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Background

This is a rare congenital anomaly of the lungs Congenital cystic adenomatoid malformation of the lung (CCAM) originate at different levels of the tracheobronchial tree.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Differential Diagnosis  
Prognosis and Treatment  
Commonly Used Terms  
Internet Links  


EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS CCAM
INCIDENCE Rare
AGE RANGE-MEDIAN Congenital

 

DISEASE ASSOCIATIONS CHARACTERIZATION
GENERAL  


Cystic Adenomatoid Change Is Common to Various Forms of Cystic Lung Diseases of Children.

Imai Y, Mark EJ.

Kobe Children's Hospital of Hyogo Prefecture, Kobe, Japan, the Department of Pathology, Massachusetts General Hospital, Boston, Mass, Kobe Operation Center, International Center for Diagnostic Pathology, Kobe, Japan, and Kobe City General Hospital, Kobe, Japan (Dr Imai); and the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (Dr Mark).

Arch Pathol Lab Med 2002 Aug;126(8):934-940 Abstract quote

Context.-Congenital cystic adenomatoid malformation, intralobar sequestration, extralobar sequestration, bronchopulmonary foregut malformation, bronchial atresia, and lobar emphysema generally are treated as separate entities, but there are commonalities among them.

Objective.-To clarify the identity of congenital cystic adenomatoid malformation in relation to other cystic diseases.

Design.-We studied 10 consecutive cases of surgically resected cystic lung disease in children. We studied the bronchial and vascular trees by mapping bronchi, pulmonary blood vessels, systemic blood vessels, the size and configuration of cysts, and associated scarring.

Results.-The cystic lesions proved to be the following: 1 case of congenital cystic adenomatoid malformation, 2 cases of bronchial atresia with congenital cystic adenomatoid malformation, 1 hybrid case of congenital cystic adenomatoid malformation and intralobar sequestration, 1 case of intralobar sequestration with an aberrant hilum, 3 cases of intralobar sequestration with bronchial obliteration, 1 case of lung abscess, and 1 case of lobar emphysema. Congenital cystic adenomatoid malformation was the sole pathologic diagnosis in 1 case, but 7 other specimens had cystic adenomatoid change to various degrees. There was no bronchial connection between the cystic lesions and the patient's airway in 8 cases. The bronchial tree was absent in the cystic lung in 2 cases. Bronchus tapered into scar near the cystic lesion in 4 cases. Only 1 case had no significant bronchial abnormality.

Conclusion.-The high incidence of cystic adenomatoid change in cystic lung disease associated with an abnormality of the bronchial tree suggests that cystic adenomatoid change may develop together with and be related to other congenital or acquired conditions in the lung.

CHROMOSOMAL 18, RECOMBINANT  

Congenital cystic adenomatoid malformation of the lung coexisting with recombinant chromosome 18. A case report.

Roberts D, Sweeney E, Walkinshaw S.

Fetal Centre, Department of Obstetrics & Gynaecology, Liverpool Women's Hospital, Liverpool, UK.

Fetal Diagn Ther 2001 Mar-Apr;16(2):65-7 Abstract quote

OBJECTIVE: Diagnosis of congenital cystic adenomatoid malformation of the lung (CCAM) in association with recombinant chromosome 18.

METHOD: Ultrasound diagnosis of a CCAM and hydrops was made. The mother was known to have a pericentric inversion of chromosome 18 and had a previous pregnancy with a recombinant chromosome 18 (partial deletion of 18p and partial duplication of 18q). Cordocentesis for karyotype was therefore performed.

RESULT: Fetal karyotype revealed a recombinant chromosome 18, this time with partial deletion of 18q and partial duplication of 18p. Postmortem confirmed a type III CCAM and a septum primum atrial defect.

CONCLUSIONS: Although deletion/duplication of chromosome 18 is commonly associated with a wide variety of anomalies, the association with CCAM is an unusual one. Fetal and parental karyotyping should be considered in cases of CCAM, because fetal therapy is increasingly being considered in these pregnancies. Current management of parents with pericentric inversions must rely on invasive diagnostic testing in the second trimester because predicting the likelihood of an unbalanced karyotype and phenotype in a fetus is difficult.

EXTRALOBAR SEQUESTRATION  


Extralobar sequestration with frequently associated congenital cystic adenomatoid malformation, type 2: report of 50 cases.

Conran RM, Stocker JT.

Department of Pediatric Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.

Pediatr Dev Pathol 1999 Sep-Oct;2(5):454-63 Abstract quote

Extralobar pulmonary sequestration (ELS) represents a mass of pulmonary parenchyma separate from the normal lung. The coexistence of congenital cystic adenomatoid malformation (CCAM) in ELS has been reported.

To define this association, the clinical, gross, and histologic features of 50 ELS cases were analyzed.The age at diagnosis varied from birth to 65 years with 24% of cases diagnosed prenatally and 61% (23/38) diagnosed within the first 3 months of life. Fifty-two percent of cases were in females and 48% in males. Forty-eight percent of ELS(s) were located in the left hemithorax, 20% in the right hemithorax, 8% in the anterior mediastinum, 6% in the posterior mediastinum, and 18% beneath the diaphragm. The blood supply to the sequestration in 77% of cases was directly from the aorta. Grossly, the lung, though hypoplastic in some cases, was otherwise unremarkable.Fifty percent (23/46) of ELS cases were associated with a coexistent CCAM. In contrast to the series as a whole, 92% (11/12) of the ELS/CCAM cases, excluding those prenatally diagnosed, were diagnosed within the first 3 months and 57% occurred in females. ELS/CCAM lesions, while randomly distributed, were more frequently seen on the left side. Gross features of the ELS/CCAM cases were similar to those cases with ELS alone. All CCAM cases had a type 2 pattern on histologic examination with 48% of those cases also displaying rhabdomyomatous dysgenesis.

