5.0 OVERVIEW: CONGENITAL LUNG LESIONS
There are multiple echogenic lung lesions that must await neonatal assessment to determine a specific diagnosis. The generic term congenital lung lesion (CLL) should be used, instead of trying to make a histologic diagnosis based on specific sonographic criteria.
There has been a rise in the number of CLLs over the past 20 years to the current rate of 4.15 cases per 10,000 births. This appears to be a true rise in incidence rather than increased antenatal recognition because of the prevalence of second- and third-trimester ultrasound examinations.
Fetal assessment/management should be based on the sonographic criteria that can be evaluated on serial examinations: gestational age at first detection, the size of the mass, mediastinal deviation, eversion of the diaphragm, cystic and solid components, detection of a feeding vessel to the mass, and signs of hydrops.
5.1 CONGENITAL HIGH AIRWAY OBSTRUCTION SYNDROME
Definition Laryngeal atresia is the most common etiology of congenital high airway obstruction syndrome (CHAOS). Other etiologies of CHAOS include tracheal agenesis, tracheal atresia, subglottic stenosis, laryngeal web, tracheal membrane, and laryngeal cyst.
Epidemiology True incidence is unknown.
Embryology Tracheal or laryngeal atresia is thought to result from failure of recanalization of the upper airway. CHAOS occurs with Fraser syndrome (autosomal recessive), which has laryngeal atresia, urogenital abnormalities, and syndactyly. Fetal hydrops or polyhydramnios may occur. It has also been reported with cri du chat (5p-) syndrome, short-rib polydactyly syndrome, and the velocardiofacial syndrome.
Inheritance Patterns Inheritance is sporadic in most cases and autosomal recessive in the case of Fraser syndrome. One case of autosomal dominant inheritance has been reported with an affected father and two children.
Teratogens None are described.
Prognosis The absence of hydrops is associated with survival but with significant morbidity. Respiratory function is rarely normal due to long-term exposure to high airway pressure. The presence of other anomalies worsens the prognosis with CHAOS.
Large diffusely echogenic lungs
Dilated airways distended with fluid
Heart compression from lung expansion
Splaying of the ribs due to enlarged fetal lungs
Preeclampsia in the mother
Main stem bronchial atresia results in unilateral CHAOS. Other than an enlarged unilateral hyperechoic lung, the sonographic findings and outcome are similar to laryngeal atresia.
CHAOS is most frequently assumed to represent type III congenital cystic pulmonary airway malformation.
The subtype of CHAOS with a pharyngotracheal or laryngotracheal communication is less severe; ultrasound findings may resolve. The fistula allows decompression of the obstructed tracheal bronchial tree.
Sonographic findings associated with CHAOS have been reported as early as 16 weeks’ gestation.
Two-dimensional (2-D) ultrasound permits an anatomic and functional evaluation of the larynx and pharynx.
Color Doppler can be used to show an absence of flow through the larynx with fetal breathing movements. The larynx is occupied by nonstructured tissue.
With a unilateral hyperechoic lung mass, three-dimensional (3-D) power Doppler can be used to look for the feeding vessel associated with bronchopulmonary sequestration (PS).
Three-dimensional multiplanar imaging can evaluate an enlarged echogenic lung lesion for the anechoic nonvascular, tubular image of a bronchus or bronchi.
Three-dimensional assessment of the larynx and pharynx, with multiplanar reconstruction, permits an assessment of basic anatomic relationships and helps in the differentiation of laryngeal atresia from a tracheal membrane.
Investigations and Consultations Required Most cases are isolated and sporadic. In those cases with sonographically detected abnormalities, chromosome studies, including microarray, should be done. Fetal echocardiography can assess both cardiac structure and function. Fetal magnetic resonance imaging (MRI) may be helpful in defining the obstructing lesion (ranging from a laryngeal web to tracheal agenesis). Consultations with a pediatric surgeon and a neonatologist are essential for planning delivery management.
Pregnancy Course Without intervention, many will progress to fetal hydrops and fetal demise. The presence of hydrops is an ominous sign.
Fetal Intervention When short-segment tracheal lesions, or webs, are demonstrated on fetal MRI, fetal bronchoscopy and tracheoplasty may be options if done by experienced interventionists at specialized centers. Successful in utero intervention has been reported.
Monitoring In the limited number of cases reported to date, there has been a high incidence of in utero deaths. There are no studies on which to base treatment recommendations. However, once the fetus has reached sufficient size that ex utero tracheotomy could be performed, weekly assessment of fetal status will help to determine the most appropriate time for delivery.
