CONGENITAL ADENOMATOID MALFORMATION OFLUNG WITH PNEUMOTHORAX

BY

ROY G. SPECTOR, ALBERT E. CLAIREAUX and E. ROHAN WILLIAMSFrom the Bernhard Baron Memorial Research Laboratories, Queen Chlarlotte's Maternity Hospital, London

and The Institute of Obstetrics and Gynaecology, Universitv ofLondon

(RECEIVED FOR PUBLICATION DECEMBER 21, 1959)

Although hamartomas of the lungs are notcommon, they cannot be considered as pathologicalcuriosities. Several cases have been reported inrecent years (Harris and Schattenberg, 1942; Jones,1949; Thomas, 1949; Timossi, 1955; Lima, Zerbiniand Bittencourt, 1955; Gottschalk and Abramson,1957; Galvez Fermin, 1958; Cornea, Dichter,Gamentay and Mindru, 1959; Bain, 1959). Onevariety of hamartoma of the lung, namely congenitalcystic disease of the lung, has received an increasingamount of attention since Koontz (1925) collected hislarge series of cases. Ch'in and Tang (1949) coinedthe expression 'congenital adenomatoid malforma-tion' for this condition. They found descriptionsof 10 cases in the literature up to that time and addedone case of their own.A comprehensive review of the literature was made

by Craig, Kirkpatrick and Neuhauser (1956). Theymentioned the 11 cases in Ch'in and Tang's paper,11 other cases and added four of their own. Coffee(1956) also reviewed the position at that time.Since then, one case by Goodyear and Shillitoe(1959) and four cases by Herrmann, Jewett andGalletti (1959) have been reported. These workersdistinguished between those cases which presentclinically in early neonatal life with cyanosis andthose which present later with signs of infection.This report is concerned with a case of congenitalcystic disease of the lung which was accompaniedby hypoplasia of the entire remaining lung tissueand in which a tension pneumothorax occurredfollowing attempts at resuscitation.

Case ReportClinical History. The mother was 26 years of age and

had had one previous normal pregnancy. Her generalhealth was good. During pregnancy the only abnor-mality detected was hydramnios at about 27 weeks.The onset of labour was spontaneous and occurred

at the end of the 28th week. The duration of the first

stage was one hour and of the second stage 20 minutes.The presentation was vertex and delivery was spon-taneous.At birth the child was oedematous, cyanosed and

apnoeic. Attempts at resuscitation were followed byonly two or three shallow gasps.

Radiological Investigation.ANTENATAL EXAMINATION. The patient was referred

for radiological examination (to exclude foetal abnor-mality or twin pregnancy) on September 22, 1959; theheight of the fundus corresponded to that normallyexpected at 34-35 weeks; by dates, the maturity was 27weeks. One foetus was present in a vertex L.O.A.position, with evident hydramnios in considerabledegree. The foetal stature corresponded to that expectedfor a maturity of 27-28 weeks. The attitude of thefoetus, both of the trunk and the limbs, was reminiscent ofthat often found in hydrops foetalis and at least suggestedthe presence of some foetal abdominal distension.POSTNATAL EXAMINATION. Radiographs (Figs. I and

2) were taken of the whole infant shortly after its deathwhich occurred at 10 minutes after birth. It was evidentthat air had been both swallowed and inhaled. Therewas slight distension of the abdomen but this was notdue to intestinal gas. The thorax presented mostunusual appearances. There was a right pneumothoraxwith a complex loculated appearance peripherally. Themargin of this pneumothorax extended well across to theleft of the mid-line and no pulmonary aeration wasobserved on either side. The volume occupied by theleft lung was evidently much reduced. The cardiacoutline could not be separately discerned. Thus theappearances bore some resemblance to those found in atension pneumothorax on the right side, but the opacitydue to the compressed lung was much greater than wouldbe expected.

