Echogenic Lungs

The most common fetal hyperechogenic lung lesions are microcystic congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestration (BPS), and Bronchial atresia.

pulmonary sequestration, cystic adenomatoid malformation, lung masses.

Fetal echogenic cystic lung lesions complicate about 1 in 3,000 live births. The incidence of CCAM is estimated at 1 in 6,000 births and 1 in 1,000 for BPS.¹

CCAM arise from the arrested maturation of bronchiolar cells early in gestation. As previously demonstrated by several histological studies, CCAM lung tissue is associated with an increased cell proliferation, decreased apoptosis and aberrant cell adhesion molecule expression ^{2, 3}. The pathogenesis of BPS is a controversial subject but it could be related with an impaired development of the pulmonary artery or a hamartomatous surplus of lung tisse⁴. It is though to originate from a supernumerary caudally positioned lung bud that migrated caudally during lung development.

CCAM is characterized by a lack of normal alveoli and an adenomatoid excessive proliferation and cystic dilatation of terminal respiratory bronchioles ranging in diameter from 1 mm to over 10 cm and that usually arise from one lobe of the fetal lung ⁵.

Stocker et al classified the microcystic CCAM as type 3, which include predominantly solid lesions with cysts sizes below 0.5cm⁵. The clinical and current classification is based primarily on echographic characteristics as macrocystic, microcystic (solid mass), and a mixed component of both solid and macrocystic types⁶.

The BPS is a bronchopulmonary segment characterized by an anomalous systemic arterial blood supply.  In a few cases, there is histological evidence of mixed component between CCAM and BPS  and also some hybrid cases which lung lesions show histologically and sonogaphic CCAMs appearance together with a systemic arterial blood supply similar to that of BPS, suggesting that a proportion of these lesions may have a common embryological origin⁷.

Bronchial atresia is a rare condition consisting of complete intrinsic obstruction of the fetal airway that is located at the level of the main bronchi resulting in retention of bronchial secretions which leads to abnormal expansion of the affected lung with bronchial dilatation.

An isolated echogenic lung mass is in general not associated with chromosomal abnormalities or genetic causes⁸. However, in the presence of any other associated malformations, the risk of chromosomal abnormalities increases to 40-50% and dictates the need for karyotype  analysis. 

There is no recurrence risk associated with these fetal anomalies.

Prenatal diagnosis is based on the demonstration of a uniformly hyperechogenic mass that appears as a solid lesion, usually unilateral, and involving one lobe of the lung ⁶. Differential diagnosis between these three conditions may be challenging.

The BPS is a portion of lung parenchyma that can  be identified as a uniformly well-defined triangular echogenic lesion, usually unilateral, supradiaphragmatic and involving the inferior lobe of the lung. The pathognomonic sign is the evidence of a systemic arterial blood supply coming from an aberrant branch of the aorta rather than the pulmonary artery that can be detected using spectral or power Doppler ultrasound ^{9, 10}. On the contrary, bronchial atresia and microcystic CCAM receive their blood supply from several vessels arising from the ipsilateral pulmonary artery. However, it is difficult to differentiate between CCAM and BPS during a  fetal ultrasound evaluation.  The differential diagnosis requires experienced observers to demonstrate the presence of an arterial branch arising from the aorta⁶. Similarly, differentiation between microcystic CCAM and bronchial atresia may be not possible by fetal ultrasound and some microcystic CCAM cases have shown bronchial atresia during fetal bronchoscopy¹¹

Other lung lesions that have to be considered in the differential diagnosis include congenital lobar emphysema (CLE), and suprarenal masses. CLE is a lobar overinflation without destruction of the alveolar sepate usually located in the upper lobe of the lung. Sonographically it is undistinguished from microcystic CCAM or bronchial atresia. In cases with a subdiaphragmatic BPS that occurs in up to 15%, suprarenal masses could be included into the differential diagnosis¹².

With the improvement in new ultrasound devices, it is not as difficult to demonstrated differences in lung echogenicity if a search is done systematically. Once a lung mass is identified, the location, size, echogenicity, and blood supply must be evaluated using conventional spectral or power Doppler ultrasound. Depending on the type and size of the lung lesion, sonographic surveillance should be performed weekly to assess the mass volume, amniotic fluid volume, and cervical length. Additionally, the evaluation of cardiac function parameters such as Doppler of the ductus venosus and tricuspid regurgitation should also be performed in the monitoring of these fetuses to identify the early occurrence of hydrops¹³. Some indirect signs could be found in the sonographic examination as a complication of the lung masses. The presence of large lung lesions can induce  esophageal compression producing difficultyfor the fetus to swallow, resulting in polyhydramnios. Similarly, hydrops fetalis (that is manifests as fetal ascitis, pleural and pericardial effusions, skin and scalp edema), is an additional ultrasonographic sing that could be found secondary to either obstruction of the inferior vena cava return or direct cardiac compression by the mass¹⁴.