Pregnancy Termination Issues Given the poor prognosis despite interventions, pregnancy termination should be presented as an option. For counseling regarding future pregnancies, an intact fetus is necessary to determine whether the airway obstruction is isolated or part of a syndrome.
Delivery In those cases where ultrasound and MRI suggest lesions amenable to postnatal repair, early EXIT (ex utero intrapartum treatment) should be considered. Delivery must occur in a center where a multidisciplinary team is skilled in the EXIT procedure. In this procedure, only the head and shoulders are delivered through the uterine incision. A saline infusion is used to maintain uterine volume and to prevent umbilical cord compression. Uterine relaxation is maintained by a high concentration of inhalation anesthetics and tocolytic agents, if necessary. If the fetal airway cannot be established by direct laryngoscopy or bronchoscopy, tracheostomy is performed. Only after the airway is established is the infant delivered and the umbilical cord clamped.
Resuscitation Emergent airway management is enhanced if there has been prenatal diagnosis. Few infants establish spontaneous ventilation following delivery. Given the severity of the prognosis, a prenatal discussion with the parents of management options is indicated. If the decision is for full resuscitative efforts, the EXIT procedure offers the potential for survival in this otherwise-lethal condition. Delivery should be arranged to facilitate rapid surgical establishment of an airway, if needed, and with full pediatric subspecialty diagnostic and intensive care capabilities available. The postnatal course of CHAOS is dependent on whether the airway obstruction is complete. In the absence of a prenatal diagnosis, emergent airway management consists of tracheoesophageal intubation or emergent tracheostomy.
Transport If the diagnosis is made antenatally and temporary stabilization of the airway is achieved at the time of delivery, emergency transport with a skilled neonatal team to a tertiary center with full pediatric and surgical subspecialty capabilities is indicated.
Testing and Confirmation Flexible endoscopy will confirm the blind tracheal pouch and in some cases identify the communication, or communications, between the esophagus and the distal airway or airways. Contrast studies or MRI may be needed to elucidate the structural anatomy of the communications in planning for surgical intervention. Evaluation for additional malformations is indicated. Multiple organ system anomalies have been documented in reported cases, including pulmonary, genitourinary, musculoskeletal, and cardiovascular malformations.
Nursery Management The first priority is a stable and functional airway, which is achievable only with skilled surgical intervention. The next focus is complete evaluation, as multiple organ system anomalies occur in many of these infants. The exact diagnostic and therapeutic management, beyond full life support, is dictated by the associated anomalies.
5.2 CONGENITAL PULMONARY AIRWAY MALFORMATION
Definition Congenital pulmonary airway malformations (CPAMs; previously called congenital cystic adenomatoid malformations) are benign hamartomatous, or dysplastic, lung tumors characterized by overgrowth of terminal bronchioles.
Epidemiology Occurrence is 1 in 25,000 to 35,000 live births (M1:F1).
Embryology CPAMs develop during the first 6 weeks of gestation. CPAM is theorized to be induced by localized overexpression of fibroblast growth factor 10. They are generally unilateral and classified into macrocystic (type I), mixed (type II), or microcystic (type III) forms. This Stocker three-stage classification of CPAM is based on clinical, radiological, and pathologic criteria in the postnatal period. Stocker subsequently expanded the classification by adding acinar dysplasia or agenesis (type 0) and large thin-walled peripheral cysts (type IV). The last two categories have been questioned, resulting in the development of other classification systems. There is a 26% incidence of associated malformations, including reports of pectus excavatum, renal agenesis, pulmonary sequestration (PS), congenital heart defects, and imperforate anus. Trisomy 18 has also been seen in association with CPAM.
Inheritance Patterns Inheritance is sporadic.
Teratogens There are no known teratogens.
Prognosis The majority of patients with CPAM detected antenatally have a good outcome. Many cases appear to regress or resolve in utero. Others can be successfully resected with normal outcomes. Early hydrops may be associated with a lethal prognosis.
Echogenic lung mass
Multicystic lung mass
Increased thoracic diameter
Antenatal sonography can only distinguish between macrocystic (one or more visible cysts) and microcystic (echogenic cysts < 5 mm) CPAM.
CPAM is usually in one pulmonary lobe (80%-95% of cases).
Multilobar or bilateral CPAM is rare.
CPAMs are evenly distributed between the right and left lung.
Microcystic CPAM with a coexisting pulmonary sequestration (PS) is frequently missed, even when a feeding vessel to the mass is specifically sought with color Doppler.
Karyotyping should be considered if additional congenital anomalies are detected.
