Keywords CPAM - congenital lung mass - fetal bronchoscopy
A 32-year-old G2P1001 at 24 4/7 weeks was referred to our center with a large fetal chest mass to possibly undergo
fetal therapy. A course of betamethasone was administered to the mother at 23 0/7 weeks in the hopes to reduce the size of the lung lesion.[1 ]
[2 ]
[3 ] Consultation ultrasound revealed a singleton fetus with an estimated fetal weight
(EFW) of 810 grams (78th percentile). Anatomical findings were significant for a large right sided hyperechogenic,
homogenous lung that measured 7.3 × 4.6 × 3.7 cm3 ; the 3D (three-dimensional) volume measured 53.1 cm3 . No normal lung tissue was seen on the right side. The CPAM volume ratio (CVR) was
2.7. Arterial systemic feeding vessels to the right lung mass were not visualized.
Within the middle of the lung lesion near the area of the right bronchus was a 1.1
cm diameter hypoechogenic cyst ([Fig. 1 ]). The left lung was compressed with a quantitative lung index (QLI) of 0.5 (< 0.1st percentile).[4 ] There was mediastinal shift and diaphragm eversion present. A small left pleural
effusion (5 mm) was noted but there was no other evidence of fetal hydrops at this
time. Amniotic fluid maximum vertical pocket (MVP) was 6.2 cm. Thus on ultrasound,
the right lung appeared enlarged, hyperechogenic, and homogenous with a solitary cyst
near the area of the right bronchus, and the left lung appeared hypoplastic secondary
to compression from the mass effect. The differential diagnosis favored bronchial
atresia with a bronchocele or an obstructive bronchogenic cyst; however, CPAM and
congenital lobar emphysema remained under consideration.
Fig. 1 Ultrasound images from consultation at 24 4/7 weeks. (Left) Axial section of the hyperechogenic right lung lesion causing mediastinal
shift. (Right) Sagittal section of lung lesion resulting in diaphragmatic flattening.
A fetal echocardiogram was performed and the right pulmonary artery was dilated and
enlarged pulmonary vessels were seen coursing through the right lung mass in a normal
pattern. The cardiac anatomy was otherwise normal. No systemic arterial blood supply
to the lung mass was identified. A fetal magnetic resonance imaging (MRI) confirmed
the presence of an enlarged right lung with a T2 hyperintense lesion at the right
hilum (1.0 × 1.3 × 1.2 cm3 ), favoring an obstructive bronchogenic cyst or a mucus filled atretic segmental bronchus
([Fig. 2 ]).
Fig. 2 Fetal T2-weighted MRI at 25 0/7 weeks. (A ) Sagittal section of the fetus in cephalic position. The enlarged right lung is seen
causing diaphragmatic flattening. (B ) Axial section of the fetus with the hyperintense cystic structure within the right
lung lesion. The left lung is compressed secondary to the mass-effect from the enlarged
right lung.
The patient was counseled that the risk of pulmonary hypoplasia was high, as there
appeared to be minimal normal appearing lung tissue, and that the prognosis remained
guarded. Management options were discussed in detail. Expectant management would allow
for an opportunity for spontaneous resolution of the lung mass, but more likely the
lesion would remain and result in pulmonary hypoplasia. Percutaneous fetal sclerotherapy
was not recommended because the primary differential diagnosis favored bronchogenic
cyst or right bronchial atresia, and not CPAM Type III.[5 ] We offer fetal percutaneous sclerotherapy as a first line treatment to patients
with hydrops fetalis secondary to type II or III CPAM.[5 ] Direct fetal tracheobronchoscopy was also discussed as an option to evaluate for
a bronchial obstruction and if present, perforate with laser energy to allow efflux
of pulmonary secretions and restore physiologic pulmonary development, as described
by Martinez et al.[6 ] The risks of operative fetoscopy including preterm premature rupture of membranes
(PPROM) and periviable delivery were discussed. The patient elected expectant management
with the intention of undergoing fetal bronchoscopy if there appeared to be worsening
of the fetal condition.
The patient returned for a repeat ultrasound at 25 6/7 weeks. The lung findings were unchanged but new onset symptomatic polyhydramnios
with a MVP of 9.2 cm was noted. Given the persistence of the severe lung findings
including pleural effusions and new onset polyhydramnios, the patient desired to proceed
with an attempt of fetal tracheobronchoscopy. A multidisciplinary meeting was held
with Maternal-Fetal Medicine, Neonatology, Pediatric Surgery, and Radiology, and the
group agreed that fetal intervention was justified. The stated goal of the fetal tracheobronchoscopy
was to decompress the obstructive lesion in the hopes this would resolve the developing
hydrops and allow for improved development of the fetal lungs.