Our findings indicate that the occurrence of CCAM in ELS is more frequent than reported in the literature and differs in presentation from ELS cases not associated with CCAM.


Congenital cystic adenomatoid malformation and extralobar sequestration occurring independently in the ipsilateral hemithorax.

Chandran H, Upadhyay V, Pease PW.

Department of Paediatric Surgery, The Royal Childrens Hospital, Parkville, Melbourne, Australia.

Pediatr Surg Int 2000;16(1-2):102-3 Abstract quote

We report a case of congenital cystic adenomatoid malformation (CCAM) and extralobar pulmonary sequestration (EPS) occurring independently in the ipsilateral hemithorax.

A literature search using Medline, Winspirs 2.0, found 14 previously reported cases of CCAM within an EPS.

There are no reports of each form of congenital pulmonary abnormality occurring separately in the same patient.

HYDROPS, NON-IMMUNE  


Spontaneous resolution of nonimmune hydrops in a fetus with a cystic adenomatoid malformation.

Higby K, Melendez BA, Heiman HS.

Department of Obstetrics/Gynecology, Wilford Hall Medical Center, Lackland Air Force Base, Tex 78236-5300, USA.

J Perinatol 1998 Jul-Aug;18(4):308-10 Abstract quote

Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary anomaly. It is a hamartomatous lesion characterized by a cessation of normal bronchiolar maturation, resulting in overgrowth of the terminal bronchioles. There is no preference for sex or location, and usually the lesion is confined to a single lobe.

CCAMs have been classified into three subtypes according to the presence of and size of the cysts. Type I lesions have large cysts (2 to 10 cm in diameter), type II have smaller cysts (< 1 cm in diameter), and type III is noncystic. There have been several reports of diminution in size of these lesions and complete regression. However, in those cases fetal hydrops was absent. In the presence of nonimmune hydrops, fetal prognosis is extremely poor without any intervention.

There are only two case reports describing fetal survival without intervention when nonimmune hydrops is present. We present a case of survival of a fetus with CCAM and nonimmune hydrops diagnosed at 24 weeks' gestation.

PLEUROPULMONARY BLASTOMA  

Pleuropulmonary blastoma in congenital cystic adenomatoid malformation: report of a case.

Federici S, Domenichelli V, Tani G, Sciutti R, Burnelli R, Zanetti G, Domini R.

Department of Pediatric Surgery, University of Bologna, Italy

Eur J Pediatr Surg 2001 Jun;11(3):196-9 Abstract quote

Pulmonary blastoma is a rare malignant tumor seen in both adults and children. Approximately only 25% of cases occur in pediatric patients, many of whom affected by a congenital pulmonary cystic lesion. The clinical features, radiological findings and management of a 3-year-old boy affected by a pulmonary blastoma which arose in a congenital cystic adenomatoid malformation are reported, and an extensive review of the literature is also made.

Because of the well-known tendency of cystic pulmonary diseases to develop malignancies, authors recommend the surgical excision of these kind of lesion or at least their close radiological follow-up.

RHABDOMYOSARCOMA  


Primary pulmonary rhabdomyosarcoma arising within cystic adenomatoid malformation: a case report and review of the literature.

Ozcan C, Celik A, Ural Z, Veral A, Kandiloglu G, Balik E.

Ege University Faculty of Medicine and the Department of Pediatric Surgery, Bornova-Izmir, Turkey

J Pediatr Surg 2001 Jul;36(7):1062-5 Abstract quote

The current report describes a 13-month-old boy with primary pulmonary rhabdomyosarcoma (RMS) that originated within a congenital cystic adenomatoid malformation (CCAM).

To the best of our knowledge, he is the youngest patient of all primary pulmonary RMS cases reported in the English-language literature. The tumor, localized in left upper lobe, was removed completely, and histologic examination showed embryonal subtype. Postoperative systemic chemotherapy was carried out. Recent evaluation 15 months after resection has not identified any residual or recurrent disease.

Primary pulmonary RMS, although very rare in the pediatric age group, should be considered in young patients with solitary pulmonary masses and associated cystic lesions.

 

PATHOGENESIS CHARACTERIZATION
GLIAL CELL-DERIVED NEUROTROPHIC FACTOR  


Glial cell-derived neurotrophic factor expression in normal human lung and congenital cystic adenomatoid malformation.

Fromont-Hankard G, Philippe-Chomette P, Delezoide AL, Nessmann C, Aigrain Y, Peuchmaur M.

Service d'Anatomie Pathologique (Drs Fromont-Hankard and Peuchmaur), de Chirurgie Pediatrique (Drs Philippe-Chomette and Aigrain), et de Foetopathologie (Drs Delezoide and Nessmann), Hopital Robert Debre, Paris, France.

 

Arch Pathol Lab Med 2002 Apr;126(4):432-6 Abstract quote

Context.-It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell-derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development.

Design.-We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis.

Results.-GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P <.005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung.

Conclusions.-Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.

MATURATION DEFECT  


Congenital cystic adenomatoid malformation of the lung: insights into the pathogenesis utilizing quantitative analysis of vascular marker CD34 (QBEND-10) and cell proliferation marker MIB-1.

Cangiarella J, Greco MA, Askin F, Perlman E, Goswami S, Jagirdar J.

Department of Pathology, and The Kaplan Comprehensive Cancer Center of New York University and Bellevue Hospital Medical Center, New York, USA.

