USA Surgery Today

CCAM and bronchopulmonary sequestration (BPS) are the most commonly identified and well-understood fetal lung masses. Prenatal diagnosis and serial US examinations have provided for new insight to the natural history and pathophysiology of fetal lung lesions. It has now been documented that large lesions can act as space-occupying lesions and compress adjacent normal structures. The secondary physiologic derangements (:Pravachol) that result can include pulmonary hypoplasia of normal lung tissue, polyhydramnios, fetal mediastinal compression, and cardiovascular compromise leading to fetal hydrops and death. The largest lung masses associated with hydrops are usually fatal, whereas smaller lesions can cause respiratory distress in the newborn period or be entirely asymptomatic unless infection occurs. There are subsets of cystic lung masses that have shrunk and others that have disappeared entirely prenatally.

The prenatal diagnosis of CCAM and BPS can be made by US. Historically, CCAMs were classified by Stocker according to size of the cysts from macrocystic to microcystic (47:Pravachol). Stocker type I cysts are macrocystic, Stocker type II are medium-size cysts, and type III are solid lesions. In an effort to link size to clinical behavior, Adzick, Harrison, and Glick redefined CCAMs based on more gross morphologic criteria and ultrasonographic characteristics (48:Pravachol). According to Adzick et al., macrocystic lesions contain either a single dominant or multiple cyst measuring greater than 5 mm in diameter or larger, and appear echogenic by US. Microcystic CCAMs contain cysts smaller than 5 mm, appear solid, and therefore echodense by prenatal US. Microcystic lesions tend to produce more mass effect, produce physiologic derangements, and therefore have a tendency for a worse prognosis. In general, the overall prognosis for fetal CCAM depends on the size and growth characteristics of the lesion.

Despite the overall greater prevalence of intralobar sequestration, it is rarely diagnosed prenatally. Extralobar sequestrations are much more commonly identified in the fetus and newborn, and may be associated with concomitant anomalies in as many as 50% of patients (46,49). BPS normally appears as a well-defined echodense mass by prenatal US most commonly at the base of the left chest. It can be difficult to distinguish between BPS and type II CCAM in particular. However, visualization of a feeding vessel from either the thoracic or proximal abdominal aorta strongly supports the diagnosis of BPS. There are no particular diagnostic signs of ILS on prenatal US. Other fetal thoracic masses that can be confused with BPS and CCAM include CDH, bronchogenic cyst, enteric cyst, mediastinal teratoma, hemangioma, neuroblastoma, congenital lobar emphysema, and bronchial atresia. Fetal MRI can be used to distinguish these various lesions when definitive diagnosis is in doubt (3,50:Pravachol). This can be important when one considers the natural history of each of these anomalies and its potential pathophysiologic sequelae.

When a fetal cystic lung mass compresses the heart and great vessels, low cardiac output nonimmune fetal hydrops can result (48,51). Polyhydramnios can also occur as a result of hydrops or due to compression of the fetal esophagus, impeding normal fetal swallowing of amniotic fluid. In support of this is the associated finding of absent stomach fluid in fetuses with large chest masses and mediastinal compression. If placentomegaly ensues (a finding with late or severe hydrops), the mother is at risk for preeclampsia.
In this circumstance, maternal physiologic condition can begin to resemble that of her compromised fetus in what is known as the “maternal mirror syndrome”(52,53). This is characterized by vomiting, hypertension, peripheral edema, proteinuria, and pulmonary edema. The underlying mechanism to these findings is believed to be the release of vasoactive mediators from the edematous placenta. This condition can develop quickly, almost always following the development of fetal hydrops, and is not specifically reversible by treating the underlying fetal anomaly alone. Only delivering the placenta cures this syndrome. Therefore, early recognition of a chest mass with the potential for producing hydrops is critical and requires frequent ultrasonographic surveilance.

