2016, Volume 32, Number 3, Page(s) 200-204
Congenital Pulmonary Airway Malformation Type 2: A Case Report with Review of the Literature
Ebru TAŞTEKİN1, Ufuk USTA1, Ayşegül KAYNAR2, Çiğdem ÖZDEMİR3, Ömer YALÇIN1, Filiz ÖZYILMAZ1, Ali Kemal KUTLU1
1Department of Pathology, Trakya University, Faculty of Medicine, EDİRNE, TURKEY
2Iskenderun State Hospital, HATAY, TURKEY
3Tekirdag State Hospital, TEKİRDAĞ, TURKEY
Keywords: Cystic adenomatoid malformation of lung, Congenital, Lung diseases, Hydrops fetalis
A congenital pulmonary airway malformation is a rare disorder of
the pulmonary airway and a hamartomatous mass of disorganized
lung tissues with various degrees of cystic change. A 20-year-old
pregnant woman who did not have previous clinical follow-up during
her pregnancy visited the gynecology department for her first check
on the 19th week of gestation. The sonogram, showed severe hydrops
fetalis. Laboratory findings were consistent with non-immune
hydrops fetalis. Medical abortion was performed and the fetus was
sent to our department for a complete fetal autopsy. Macroscopically,
whole parts of the fetus had striking oedema. Massive pleural and
peritoneal effusions were seen on dissection. The left lung filled
the whole thoracic cavity. The heart was displaced to the right and
the right lung was compressed. Microscopically, the left lung mass
showed dilated bronchiole-like structures (1-20 mm) that were lined
with ciliated columnar cells without any intervening mucinous cells.
The subepithelial stroma contained thin, interrupted smooth muscle
fibers and elastic connective tissue without cartilage plates. Our case
is a very good example of non-immune hydrops fetalis associated
with congenital pulmonary airway malformation type 2. Prenatal
clinical and ultrasonographic follow-ups during pregnancy are very
important for early diagnosis of congenital malformations.
Congenital pulmonary airway malformation (CPAM) of the
pulmonary airway is an unusual lesion, combining features
of hamartoma, malformation or dysplastic proliferation.
CPAM was first described using the past terminology of
congenital cystic adenomatoid malformation by Ch'in and
Tang in 19491-3
suggested an expanded
classification renaming this group of malformations as
congenital pulmonary airway malformation (CPAM). There are five types. Only one of the types (type 3) is adenomatoid
and only three (types 1, 2 and 4) are cystic. CPAM is quite
rare and the etiology and incidence are unknown5
However CPAM represents about 25% of all congenital
lung lesions. In the literature, male and female populations
are affected equally. Lower lobe lesions predominate with
44% of all cases while the rest of the cases are scattered
in other lobes and is primarily unilateral, but may also
. Associated findings in CPAMs are polyhydramnios, pleural effusion and rarely non-immune
CPAM is characterized by the lack of normal alveoli, an
excessive proliferation and cystic dilatation of terminal
respiratory bronchioles with various types of epithelial
lining. Microscopically the cyst linings are composed of
ciliated, cuboidal or columnar cells and those cysts have
lack of normal architecture and are frequently devoid of
cartilage8. Type 2 CPAM that is associated with other
congenital anomalies is seen more frequently than other
types2. We report a fetal autopsy case of type 2 CPAM
with an unusual combination of accompanying extra
pulmonary abnormalities with prenatal diagnosis at the
19th week of gestation.
A 20-year-old woman who did not have previous clinical
follow-up during her pregnancy was referred to the
gynecology department for her first control at the 19th
week of gestation. The ultrasonogram (USG) showed severe
hydrops fetalis with other sonographic abnormalities
including a large mediastinal mass filling the left thoracic
cavity, causing the mediastinal shift, displacing the heart to
the right side, and compressing the right lung, vena cava
superior and vena cava inferior. There was dilatation in the
lateral ventricle of the brain and the choroid plexus was
depressed. There was no relationship between mass and
vascular system in Doppler USG. Medical abortion was
performed at 30th week of gestation and the fetus was sent
to the pathology laboratory for a complete medical autopsy.
Macroscopically whole body parts of the male fetus had a
striking oedema. There were massive pleural and peritoneal
effusions on dissection of peritoneal and pleural cavities.
The left and right main bronchus and their relationships
with mass were evaluated. The left lung was enlarged with
dimensions of 12x11x7 cm, filling the entire thoracic cavity.
It had cystic dilated structures of various size (Figure 1).
The heart was displaced to the right side and the right
lung was compressed and atrophied with dimensions of
1.5x1.3x1 cm. Massive fetal oedema was present due to
compression of both vena cava inferior and superior by the
huge mass of the left lung. Thus, hydrops fetalis was caused
by a non-immune reason, which was later also supported
by the absence of maternal antibodies.
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|Figure 1: Macroscopic appearance of congenital pulmonary
Microscopically, the left lung mass showed dilated
bronchiole-like structures that were lined by ciliated
columnar cells without any intervening mucinous epithelial
cells. The sub-epithelial stroma between the cystic spaces
contained thin, interrupted bands of smooth muscle fibers and elastic connective tissue without any cartilage plates
(Figure 2A,B). Immunohistochemically dilated cystic
structures showed positive staining for CK7 and TTF1 and
subepithelial stroma revealed SMA positive smooth muscle
fibers (Figure 3). Other fetal tissue and organs showed
massive oedema and immaturity development concordant
with the gestational age. The diagnosis was CPAM, type II,
according to the modified Stocker's classification3.