Mod Pathol 1995 Dec;8(9):913-8 Abstract quote

Congenital cystic adenomatoid malformation (CCAM) encompasses a spectrum of variably cystic developmental anomalies of the lung histologically characterized by immature lung tissue. The pathogenesis is uncertain, but many investigators favor a maturation arrest in bronchopulmonary development.

To investigate this hypothesis, the vascular development and proliferation capacity of lung tissue with CCAM type I from nine infants ranging in age from 20 weeks gestation to 42 days old were studied immunohistochemically utilizing CD34 for the former and MIB-1 for the latter. Both markers were quantitated on an image analysis system. CCAM was hypovascular with a mean vascular index of 20.05% +/- 6.58 compared to 40.06% +/- 4.19 for the age-matched controls (P < 0.000001). The proliferation index of both epithelial and mesenchymal components was higher in CCAM (10.46 +/- 3.48) than in control tissue (7.14 +/- 1.88; P < 0.012). In contrast to the control lung tissue which showed a remarkable synchrony between the vascular development and proliferation throughout the parenchyma, focal asynchrony between the proliferation of the epithelial and stromal components was noted in CCAM. The vascularity in CCAM corresponds to that seen in early gestation. The cellular proliferation in CCAM is higher than in full-term infants and corresponds to late second trimester or early third trimester fetuses.

These findings support the proposed pathogenesis of a maturation defect in lung embryogenesis.

THYROID TRANSCRIPTION FACTOR-1  


Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of the lung.

Morotti RA, Gutierrez MC, Askin F, Profitt SA, Wert SE, Whitsett JA, Greco MA.

Department of Pathology, Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.

Pediatr Dev Pathol 2000 Sep-Oct;3(5):455-61 Abstract quote

Congenital cystic adenomatoid malformation (CCAM) is an abnormality of branching morphogenesis of the lung. CCAM types 1, 2, and 3 exhibit a cellular composition that is different from that of CCAM type 4 when evaluated with bronchiolar and alveolar cell markers. Thyroid transcription factor 1 (TTF-1) regulates early lung development.

To evaluate the potential role of TTF-1 in the development of CCAM, TTF-1 expression in CCAM was compared to that of fetal lungs at varying gestational ages. Twenty-three CCAM cases (17 type 1, two type 2, two type 3, and two type 4) and 11 fetal lungs (3 pseudoglandular, 4 canalicular, and 4 terminal sac stages) were analyzed using a rabbit polyclonal antiserum to rat TTF-1. Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells of the bronchial and bronchiolar epithelia and in cells lining the distal air spaces by 12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1 negative, except for the basal cells, while TTF-1 staining was maintained in distal bronchiolar and alveolar cells. TTF-1 expression decreased in both bronchial, bronchiolar, and alveolar epithelia with advancing gestational age and cytodifferentiation. At term, TTF-1 expression persisted in a few bronchial and bronchiolar basal cells and in all alveolar type II cells, whereas type I cells were negative. In CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts. TTF-1 was expressed in a majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the cells were TTF-1 positive. In contrast, TTF-1 expression in the alveolar-like epithelium of CCAM type 4 cysts was restricted to type II cells and only 30%-60% of the lining cells were TTF-1 positive.

These results support the hypothesis that CCAM types 1, 2, and 3 reflect abnormalities in lung morphogenesis and differentiation that are distinct from those for CCAM type 4. The role played by TTF-1 in the development of CCAM, if any, is not clear.

 

LABORATORY/RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  


Congenital cystic adenomatoid malformation of the lung: antenatal ultrasound findings and fetal-neonatal outcome. Fifteen years of experience.

De Santis M, Masini L, Noia G, Cavaliere AF, Oliva N, Caruso A.

Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy.

Fetal Diagn Ther 2000 Jul-Aug;15(4):246-50 Abstract quote

Seventeen cases of congenital cystic adenomatoid malformation of the lung (CCAM) are reported. They were followed up over a period of 1 month to 15 years. Diagnosis was made by prenatal ultrasound.

Our purpose was to evaluate the fetal-neonatal outcome and the prognostic elements observable through ultrasound techniques, and to compare all types of CCAM. The outcome observed ranged from total prenatal resolution to postnatal spontaneous regression of the lesion, to complications due to the presence of nonimmune fetal hydrops (NIFH), intrauterine death and the necessity of surgical intervention. In our experience only hydrops represented a negative predictor of outcome since death occurred in all cases with this pathology.

In the absence of NIFH, counselling should stress the prevalence of a positive outcome, even in cases of surgical intervention


Prenatal ultrasound diagnosis of congenital cystic adenomatoid malformation of the lung: a report of 26 cases and review of the literature.

Monni G, Paladini D, Ibba RM, Teodoro A, Zoppi MA, Lamberti A, Floris M, Putzolu M, Martinelli P.

Department of Obstetrics and Gynecology, Prenatal and Preimplantation Genetic Diagnosis, Ospedale Regionale per le Microcitemie, Via Jenner, 09121 S/N, Cagliari, Italy.

Ultrasound Obstet Gynecol 2000 Aug;16(2):159-62 Abstract quote

OBJECTIVES: To evaluate the sonographic appearances and prenatal natural history of congenital cystic adenomatoid malformation of the lung.

METHODS: In each case a detailed examination of the thoracic lesion and a complete fetal survey was performed. The pregnancies that elected to continue were followed to term.

RESULTS: A total of 26 cases were identified. The pregnancy was electively terminated in nine cases (35%). All the remaining 17 pregnancies ended in liveborn infants (100%). The lesion disappeared completely in three fetuses (18%). Of the 14 infants in whom the lesion was confirmed at birth nine required surgery in the neonatal or post-natal period. Five children did not undergo surgery.