A second course of betamethasone was given for the purposes of fetal lung maturation
with the added possible benefit of decreasing the size of the lung mass.[7 ]
[8 ] After obtaining verbal and written consent, the patient was taken to the operating
room at 29 5/7 weeks. Amniocentesis was performed for fetal karyotype and microarray. Then the needle
was redirected and intramuscular injection of fentanyl (1 µg/kg) and rocuronium (1.5
mg/kg) for fetal anesthesia was provided. Next, operative fetoscopy and fetal tracheobronchoscopy
was performed as previously described.[9 ] Under ultrasound guidance, a 3.8 mm cannula with a trocar (Richard Wolf, IL) was
inserted into the amniotic cavity. The trocar was removed and a 3.5 mm 30-degree rigid
diagnostic endoscope (Richard Wolf, IL) was used to identify and gain access into
the fetal mouth. The cannula was advanced into the fetal mouth and the glottis was
identified. The diagnostic endoscope was advanced past the vocal cords and into the
trachea where the carina was visualized. The rigid endoscope was advanced into the
right and left main bronchus, and both appeared normal. The cannula was held in place
above the carina and the rigid endoscope was exchanged for a flexible 4.9 French ureteroscope.
Fetal bronchoscopy was then performed to assess the left and right bronchi. Mucoid
debris was noted within the bronchi. To improve visualization, intermittent bronchial
lavage was performed using normal saline infusion through the operating channel of
the ureteroscope. The total volume of saline lavage was estimated at 60 mL. Both right
and left bronchial trees were inspected in all lobes down to the segmental level.
All bronchi were patent and had normal branching patterns, ruling out a possible segmental
bronchial atresia. Combined direct visualization and ultrasound demonstrated that
the 1.1 cm cystic lesion was not in close proximity (more than 1 cm away) from the
right main or lobar bronchi.
Postoperative ultrasound 24 hours later showed the right lung lesion with a slightly
decreased CVR of 2.0. The patient was discharged and followed by her referring perinatologist
with serial ultrasounds. The fetal karyotype and prenatal microarray were found to
be normal. At 30 5/7 weeks the right lung mass had significantly decreased to approximately one-third
the size, measuring 4.8 × 2.5 × 3.0 cm3 , with a calculated volume of 18.7 cm3 . At 34 0/7 weeks, repeat fetal echocardiogram was notable for improved mediastinal shift and
mild cardiomegaly. The last ultrasound at 34 4/7 weeks prior to delivery showed the right lung mass measuring 3.3 × 2.4 × 3.7 cm3 and calculated volume of 15.2 cm3 . The cystic structure within the lung remained stable in appearance. The patient
went into labor and underwent a vaginal delivery at 35 3/7 weeks.
In the neonatal intensive care unit, the baby was initially supported by continuous
positive airway pressure. On day of life 4, computerized tomography (CT) of the thorax
showed that the right upper lobe was enlarged, demonstrated air trapping, and also
had a unilocular intrapulmonary cyst (1.8 × 1.2 × 1.3 cm3 ; [Fig. 3 ]). Due to persistent respiratory insufficiency requiring high-flow nasal cannula,
on day of life 9, the newborn underwent a right thoracotomy and right upper lobectomy.
The cyst seen on prior imaging was grossly visualized on the inferior aspect of the
right upper lobe. The small size of the cyst prevented the surgeon from determining
if it had a clear bronchial connection. Aside from asymptomatic tachypnea, the baby
had an otherwise uneventful course and was discharged from the hospital on day of
life 26.
Fig. 3 Computerized tomography scan on day of life 4. (A ) Axial view with an intrapulmonary cyst (1.8 × 1.2 × 1.3 cm3 ) (*) in right upper lobe. (B ) Coronal view with cyst (*) and prominent lucency suggesting air trapping (outline).
(C ) Coronal view with secondary effects of hyperinflated right upper lobe (outline)
included compressed right middle lobe and right to left mediastinal shift (arrow).
At 4 months of age, an echocardiogram was normal. At 6 months of age, the baby required
a 5-day hospitalization for an episode of metapneumovirus bronchiolitis. At 8 months
of age, due to the persistent tachypnea, the baby underwent a bronchoscopy without
abnormal findings. Flexible laryngoscopy was also performed at 9 months of age and
demonstrated mild laryngomalacia but normal subglottic lumen and normal range of motion
of the vocal folds. Aside from bouts of tachypnea, the baby was doing well at 12 months
of age without cardiopulmonary issues. The child does not require supplemental oxygen.
The baby has pectus excavatum which is being expectantly managed.