Click Here to Zoom
|Figure 2: Microscopic appearance of congenital pulmonary
airway malformation. A) Dilated bronchiole-like structures of
various sizes were seen (H&E x50), B) Dilated bronchiole-like
structures were lined with ciliated columnar cells without any
intervening mucinous epithelial cells (H&E x400).
Click Here to Zoom
|Figure 3: Immunohistochemically, columnar cells of dilated
cystic structures showed positive staining for TTF1 (A) and SMA
(B) positive smooth muscle fibers in the subepithelial stroma.
Cystic malformation of the lung is an unusual congenital
lesion characterized by cystic spaces of various sizes
composed of airway or alveolar-like structures6
was first described by Ch'in and Tang in 19491
is generally a unilateral lesion of one lobe and represents about 25% of all congenital lung lesions5
. The lesion
consists of cysts and solid airless tissue with no cartilage
in the wall. It may affect the pulmonary lobes partially or
Congenital pulmonary airway malformation is a
hamartomatous, dysplastic developmental abnormality
of the lung. It shows hamartoma, dysplasia or tumorous
features. There is a putative differentiation from proximal to
distal with type 0 originating from the trachea and bronchi
and type 4 is originating from the acinus. It is apparent
that narrowing or obliteration of the bronchial lumen is a
common pathological feature most of the time. Bronchial
atresia may especially cause this morphology. The primary
bronchial atresia, bronchial segmental disability, pause in
the development of the fetal lung, parenchymal differential
disability, and dysplastic bronchopulmonary tissue are
generally seen at 5-7th weeks of gestation9. Abnormal
Hoxb-5 regulation causes specific alterations in airway
branching. Normal lung tissue does not express significant
levels of Hoxb-5 protein, while the adjacent CCAM with
abnormal and immature airway express the high levels of
Hoxb-5. The abnormal expression of this Hox gene could
be associated with the development of aberrant branching
patterns in BPS and CCAM10.
Congenital pulmonary airway malformation classification
scheme has been revised in 2002 by Stocker and categorized
them as: type 0, trachea-bronchial; type 1, bronchial/
bronchiolar; type 2, bronchiolar; type 3, bronchiolar/
alveolar duct; and type 4, distal acinar16 (Table I).
The prenatal rate of detection of lung cysts at the routine
18–20th week scan is almost 100% and may be the most
common example of actual presentation. Late pregnancy
diagnosis of CPAM is less sensitive. Once a cystic lung
lesion is detected on ultrasound, the location, volume, size,
macrocystic or microcystic classification, and blood supply
should be evaluated11.
Serial prenatal sonographic examinations are important
for helping to determine the prognosis and necessity for
possible intrauterine treatment in patients with CPAM. The
prognosis is highly variable and depends on the presence of
fetal hydrops and the size of the mass12.
Hung-wen Chen et al.13 proposed an algorithm for
practical management of patients with CPAM. They
suggested that if prenatal ultrasonographic screening reveals
a suspicious fetal lung lesion, a series of ultrasonographic
examinations should be planned to evaluate the size, content (microcystic, macrocystic or solid) and distribution of the
lesion. Fetal therapies such as needle aspiration, catheter
shunt placement and fetal surgical resection can be applied.
The majority of these lesions will regress or become normal
echoic in late pregnancy.
The two major factors affect the management after the birth:
the timing of respiratory decompansation and the presence
of associated complications. Most cystic lesions can be
resected with thoracic surgery (at the age of 3−6)14.
Sometimes recurrent pulmonary infections with severe
respiratory decompansation can develop in an asymptomatic
one month-old patient. Although small asymptomatic
lesions can regress, there has been an increasing number
of reports of malignancy associated with CPAM over the
last decade, which cannot be ignored. These associated
neoplasms consist mainly of pleuropulmonary blastoma in
infants and young children, and bronchoalveolar carcinoma
in older children and adults. Type 4 CPAM is accepted by
most authors as type 1 pulmonary blastoma15. Other
cystic or pseudocystic lung lesions include post-infarction
peripheral cysts resulting from intrauterine pulmonary
artery thrombosis. The cysts have also been noted in
Down's syndrome. Air-filled cysts within the interstitium
are features of acute and persistent interstitial pulmonary
emphysema, and limited to the interlobular septa. Fluidfilled
cysts of congenital pulmonary lymphangiectasia
are present within the interlobular septa, and extend
laterally from the septa beneath the pleura. Congenital
pulmonary lymphangiectasia is also frequently associated
with congenital malformations of the heart. Bronchogenic
cysts are rarely seen in infants, and are solid lesions usually
separate from the lung. Extralobar sequestrations are also
unaerated lesions separate from the lung and occasionally
found within or beneath the diaphragm. Intralobar
sequestrations are usually acquired lesions (through
infection), and may display air- or fluid-filled cysts,
representing re-epithelialized post-infectious abscesses.
The infantile lobar emphysema, one of the most common
pulmonary lesions in infants and children, is not cystic but
simply the over inflation of a segment of lung16.
Congenital pulmonary airway malformation is a quite
rare malformation of fetus. In our case, fetal left lung was
larger than that of a stillborn term fetus. The compression
of large vessels and the heart was the cause of hydrops
fetalis. With these clinical and laboratory findings, the
present case is a very good example of non-immune
hydrops fetalis associated with CPAM type 2. Thus prenatal
clinical and ultrasonographic follow-up during pregnancy
is very important for the early diagnosis of such congenital
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