CONCLUSIONS: Conservative management appears to be an adequate medical practice in cases of isolated congenital unilateral cystic adenomatoid malformation of the lung, in the absence of hydrops and/or acute polyhydramnios.


Echocardiographic evaluation of the fetus with congenital cystic adenomatoid malformation.

Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ, Crombleholme TM, Flake AW, Adzick NS.

Division of Cardiology, Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA

Ultrasound Obstet Gynecol 2000 Dec;16(7):620-4 Abstract quote

OBJECTIVES: The development of nonimmune hydrops is a known complication of congenital cystic adenomatoid malformation (CCAM) in the fetus. The aim of this study was to investigate the impact of CCAM on hemodynamics in the fetus and to determine whether cardiac dysfunction contributes to the development of hydrops in this patient population.

METHODS: The echocardiographic data from 41 consecutive fetuses diagnosed prenatally with CCAM were reviewed. The presence or absence of hydrops was noted in each patient. Two-dimensional ultrasonographic and Doppler data were compared between the two groups (with or without hydrops).

RESULTS: The mean gestational age for the study group at the time of imaging was 23.2 +/- 3.0 weeks. Hydrops was noted in 15 of 41 fetuses (36.5%). The fetuses that developed hydrops had a lower cardiac/thoracic ratio than those which did not develop hydrops (0.18 vs. 0.23, P = 0.001). The fetuses with hydrops also demonstrated an increase in early ventricular filling. The ratio of early ventricular filling to atrial contraction (E/A ratio) at both the tricuspid and mitral valves was significantly higher in the fetuses with hydrops (P = 0.005 and P = 0.03, respectively). Doppler interrogation of the inferior vena cava demonstrated a greater degree of reversal with atrial contraction in the hydrops group (29.7% vs. 15.1%, P = 0.003). The development of significant atrioventricular valve insufficiency was rare in the fetuses with hydrops (one of 15 cases).

CONCLUSIONS: Cystic adenomatoid malformation can result in significant cardiac compression in the fetus. This alters hemodynamics and may result in hydrops on the basis of elevated central venous pressure.


Radiolucent chest lesions in a neonate due to congenital cystic adenomatoid malformation.

Vandaele PE, Delanote GJ.

Department of Radiology, AZ Damiaan, Oostende, Belgium.

JBR-BTR 2001 Aug;84(4):164-5 Abstract quote

A localized radiolucent cystic lesion in the left lower lobe with shift of the mediastinum to the opposite side in a neonate is shown on chest X-ray and CT.

Findings on conventional X-ray and particularly on CT are very suggestive for congenital cystic adenomatoid malformation type 1. Histology after lobectomy confirmed the diagnosis.

LABORATORY MARKERS  

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
ABSCESS  


Congenital cystic adenomatoid malformation in an adult presenting as lung abscess.

Dahabreh J, Zisis C, Vassiliou M, Arnogiannaki N.

Thoracic Surgery Department, Saint Savas Anticancer Hospital, Athens, Greece.

Eur J Cardiothorac Surg 2000 Dec;18(6):720-3 Abstract quote

The case of a 21-year-old male with congenital cystic adenomatoid malformation is presented.

His medical history started after his birth with recurrent pulmonary infections during his infancy. Lung abscess of the right lower lobe was suspected and right lower lobectomy was performed to remove a sizeable mass infiltrating the largest part of the lobe.

The clinical features, diagnostic procedures, differential diagnosis, pathologic characteristics, therapeutic assessment, etiopathology and prognosis of the tumor are discussed.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
TYPE 1
Large cysts (2 to 10 cm in diameter)
TYPE 2
Smaller cysts (< 1 cm in diameter)
TYPE 3
Non-cystic
TYPE 4
 


Fetal congenital cystic adenomatoid malformations of the lung: a clinicopathologic study of eleven cases.

Cha I, Adzick NS, Harrison MR, Finkbeiner WE.

Department of Pathology, UCSF Fetal Treatment Center 94143-0506, USA.

Am J Surg Pathol 1997 May;21(5):537-44 Abstract quote

We describe the pathological examination of 11 cases of fetal congenital cystic adenomatoid malformation of the lung.

All patients were treated in utero between 21 and 27 weeks of gestation with either lobectomy or placement of a thoracoamniotic shunt. Ten cases involved a single lobe, and one case involved two lobes. The lesions contained both solid and cystic areas. On the basis of microscopic appearances, we separated the malformations into two distinct types. The first type consisted of seven cases showing scattered bronchiole-like dilated spaces lined by pseudostratified ciliated epithelium with intervening tightly packed small tubules lined by columnar cells with subnuclear vacuoles. This pattern superficially resembled the pseudoglandular period of lung development. The remaining four cases were of the other histologic type. They contained scattered bronchiole-like structures with intervening irregularly branching glands lined by cuboidal epithelium within loose mesenchymal stroma. This pattern superficially resembled the canalicular period of lung development.

We observed that the malformations contained cysts of various sizes and that cyst size varied widely within a single lesion. Moreover, predominantly cystic and predominantly solid lesions could not be separated histologically. Thus, we identify two patterns of fetal congenital cystic adenomatoid malformations, pseudoglandular and canalicular, the clinical significance of which is yet to be determined.


The glandular component in congenital cystic adenomatoid malformation of the lung.

Wang NS, Chen MF, Chen FF.

Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Respirology 1999 Jun;4(2):147-53 Abstract quote

Although severe congenital cystic changes (CCC) of the lung may be fatal, less severe forms may regress or vanish spontaneously. With recent advances in sonography, asymptomatic CCC are increasingly found. Whether all CCC should be promptly excised, or not, is uncertain. Congenital cystic changes conceptually are bronchopulmonary foregut malformations (BPFM) with a predilection for malignant degeneration. Among all BPFM, congenital cystic adenomatoid malformation (CCAM) is most common.

