Congenital Cystic Adenomatoid
Malformation of the Fetal Lung
Author:
Elizabeth A. Stillwell, RT, RDMS
Scott W. Roberts M.S., M.D.
Objectives: Upon the completion of this CME article, the reader will be able to
1.
State the diagnostic criteria for the three different types of congenital cystic adenomatoid
malformation of the fetal lung.
2.
Describe the factors related to making a differential diagnosis for fetal chest masses.
3.
Describe the possible associated congenital anomalies that may co-exist with congenital
cystic adenomatoid malformation and what to look for sonographically as a patient is
followed through the pregnancy.
Case Study
A 30-year-old G3P2002 white female presented at 20 1/7-weeks’ gestational age by last
menstrual period for a consult and complete pregnancy sonogram secondary to an outside study that
was suspicious for an abnormal appearing fetal chest.
An ultrasound was performed using an Acuson 128 XP (Acuson, Mountain View, CA). A
male fetus was identified and fetal biometry was consistent with a 20-week gestation. A
hyperechoic mass was imaged that completely filled the left thorax of the fetus, which resulted in the
right axis deviation of the fetal heart with compression of lung tissue and displacement of the left
hemi-diaphragm inferiorly. The overall dimensions of the mass were 4.1 x 2.9 x 3.7 cm. The
amniotic fluid index was within normal limits at 13.0 cm. No other fetal anomalies were noted.
Examination of the fetal abdomen was normal with a normal placement of the fetal stomach bubble,
etc. These ultrasound findings were most consistent with congenital cystic adenomatoid
malformation (CCAM) of the fetal lung – the microcystic type (figures 1, 2, & 3).
The patient was offered genetic counseling and possible genetic testing along with fetal
echocardiography. She also underwent prenatal counseling with pediatric surgeons and received a
tour of the newborn intensive care unit. The patient chose conservative management and had fetal
echocardiography performed at 24 3/7-weeks’ gestational age. This examination only identified
dextroposition of the fetal heart, but was otherwise a normal study.
The patient was followed serially with ultrasound examinations for interval growth, thoracic
mass evaluation, and for the development of hydrops or polyhydramnios. The mass dimensions
reached a maximum of 4.9 x 4.1 x 3.3 cm. Her last ultrasound evaluation was performed at 36
4/7-weeks’ gestational age and the echogenicity of the left thoracic mass had regressed to being
similar to that of the right lung (figure 4). The heart remained deviated to the right and no
sonographic evidence for fetal hydrops or polyhydramnios developed. The patient was delivered at
term and the newborn did not develop any signs of respiratory distress. Therefore, pulmonary
hypoplasia did not develop. The neonate was eventually discharged in good condition.
Discussion:
Congenital cystic adenomatoid malformations are rare pulmonary lesions that can be
diagnosed prenatally by ultrasound. CCAMs are “hamartomas” of the lung and are composed of an
abnormal overgrowth of the terminal bronchioles. (Hamartomas are benign tumor-like growths
that consist of cells, which are part of the organ from where it is located, but these cells reproduce in
an abnormal disorganized fashion.) Large CCAMs can displace mediastinal structures (like the
heart, esophagus, and inferior vena cava) by its mass effect. These lesions are usually unilateral
involving one lobe or segment of the lung. There is also no predilection for one lung side over the
other.
Polyhydramnios can develop in some cases. Under normal circumstances, the production
of amniotic fluid is a continuum of production and resorption. The amniotic fluid in the first
trimester primarily comes from a transudation off the membranes and umbilical cord. In the
second and third trimesters, this switches to the fetal kidneys, which produce the majority of
amniotic fluid up to delivery. The fetal lungs, membranes, and umbilical cord also contribute, but
in very small quantities when compared to the fetal kidneys. The majority of amniotic fluid
resorption comes from fetal swallowing. In addition, some resorption also occurs in the fetal lungs
through fetal breathing movements. It is thought that the polyhydramnios associated with CCAM
is most often caused by a decrease in effective swallowing of amniotic fluid due to compression of
the esophagus within the mediastinum (due to pressure or shifting). Other possible factors that
may contribute to an increase in amniotic fluid are a decrease in resorption from the remaining lung
tissue and an increase in fluid production by the malformation itself.