Necropsy. This revealed a premature male infantweighing 1,550 g. whose crown-rump length was 28 cm.and crown-heel length was 39 cm. There was markedoedema of the arms and back and the abdomen wasdistended. There were no other abnormalities seen onexternal examination. The pleural sacs contained no

475

by copyright. on N

ovember 29, 2021 by guest. P

rotectedhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.35.183.475 on 1 O

ctober 1960. Dow

nloaded from

ARCHIVES OF DISEASE IN CHILDHOOD

FIG. 1.-Radiograph. Antero-posterior view showing right-sidedpneumothorax. There is a cystic space containing air in the mass inthe right lung. The mediastinum is displaced to the left.

excess fluid. There was a pneumothorax on the rightside which was under tension. The pleurae wereglistening. The larynx, trachea and main bronchi werenormal. A large, firm, pink, nodular mass involvedthe upper lobe of the right lung (Fig. 3). On slicing,several cystic cavities were opened (Fig. 4). The masswas approximately three times the usual size of the rightupper lobe. A probe could be passed from the rightupper lobe bronchus into one of the cysts. The mal-formation was so large that it had herniated across themidline. The left lung and the middle and lower lobesof the right lung were hypoplastic. The pericardial saccontained no excess fluid. The heart was of the expectedsize and there were no congenital abnormalities ofeither the heart or great vessels but the organ was dis-placed to the left. There was a moderate excess of clear,yellow fluid in the peritoneal sac. The tongue, pharynx,oesophagus, stomach and intestines were normal. Theliver was of the expected size and appeared macroscopi-cally normal. The bile passages were patent. The falxcerebri and tentorium cerebelli were intact. There wasa small amount of blood diffusely spread in the sub-arachnoid space over both cerebral hemispheres andover the cerebellum. The brain and choroid plexuseswere congested. The adrenals (each 1-5 g.), pituitary,

FIG. 2.-Radiograph. Lateral view. Air can be seen in the smallintestine.

thymus and thyroid glands were normal. The kidneys(each 8 g.) showed foetal lobulation. The ureters,bladder and external genitalia were normal. Theplacenta weighed 370 g. and measured 17 x 14 cm.The placental/foetal weight ratio was 1:4-1. Therewas a velamentous insertion of the cord. The mem-branes were complete. The placenta was not oedema-tous and appeared normal on slicing.

Histology.UPPER LOBE OF RIGHT LUNG. The pleura showed

little change. The mass consisted of innumerable smallacini lined by a low cuboidal epithelium (Fig. 5). Theywere separated from one another by a loose connectivetissue stroma which contained elastic fibres. Somelarger cystic spaces lined by columnar epithelium werealso present. These were surrounded by smooth muscle1-3 layers thick. These structures had the appearanceof terminal bronchioles and some showed very markeddilatation (Fig. 6). There was no evidence of cartilageformation in the wall of any of the bronchial-likestructures and no glands were present in their sub-mucosa. In a number of areas there were collectionsof several acini lined by tall, columnar, mucus-secretingepithelium (Fig. 7). The material in the lumen of these

476

by copyright. on N

ovember 29, 2021 by guest. P

rotectedhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.35.183.475 on 1 O

ctober 1960. Dow

nloaded from

CONGENITAL ADENOMATOID MALFORMATION OF LUNG

FIG. 4.-Section of the mass showing several large cysts. Themiddle and lower lobes of the right lung are hypoplastic.

FIG. 3.-Large mass replacing the upper lobes of the right lung.A ruptured cyst is seen in the centre. The left lung is extremely

hypoplastic.

structures gave a strongly positive reaction when stainedby the periodic acid-schiff technique. The appearanceof the mass was consistent with a diagnosis of congenitaladenomatoid malformation. There was no subdivisionof the mass into lobules. There was a sharp demarcationat the lower border of the mass between malformedtissue and adjoining hypoplastic lung (Fig. 5). A narrowconnective tissue septum appeared to separate the onefrom the other.MIDDLE AND LOWER LOBE OF RIGHT LUNG. The

pleura was healthy. The lobes showed marked hypo-plasia and were unexpanded. The bronchi, bronchioles,alveolar ducts and alveoli showed no structural lesion.

LEFr LUNG. This lung was also extremely hypoplastic.The bronchial structure appeared to be normal.No lesion was found on histological examination of

the other organs.Discussion

Willis (1958) defined hamartomas as tumour-like,but primarily non-neoplastic malformations or

errors of tissue development. characterized byabnormal mixture of tissues indigenous to the partwith excess of one or more of these. On thesegrounds he does not consider 'chondromatoushamartomas' of the lung to be malformations buttrue tumours. Nevertheless, cartilage-containing

FIG. 5.-Showing adjacent areas of hamartoma (above) and hypo-plastic lung. H. and E. x 26.