We therefore searched for evidence of early malignant transformation in five surgically excised and three autopsy lungs with CCAM. By light microscopy, CCAM resembled poorly formed and dilated bronchi, bronchioles and respiratory air spaces. Four lungs had multiple nodular aggregates of mucus producing cells; the glandular component (GC). By scanning electron microscopy, GC appeared as multiple micropolyps, resembling neuroepithelial bodies. By transmission electron microscopy, GC had a surface proliferation of cells with granules of the mucous type and a basal increase in cells with owl-eyed neuroendocrine granules. The glandular component in CCAM appeared similar to the mucous cells in hyperplastic polyps of the colon and a type of mucus producing bronchioloalveolar carcinoma.

Our findings support the hypothesis that CCAM is caused by dysregulated paracrine growth of mature cells and extracellular matrices and that GC could have the potential for malignant transformation. Further clinical and laboratory studies of BPFM are needed for the appropriate management of congenital cystic changes.


Congenital cystic adenomatoid malformation of the lung (CCAM): evaluation of the cellular components.

Morotti RA, Cangiarella J, Gutierrez MC, Jagirdar J, Askin F, Singh G, Profitt SA, Wert SE, Whitsett JA, Greco MA.

Department of Pathology, New York University Medical Center, NY 10016, USA.

Hum Pathol 1999 Jun;30(6):618-25 Abstract quote

Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital lesion whose pathogenesis is not well defined. It is generally accepted that the various types of CCAMs originate at different levels of the tracheobronchial tree.

To further define the pathogenesis of CCAM, we evaluated the cellular composition of different CCAM types by immunohistochemistry. Twenty-two CCAMs (17 CCAM type 1, two type 2, one type 3, and two type 4) were collected. The cellular composition was determined using immunohistochemical stains for type I cell-associated antigen (T1 cell-Ag), surfactant proteins and surfactant protein precursors (SP-A, SP-B, proSP-B, and proSP-C), neuroendocrine cells (GRP), Clara cells (UP-1), and the adhesion molecule CD44v6, a glycoprotein thought to be involved in cell-matrix and cell-cell interactions. Eleven fetal lungs also were analyzed to compare cytodifferentiation of the epithelial-lined cysts of the different types of CCAM with the stages of normal lung development.

Our results indicate that CCAM is caused by an arrest in lung development, and, on the basis of cytodifferentiation, two major subtypes can be distinguished. One subtype consisting of CCAM types 1, 2, and 3 that shows a bronchiolar type of epithelium and a second subtype, consisting of CCAM type 4, that has an acinar-alveolar type of epithelium. Our findings also suggest that these two subtypes may arise at different stages of the branching of the bronchopulmonary tree, the first at the pseudoglandular stage and the second at the saccular stage.

TYPE 4  

Congenital cystic adenomatoid malformation type 4.

van Koningsbruggen S, Ahrens F, Brockmann M, Michalk D, Rietschel E.

Department of Pediatrics, Children's University Hospital Cologne, Cologne, Germany.

Pediatr Pulmonol 2001 Dec;32(6):471-5 Abstract quote

A 9-day-old boy presented in respiratory distress and with failure to thrive. The chest X-ray showed a hyperlucent area of the left lung.

A resection of the markedly emphysematous segment 2 of the left upper lobe was performed assuming the emphysematous tissue was due to congenital lobar emphysema (CLE). Histological examination of the lung tissue, however, revealed a pattern consistent with congenital cystic adenomatoid malformation (CCAM) type 4. The therapy for CLE as well as for CCAM is similar, i.e., resection of the emphysematous tissue. As far as the prognosis is concerned, it is important to diagnose the exact type of malformation in order to exclude associated anomalies, as well as the risk of development of malignancies in later life. The frequency of associated malformations of CCAM type 4 is unknown.

Although the risk for development of malignancies from CCAM type 4 is not clear at the moment, the possible development of malignancies justifies prompt resection shortly after diagnosis, even in asymptomatic patients. A life-long follow-up in those patients who had a resection of CCAM in early childhood is recommended.

VARIANTS  

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
CONGENITAL CYSTIC LESIONS  


Congenital cystic disease of the lung in infants and children (experience with 57 cases).

Al-Bassam A, Al-Rabeeah A, Al-Nassar S, Al-Mobaireek K, Al-Rawaf A, Banjer H, Al-Mogari I.

King Khalid University Hospital, Riyadh, Saudi Arabia.

Eur J Pediatr Surg 1999 Dec;9(6):364-8 Abstract quote

A retrospective analysis of 57 consecutive cases with congenital cystic disease of the lung admitted to King Faisal Specialist Hospital and Research Center and King Khalid University Hospital, Riyadh, between 1985-1995 is presented.

There were 37 congenital lobar emphysema (CLE), 7 cystic adenomatoid malformation (CAM), 8 bronchogenic cyst (BC) and 5 pulmonary sequestrations (PS). There were 39 males and 18 females with ages ranging from 1 day to 5 years. All patients were symptomatic except three. Respiratory distress, repeated chest infections, and cystic changes noted in chest x-ray were the commonest presentation. Five of eight patients with BC presented with symptoms related to pressure effect of the cyst on the surrounding structures, these included bronchiectasis in two patients, bronchopleural fistula in one, pulmonary artery stenosis and bronchomalacia in one, airway obstruction mimicking bronchial asthma in one. Seven patients (12.2%) were treated conservatively, the remaining underwent surgery. Surgery included excision of the bronchogenic cyst and lobectomy for CLE, CAM, and intralobar sequestration.