Two other complications of CCAM are the development of pulmonary hypoplasia and
nonimmune hydrops. For congenital cystic adenomatoid malformation, the worst prognosis is
found in cases where hydrops, pulmonary hypoplasia, and or polyhydramnios develops.
In classifying congenital cystic adenomatoid malformations, three types have been described:
Type I:
Has large cysts (often > 2 cm) that appear macrocystic on ultrasound examination –
this type accounts for about 50% of the cases and is reported to have the best
prognosis.
Type II:
Has medium-sized cysts that are usually between 0.5 and 1.5 cm in diameter – this
type accounts for about 40% of the cases.
Type III:
Are microcystic growths that typically appear as large hyperechoic masses – this type
accounts for about 10% of the cases. They are thought to appear solid, secondary
to the numerous reflections from interfaces of the myriad of very tiny cysts (cysts are
0.5 to 3 mm in size).
The majority of CCAMs derive their blood supply from the pulmonary circulation and drain
via the pulmonary veins. Color Doppler can be used to search for the presence of a systemic
feeding vessel. The differential diagnosis of fetal thoracic masses includes:
1.
Congenital diaphragmatic hernia (CDH)
2.
Congenital cystic adenomatoid malformation
3.
Bronchogenic or enteric cysts
4.
Bronchopulmonary sequestration
5.
Mediastinal meningocele
6.
Bronchial atresia or stenosis
7.
Neuroblastoma, teratoma, and other tumors
A Type I - CCAM is most easily confused with a congenital diaphragmatic hernia. The
observation of peristalsis in the mass and the absence of a normal appearing stomach bubble in the
fetal abdomen may help to differentiate the two. Bronchogenic cysts are usually unilocular and are
located adjacent to major bronchi, but sometimes may also be confused with a Type I - CCAM.
Type II CCAM 's may be associated with other congenital anomalies. Prognosis often
depends upon the severity of the associated anomaly. The more common reported associated
anomalies include genitourinary abnormalities such as renal agenesis; cardiac disorders such as
truncus arteriosus and Tetralogy of Fallot; intestinal anomalies such as jejunal atresia; and other
abnormalities such as diaphragmatic hernia; hydrocephalus; and skeletal anomalies. Congenital
cystic adenomatoid malformations are not usually associated with aneuploidy.
The echogenicity of Type III - CCAMs can be helpful in differentiating this from solid
tumors such as neuroblastoma. The most difficult diagnosis to differentiate from type III – CCAM
is bronchopulmonary sequestration (BPS). Here, color Doppler may be helpful in defining the
origin of the blood supply. Bronchopulmonary sequestration derives its blood supply from the
systemic circulation as opposed to the pulmonary supply more commonly associated with CCAM.
Occasionally CCAM and BPS can occur together as "hybrid" lesions. (See Table 1 for easy
comparison)
Recently, Adzick has proposed a classification of CCAMs based on anatomy and
sonographic appearance to aid in prognosis. In this system, macrocystic CCAMs have single or
multiple cysts > 5 mm in diameter. Microcystic CCAMs are more solid and bulky, with cysts that
are < 5 mm in diameter. Macrocystic lesions appear sonographically as fluid filled cysts, while
microcystic lesions appear solid due to the multiple and fine contiguous interfaces with the
ultrasound beam. This distinction is helpful as the microcystic lesions may carry a worse prognosis.
However, overall a higher mortality is due to the size of the lesion and the development of
secondary sequela such as mediastinal shifts, pulmonary hypoplasia, polyhydramnios, and
nonimmune hydrops (rather than the specific type of CCAM).
The lesion can sometimes be completely asymptomatic and may only come to attention with
incidental X-rays that are obtained postnatally. However, most lesions present at birth with the
development of cardio-respiratory compromise. Serial ultrasound evaluations for the detection of
hydrops are crucial in the management of CCAM. After 32 weeks’ gestation, detection of hydrops
may be an indication for the administration of corticosteroids (for the purpose of promoting fetal
lung maturity) followed by delivery. Once delivered, surgery can be performed to potentially relieve
the affects of the CCAM. Usually the malformation is confined to a single lobe. In the past, there
have been reports of fetal surgery performed in order to remove the CCAM inutero followed by the
resolution of hydrops and delivery at term. However, due to reports of spontaneous regression and
the benign course of many of these lesions postnatally, it may not be appropriate to offer a dismal
prognosis with certainty to parents of affected fetuses. Serial ultrasound examinations will add
important information for both physicians and patients in the management of this relatively rare
condition.