Is difficult to differentiate between CCAM and BPS in the fetal ultrasound evaluation and the differential diagnosis required the evaluation by experienced observers to demonstrate the presence of an arterial branch arising from the aorta.¹⁰ There is however a huge possible histological variations and combinations of CCAM and BPS (Hybrids) that may result in different sonographic appearances where the magnetic resonance imaging may be helpful to differentiated and to determine lobe localization and the presence of lung hypoplasia.¹⁹

The prenatal prognosis of fetal lung masses depends on the mass size and the presence of hydrothorax or hydrops.

Cases without hydrothorax or hydrops show a survival rate above 95%, and the majority of the lung lesions regresses antenatally with expectant management, and resolve in up to 50% without need for postnatal surgery¹⁵. A small proportion of cases show large masses that can cause massive pleural effusion and severe mediastinal shift with fetal hydrops and thus are at risk of intrauterine fetal demise. Compression of the esophagus can also cause polyhdramnios and preterm delivery with risk of neonatal death due to the combination of lung compression and prematurity.

In the case of BPS, the prognosis seems to be very good and the best predictor of poor prognosis is the presence or abscense of pleural effusion. Cases of BPS without hydrothorax show a survival rate above 95%, and the majority of the lung lesions regresses antenatally with expectant management, and resolve in up to 50% without need for postnatal surgery21. In the presence of hydrothorax the condition may progress to hydrops and the development of pulmonary hypoplasia with a less than 50% of survival probability 25.

Expectant management with continuing ultrasonographic follow-up seems to be a reasonable recommendation for small, nonhydropic lung lesions.  However, development of hydrothorax or hydrops represents an indiction for fetal therapy. 

In large microcystic CCAM that develop hydrops, fetal therapeutic options are limited. Thoracoamniotic shunts can not be placed since the lung mass is solid, and there are no large cysts to be drained. Preliminary studies using open fetal surgery with resection of the lesion between 22 to 32 weeks of gestation, reported a survival rate of 50% ¹⁶. Likewise, percutaneous laser ablation of the microcystic lesions have been proposed ^{17, 18}, but further studies are necessary to consider these techniques as a therapeutic option. In addition to fetal surgery, non-invasive treatments have been published. Small-case series have reported a potential negative effect of prenatal steroid management on the growth of microcystic CCAM with a substantial positive effect in hydrops resolution and survival ^19-21. They reported a CCAM volume decrement in >70%, resolution of hydrops above 80% and on average 30 days later, and survival rate >90% in cases managed with maternal betamethasone (12mg intramuscularly, 2 doses, 24-hours apart). Preliminary evidence has suggested the use of fetal bronchoscopy for prenatal management of bronchial atresia^{11, 22}.

In cases with BPS and pleural effusions, several treatments have been performed in an attempt to decrease the risk of perineatl death but recent evidence has demonstrated a potential superiority with occlusion of the feeding blood vessel by ultrasound-guided laser coagulation. This intervention prevents the risk of intrauterine fetal demise and avoids the need for postnatal removal of the tumor^{23, 24}.

Postnatal thoracotomy with lung mass resection is often indicated by the size of the mass or by symptoms such as respiratory distress, pneumonia, hydrothorax or pneumothorax²⁵.   

Investigation of histological, genetic patterns or growth factor expressions in these subgroups might help to understand the differences observed in the behavior and growth of these lung tumors to further improvement in predicting survival and neonatal morbidity and may provide new therapeutic approaches.

1.         Burge D and Wheeler R. Increasing incidence of detection of congenital lung lesions. Pediatr Pulmonol 2010; 45: 103; author reply 104.

2.         Cass DL, Crombleholme TM, Howell LJ, Stafford PW, Ruchelli ED and Adzick NS. Cystic lung lesions with systemic arterial blood supply: a hybrid of congenital cystic adenomatoid malformation and bronchopulmonary sequestration. J Pediatr Surg 1997; 32: 986-990.

3.         Volpe MV, Chung E, Ulm JP, Gilchrist BF, Ralston S, Wang KT and Nielsen HC. Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation. Am J Physiol Lung Cell Mol Physiol 2009; 297: L143-152.

4.         Corbett HJ and Humphrey GM. Pulmonary sequestration. Paediatr Respir Rev 2004; 5: 59-68.

5.         Stocker JT, Madewell JE and Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol 1977; 8: 155-171.

6.         Adzick NS. Management of fetal lung lesions. Clin Perinatol 2009; 36: 363-376.

7.         Samuel M and Burge DM. Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation. Thorax 1999; 54: 701-706.

8.         Adzick NS, Harrison MR, Crombleholme TM, Flake AW and Howell LJ. Fetal lung lesions: management and outcome. Am J Obstet Gynecol 1998; 179: 884-889.

