Histoputhologu 1992.21. 315-321
Pathogenesis of congenital cystic adenomatoid malformation of the lung P .MOERMAN*, J .-P .FRYNSt , K.VANDENBERGHES , H.DEVLIEGER5 & J.M.LAUWERYNS* Departments of *Pathology I, ?Human Biology, Division of Human Genetics, *Obstetrics and Gynaecology and SPaediatrics, Katholieke Universiteit, Leuven, Belgium Date of submission 29 January 1992 Accepted for publication 24 April 1992
MOERMAN P., FRYNS J.-P., VANDENBERGHE K., DEVLIEGER H. & LAUWERYNS J.M.
(1992) Histopathology 21, 315-321
Pathogenesis of congenital cystic adenomatoid malformation of the lung Congenitalcystic adenomatoidmalformation is a rare developmental abnormality of the lung. In most earlier reported cases, the anatomy of the bronchial tree was poorly documented. We describe four cases studied following autopsy. Post-mortem bronchography or serial microscopical examination showed segmental bronchial absence or atresia in each of them. Our observations provide further evidence pointing to bronchial atresia as being the primary defect leading to the developmentof congenital cystic adenomatoid malformation. The morphology of the lesion, i.e. the type of malformation, is determined by the extent of dysplastic lung growth beyond the atretic segment. The aetiology of the bronchial atresia is probably heterogeneous and may either represent a primary malformation, or be the result of vascular disruption. Keywords: bronchial atresia. congenital cystic adenomatoid malformation, perinatal autopsy
Introduction Congenitalcystic adenomatoid malformation of the lung is an uncommon condition. Early descriptions date from the 19th century, but it was 6rst delineated as a distinct pathological entity in 1949 by Ch'in & Tang'. Van Dijk & Wagenvoort2 distinguished a cystic, an intermediate and a solid type. Stocker et ale3described 38 cases and separated three types based on clinical, gross and histological criteria. Type I consists of a single cyst or multiple large cysts, lined by pseudostratified ciliated columnar epithelium. The cyst walls are thick and contain smooth muscle and elastic tissue. Cartilage is rarely present. Normal-appearing alveoli are found between these cysts. Type 11contains numerous smaller cysts, usually less than 1 cm in diameter, resembling ectatic terminal bronchioles. Large alveolus-like structures are present between the cysts. The type III lesion ' Address for correspondence: Dr P.Moerman. Department of Pathology I. University Hospital St.-Rafael,Minderbroedersstraat 12, B3000 Leuven, Belgium.
forms a solid and bulky mass, composed of regularly spaced bronchiole-like structures separated by masses of alveolus-likestructures lined by cuboidal epithelium. In a critical analysis, Ostiir &Fortune*pointed out that only Stocker's type 111 lesion is truly adenomatoid. There is conjecture and controversy concerning the aetiology and pathogenesis of congenital cystic adenomatoid malformation. It is not a true neoplasm but has been considered a hamartomatous lesion, i.e. a developmental abnormality with excess of one or several tissue components. We describe the autopsy findings in four cases, with special emphasis on the anatomy of the tracheobronchial tree. From the obtained morphological evidence, a pathogenetic mechanism for the lesion is proposed.
Materials and methods w e studied four fetuseswith congenital cystic adenomatoid malformation of the lung (Table 1).In cases 3 and 4, 31 5
316
P.Moerman et al.