The need for surgery after delivery is most often determined by the presence of respiratory
distress requiring ventilatory support. In some newborns, particularly those in which an early
diagnosis was made, the pulmonary symptoms can be very severe and may be unresponsive to
standard ventilatory techniques. Therefore, delivery at or near a tertiary center, which offers
extracorporeal membrane oxygenation (ECMO), may be preferable. Some experts suggest
conservative management of the affected infant if the child is asymptomatic after birth. However,
other authorities feel that there could be an increased risk for future malignancy arising from the
unresected cystic adenomatoid malformation tissue (such as myxosarcoma or rhabdomyosarcoma)
and therefore they should be removed.
Long-term outcome for children with resected cystic adenomatoid malformations is
excellent if there has not been severe pulmonary sequela at the time of birth (such as pulmonary
hypoplasia, which is lethal). If residual CCAM is left behind, there is a risk for air trapping as well
as the possibility for an increased risk of malignancy, as previously discussed.
A recurrence for this abnormality is sporadic with no known hereditary risk. There have
been no reported cases of recurrence in an offspring or sibling. In addition, there appears to be no
known empiric risk for aneuploidy.
Table 1: Comparison of the 3 types of Congenital Cystic Adenomatoid Malformation
Type
I
II
III
Sonographic Appearance
– Usually unilateral
– May involve all or part of a
lung lobe
– Single large cyst with
small cystic out pouchings
– Echogenicities may be seen
within the cyst
– Similar to Type 1 except
there are numerous
similar
sized cysts
Histologic Findings
– Single large cyst
that is 2 cm or
greater in size
– Trabeculated cyst
walls with smaller
out pouching
cysts
– Mass consists of
multiple similar
sized cysts that
are
0.5 to 1.5 cm
– Cysts that are too small to
be distinctly identified
sonographically
– Appears as a solid
echogenic mass
– Multiple tiny cysts
that are 0.5 to 3
mm in size
Differential Diagnosis
– Congenital diaphragmatic
hernia
– Bronchogenic cyst
– Mediastinal mass
– Pleural or Pericardial
effusions
– Congenital diaphragmatic
hernia
– Bronchogenic cyst
– Mediastinal mass
– Pleural or Pericardial
effusions
– Pulmonary Sequestration
– Lung tumors such as
teratoma /
rhabdomyoma
– Herniated liver or spleen
Figures
1
Transverse view of fetal thorax with measurement of mass at 20 plus weeks.
2
Transverse view of fetal thorax with chest/heart circumference measurement at 20 plus
weeks
3
Longitudinal view of left thorax with measurement of mass at 20 plus weeks
4
Follow-up transverse view of fetal thorax at 36 plus weeks
References or Suggested Reading:
1.
Fetology: Diagnosis and management of the fetal patient. McGraw Hill. Bianchi DW,
Crombleholme TM, D’Alton ME. 2000. Pg. 289-298. Cystic adenomatoid malformation.
2.
Adzick NS, Harrison MR, Glick PL, and et al. Fetal cystic adenomatoid malformation:
prenatal diagnosis and natural history. J Pediatr Surg 1985;20:483-488.
3.
Adzick NS, Harrison MR, Crombleholme TM. Fetal lung lesions: management and outcome.
Am J Obstet Gynecol 1998;179:884-889.
4.
Bagalan P, et al. Cystic adenomatoid malformation of the lung: clinical evaluation and
management. Eur J Pediatr. 1999 Nov; 158 (11): 879-82.
5.
Lacy DE, Shaw NJ, Pilling DW, Walkinshaw S. Outcome of congenital lung abnormalities
detected antenatally. Acct Pediatric. 1999 Apr; 88 (4): 454-8.
6.
Roggin KK, Breuer Ck, Carr SR, et al. The unpredictable character of congenital cystic lung
lesions. J Pediatr Surg 2000;35:801-5.
