congenital cystic adenomatoid malformations ( ccam ) of lung are rare congenital cystic lung lesions that arise from excessive proliferation of tubular bronchial structures .
it is a rare lesion with incidence of 1 in 25,000 to 1 in 35,000 pregnancies and represents 25% of congenital lung malformations and 95% of congenital lung lesions .
it was classified into 3 subtypes in 1977 , and expanded into five types and renamed as congenital pulmonary airway malformation ( cpam ) by stocker in 2002 .
eighty percent of the lesions are recognized in neonatal period ; however , there are reports even in adult population . here , we have described two cases of ccam , stocker type ii and i , which were diagnosed by fetal autopsy .
a 30-year - old g2 p1 l1 , of nonconsanguineous marriage , had a normal antenatal course until 20.5 weeks of gestation , when she presented with history of per vaginal bleeding and abdominal pain since three days .
; she delivered a stillborn fetus , clinically it was concluded as inevitable abortion and after informed consent the fetus was sent for pathological examination . on autopsy , it was a male fetus weighing 1,450 g. external examination did not reveal any anomaly . on internal examination
the right lung was enlarged ( 7  5  3 cm ) cut - section showed cysts of varying sizes majority of them were < 2 cm .
on histology , right lungs showed multiple cysts relatively uniform in size resembling bronchioles , lined by stratified columnar epithelium , and having thin fibromuscular septa .
mucus production was not evident on periodic acid schiff ( pas ) staining [ figure 1a - d ] .
all other visceral organs were congested , but well - developed and revealed no anomalies . with the above features , a pathological diagnosis of ccam stocker type ii was offered .
( b and c ) microscopy showing large cyst ( bronchiole like ) surrounded by small cysts , lined by stratified columnar epithelium and having thin fibromuscular septa ( hematoxylin and eosin ( h and e ) , 100 ) .
( d ) high power of the large cyst showing lining epithelium ( h and e , 400 ) a 29-year - old female g4 p3 l2 , with history of 24.6 weeks of amenorrhea sought routine antenatal check - up .
her third baby girl died 3 days after birth , details of which was not available .
routine anomalous scan revealed polyhydramnios along with features of congenital diaphragmatic hernia ( cdh ) .
pregnancy was terminated after informed consent and the fetus was sent for pathological evaluation . on autopsy , it was a female fetus .
external examination revealed low set ears , short neck , and subcutaneous edema . on internal examination
the left lung was enlarged ( 8  6  4 cm ) , and cystic in consistency .
the enlarged left lung was pushing the diaphragm inferiomedially ; hence , the spleen was found in umbilical region [ figure 2a - c ] .
cut - section of the left lung revealed multiple cysts , the larger one was occupying whole of the upper lobe [ figure 2d ] . on histology , left lung revealed cysts of varying sizes dominated by larger cysts accompanied by smaller cysts .
the cysts were lined by flattened cuboidal epithelial cells having fibromuscular septa [ figure 2e - g ] .
focally , few of the cysts showed mucin production which was evident on periodic acid - schiff ( pas ) staining [ figure 2h and i ] .
all other visceral organs were congested , but well developed and revealed no anomalies . with the above
( a and b ) gross photographs showing enlarged left lung occupying most of the thorax compressing heart and right lung .
( c ) gross photograph of enlarged left lung with hypoplastic right lung and heart .
( d ) cut - section of left lung showing multiple cysts , dominated by large cysts .
( e ) whole mount showing large cyst surrounded by small cysts ( h and e , 2 ) .
( f and g ) microscopy showing large cysts with surrounded small cysts , lined by flattened epithelium with fibromuscular septa ( h and e , 100 ) .
( h and i ) microscopy showing cysts with mucus production ( arrow ) ( periodic acid schiff staining ( pas ) , 100 )
a 30-year - old g2 p1 l1 , of nonconsanguineous marriage , had a normal antenatal course until 20.5 weeks of gestation , when she presented with history of per vaginal bleeding and abdominal pain since three days .