The post-operative course in most cases was uneventful. There were no deaths in this series, and the majority of patients had a satisfactory outcome with follow-up ranging from 1-72 months (mean 24 months). It appears that lobectomy for symptomatic CLE, CAM, and intralobar sequestration and excision for bronchogenic cyst offer the best treatment modality and is well tolerated by pediatric patients. Careful search for associated anomalies is important to obtain better outcome.


The unpredictable character of congenital cystic lung lesions.

Roggin KK, Breuer CK, Carr SR, Hansen K, Kurkchubasche AG, Wesselhoeft CW Jr, Tracy TF Jr, Luks FI.

Division of Pediatric Surgery, Brown University School of Medicine and Hasbro Children's Hospital, Providence, RI 02905, USA.

J Pediatr Surg 2000 May;35(5):801-5 Abstract quote

BACKGROUND: The spectrum of congenital cystic disease of the lung ranges from hydrops and neonatal respiratory distress to asymptomatic lesions. Surgical management is dictated by the presence of symptoms, recurrent infection, and the potential risk of malignant transformation.

METHODS: Since 1995, all consecutive patients with congenital cystic lung lesions underwent follow-up for symptoms, treatment, and correlation of presumptive with pathological diagnosis.

RESULTS: Twelve cystic lung lesions were identified. Seven were diagnosed with mediastinal shift in utero; in 6 of 7, the shift subsequently resolved. Overall, 6 of 7 lesions that were followed up serially decreased in size. Two patients were symptomatic in utero; 1 underwent thoracoamniotic shunting, 1 pleurocentesis for impending hydrops. Postnatally, these 2, and 2 other newborns required urgent surgery. Five of 8 asymptomatic patients had elective resection by 16 months, and 4 await operation. In 6 of the 9 surgical cases (67%), there was a discrepancy between preoperative and pathological diagnosis. There were 4 hybrid congenital cystic adenomatoid malformation (CCAM)/sequestrations.

CONCLUSIONS: At least 6 of 7 congenital cystic lung lesions decreased in size regardless of gestational age or presence of mediastinal shift. Antenatal intervention is therefore rarely indicated. Hybrid morphology may necessitate resection of stable, asymptomatic lesions to prevent the theoretical concern for associated malignancies as well as other complications of CCAM.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  
GENERAL  


Long-term outcome of congenital cystic adenomatoid malformation.

Pinter A, Kalman A, Karsza L, Verebely T, Szemledy F.

Department of Paediatrics, Medical University, 7623 Pecs, Hungary.

Pediatr Surg Int 1999 Jul;15(5-6):332-5 Abstract quote

To determine the long-term outcome of congenital cystic adenomatoid malformation (CCAM), the records of all patients with CCAM treated in three Hungarian paediatric surgical centers between 1977 and 1996 were reviewed. Patients were followed for up to 20 years following diagnosis and treatment. In 20 patients CCAM was diagnosed postnatally and in 3 prenatally. Biodata including the operative procedures are presented.

Follow-up findings between 18 months and 20 years after diagnosis showed better height and weight growth in patients operated upon in later childhood compared with those operated upon in infancy. The older the patient at the time of diagnosis, the better was the long-term outcome.


Prognostic factors associated with congenital cystic adenomatoid malformation of the lung.

Bunduki V, Ruano R, da Silva MM, Miguelez J, Miyadahira S, Maksoud JG, Zugaib M.

Fetal Medicine Unit, Department of Obstetrics and Gynaecology and Department of Paediatric Surgery, University of Sao Paulo, Medical School Hospital, Brazil.

Prenat Diagn 2000 Jun;20(6):459-64 Abstract quote

This study presents 18 cases of prenatally diagnosed congenital cystic adenomatoid malformation (CCAM) to identify potential factors that could predict prognosis.

Comparisons of prenatal parameters were made between fetuses that survived and those that died perinatally. It was found that microcystic lesion, bilateral lung involvement and hydrops were each highly correlated with poor prognosis, while neither polyhydramnios nor mediastinal shift was significantly associated with had outcome.

Fetal interventions were indicated only in two of the surviving cases: a thoracocentesis and a cysto-amniotic shunt. A therapeutic amniocentesis was performed in one case of polyhydramnios. The diagnosis of CCAM was histologically confirmed in all cases by necropsy or by postnatal lobectomy.


Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience.

Laberge JM, Flageole H, Pugash D, Khalife S, Blair G, Filiatrault D, Russo P, Lees G, Wilson RD.

Department of Surgery, Montreal Children's Hospital, Montreal, Canada.

Fetal Diagn Ther 2001 May-Jun;16(3):178-86 Abstract quote

Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by prenatal ultrasonography with an increasing frequency but controversy persists as to its prognosis and prenatal management.

METHOD: A multi-institutional study of cases of CCAM diagnosed antenatally identified by ultrasonographers and by a review of hospital charts.

RESULTS: We obtained 48 cases from five centers. We estimate the incidence of CCAM at 1:25,000 to 1:35,000 pregnancies. The incidence of voluntary abortions was 15% (7/48), of spontaneous abortions 2% (1/41) and of postnatal death 10% (4/40). One of the postnatal deaths was from trisomy 18. Of the 7 aborted fetuses, 2 had multiple malformations and 1 had severe hydrops and oligohydramnios; the other 4 had a large mass with mediastinal displacement but without hydrops. When pregnancy was allowed to continue, 56% of the lesions regressed spontaneously, even though one third of these had initial progression. In 17 cases (42%) the mediastinal shift corrected itself, sometimes by simple growth of the fetus but most often by a decrease in the size of the lung mass. In 1 fetus, repeated needle decompressions followed by double-pigtail catheter drainage of large cysts allowed regression of hydrops. Despite this, neonatal death occurred from pulmonary hypoplasia.