Surgical pathology demonstrated a 5.4 × 4.6 × 2.0 cm3 (18 grams) specimen with scattered dilated bronchiolar like cysts (0.5–2.0 cm) as
well as possible collapsed cysts up to 1.0 cm in diameter, consistent with a CPAM
Type II ([Fig. 4 ]). The cysts were lined with a single layer of ciliated columnar respiratory epithelial
cells. The cysts were separated by alveolar structures, small arterioles, and venules.
The surrounding stroma contained cells with skeletal muscle differentiation. Mucin
producing cells were identified. Patchy areas of interstitial emphysema and intra-alveolar
mucin inspissation was noted, which resulted in mucus plugs within the cysts and alveolar
spaces ([Fig. 4 ]).
Fig. 4 (A ) Hematoxylin and eosin section (magnification: ×40) shows several small uniform cysts
resembling dilated terminal bronchioles within the lung parenchyma. (B ) Section (magnification: ×40) shows mucus plugs mixed with few mononuclear cells
present within cysts and alveolar spaces.
Discussion
In this case report, fetal ultrasound and MRI revealed a large chest mass that was
suspicious for an obstructive bronchial lesion. Fetal tracheobronchoscopy provided
the following potential diagnostic and therapeutic benefits: (1) exclusion of an obstructive
bronchial lesion; (2) disimpaction of bronchial debris from the saline lavage, which
we posit may have been a contributing factor to the rapid reduction in CPAM size post
procedure.
Differentiating congenital lung lesions prenatally with ultrasound can be challenging
as they have several overlapping features. All of these lung lesions have the potential
to cause mediastinal shift, diaphragmatic eversion, fetal hydrops, and lethal pulmonary
hypoplasia. The finding of a congenital lung lesion requires postnatal histologic
follow-up to ensure an accurate diagnosis.[10 ] Furthermore, congenital lung lesions often contain histologic features of more than
one lesion, referred to as “hybrid” lesions.[11 ] CPAMs are usually limited to one lobe.[12 ] Hence, prenatal ultrasound of a microcystic CPAM often demonstrates an echogenic
solid appearing lesion neighboring normal ipsilateral lung tissue. However, our preoperative
images demonstrated an unconventional appearance of the microcystic CPAM; the entire
right thorax was filled with an echogenic mass. The overexpanded echogenic right lung
was remarkably similar to prenatal ultrasound images of a congenital diaphragmatic
hernia (CDH) treated with fetoscopic endotracheal occlusion[13 ]
[14 ]
[15 ]
[16 ] or a CHAOS.[17 ] However, in the setting of CDH or CHAOS, both lungs appear symmetrically enlarged
and echogenic due to an obstruction at the level of the trachea or more superiorly.
Given the unusual presentation of our patient, fetal bronchoscopy allowed us to exclude
the presence of a bronchial lesion from the differential diagnosis. The 1.1 cm cystic
structure within the lung parenchyma did not provide an explanation for the enlarged
right lung due to its relative small size and absence of dilated distal bronchi. Had
an obstructive bronchial lesion been identified, laser perforation could have removed
the obstruction and allowed efflux of the trapped fluid. Thus, fetal bronchoscopy
provided important diagnostic information in this case.
With a bronchial obstruction ruled out, the leading diagnosis was a microcystic CPAM,
which could be treated in utero via maternal steroid administration,[3 ] open fetal resection,[2 ] or percutaneous sclerotherapy.[5 ]
[18 ] However, this was not necessary because the CPAM significantly reduced in size after
the fetal bronchoscopy. There are three potential reasons why the CPAM reduced in
size. First, the natural history of CPAMs is such that reduction in size in the third
trimester is common.[19 ] Second, the two courses of steroids given in this case may have facilitated the
reduction in tumor size.[7 ]
[8 ] The mean (one standard deviation) time for resolution of hydrops after multiple
betamethasone courses for congenital lung lesions was previously reported as 33 ± 32
days.[8 ] Hence, it remains plausible that continued expectant management after the two courses
of betamethasone could have still ultimately led to the decrease in lung mass size
and resolution of hydrops. A third possible reason for the apparent reduction in tumor
size post procedure may be due to the procedure itself. We hypothesize that the saline
used to aide in visualization inadvertently dislodged debris that was, in part, obstructing
the lower airways. Perhaps the origin of this debris was mucoid material produced
by the aggregates of mucus producing cells within the CPAM, as was noted in the histopathological
specimens ([Fig. 4 ]). We speculate that prior to the lavage, the mucus produced by the CPAM located
in the right upper lobe was disseminated diffusely and obstructing multiple bronchi
in all three lobes of the right lung. Hence, the lavage may have dislodged and washed
out enough of the mucus to restore the natural efflux of pulmonary secretions over
time, leaving only the focal echogenic CPAM seen on postoperative ultrasounds and
postnatal CT. In other words, we posit that the saline lavage may have had an inadvertent
therapeutic benefit in this case. This assertion is purely conjecture at this time
based on the fetoscopic visualization of mucoid material at the time of saline lavage
and the pathological confirmation of mucus producing cells in the specimen. Furthermore,
we acknowledge the possibility that the mucoid material is a normal component of fetal
lung development and may be present in a great majority of normal fetuses.
