid-2010s, thoracoscopic lobectomy has become the most popular technique employed for elective CPAM resection. ^{, ,} The thoracoscopic approach has been shown to be safe and effective, particularly when performed by experienced surgeons trained in advanced minimally invasive procedures. ^, Drawbacks of the thoracoscopic approach include the need for single-lung ventilation to enable adequate working space, a steep operative learning curve, and prolonged operative times when compared to open lobectomy. Both meticulous surgical technique and a clear understanding of the three-dimensional anatomical relationships within the lung are essential to reduce perioperative complications including bronchial injury and catastrophic exsanguinating hemorrhage. The reported conversion rates from thoracoscopic to open lobectomy are less than 20% based on multiinstitutional data. Excellent peripheral venous access is essential, but arterial line monitoring can generally be avoided in the hands of an experienced operating room team.

Single-lung ventilation is required to attain parenchymal collapse and optimal visualization for thoracoscopic dissection. In infants, intubation of the contralateral mainstem bronchus is the most common approach and can be achieved by using a 3–0 microcuffed endotracheal tube introduced under fluoroscopic and/or flexible bronchoscopic guidance. For left-sided thoracoscopic lobectomy, it is important to introduce the tube deep enough into the right mainstem bronchus to avoid inadvertent displacement into the left mainstem bronchus or trachea, but not so deeply to bypass the right upper lobe bronchus. An alternative method for lung isolation in young infants is the deployment of a bronchial blocker placed outside of the endotracheal tube to occlude the ipsilateral mainstem bronchus of interest. Children who are at least 8 years of age may have a large enough trachea to be candidates for intubation with a double-lumen tube, which is generally a more effective approach for selective lung isolation.

The child is positioned in lateral decubitus with an axillary roll and slightly prone angulation ( Fig. 20.9 ). The arms should be stacked on top of each other, with padding between, to prevent excess stretch on the brachial plexus. The patient should be widely draped, from the spine to the sternum for exposure of the entire hemithorax. Prior to starting the case, the location for a thoracotomy incision below the scapula tip should be carefully marked in case the surgeon needs to emergently convert to an open procedure. Three ports, all placed along the anterior and midaxillary lines to help triangulate the major fissure, work best to facilitate an anterior-to-posterior dissection. In contrast to the open approach, both the surgeon and the assistant stand on the anterior side of the patient. Although 3-mm instruments are most often used in infants, 5-mm ports allow for the use of larger instruments (e.g., endoscopic staplers, locking clip appliers). In addition to single-lung ventilation, low-pressure carbon dioxide insufflation (e.g., 4–6 mmHg) also helps aid in visualization.

Schematic illustration of left lateral decubitus positioning in an infant in preparation for a thoracoscopic resection of a CPAM involving the right lower lobe (RLL). The three ports should be placed anterior to the scapula tip to facilitate an anterior-to-posterior dissection along the major fissure ( right line ).

A systematic approach for identifying all critical vascular and bronchial structures is essential in the thoracoscopic approach. Lower lobectomies are technically less challenging than middle and upper lobectomies. In lower lobectomy cases, early release of the inferior pulmonary ligament up to the level of the inferior pulmonary vein helps to facilitate traction when exposing the major fissure. In BPS and hybrid lesions, ligation of the systemic feeding artery should also be addressed at that time. Working through the major fissure from anterior to posterior direction, the surgeon will sequentially encounter the basilar arterial trunk followed by the superior segmental arterial branch more posteriorly. In infants, vascular arterial branches off of the basilar trunk can usually be taken with a 3-mm vessel-sealing device. The inferior pulmonary vein can be dissected out in similar fashion, taking care to stay away from the pericardium ( Fig. 20.10 ). The lower-lobe bronchus, which lies deep and posterior to the basilar arterial trunk, should generally be taken last and closed with a 5-mm endoscopic stapler, locking clip, or suture ligature depending on surgeon preference. Once the lobe has been completely detached, one of the port sites can be slightly enlarged slightly (e.g., 1.5 cm) to remove the specimen in piecemeal fashion with or without a specimen bag. As in open lobectomy, the bronchial stump should be tested under saline immersion to 30 cm H ₂ O to ensure adequate closure, and a chest tube is then exteriorized from the lower aspect of the chest wall. During the case, loss of end-tidal CO ₂ may sometimes occur secondary to inadvertent occlusion of the endotracheal tube by small clots that form as blood inadvertently enters the airway during lung dissection. In such cases, deep suctioning and/or acute replacement of the endotracheal tube may be required.

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