Table 1. Clinical data and pathological findings in four fetuses with congenital cystic adenomatoid malformation (CCAM) Case 1 Clinical data Sex Gestational age (week) Fetal weight (g) Pregnancy history
Fetal karyotype Pathological findings Lung weight (8) Left Right CCAM AlTected lobe Type Maximum size of cysts (mm) Bronchial anomaly Additional autopsy Andings
F 30 985 Polyhydramnios
Case 2
M 23* 620 Severe oligohydramnios
Case 3
M 32 1575 Polyhydramnios
Case 4
M 31 2530 Twin gestation, polyhydramnios. severe fetal hydrops, ruptured membranes at 29 weeks 46,XY
47,xx,+ 18
46,XY
46,XY
8.5 23.0
3.7 4.4
7.6 73.0
25.9 6.7
RUL I1
RUL
RUL
LLL
n
m
n
6 1-2 2-3 2-3 Absent RUA segmental Absent RUA segmental Absent RUA segmental Atretic LLA segmental bronchus bronchus bronchus bronchus Oligohydramnios Typical trisomy 18 sequence, agenesis of phenotype, left kidney, pulmonary valve multicystic dysplasia stenosis (dysplastic of right kidney bicuspid valve), perimembranous associated with VSD,Meckel’s ureteral atresia diverticulum, dysgenetic ovaria
* Induction of labour. LLA =left lower anterior; LLL =left lower lobe: RUA =right upper anterior; RUL =right upper lobe: VSD =ventricular septa1defect.
its presence had been suggested by prenatal ultrasono-
graphy. In case 2, pregnancy was terminated by prostaglandin induction at 23 weeks, following the prenatal detection of severe oligohydramnios, agenesis of the left kidney and a multicystic right kidney. A diagnosis of hereditary renal adysplasia5was establishedafter examination of the father revealed agenesisof the right kidney associatedwith ipsilateral absence of the epididymis,vas deferens and seminal vesicle. Cases 1, 3 and 4 were premature infants who died shortly after birth. Case 4 was the first of monochorial diamniotic twins. The other twin had no congenital anomalies, but died on the second day of life of hyaline membrane disease and severe bilateral intrauterine pneumonia. Trisomy 18 was found in case 1: the three others had normal
chromosomes. Family histories were negative with regard to parental consanguinity. Autopsies were done following standard procedures, with the exception that special techniques were used to explore the relation of the bronchial tree to the adenomatoid malformation. In cases 1 and 4, post-mortem bronchography was performed in the fresh state after instillation of a barium-gelatin contrast medium into the trachea, and in all cases serial sections were cut starting from the main bronchus up to the malformation, after formalin-fixation of the entire organ block. Histological sections were stained by haematoxylin and eosin, Verhoeff-van Gieson,Masson’s trichrome and mucicarmine. The lesions were classified into three types using the criteria of Stocker and co-workers3.
Congenital cystic adenomatoid maljormation
3 17
Figure 1. Histology of congenital cystlc adenomatoid malformation type II, showing a proliferation of Irregularly dilated terminal bronchiolelike structures with only few interspersed alveoli (case 1). H & E. x 15.
ReSultS The pathological features are summarized In Table 1. Bronchography and/or serial microscopical examination demonstrated absence of the anterior segmental bronchus of the right upper lobe in cases 1-3, the right upper lobar bronchus branching into two instead of the normal three segmental bronchi. In case 4, there was focal atresia of the anterior segmental bronchus of the left lower lobe. None of the cases showed an abnormal systemic arterial blood supply to the pulmonary lesion. A type 11 lesion was diagnosed in cases 1, 2 and 4. These lesions (Figure 1)were predominantly composed of irregularly dilated terminal bronchiole-likestructures, lined by a single-layered ciliated columnar epithelium. The walls of these small cysts contained a thin and discontinuous smooth muscle layer. Bronchial cartilage plates were found in cases 1and 4. A variable amount of alveolar structures, lined by non-ciliated cuboidal epithelium, was interspersed between the bronchiole-like structures. In case 4 (Figure 2a & b), the lesion contained
a well-developed centrally located cartilaginous bronchus, showing dichotomous branching. This represented the post-atretic continuation of the anterior segmental bronchus of the left lower lobe. Case 3 had a type 111lesion. The lesion was bulky and solid (Figure 3a) and histologically resembled a fetal lung in the pseudoglandular stage. It consisted of numerous immature canalicular structures, lined by a cuboidal epithelium with basal vacuoles, and interspersed with small bronchiolar structures. Cystically dilated larger bronchuslike ducts lay regularly spaced in this adenomatoid tissue. These were lined by a pseudostratified respiratory epithelium thrown into micropapillary folds overlying a well-formed continuous smooth muscle layer (Figure 3b). Cartilage was absent. Collections of mucigenic cells were found in both bronchiole-like structures and larger ducts. The remainder of the parenchyma on the affected sides, and the contralateral lungs, showed variable degrees of pulmonary hypoplasia. In case 1. polymorphonuclear leucocytes were found in the surrounding
318
P.Moerman et al.