7.
Bunduki V, Ruano R, da Silva MM, et al. Prognostic factors associated with congenital cystic
adenomatoid malformation of the lung. Prenat Diagn 2000;20:459-64.
8.
Berbel O, Pellicer C, Lopez-Andreu JA, et al. Cystic Adenomatoid malformation of the lung:
clinical evolution and management. Eur J Pediatr 2000;159:621-2.
9.
Sittig SE, Asay GF. Congenital cystic adenomatoid malformation in the newborn: two case
studies and review of the literature. Respir Care 2000;45:1188-95.
10.
Marshall KW, Blane CE, Teitelbaum DH, van Leeuwen K. Congenital cystic adenomatoid
malformation: impact of prenatal diagnosis and changing strategies in the treatment of the
asymptomatic patient. AM J Roentgenol 2000;175:1551-4.
11.
Monni G, Paladini D, Ibba RM, et al. Prenatal ultrasound diagnosis of congenital cystic
adenomatoid malformation of the lung: a report of 26 cases and review of the literature.
Ultrasound Obstet Gynecol 2000;16:159-62.
12.
Bratu I, Flageole H, Chen MF, et al. The multiple facets of pulmonary sequestration. J Peditr
Surg 2001;36:784-90.
About the Author
Elizabeth A. Stillwell is currently a Senior Staff sonographer for the Maternal-Fetal Medicine
Group that is affiliated with the Department of Obstetric and Gynecology at the University of
Kansas – Wichita. She received her RT in 1986 after her training in Garden City, Kansas and she
then received her RDMS in Obstetrics & Gynecology in 1990 and in Abdomen in 1991. She has
worked with the Perinatal Group since 1992 and has also been Adjunct Faculty instructing
OB/GYN ultrasound at Newman University in Wichita, Kansas.
Dr. Scott Roberts is board certified in Obstetrics and Gynecology and is also board certified
in Maternal-Fetal Medicine. He currently is the Director of the Maternal-Fetal Medicine Division in
the Department of Obstetrics and Gynecology at the University of Kansas School of Medicine –
Wichita. He has authored several articles in peer-review medical journals and has lectured on many
different topics across the country.
Examination:
1.
Regarding the case study presented in the article, all of the following are correct except
A.
The heart remained deviated to the left.
B.
No sonographic evidence for fetal hydrops or polyhydramnios developed.
C.
The patient was delivered at term and the newborn did not develop any signs of
respiratory distress.
D.
Pulmonary hypoplasia did not develop.
E.
The neonate was eventually discharged in good condition.
2.
Congenital cystic adenomatoid malformations are
A.
rhabdomyomas
B.
teratomas
C.
hamartomas
D.
fibromas
E.
neuroblastomas
3.
Congenital cystic adenomatoid malformations
A.
are usually bilateral involving one lobe or segment of the lung.
B.
are usually unilateral involving one lobe or segment of the lung.
C.
have a predilection for the left lung side over the right.
D.
A & C above.
E.
B & C above.
4.
In the second and third trimesters, the majority of amniotic fluid is produced by the
A.
umbilical cord
B.
membranes
C.
fetal kidneys
D.
fetal lungs
E.
fetal gastrointestinal tract
5.
The majority of amniotic fluid resorption comes from
A.
fetal breathing
B.
the fetal kidneys
C.
the maternal kidneys
D.
the placenta
E.
fetal swallowing
6.
Polyhydramnios can develop in some CCAM cases and is most often due to
A.
a decrease in effective swallowing of amniotic fluid due to compression of the
esophagus within the mediastinum.
B.
a decrease in absorption from the remaining lung tissue
C.
an increase in fluid production by the malformation itself
D.
an associated anomaly that be occur with this disorder.
E.
the increase in placental blood flow caused by the disorder.
7.
Pregnancies that involve the anomaly of cystic adenomatoid malformation should be
followed because complications can develop that include all of the following except
A.
pulmonary hypoplasia
B.
nonimmune hydrops
C.
polyhydramnios
D.
pulmonary sequestration
E.
a shift in mediastinal structures
8.
In classifying congenital cystic adenomatoid malformations, three types have been described.
Which of the following are true?