9.         Ruano R, Benachi A, Aubry MC, Revillon Y, Emond S, Dumez Y and Dommergues M. Prenatal diagnosis of pulmonary sequestration using three-dimensional power Doppler ultrasound. Ultrasound Obstet Gynecol 2005; 25: 128-133.

10.       York D, Swartz A, Johnson A, Fielding J and Phillips JD. Prenatal detection and evaluation of an extralobar pulmonary sequestration in the posterior mediastinum. Ultrasound Obstet Gynecol 2006; 27: 214-216.

11.       Cruz-Martinez R, Mendez A, Perez-Garcilita O, Monroy A, Aguilar-Vidales K, Cruz-Martinez MA and Martinez-Morales C. Fetal bronchoscopy as a useful procedure in a case with prenatal diagnosis of congenital microcystic adenomatoid malformation. Fetal Diagn Ther 2015; 37: 75-80.

12.       Yildirim G, Gungorduk K, Aslan H and Ceylan Y. Prenatal diagnosis of an extralobar pulmonary sequestration. Arch Gynecol Obstet 2008; 278: 181-186.

13.       Mann S, Wilson RD, Bebbington MW, Adzick NS and Johnson MP. Antenatal diagnosis and management of congenital cystic adenomatoid malformation. Semin Fetal Neonatal Med 2007; 12: 477-481.

14.       Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ, Crombleholme TM, Flake AW and Adzick NS. Echocardiographic evaluation of the fetus with congenital cystic adenomatoid malformation. Ultrasound Obstet Gynecol 2000; 16: 620-624.

15.       Cavoretto P, Molina F, Poggi S, Davenport M and Nicolaides KH. Prenatal diagnosis and outcome of echogenic fetal lung lesions. Ultrasound Obstet Gynecol 2008; 32: 769-783.

16.       Grethel EJ, Wagner AJ, Clifton MS, Cortes RA, Farmer DL, Harrison MR, Nobuhara KK and Lee H. Fetal intervention for mass lesions and hydrops improves outcome: a 15-year experience. J Pediatr Surg 2007; 42: 117-123.

17.       Bruner JP, Jarnagin BK and Reinisch L. Percutaneous laser ablation of fetal congenital cystic adenomatoid malformation: too little, too late? Fetal Diagn Ther 2000; 15: 359-363.

18.       Ong SS, Chan SY, Ewer AK, Jones M, Young P and Kilby MD. Laser ablation of foetal microcystic lung lesion: successful outcome and rationale for its use. Fetal Diagn Ther 2006; 21: 471-474.

19.       Curran PF, Jelin EB, Rand L, Hirose S, Feldstein VA, Goldstein RB and Lee H. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg 2010; 45: 145-150.

20.       Peranteau WH, Wilson RD, Liechty KW, Johnson MP, Bebbington MW, Hedrick HL, Flake AW and Adzick NS. Effect of maternal betamethasone administration on prenatal congenital cystic adenomatoid malformation growth and fetal survival. Fetal Diagn Ther 2007; 22: 365-371.

21.       Tsao K, Hawgood S, Vu L, Hirose S, Sydorak R, Albanese CT, Farmer DL, Harrison MR and Lee H. Resolution of hydrops fetalis in congenital cystic adenomatoid malformation after prenatal steroid therapy. J Pediatr Surg 2003; 38: 508-510.

22.       Martinez JM, Prat J, Gomez O, Crispi F, Bennasar M, Puerto B, Castanon M and Gratacos E. Decompression through tracheobronchial endoscopy of bronchial atresia presenting as massive pulmonary tumor: a new indication for fetoscopic surgery. Fetal Diagn Ther 2013; 33: 69-74.

23.       Cruz-Martinez R, Mendez A, Duenas-Riano J, Ordorica-Flores R, Nieto-Zermeno J, Malagon-Salazar P, Medina-Noyola C and Rebolledo-Fernandez C. Fetal laser surgery prevents fetal death and avoids the need for neonatal sequestrectomy in cases with bronchopulmonary sequestration. Ultrasound Obstet Gynecol 2015; 46: 627-628.

24.       Cruz-Martinez R, Nieto-Castro B, Martinez-Rodriguez M, Gamez-Varela A, Ahumada-Angulo E, Luna-Garcia J, Pineda-Perez MJ and Rebolledo-Fernandez C. Thoracic Changes after Full Laser Ablation of the Feeding Artery in Fetuses with Bronchopulmonary Sequestration. Fetal Diagn Ther 2018; 44: 166-172.

25.       Lopoo JB, Goldstein RB, Lipshutz GS, Goldberg JD, Harrison MR and Albanese CT. Fetal pulmonary sequestration: a favorable congenital lung lesion. Obstet Gynecol 1999; 94: 567-571.

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