Figure 2. Case 4. a Section of the leR lung after instillation with barium-gelatin and Bxation, illustrating segmental bronchial atresia. b Whole mounted section. The arrow indicates the post-atretic continuation of the segmental bronchus. Continuing bronchial branchlng beyond the atretic segment gives rise to a proliferation of ectatic terminal bronchiole-like structures. The alveolar development Is mppressed.
alveoli, but were absent from the lumina of the malformation. In case 4, cytogenetic examination of the lesion showed a normal karyotype.
Discussion We describe four cases of congenital cystic adenomatoid malformation, each characterized by a lack of communication between the lesion and the tracheobronchialtree. The supplying segmental bronchus was either absent or
atretic. In most previously reported cases, the tracheobronchial tree was not examined in detail. However, bronchial absence or atresia was a constant observation in those cases studied by pre-operative or post-mortem bronchography6-8. We believe that this association provides an important clue for the pathogenesis of adenomatoid malformations and suggest that the primary defect is a localized arrest or deficiency in the bronchopulmonary budding and branching process, causing bronchial atresia. The atretic segment may
Congenital cystic adenomatoid malformation
3 19
Figure 3. Case 3. a Bulky and solid type III lesion. b Histologically, this type of lesion is composed of a massive overgrowth of immature
terminal air spaces: numerous canalicularstructures (short arrows),interspersed small bronchiolar structures (long arrows),and a cystically dilated larger bronchus-like duct (asterisk).H & E. x 20.
eventually involute completely, resulting in bronchial absence. Occasionally a fibrous band can be traced joining the lesion to the parent bronchusg. The bronchial branching arrest may be complete. If growth proceeds beyond the atretic or absent segment, it develops abnormally. Despite absence or atresia of the parent bronchus, congenital cystic adenomatoid malformations communicate with the surrounding normally
ventilateil lung tissue, allowing air trapping and expansion after birth by a process of collateral ventilation through the pores of Kohn. Congenital cystic adenomatoid malformation is a developmental anomaly of the lung. Its occurrence in certain genetic syndromes such as trisomy 18 and hereditary renal adysplasia supports a primary malformation as one possible aetiology. The term malformation