The risk of a karyotypic abnormality is not increased with an isolated CPAM.
Rapid growth of microcystic CPAMs occurs between 20 and 26 weeks’ gestation.
At 26 weeks’ gestation, growth patterns of microcystic CPAMs begin to regress.
Macrocystic lesions generally do not regress.
In the third trimester, microcystic CPAM becomes isoechoic with normal lung parenchyma, resulting in their apparent “disappearance.”
Weekly ultrasound examinations should be performed to look for hydrops when a microcystic CPAM has a mediastinal shift, a mass-to-thoracic ratio of 0.56 or greater, and diaphragmatic eversion.
After 28 weeks, ultrasound surveillance can be individualized based on the lesion’s size.
In the presence of macrocystic CPAM, serial ultrasound examinations until delivery are required.
The cysts in macrocystic CPAM have intracystic communication.
Compression of the contralateral lung by a large CPAM can result in pulmonary hypoplasia.
A CPAM volume ratio (CVR) has been used to predict survival.
CVR volume: Length × Height × Width × 0.52 of the CPAM divided by the head circumference.
A CVR of 1.6 or less predicts a 97% survival if a dominant cyst is not present. This is in contrast to a survival of 56% with a CVR of 1.6 or greater.
CVR measurements extend along a continuum; the cutoff selected (1.4, 1.6, or 2.0) determines its sensitivity and specificity for the development of fetal hydrops.
Accurate predictors of outcome are as follows:
Decrease in size of the lung mass over serial ultrasound examinations predicts survival.
The presence of hydrops is strongly associated with demise.
Regression of a microcystic CPAM lesion occurs in 50% of cases, even in the presence of associated hydrops.
Pulmonary sequestration may resemble microcystic CPAM and can only be differentiated by the detection of a feeding vessel to a PS.
Congenital lobar emphysema is an intrinsic obstruction due to a mucous plug or defective bronchial cartilage. A mucous plus obstructing a bronchus can create an echogenic lung lesion. If the obstruction is relieved, the echogenic lung lesion resolves.
Lobar bronchial atresia resembles microcystic CPAM. A fluid-filled bronchus distal to an obstruction will assist in the diagnosis. There is an associated mediastinal shift and eversion of the diaphragm. Severe cases are associated with ascites and polyhydramnios.
Bronchogenic cysts. A simple or septated bronchogenic cyst may have the same appearance as a macrocystic CPAM. A bronchogenic cyst is derived from the foregut and therefore originates in the midline. As its size increases, a bronchogenic cyst becomes more difficult to distinguish from a CPAM. Three-dimensional multiplanar imaging can help to distinguish between a bronchogenic cyst compressing surrounding lung and a CPAM.
Investigations and Consultations Required An extended ultrasound examination is indicated to exclude other anomalies and possible coexisting bronchopulmonary sequestration (BPS). Invasive testing is not indicated if a precise diagnosis can be made by ultrasonography and other anomalies are not present. Cardiac status should be assessed by fetal echocardiography. Early consultation with a neonatologist or pediatric surgeon is warranted to establish a perinatal management plan.
Fetal Intervention Most of these masses are stable, and many regress during pregnancy. Fetal intervention would only be considered in cases without associated anomalies in which there is rapid growth of the lesion or hydrops is present or develops. In microcystic lesions with rapid growth early in gestation, one or two courses of betamethasone may arrest the growth of the CPAM lesion. In macrocystic lesions with rapid growth, mediastinal shift, or hydrops development early in gestation, aspiration of the cyst may be therapeutic. If the cyst reaccumulates, a cyst-amniotic shunt may be placed. Multicystic lesions are generally not appropriate for shunt placement.
Monitoring Ultrasonographic examinations every 4 weeks are appropriate to monitor the size of the mass and to detect early evidence of hydrops.
Pregnancy Course Polyhydramnios may develop in some cases and may result in preterm labor. However, many lesions regress or disappear during pregnancy.
Pregnancy Termination Issues Unless a clear diagnosis is made by ultrasound, a nondestructive procedure that provides both anatomic and microscopic evaluation is appropriate.
Delivery In the absence of fetal hydrops, delivery should be at term. After 32 weeks’ gestation, any evidence of fetal compromise should prompt steroid administration to enhance fetal lung maturity and early delivery. If hydrops is present after 32 weeks, consideration should be given to delivery via an EXIT procedure. Because immediate resuscitation may be necessary in any infant with CPAM, delivery should occur in a tertiary center.