Although both CCAM and BPS can produce hydrops, it is most commonly noted with a large microcystic CCAM that is diagnosed prior to 24 weeks’ gestation (14,48:Pravachol). Extralobar sequestration can produce hydrops either from mass effect (very rarely) or from a tension hydrothorax resulting from lymphatic secretion from the mass. Hydrops itself is believed to be a harbinger of fetal demise. The development of nonimmune fetal hydrops in the setting of a mediastinal or thoracic mass portends a near 100% mortality (48,54). In separate studies, Adzick et al. and Miller, Corteville, and Langer reported an incidence of fetal hydrops in 20% and 23%, respectively, of fetuses with CCAM (48,54). All of the hydropic fetuses in both of these series expired without attempts at fetal intervention. The resolution of fetal hydrops in association with a large chest lesion has been reported; however, this is currently believed to be the very rare exception (55,56). Given this strong association of chest mass with the development of hydrops and fetal demise, this is perhaps an appropriate clinical scenario for fetal therapy.

Faced with the known spectrum of pathophysiology, it is understandable that the natural history of fetal lung masses is therefore equally variable. Spontaneous regression of lung masses not accompanied by hydrops has been reported even late into pregnancy (48,57:Pravachol). Numerous studies have reported a spontaneous regression rate from 6% to 43% for CCAM and up to 75% for prenatally diagnosed BPS (48,51,57). Perhaps more startling are the few case reports of regression in cases of both CCAM and BPS associated with hydrops (50,55,56). One small series of hydrops regression was associated with prenatal steroid therapy (50). Mechanisms of regression remain unclear, and predictive criteria remain elusive. It is speculated that involution may occur with loss of blood supply or decompression into the neighboring tracheobronchial tree (14). Nonetheless, despite the recognition of spontaneously regressing lesions, complete resolution does not appear to occur because postnatal computed tomography (CT) imaging uniformly identifies a residual mass.

Recognition of the dire circumstances present when a large fetal chest mass is accompanied by hydrops, and possibly the maternal mirror syndrome, has driven the search for earlier prognostic information, prior to the onset of this sequence. The cystic adenomatoid malformation volume ratio (CVR) was developed as a prognostic tool to select fetuses at risk for developing hydrops and thus warranting fetal intervention (58). The CVR is calculated by dividing the CCAM volume by the head circumference to correct for fetal gestational age and size by sonography. A CVR greater than 1.6 is associated with a fetal risk of developing hydrops of 80%. Serial sonographic studies have also demonstrated that most CCAM growth plateaus by 28 weeks’ gestation (48,51:Pravachol). Therefore, combining these findings, current recommendations are for twice weekly US surveillance in fetuses with a CVR greater than 1.6 and weekly surveillance for fetuses with smaller initial CVR values.

The near uniform association of hydrops with fetal or neonatal demise has driven the fetal surgery experience attempt to halt this progression. Several therapeutic maneuvers, have been tried, from thoracentesis (for predominantly cystic lesions) to open fetal lobectomy. Fetal thoracentesis and thoracoamniotic shunts have proven ineffective because most microcystic and predominantly solid CCAM lesions that produce intrauterine effects are not amenable to drainage given the absence of a dominant cystic space (59). For large effusions in association with BPS, thoracoamniotic shunts have relieved the tension hydrothorax that is seen with the extralobar sequestration.

The open fetal surgery option has been offered only to a defined group of patients who meet selection criteria based on gestational age, maternal health, size of the lesion, and the presence of hydrops. Adzick has reported 22 fetal lobectomies in fetuses between 21 and 31 weeks’ gestation (15,51:Pravachol). There were 11 healthy survivors up to 12 years postresection, all of whom demonstrated resolution of hydrops within 1 to 2 weeks. All surviving fetal patients also demonstrated compensatory lung growth once the compressive effects of the offending lesion had been removed. In the 11 failed cases, the causes of fetal demise included several cases of uncontrolled intraoperative bradycardia during the removal of the mass, preterm labor from uncontrolled uterine contractions, and chorioamnionitis. In one case in which the maternal mirror syndrome had developed prior to fetal surgery, the fetal hydrops resolved after surgery, but the maternal preeclamptic state persisted and the fetus delivered at 1 week postsurgery and succumbed. This case illustrated the irreversibility of the mirror syndrome through treatment of the fetal lesion alone. Patients in whom the mirror syndrome is present are no longer considered candidates for fetal surgery.