320 P.Moerman et al.
applies to an intrinsic abnormality of an organ or tissue, i.e. a true defect in organogenesislO.In most instances however, congenital cystic adenomatoid malformation represents a sporadic non-hereditary lesion. In these cases, the primary bronchial defect may be caused by a vascular disruption. Disruption means destruction of a previously normally developing organ by an extrinsic factor1’. This theory is corroborated by the report of three patients with adenomatoid malformation and associated intestinal atre~ia~-’l-’~, i.e. a visceral abnormality that has been recognized as secondary to vascular disruption. Several authors have stressed the microscopical resemblance between these malformationsand some cases of pulmonary seq~estration’~*‘~. Pulmonary sequestration may also consist of immature or dysplastic lung tissue and show absence or a reduced number of bronchial cartilage plates. There are a few reports of a congenital cystic adenomatoid malformation receiving its blood supply from an anomalous systemic It is our opinion that a systemic arterial supply indicates that such lesions are intralobar pulmonary sequestrations. In true adenomatoid malformations there is isolated bronchial sequestration. In intralobar pulmonary Sequestration, the bronchial defect is associated with a deficient pulmonary artery that fails to join up with the pulmonary capillary plexus, resulting in persistence of the embryonic splanchnic (systemic) arterial supply. The frequent concurrence of congenital cystic adenomatoid malformation with renal agenesis or cystic dysplasia3 is of special interest suggesting that this pulmonary lesion can be regarded as an example of organ dysplasia, meaning disturbed histogenesis. Nonsyndromatic renal cystic dysplasia is frequently associated with ureteral atresia, and likewise adenomatoid malformatton is frequently associated with bronchial atresia. The pathogenetic mechanisms responsible for renal dysplasia and adenomatoid malformation evidently show marked parallelism. Congenital cystic adenomatoid malformation is often complicated by non-immune fetal hydrops or maternal polyhydramnios16. Compression of the inferior vena cava with increased capillary hydrostatic pressure is the accepted explanation for the fetal hydrops. The fetal lung actively secretes liquid in utero. and this liquid contributes to the amniotic fluid vol~me’~. Based on this and the absence of a communication between adenomatoid malformations and the tracheobronchial tree, it can be concluded that the earlier theories of overproduction of fluid by the lung lesion, or impaired fluid absorption by the malformed and hypoplastic lungs, are no longer tenable17.The polyhydramniosassociated with congenital cystic adenomatoid malformation can only be satis-
factorily explained by either defective swallowing of amniotic fluid due to oesophageal compression, or increased voiding of urine by the fetus. Our findings support the unifying concept of Demos & Teresi18 that puts the adenomatoid malformations into a spectrum of congenital lung anomalies. A localized developmental arrest of the endodermal tracheobronchial bud is the basic defect shared by bronchial atresia, bronchogenic cyst, the various types of congenital cystic adenomatoid malformation, pulmonary sequestration, and probably congenital lobar emphysema. We agree with Cachia & Sobonya8 that bronchial absence or atresia is unlikely to be identified without the use of specimen or post-mortem bronchography.
Acknowledgements We thank Miss H.Vanden Bosch and Miss K.Konings for expert technical assistance, and Mr A.Van Dormael for photography.
References 1. Win KY, Tang MY. Congenital adenomatoidmalformationof one lobe of a lung with general anasarca. Arch. Pathol. 1949:48;221229. 2, van Dtjk C, Wagenvoort CA. The various types of congenital adenomatoid malformation of the lung. 1. Pathol. 1973: 110; 131-134. 3. Stocker JT,Madewa,JE.Drake RM.Congenital cystic adenomatoid malformation of the lung. Hum. Pathol. 1977; 8; 156-171. 4. bt6r AG, Fortune DW. Congenital cystic adenomatoid malformation of the lung. Am. 1. C h . Pathol. 1978;70; 595-604. 5. Buchta RM, VWul C, Gilbert EF. Sarto GE. Oplta JM.Familial bilateral renal agenesis and hereditary renal adysplasia. Z. Klnderheflkd. 1973:115; 111-129. 6. HutchinP. PriedmanPJ,SaltzsteinSL. Congenital cystic adenomatoid malformation with anomalous blood supply. 1. Thorac. Cardiovasc. Surg. 1974;62; 220-225. 7. Miller RK,Sleber WK,Yunls EJ.Congenital adenomatold malformation of the lung. A report of 17 cases and review of the literature. Pathol. Annu. 1980 15(1); 387407. 8. Cachia R. Sobonya RE. Congenital cystic adenomatoid malformation of the lung with bronchial atresia. Hum. Pathol. 1981: 12; 947-950. 9. Dempster AG. Adenomatoid hamartoma of the lung in a neonate. 1. Clin. Pathol. 1969;22: 401-406. 10. Spranger J, Benirschke K, Hall JG et al. Brrora of morphogenesis: Concepts and terms. Recommendations of an International Working Group. I. Pediatr. 1982:100;160-165. 11. B W U DC,Wentworth P, ReUy BJ, Donohue WL. Congenital cystic adenomatoid malformation of the lung: A report of eight cases. Can. 1. Surg. 1966;9 350-356. 12. Moncrieff MW, Cameron AH,Astley R. Roberts KD,Abrams LD, Mann JFL Congenital cystic adenomatoid malformation of the lung. Thorax 1969;24: 476-487. 13. WigglesworthJS.Pathology of the lung in the fetus and neonate, with particular reference to problems of growth and maturation. H f S t o ~ t h o 1987; l ~ ~ 11; 671-689.