; she delivered a stillborn fetus , clinically it was concluded as inevitable abortion and after informed consent the fetus was sent for pathological examination . on autopsy , it was a male fetus weighing 1,450 g. external examination did not reveal any anomaly . on internal examination
the right lung was enlarged ( 7  5  3 cm ) cut - section showed cysts of varying sizes majority of them were < 2 cm .
on histology , right lungs showed multiple cysts relatively uniform in size resembling bronchioles , lined by stratified columnar epithelium , and having thin fibromuscular septa .
mucus production was not evident on periodic acid schiff ( pas ) staining [ figure 1a - d ] .
all other visceral organs were congested , but well - developed and revealed no anomalies . with the above features , a pathological diagnosis of ccam stocker type ii was offered .
( b and c ) microscopy showing large cyst ( bronchiole like ) surrounded by small cysts , lined by stratified columnar epithelium and having thin fibromuscular septa ( hematoxylin and eosin ( h and e ) , 100 ) .
( d ) high power of the large cyst showing lining epithelium ( h and e , 400 )
a 29-year - old female g4 p3 l2 , with history of 24.6 weeks of amenorrhea sought routine antenatal check - up .
her third baby girl died 3 days after birth , details of which was not available .
routine anomalous scan revealed polyhydramnios along with features of congenital diaphragmatic hernia ( cdh ) .
pregnancy was terminated after informed consent and the fetus was sent for pathological evaluation . on autopsy , it was a female fetus .
external examination revealed low set ears , short neck , and subcutaneous edema . on internal examination
the left lung was enlarged ( 8  6  4 cm ) , and cystic in consistency .
the enlarged left lung was pushing the diaphragm inferiomedially ; hence , the spleen was found in umbilical region [ figure 2a - c ] .
cut - section of the left lung revealed multiple cysts , the larger one was occupying whole of the upper lobe [ figure 2d ] . on histology , left lung revealed cysts of varying sizes dominated by larger cysts accompanied by smaller cysts .
the cysts were lined by flattened cuboidal epithelial cells having fibromuscular septa [ figure 2e - g ] .
focally , few of the cysts showed mucin production which was evident on periodic acid - schiff ( pas ) staining [ figure 2h and i ] .
all other visceral organs were congested , but well developed and revealed no anomalies . with the above
( a and b ) gross photographs showing enlarged left lung occupying most of the thorax compressing heart and right lung .
( c ) gross photograph of enlarged left lung with hypoplastic right lung and heart .
( d ) cut - section of left lung showing multiple cysts , dominated by large cysts .
( e ) whole mount showing large cyst surrounded by small cysts ( h and e , 2 ) .
( f and g ) microscopy showing large cysts with surrounded small cysts , lined by flattened epithelium with fibromuscular septa ( h and e , 100 ) .
( h and i ) microscopy showing cysts with mucus production ( arrow ) ( periodic acid schiff staining ( pas ) , 100 )
ccam is a rare developmental , non - hereditary , hamartomatous abnormality of lung with unknown etiology .
it is usually a unilateral condition and restricted to one lobe , but can involve whole of one lung ( as observed in our cases ) , or both the lungs .
based on the anatomical changes , development of human lung is subdivided into embryonal ( 3 - 7 weeks ) , pseudo glandular ( 7 - 17 weeks ) , canalicular ( 17 - 29 weeks ) , saccular ( 24 - 36 weeks ) , and alveolar ( 36 weeks to maturity ) .
ccam develops during the pseudo glandular and saccular period ( 7 - 35 weeks ) .
type i lesion constitute 50 - 70% and is composed of single or multiple large cysts ( > 2 cm ) lined by flattened , cuboidal cells frequently producing mediastinal herniation .
mucin production is unique to type i lesion ( as observed in our case 2 ) .
type ii lesion constitute 15 - 30% and are composed of multiple small cysts ( < 2 cm ) , lined by ciliated cuboidal to columnar epithelium , structure resembling that of respiratory bronchioles , and distended alveoli are present between the epithelium lined cyst .
type iii lesion constitutes 5 - 10% and are usually large bulky noncystic lesions producing mediastinal shift .
bronchial - like structures are lined by ciliated cuboidal epithelium and separated by masses of alveolus - sized structures by nonciliated cuboidal epithelium .