A.
Type I – CCAM has medium-sized cysts that are usually between 0.5 and 1.5 cm in
diameter.
B.
Type II – CCAM has large cysts (often > 2 cm) that appear macrocystic on
ultrasound examination.
C.
Type III – CCAM has medium-sized cysts that are usually between 0.5 and 1.5 cm in
diameter.
D.
Type I – CCAM has large cysts (often > 2 cm) that appear macrocystic on
ultrasound examination.
E.
Type II – CCAM are microcystic growths that typically appear as large hyperechoic
masses.
9.
The majority of CCAMs derive their blood supply from the
A.
left subclavian artery
B.
pulmonary circulation
C.
right subclavian artery
D.
splenic artery
E.
aorta
10.
The differential diagnosis of fetal thoracic masses includes all of the following EXCEPT:
A.
Congenital diaphragmatic hernia (CDH)
B.
Congenital cystic adenomatoid malformation
C.
Bronchogenic or enteric cysts
D.
Bronchopulmonary sequestration
E.
Pulmonary hypoplasia
11.
A Type I congenital cystic adenomatoid malformation is most easily confused with
A.
Bronchopulmonary sequestration
B.
Congenital diaphragmatic hernia
C.
Bronchogenic cysts
D.
E.
Mediastinal meningocele
Bronchial neuroblastoma
12.
Type II congenital cystic adenomatoid malformations may be associated with congenital
anomalies including all of the following except
A.
renal agenesis
B.
truncus arteriosus
C.
jejunal atresia
D.
gastroschisis
E.
hydrocephalus
13.
The most difficult diagnosis to differentiate from a Type III congenital cystic adenomatoid
malformation is
A.
Congenital diaphragmatic hernia
B.
Bronchogenic cysts
C.
Bronchopulmonary sequestration
D.
Mediastinal meningocele
E.
Enteric cysts
14.
Overall, a higher mortality is seen with congenital cystic adenomatoid malformation for all of
the following findings except
A.
the size of the lesion
B.
the presence of pulmonary hypoplasia
C.
the development of polyhydramnios
D.
a right sided lesion
E.
the development of nonimmune hydrops
15.
The need for surgery after delivery is most often determined by
A.
the size of the mass.
B.
the presence of respiratory distress requiring ventilatory support.
C.
the type of CCAM.
D.
the presence of polyhydramnios.
E.
which side the CCAM is located.
16.
Regarding conservative management following delivery, some authorities feel that there
could be an increased risk for future ________ arising from the unresected cystic
adenomatoid malformation tissue.
A.
shifts in the mediastinum
B.
development of pulmonary sequestration
C.
development of pulmonary hypoplasia
D.
development of cardiac dysfunction
E.
malignancy
17.
Which of the following statements is (are) true?
A.
Long-term outcome for children with resected CCAMs is excellent if there has not
been severe pulmonary sequela at the time of birth.
B.
If pulmonary hypoplasia has developed because of a CCAM, over time the majority
of newborns will outgrow this condition.
C.
D.
E.
If residual CCAM is left behind, this is not really a problem because future
complications will not occur.
A & B above are true
B & C above are true.
18.
Regarding the recurrence risk for CCAM,
A.
it is 50% because it is autosomal dominant in inheritance.
B.
it is 25% because it is autosomal recessive in inheritance.
C.
it varies because it is a chromosomal abnormality
D.
it is 50% for male offspring because it is X-linked recessive in inheritance.
E.
it is sporadic with no known hereditary risk.
19.
All of the following are true for Type I – CCAM except
A.
It is usually unilateral.
B.
There is usually a single large cyst > 2 cm in size.
C.
The main differential diagnosis to exclude is pulmonary sequestration.
D.
The cyst walls can be trabeculated with smaller out pouching cysts.
E.
It could be confused with a bronchogenic cyst.
20.
All of the following are true for Type III – CCAM except
A.
The main differential diagnosis to exclude is congenital diaphragmatic hernia.
B.
The cysts are too small to be distinctly identified sonographically.
C.
The cysts are tiny measuring about 0.5 to 3 mm in size.
D.
It appears as a solid echogenic mass.
E.
It could be confused with a lung tumor such as a rhabdomyoma.