Congenital cystic adenomatoid malformation
14. Katzenstein A-LA, Askin FB. Pediatric disorders I. Congenital malformations. In Surgical Pathologu of Non-Neoplastic Lung Disease, 2nd edn. Philadelphia: W.B. Saunders Company, 1 9 9 0 468-490. 15. Aslam PA, Korones SB, RichardsonRL,Pate JW. Congenitalcystic adenomatoid malformation with anasarca. IAMA 1970; 21 2: 622-624. 16. Keeling JW. Gough DJ, IliE P. The pathology of non-Rhesus hydrops. Diugn. Histopathol. 1983; 6; 89-111.
32 1
17. Kohler HG, Rymer BA. Congenitalcysticmalformationof the lung and its relation to hydramnios. 1. Obstet. Gynaecol. Br. Cornrnonw. 1973; 8 0 130-134. 18. Demos NJ, Teresi A. Congenital lung malformations. A unified concept and a case report. 1. Thorac. Cardiovasc. Surg. 1975; 70; 260-264.
Pathogenesis of congenital cystic adenomatoid malformation of the lung P .MOERMAN*, J .-P .FRYNSt , K.VANDENBERGHES , H.DEVLIEGER5 & J.M.LAUWERYNS* Departments of *Pathology I, ?Human Biology, Division of Human Genetics, *Obstetrics and Gynaecology and SPaediatrics, Katholieke Universiteit, Leuven, Belgium Date of submission 29 January 1992 Accepted for publication 24 April 1992
MOERMAN P., FRYNS J.-P., VANDENBERGHE K., DEVLIEGER H. & LAUWERYNS J.M.
(1992) Histopathology 21, 315-321
Pathogenesis of congenital cystic adenomatoid malformation of the lung Congenitalcystic adenomatoidmalformation is a rare developmental abnormality of the lung. In most earlier reported cases, the anatomy of the bronchial tree was poorly documented. We describe four cases studied following autopsy. Post-mortem bronchography or serial microscopical examination showed segmental bronchial absence or atresia in each of them. Our observations provide further evidence pointing to bronchial atresia as being the primary defect leading to the developmentof congenital cystic adenomatoid malformation. The morphology of the lesion, i.e. the type of malformation, is determined by the extent of dysplastic lung growth beyond the atretic segment. The aetiology of the bronchial atresia is probably heterogeneous and may either represent a primary malformation, or be the result of vascular disruption. Keywords: bronchial atresia. congenital cystic adenomatoid malformation, perinatal autopsy
Introduction Congenitalcystic adenomatoid malformation of the lung is an uncommon condition. Early descriptions date from the 19th century, but it was 6rst delineated as a distinct pathological entity in 1949 by Ch'in & Tang'. Van Dijk & Wagenvoort2 distinguished a cystic, an intermediate and a solid type. Stocker et ale3described 38 cases and separated three types based on clinical, gross and histological criteria. Type I consists of a single cyst or multiple large cysts, lined by pseudostratified ciliated columnar epithelium. The cyst walls are thick and contain smooth muscle and elastic tissue. Cartilage is rarely present. Normal-appearing alveoli are found between these cysts. Type 11contains numerous smaller cysts, usually less than 1 cm in diameter, resembling ectatic terminal bronchioles. Large alveolus-like structures are present between the cysts. The type III lesion ' Address for correspondence: Dr P.Moerman. Department of Pathology I. University Hospital St.-Rafael,Minderbroedersstraat 12, B3000 Leuven, Belgium.