Resuscitation The management of newborns with CPAM depends on whether the infant presents with signs of respiratory distress. Approximately half of infants diagnosed prenatally with CPAM are asymptomatic at birth. Infants with symptomatic CPAM typically present with early-onset respiratory distress and may require intubation following delivery and assisted ventilation.
Transport Symptomatic patients require transfer to a tertiary center with the availability of pediatric surgery. Mechanical ventilator support may be required, and the infant should be positioned with the involved side dependent in an attempt to avoid overdistension.
Testing and Confirmation Asymptomatic infants with a prenatal diagnosis of CPAM require a chest radiograph at the time of delivery. If the infant is stable, subsequent evaluation with a chest computerized tomographic (CT) scan or MRI at 3-6 months should performed. Elective surgical resection at a future date is recommended. In symptomatic patients, a CT scan or MRI are recommended, and prompt surgical resection is often indicated in the immediate newborn period. Classification of the type of CPAM is made based most definitively on the characteristics of the lesion as assessed by the pathologist after excision. This may be different from the classification assigned antenatally by ultrasound criteria.
Nursery Management Larger and more extensive CPAM lesions are associated with an increased incidence, and severity, of respiratory distress. Type 0 CPAM is the rarest form and is lethal. Infants with types 1, 2, and 4 CPAM may require respiratory support depending on the size of the cyst(s) and presence of respiratory distress at birth. Infants with type 3 CPAM typically present with severe respiratory distress and may require prolonged mechanical ventilation. Infants with a large CPAM who present with hydrops often require mechanical ventilation and additional pharmacologic support. Asymptomatic patients may be seen as outpatients by pediatric surgery for further evaluation and management
Preoperative Assessment The newborn should be evaluated in the nursery to confirm the prenatal diagnosis and exclude other associated anomalies. Most neonates will be hemodynamically stable, without signs of respiratory distress. A chest x-ray should be obtained to assess for the CPAM or mediastinal shift. In the setting of a stable infant without significant findings on chest x-ray, further evaluation may be deferred until later in infancy, allowing the neonate to be discharged home with his or her family. Even in the setting of a normal chest x-ray, further evaluation with either a CT scan or an MRI should be completed within the next several months of age. Many CPAM lesions will not be evident on chest x-ray but will be identified on more definitive 3-D imaging.
Operative Indications CPAM is usually confined to a single lobe. Rare cases have been reported of multilobar involvement of one lung or bilateral lesions. Complete resection of the CPAM, usually by lobectomy, is the treatment of choice. In cases of extensive involvement of nearly the entire lung, resection of multiple lobes, or pneumonectomy, may rarely be necessary. There should be consideration of the infant’s stability and the long-term risk of the lesion prior to proceeding with extensive pulmonary resection. The need for urgent surgery is determined by the presence of respiratory distress requiring ventilatory support. In a minority of patients, and particularly those with an early intrauterine diagnosis, the pulmonary symptoms are severe and unresponsive to standard respiratory support.
The newborn with a CPAM detected antenatally that subsequently regressed needs postnatal evaluation. Often, subtle abnormalities will be evident on chest radiograph, but chest CT or MRI may be necessary to detect residual CPAM. Several authors have recommended that, as long as these lesions are asymptomatic, they be observed closely and managed without resection. The argument against this approach includes the reported cases of myxosarcoma, embryonal rhabdomyosarcoma, and bronchoalveolar carcinoma arising in CPAMs. Although primary lung tumors are rare in the first two decades of life, 4% of those reported were associated with congenital cystic lesions of the lung, including CPAM. A more common concern is the risk of secondary infection of the CPAM, with the potential for the development of an abscess or difficult-to-eradicate infection, confusion with recurrent pneumonia that results in multiple courses of antibiotics, and technical difficulty at the time of resection.
Types of Procedures CPAMs may be approached by either thoracoscopy or thoracotomy. The advantage of deferring surgical excision until later in infancy is the greater likelihood of success via a thoracoscopic approach in the older, larger infant, as compared to the neonate. Most commonly, the CPAM is removed via lobectomy, but smaller lesions may be resected with a nonanatomic approach.
Surgical Results/Prognosis The long-term outcome of infants with CPAM following resection is excellent. If residual CPAM is left behind or the mass is not resected, the child will be at risk for complications. These complications include infection and malignancy arising within the CPAM. The infants usually have remarkable compensatory growth of the residual lung following resection, with continued alveolarization for several years. These children appear to have no excessive limitations and are no more at risk for respiratory infections than other children. The small number of children who have survived open fetal surgery for CPAMs associated with hydrops are doing well several years after their procedure.