systemic anomalies reported in type ii lesions include ; renal anomalies ( b / l renal agenesis , abnormalities of ureter , bladder , and urethra ) , abdominal wall defects , central nervous system defects ( hydrocephalus ) , spinal deformities , gastrointestinal defects ( diaphragmatic hernia , jejuna atersia , tracheoesophageal fistula , and imforforate anus ) , cardiac anomalies ( ventriculoseptal defects , tetralogy of fallot , and truncus arteriosis ) , sirenomelia , and anomalies of reproductive tract . in 2002 stocker ,
modified this classification by adding two more types ( type 0 and iv ) and renamed the lesion as cpam , type 0 of tracheobronchial origin has solid appearance with small and firm lungs ; and microscopically shows bronchiolar type airway with cartilage , smooth muscle , and glands separated by abundant mesenchymal tissue .
type iv of distal acinar origin , has peripheral cystic type , large cysts ( > 10 cm ) lined by flattened epithelium and resting on loose mesenchymal tissue .
the new classification is not much used as type 0 lesions are very difficult to differentiate from bronchogenic cyst and the similarities between type iv cyst and pleura pulmonary blastoma may cause problem in diagnosis .
the diagnostic sonographic ultrasonographic feature of ccam is , multicystic lesions at the lung field and common differential diagnosis includes diaphragmatic hernia , bronchogenic cyst , cystic fibrosis , congenital lobar emphysema , and pulmonary sequestration .
ccam will have connections to tracheobronchial tree and derives its blood supply from pulmonary circulation .
in contrast , pulmonary sequestration contains immature lung tissue without connection to tracheobronchial tree and derives its blood supply from aberrant systemic blood vessel . in the past ,
patients whose fetuses presented with presumed diagnosis of ccam were informed of poor prognosis and advised for termination , but recent studies revealed aggressive obstretric management and termination of pregnancy is not appropriate for patients with affected fetuses .
termination was offered to our case 2 since it was misdiagnosed as cdh in usg . for the lung masses , the intrauterine prognosis of the fetus
is determined by fetal lung mass size ( a single measurement of lung mass at the maximum diameter ) or by the ccam volume ratio ( cvr ) .
ccam volume is calculated by using a formula for prolate ellipse , with measurements of lung mass in three perpendicular planes .
the cvr is calculated by dividing the ccam volume by head circumference ( hc , measured in centimeter ) . thus cvr = ( l  b  w  0.52/hc ) .
cass et al . , in their large study observed that the size of the lung mass or cvr correlated strongly with the fetal outcome .
the observed threshold values in their study were 5.2 cm for mass size and 2 for cvr .
there was 100% survival of fetuses with mass values less than 5.2 cm and cvr < 2 .
in the fetuses with lung mass size more than 5.2 cm or cvr more than 2 were associated with marked mediastinal deviation , hydrops , ascites , and heart failure .
if there are no signs of heart failure , then the fetuses will be benefited by maternal steroid therapy and serial thoracocentesis .
the commonest presentation of ccam in postnatal life is progressive respiratory distress including tachypnea , grunting , retraction , and cyanosis ; and in adults it usually presents as repeated chest infections .
chest x - ray , computed tomography ( ct ) , and magnetic resonance imaging ( mri ) are helpful in diagnosis .
the main complication of ccam in neonatal period is compression of the mediastinal structure producing cardiovascular compromise . in adult patient , ccam is a nidus for pneumonia , abscess formation , fungal infections , spontaneous pneumothorax , hemoptysis , air embolism , intralobar sequestration , and development of bronchogenic carcinoma .
serial antenatal sonographic evaluation , good obstetric care , and delivery at a tertiary care center are preferred plan of treatment for antenataly detected cases .
postnatal and in adults patients , lobectomy is the treatment of choice for symptomatic cases .
prognosis also depends on stocker type , type i lesions carry overall good prognosis . in type ii lesion , it is the associated anomalies that determine the prognosis .
type iii lesions carry bad prognosis as they are usually large and presents with cardiovascular compromise .
serial ultrasonographic evaluation , fetal lung mass size , cvr , and fetal echocardiography are needed for management of antenatally detected cases .
 congenital cystic adenomatoid malformations ( ccam ) also known as congenital pulmonary airway malformation is a developmental , non - hereditary , hamartomatous abnormality of lung with unknown etiology . 
 it is a rare disease with an incidence of 1 in 25,000 to 1 in 35,000 . 
 it is a disease of infancy with most of the cases diagnosed within first 2 years of life . 
 we report autopsy findings of two fetuses with congenital cystic adenomatoid malformation ( stocker type ii and i ) with brief review of literature . 