Mucus producing cells are seen in approximately 35% of CPAM Type I cases but traditionally
not associated with CPAM Type II.[20 ] However, there is a case report of an adult patient with recurrent pneumonia that
underwent a left lower lobectomy for a CPAM Type II. There was no mention of diffuse
mucoid material as seen in our case, but a 1.5 × 1.5 cm2 cyst did contain inspissated mucus.[21 ] Perhaps the subset of children that are expectantly managed with CPAM and later
develop pulmonary infections, do in part, because of a build-up of mucoid secretions.
Quintero et al described a similar case in which a fetus with a large left hyperechogenic
lung mass and a small hypoechoic cystic structure near the hilum underwent fetal bronchoscopy
at 31 5/7 weeks.[9 ] Preoperatively, the fetus had no normal lung tissue on the affected left side and
a compressed contralateral right lung. The differential diagnosis included CPAM Type
III, pulmonary sequestration, bronchogenic cyst or lobar bronchial atresia. During
the fetal bronchoscopy, normal left lung tissue became delineated and there was expansion
of the right lung. Following the bronchoscopy, the left hyperechogenic mass significantly
regressed and the right lung expanded prior to delivery. The saline lavage utilized
during bronchoscopy was believed to have increased airway pressure and established
luminal patency in bronchi that may have been occluded with inspissated material.
Postnatally, surgical pathology was consistent with a hybrid lesion of CPAM Type III
and extralobar sequestration.[9 ]
The case by Quintero et al[9 ] and the current case further highlight the challenges in classifying CPAMs.[22 ]
[23 ] Perhaps these cases represent a rare form of CPAM in which a transient diffuse bronchial
obstruction is caused by excessive mucus production. This theory offers an explanation
for the antenatal ultrasound appearance of the microcystic appearance of the enlargement
of the entire right lung, and the potential therapeutic effect the bronchial lavage
had in restoring normal lung size and appearance. However, it remains unclear if the
mucin inspissation was the underlying pathology leading to subsequent abnormal bronchial
development, or it was an incidental finding in a primary developmental malformation
of the lower respiratory tract.
Fetal bronchoscopy has advantages over neonatal bronchoscopy. First, fetal bronchoscopy
is performed while on placental circulation and therefore does not have the same risks
of deoxygenation as in a neonatal bronchoscopy. Second, direct visualization narrows
the differential diagnosis. As previously discussed, the degree of hyperechogenicity
and diaphragm eversion in our case was not consistent with the typical findings of
a microcystic CPAM. If an obstruction, such as bronchial atresia is encountered in
utero, laser energy can be used to perforate the obstruction and re-establish luminal
patency.[6 ]
[24 ] This not only allows the stored pulmonary mucus secretions to be expelled, but also
normalization of the fetal lung tissue, correction of the mediastinal shift, and resolution
of the hydrops fetalis.[6 ]
[24 ]
The advantages of fetal bronchoscopy need to be weighed against its limitations. First,
the risk of PPROM and preterm delivery should be considered when determining the timing
of the intervention. Such risks should not be underestimated, particularly when prematurity
would compound the morbidity to an already at risk fetus. To mitigate complications,
an invasive procedure as rare as fetal bronchoscopy should be performed only by an
experienced team of providers. Second, fetal position may not be optimal for bronchoscopy
and external manipulation may be required. Third, fetal bronchoscopy should be reserved
for obstructive lower airway diseases that potentially can be improved by re-establishing
bronchial patency. Alternative management strategies need to be considered carefully,
and fetal bronchoscopy should be attempted only if the alternatives are deemed inadequate
treatment. In our case, performing only an amnioreduction without a fetal bronchoscopy
would potentially have prolonged the gestation without correcting the risk of pulmonary
hypoplasia. Given the paucity of literature on fetal bronchoscopy, it remains unclear
to what extent, if any, the saline irrigation used during bronchoscopy is helpful
in clearing obstructive debris.
In summary, the collective evidence from previously published fetal tracheobronchoscopy
cases[6 ]
[9 ]
[24 ]
[25 ] and ours adds to the current understanding of prenatal diagnosis and management
of congenital lung lesions. Under the proper circumstances, fetal tracheobronchoscopy
can serve as a diagnostic tool, as well as a possible therapeutic measure if an obstructive
lesion is identified. The role of fetal bronchial lavage in the rare instances of
a mucoid producing CPAM requires further investigation at specialized fetal therapy
centers.