forms a solid and bulky mass, composed of regularly spaced bronchiole-like structures separated by masses of alveolus-likestructures lined by cuboidal epithelium. In a critical analysis, Ostiir &Fortune*pointed out that only Stocker's type 111 lesion is truly adenomatoid. There is conjecture and controversy concerning the aetiology and pathogenesis of congenital cystic adenomatoid malformation. It is not a true neoplasm but has been considered a hamartomatous lesion, i.e. a developmental abnormality with excess of one or several tissue components. We describe the autopsy findings in four cases, with special emphasis on the anatomy of the tracheobronchial tree. From the obtained morphological evidence, a pathogenetic mechanism for the lesion is proposed.
Materials and methods w e studied four fetuseswith congenital cystic adenomatoid malformation of the lung (Table 1).In cases 3 and 4, 31 5
316
P.Moerman et al.
Table 1. Clinical data and pathological findings in four fetuses with congenital cystic adenomatoid malformation (CCAM) Case 1 Clinical data Sex Gestational age (week) Fetal weight (g) Pregnancy history
Fetal karyotype Pathological findings Lung weight (8) Left Right CCAM AlTected lobe Type Maximum size of cysts (mm) Bronchial anomaly Additional autopsy Andings
F 30 985 Polyhydramnios
Case 2
M 23* 620 Severe oligohydramnios
Case 3
M 32 1575 Polyhydramnios
Case 4
M 31 2530 Twin gestation, polyhydramnios. severe fetal hydrops, ruptured membranes at 29 weeks 46,XY
47,xx,+ 18
46,XY
46,XY
8.5 23.0
3.7 4.4
7.6 73.0
25.9 6.7
RUL I1
RUL
RUL
LLL
n
m
n
6 1-2 2-3 2-3 Absent RUA segmental Absent RUA segmental Absent RUA segmental Atretic LLA segmental bronchus bronchus bronchus bronchus Oligohydramnios Typical trisomy 18 sequence, agenesis of phenotype, left kidney, pulmonary valve multicystic dysplasia stenosis (dysplastic of right kidney bicuspid valve), perimembranous associated with VSD,Meckel’s ureteral atresia diverticulum, dysgenetic ovaria
* Induction of labour. LLA =left lower anterior; LLL =left lower lobe: RUA =right upper anterior; RUL =right upper lobe: VSD =ventricular septa1defect.
its presence had been suggested by prenatal ultrasono-
graphy. In case 2, pregnancy was terminated by prostaglandin induction at 23 weeks, following the prenatal detection of severe oligohydramnios, agenesis of the left kidney and a multicystic right kidney. A diagnosis of hereditary renal adysplasia5was establishedafter examination of the father revealed agenesisof the right kidney associatedwith ipsilateral absence of the epididymis,vas deferens and seminal vesicle. Cases 1, 3 and 4 were premature infants who died shortly after birth. Case 4 was the first of monochorial diamniotic twins. The other twin had no congenital anomalies, but died on the second day of life of hyaline membrane disease and severe bilateral intrauterine pneumonia. Trisomy 18 was found in case 1: the three others had normal
chromosomes. Family histories were negative with regard to parental consanguinity. Autopsies were done following standard procedures, with the exception that special techniques were used to explore the relation of the bronchial tree to the adenomatoid malformation. In cases 1 and 4, post-mortem bronchography was performed in the fresh state after instillation of a barium-gelatin contrast medium into the trachea, and in all cases serial sections were cut starting from the main bronchus up to the malformation, after formalin-fixation of the entire organ block. Histological sections were stained by haematoxylin and eosin, Verhoeff-van Gieson,Masson’s trichrome and mucicarmine. The lesions were classified into three types using the criteria of Stocker and co-workers3.