CONCLUSION: CCAM can lead to fetal or neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated malformations, but has a good prognosis in the majority of cases.

MALIGNANCIES  



Bronchioloalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: a case report and review on malignancies originating in congenital cystic adenomatoid malformation.

Granata C, Gambini C, Balducci T, Toma P, Michelazzi A, Conte M, Jasonni V.

Department of Paediatric Surgery, Giannina Gaslini Hospital for Children, Genova, Italy.

 

Pediatr Pulmonol 1998 Jan;25(1):62-6 Abstract quote

A type I congenital cystic adenomatoid malformation (CCAM) in the left lower lobe was removed from a 11-year-old boy with a 3-month history of recurrent pneumonia.

As incidental finding, a bronchioloalveolar carcinoma (BAC) was found in the lung parenchyma adjacent to the cyst. A left lower lobectomy was performed. At 18 months after surgery the patient is well and free of neoplastic disease. To the best of our knowledge, this association has not been reported previously in a pediatric patient. Malignancies complicating CCAM are rarely seen, but have been reported in adults. Including our case, eight cases of BAC and five cases of rhabdomyosarcoma (RMS) in association with CCAM have been reported so far. As CCAM can host metaplastic mucous cells, primitive mesenchymal cells and differentiated but poorly organized striated muscle fibers, it has been proposed that CCAM may act as a predisposing condition for oncogenesis.

Our experience adds further support that CCAM can act as a premalignant lesion. Previous reports of both BAC and RMS in asymptomatic CCAM suggest prompt resection shortly after diagnosis.

SUDDEN DEATH  

Sudden neonatal death from congenital cystic adenomatoid malformation.

Suarez-Penaranda JM, Rodriguez-Calvo MS, Munoz JI, Pumarega-Vergara M, Sanchez-Herrero MJ, Concheiro-Carro L.

Instituto de Medicina Legal, Facultad de Medicina, Santiago de Compostela, Spain

Int J Legal Med 2001 Oct;115(2):76-8 Abstract quote

We report a case of congenital cystic adenomatoid malformation (CCAM) of the lungs resulting in sudden death immediately after birth. The case is extremely unusual because of the diffuse bilateral involvement. The extensive involvement of both lungs could explain the abrupt onset of the symptoms and the ineffectiveness of resuscitation attempts.

The presence of cartilage as a part of the malformation adds interest to the case, since it is seldom found in this malformation and to the best of our knowledge has been reported only exceptionally in a type II CCAM.

TREATMENT  


Cystic adenomatoid malformation of the lung: neonatal management of 21 cases.

Waszak P, Claris O, Lapillonne A, Picaud JC, Basson E, Chappuis JP, Salle BL.

Neonatal Intensive Care Unit, Pavillon J, Hopital Edouard Herriot, place d'Arsonval, 69437 Lyon Cedex 03, France.

Pediatr Surg Int 1999 Jul;15(5-6):326-31 Abstract quote

Currently, congenital cystic adenomatoid malformation of the lung (CCAM) is often diagnosed antenatally by ultrasound, allowing prompt and appropriate medical and surgical management after birth. The authors report 21 cases of CCAM admitted from 1988 to 1997 to a neonatal intensive care unit and treated by high-frequency oscillation (HFO) and early surgery. Six infants developed respiratory distress, of whom 4 required ventilation by HFO. HFO was also the mode of ventilation used in all cases except 1 during the perioperative period. There was no death from respiratory failure.

The authors emphasize the usefulness of antenatal diagnosis, the efficiency of HFO in cases with severe respiratory failure, and well-tolerated early surgery.


Cystic adenomatoid malformation of the lung: clinical evolution and management.

Bagolan P, Nahom A, Giorlandino C, Trucchi A, Bilancioni E, Inserra A, Gambuzza G, Spina V.

"Bambino Gesu" Paediatric Hospital, Department of Neonatal Surgery, Piazza S. Onofrio 4, I-00165 Rome, Italy.

Eur J Pediatr 1999 Nov;158(11):879-82 Abstract quote

Cystic adenomatoid malformation of the lung (CAML) is a rare pulmonary maldevelopment resulting from an abnormal growth of the terminal bronchial structures.

This study proposes a possible management of prenatally diagnosed CAML. A group of nine cases of CAML diagnosed prenatally between January 1990 and December 1995 was studied retrospectively. The evolution of lesions was followed in utero by serial ultrasound monitoring. Chest X-ray was performed at birth in all neonates and CT only in the symptomatic ones. CAML was macrocystic in three cases and microcystic in six. No polyhydramnios, hydrops or associated malformations were seen. In four cases, CAML was confirmed at birth and required surgery. The lesion decreased in size prenatally in five fetuses, of whom only one underwent surgery. In two further cases a prenatal diagnosis of CAML was changed to diaphragmatic hernia.

CONCLUSION: Given the possible clinical disappearance or resolution of cystic adenomatoid malformation of the lung, we believe that surgery is justified at birth only in symptomatic and radiologically positive neonates. It could be safely delayed in those asymptomatic patients with either positive or negative chest X-ray. The former need computed tomography at birth, whereas, in the latter, it should be performed at 6 months of age for a more definitive assessment of the patient.


Percutaneous laser ablation of fetal congenital cystic adenomatoid malformation: too little, too late?

Bruner JP, Jarnagin BK, Reinisch L.

Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN 37232-2519, USA

Fetal Diagn Ther 2000 Nov-Dec;15(6):359-63 Abstract quote

OBJECTIVE: Congenital cystic adenomatoid malformation, type III (CCAM III) lesions are large, bulky tumors which can cause mediastinal shift, prevent normal pulmonary growth, and compress the esophagus, thus leading to complications of nonimmune hydrops, pulmonary hypoplasia and polyhydramnios. Because the mortality rate of untreated fetuses with CCAM and hydrops is high, early delivery or intrauterine resection of the enlarged pulmonary lobe (lobectomy) is indicated; however, open fetal resection of CCAM at less than 30 weeks is associated with perioperative mortality that approaches 40%, as well as the usual maternal and fetal morbidity of open fetal surgery. As an alternative, percutaneous laser ablation of a CCAM III lesion with hydrops was attempted.

METHODS: A 30-year-old G3 P1011 with CCAM III in the left fetal hemithorax developed mediastinal shift, hydrops and polyhydramnios at 23 weeks' gestation. After pregnancy termination and open fetal resection were declined, an 18-gauge needle was placed into the fetal tumor percutaneously under real-time ultrasonographic guidance, using sterile technique with light sedation. A cleaved 400-microm Nd:YAG laser fiber was passed through the needle lumen, and using a power setting of 15 W, a total of 2,943 J of laser energy was delivered in pulses of 1.0 s at 0.2-second intervals over two sessions one week apart.

RESULTS: Although tumor size decreased, the hydrops worsened and fetal death occurred.

CONCLUSIONS: The fetus with CCAM complicated by hydrops is already so compromised by the advanced state of the disease that insufficient time is available for necrotic tissue reabsorption after minimally invasive therapy with laser energy. Until earlier markers for intervention are determined, percutaneous laser debulking of CCAM is unlikely to be successful.


Congenital cystic adenomatoid malformation: impact of prenatal diagnosis and changing strategies in the treatment of the asymptomatic patient.

Marshall KW, Blane CE, Teitelbaum DH, van Leeuwen K.

Department of Radiology, University of Michigan Health Systems, 1500 E. Medical Center Dr., F-3503, Ann Arbor, MI 48109-0252, USA.

 

AJR Am J Roentgenol 2000 Dec;175(6):1551-4 Abstract quote

OBJECTIVE: This study was designed to assess the effect of prenatal sonographic diagnosis on the treatment of congenital cystic adenomatoid malformation of the lung.

MATERIALS AND METHODS: The medical records of 27 patients with pathologically proven congenital cystic adenomatoid malformations were retrospectively reviewed. Patients were divided into four groups based on mode of presentation: with or without abnormal findings on prenatal sonography and with or without symptoms at birth. Age at diagnosis, age at surgical intervention, complications, and length of hospital stay were recorded for each group.

RESULTS: Twenty-seven patients with 31 proven congenital cystic adenomatoid malformations were included. Eleven patients underwent prenatal sonography establishing the diagnosis (6 asymptomatic at birth, 5 symptomatic), and 16 did not have a prenatal diagnosis (10 asymptomatic at birth, 6 symptomatic). In the symptomatic populations, prenatal diagnosis had no impact on age at surgery, length of stay, or surgical complication rate (p = 0.78-0.83). In the asymptomatic population, prenatal diagnosis allowed early diagnosis (p < 0.001) and resection in the asymptomatic period. It was also associated with a shorter length of stay at the time of surgical resection (mean time, 4.2 days for patients with prenatal diagnosis versus 12.9 days for those without it;p < 0.001) and with a trend toward lower serious complication rate (3 patients without prenatal diagnosis versus 1 patient with it).

CONCLUSION: Prenatal sonography provides the radiologist a means to identify congenital cystic adenomatoid malformations in a population of infants who are asymptomatic at birth. Surgical intervention in the asymptomatic infant is associated with a shorter length of stay, a trend toward fewer complications, and decreased medical cost compared with intervening after symptoms develop.


The postnatal management of congenital cystic adenomatoid malformation.

Keidar S, Ben-Sira L, Weinberg M, Jaffa AJ, Silbiger A, Vinograd I.

Department of Pediatric Surgery, Dana Children's Hospital, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Israel.

 

Isr Med Assoc J 2001 Apr;3(4):258-61 Abstract quote

BACKGROUND: Routine prenatal ultrasound has increased the frequency of prenatal diagnosis of congenital cystic lung malformation, such as cystic adenomatoid malformation, pulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst.

OBJECTIVES: To evaluate the methods of postnatal diagnosis, the optimal age for operation since surgery is always required, and the optimal extent of lung resection.

METHODS: The clinical courses of 11 patients with congenital lung cysts who underwent surgical lung resection (8 lobectomies and 3 segmentectomies) were reviewed.

RESULTS: The diagnosis was confirmed by computed tomography scan in all. In nine patients the diagnosis was made prenatally. Chest X-ray was normal postnatally in all patients except for two who had recurrent pneumonia. Postoperative follow-up showed excellent recovery in all operated children. One patient who underwent surgery for CCAM following episodes of severe pneumonia died from another cause 5 months later. Postoperative chest CT scan showed no residual disease in eight patients. In two who had undergone limited resection, tomography showed a small segment of residual disease in one and a suspected residual lesion in the other.

CONCLUSION: With prenatal ultrasound the true frequency of congenital cystic lung anomaly appears to be higher than previously reported. Postnatal CT is mandatory to confirm or to rule out the diagnosis. The mere presence of cystic lung malformation is an indication for surgery. Complete removal of the affected lung lobe is recommended. Segmental resection may be inadequate. Early operation is tolerated well by infants and small children and we recommend that surgery be performed in children between 6 and 12 months of age.

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Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.


Commonly Used Terms

Lungs


Last Updated 8/22/2002

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