Congenital cystic adenomatoid maljormation
3 17
Figure 1. Histology of congenital cystlc adenomatoid malformation type II, showing a proliferation of Irregularly dilated terminal bronchiolelike structures with only few interspersed alveoli (case 1). H & E. x 15.
ReSultS The pathological features are summarized In Table 1. Bronchography and/or serial microscopical examination demonstrated absence of the anterior segmental bronchus of the right upper lobe in cases 1-3, the right upper lobar bronchus branching into two instead of the normal three segmental bronchi. In case 4, there was focal atresia of the anterior segmental bronchus of the left lower lobe. None of the cases showed an abnormal systemic arterial blood supply to the pulmonary lesion. A type 11 lesion was diagnosed in cases 1, 2 and 4. These lesions (Figure 1)were predominantly composed of irregularly dilated terminal bronchiole-likestructures, lined by a single-layered ciliated columnar epithelium. The walls of these small cysts contained a thin and discontinuous smooth muscle layer. Bronchial cartilage plates were found in cases 1and 4. A variable amount of alveolar structures, lined by non-ciliated cuboidal epithelium, was interspersed between the bronchiole-like structures. In case 4 (Figure 2a & b), the lesion contained
a well-developed centrally located cartilaginous bronchus, showing dichotomous branching. This represented the post-atretic continuation of the anterior segmental bronchus of the left lower lobe. Case 3 had a type 111lesion. The lesion was bulky and solid (Figure 3a) and histologically resembled a fetal lung in the pseudoglandular stage. It consisted of numerous immature canalicular structures, lined by a cuboidal epithelium with basal vacuoles, and interspersed with small bronchiolar structures. Cystically dilated larger bronchuslike ducts lay regularly spaced in this adenomatoid tissue. These were lined by a pseudostratified respiratory epithelium thrown into micropapillary folds overlying a well-formed continuous smooth muscle layer (Figure 3b). Cartilage was absent. Collections of mucigenic cells were found in both bronchiole-like structures and larger ducts. The remainder of the parenchyma on the affected sides, and the contralateral lungs, showed variable degrees of pulmonary hypoplasia. In case 1. polymorphonuclear leucocytes were found in the surrounding
318
P.Moerman et al.
Figure 2. Case 4. a Section of the leR lung after instillation with barium-gelatin and Bxation, illustrating segmental bronchial atresia. b Whole mounted section. The arrow indicates the post-atretic continuation of the segmental bronchus. Continuing bronchial branchlng beyond the atretic segment gives rise to a proliferation of ectatic terminal bronchiole-like structures. The alveolar development Is mppressed.
alveoli, but were absent from the lumina of the malformation. In case 4, cytogenetic examination of the lesion showed a normal karyotype.
Discussion We describe four cases of congenital cystic adenomatoid malformation, each characterized by a lack of communication between the lesion and the tracheobronchialtree. The supplying segmental bronchus was either absent or
atretic. In most previously reported cases, the tracheobronchial tree was not examined in detail. However, bronchial absence or atresia was a constant observation in those cases studied by pre-operative or post-mortem bronchography6-8. We believe that this association provides an important clue for the pathogenesis of adenomatoid malformations and suggest that the primary defect is a localized arrest or deficiency in the bronchopulmonary budding and branching process, causing bronchial atresia. The atretic segment may
Congenital cystic adenomatoid malformation
3 19
Figure 3. Case 3. a Bulky and solid type III lesion. b Histologically, this type of lesion is composed of a massive overgrowth of immature
terminal air spaces: numerous canalicularstructures (short arrows),interspersed small bronchiolar structures (long arrows),and a cystically dilated larger bronchus-like duct (asterisk).H & E. x 20.
eventually involute completely, resulting in bronchial absence. Occasionally a fibrous band can be traced joining the lesion to the parent bronchusg. The bronchial branching arrest may be complete. If growth proceeds beyond the atretic or absent segment, it develops abnormally. Despite absence or atresia of the parent bronchus, congenital cystic adenomatoid malformations communicate with the surrounding normally
ventilateil lung tissue, allowing air trapping and expansion after birth by a process of collateral ventilation through the pores of Kohn. Congenital cystic adenomatoid malformation is a developmental anomaly of the lung. Its occurrence in certain genetic syndromes such as trisomy 18 and hereditary renal adysplasia supports a primary malformation as one possible aetiology. The term malformation
320 P.Moerman et al.
applies to an intrinsic abnormality of an organ or tissue, i.e. a true defect in organogenesislO.In most instances however, congenital cystic adenomatoid malformation represents a sporadic non-hereditary lesion. In these cases, the primary bronchial defect may be caused by a vascular disruption. Disruption means destruction of a previously normally developing organ by an extrinsic factor1’. This theory is corroborated by the report of three patients with adenomatoid malformation and associated intestinal atre~ia~-’l-’~, i.e. a visceral abnormality that has been recognized as secondary to vascular disruption. Several authors have stressed the microscopical resemblance between these malformationsand some cases of pulmonary seq~estration’~*‘~. Pulmonary sequestration may also consist of immature or dysplastic lung tissue and show absence or a reduced number of bronchial cartilage plates. There are a few reports of a congenital cystic adenomatoid malformation receiving its blood supply from an anomalous systemic It is our opinion that a systemic arterial supply indicates that such lesions are intralobar pulmonary sequestrations. In true adenomatoid malformations there is isolated bronchial sequestration. In intralobar pulmonary Sequestration, the bronchial defect is associated with a deficient pulmonary artery that fails to join up with the pulmonary capillary plexus, resulting in persistence of the embryonic splanchnic (systemic) arterial supply. The frequent concurrence of congenital cystic adenomatoid malformation with renal agenesis or cystic dysplasia3 is of special interest suggesting that this pulmonary lesion can be regarded as an example of organ dysplasia, meaning disturbed histogenesis. Nonsyndromatic renal cystic dysplasia is frequently associated with ureteral atresia, and likewise adenomatoid malformatton is frequently associated with bronchial atresia. The pathogenetic mechanisms responsible for renal dysplasia and adenomatoid malformation evidently show marked parallelism. Congenital cystic adenomatoid malformation is often complicated by non-immune fetal hydrops or maternal polyhydramnios16. Compression of the inferior vena cava with increased capillary hydrostatic pressure is the accepted explanation for the fetal hydrops. The fetal lung actively secretes liquid in utero. and this liquid contributes to the amniotic fluid vol~me’~. Based on this and the absence of a communication between adenomatoid malformations and the tracheobronchial tree, it can be concluded that the earlier theories of overproduction of fluid by the lung lesion, or impaired fluid absorption by the malformed and hypoplastic lungs, are no longer tenable17.The polyhydramniosassociated with congenital cystic adenomatoid malformation can only be satis-
factorily explained by either defective swallowing of amniotic fluid due to oesophageal compression, or increased voiding of urine by the fetus. Our findings support the unifying concept of Demos & Teresi18 that puts the adenomatoid malformations into a spectrum of congenital lung anomalies. A localized developmental arrest of the endodermal tracheobronchial bud is the basic defect shared by bronchial atresia, bronchogenic cyst, the various types of congenital cystic adenomatoid malformation, pulmonary sequestration, and probably congenital lobar emphysema. We agree with Cachia & Sobonya8 that bronchial absence or atresia is unlikely to be identified without the use of specimen or post-mortem bronchography.
Acknowledgements We thank Miss H.Vanden Bosch and Miss K.Konings for expert technical assistance, and Mr A.Van Dormael for photography.
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