477

by copyright. on N

ovember 29, 2021 by guest. P

rotectedhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.35.183.475 on 1 O

ctober 1960. Dow

nloaded from

ARCHIVES OF DISEASE IN CHILDHOOD

FIG. 6.-Malformation showing large cystic spaces lined by respiratoryepithelium and surrounded by some layers of smooth muscle.A focus of mucus secreting epithelium is present. H. and E. x 48.

hamartomas are occasionally found in the lungs ofinfants. Jones (1949) described such a case inwhich there was an admixture of foetal lung tissue,cartilage and fibrous tissue which had replacedpart of one lung of an infant. The appearanceswere not those of a neoplasm but of a malformationof lung tissue, and the author suggested that thiswas a true cartilage-containing hamartoma. Aswell as the more solid type of hamartoma such asdescribed by Harris and Schattenberg (1942),Willis includes congenital cystic disease in thisclass of disorders of the lungs. Klosk, Bernstein andParsonnet (1946) define cystic disease of the lung as'any condition in which the lung parenchyma isreplaced by sharply defined cavities containingfluid or air'. These authors divide this diseaseinto the variety which exhibits solitary large cystsand that characterized by multiple cysts. Herrmannet al. (1959) describe an acquired type. The cystsin the congenital form of the disease are lined bypseudo-stratified ciliated columnar epithelium orrespiratory cuboidal epithelium. In the morecommon form of cystic disease of the lung, however,cartilage is present in the bronchial wall. It isnotably absent in adenomatoid malformation.

FIG. 7.-High power view of part of field in Fig. 3 showing detailof mucus secreting tissue. H. and E. x 103.

Histological examination of the lung in this caseshowed small cystic spaces lined by a low columnarepithelium of the respiratory variety in most areas.Other parts of the hamartoma contained spaceslined by cuboidal and tall columnar epithelium.Levine (1950) postulates that this form ofhamartoma arises by pinching off of portions ofthe main lung buds and their derivatives in thesecond half of intrauterine life. Some of theseportions of bronchial tissue may completely separatefrom the bronchial tree and continue to secretefluid which will distend the cysts. Other portionsdo not completely separate but maintain a narrowcommunication with the bronchi. In our case, wewere able to pass a probe from a main bronchusinto one of the larger cysts. This apparentlysupports Levine's suggestion as to their mode oforigin. Herrmann et al. (1959) mention, in addition,a second possible mode of origin, namely a dis-turbance occurring in the fourth foetal week. Atthis time two septa divide the foregut into an anteriorand posterior part. If cells from this region detachthemselves at about this period, then bronchial orgastric cysts would arise. The occurrence ofcystic spaces lined by mucus secreting epithelium

478

by copyright. on N

ovember 29, 2021 by guest. P

rotectedhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.35.183.475 on 1 O

ctober 1960. Dow

nloaded from

CONGENITAL ADENOMATOID MALFORMATION OF LUNG

has been noted by previous authors (Ch'in andTang, 1949; Koboth, 1936) and this suggests thatthe anomaly may have its origin during the fourthfoetal week. Craig et al. (1956), however, regardthese as aberrant forms of bronchial mucous glands.Conway (1951) believes congenital cystic diseaseof the lung is the result of some unknown processwhich interferes with canalization at some pointproximal to the termination of the lung bud. Distalto this point canalization begins again producing anisolated canalized segment lined by normal bronchialmucosa. In adenomatoid hyperplasia there is agreat increase in the number of structures whichhave the appearance of terminal bronchioles. Thesmaller spaces lined by cuboidal epithelium pro-bably represent incompletely formed alveolar ducts.At necropsy the hamartoma is usually found to

increase both the size and weight of the affectedlung (the increase in bulk often causing herniationof the lung across the midline with mediastinaldisplacement) both of which occurred in the presentcase. In most cases, only one lobe of the lung isaffected; indeed, we have found records of onlytwo cases in which an entire lung was involved(Wolman, 1930; Goodyear and Shillitoe, 1959).We have found no preference for the right or leftlung and for upper, lower or middle lobes. Onslicing the abnormal tissue mass, cysts of varyingsize are usually seen lying in firm, pale, macro-scopically homogeneous tissue. Our case showedrelatively few cysts. We found no cartilage in theaffected part of the lung and this favours the theoryof a valve-like mechanism by which air can enterthe spaces of the hamartoma during inspirationbut, because of lack of supporting tissue around thecommunicating channels with the bronchi, air istrapped during expiration. In this way the size ofthe malformation progressively increases afterbirth and the 'expanding lung syndrome' is pro-duced. This causes not only displacement of themediastinum but distortion of the venae cavae andmaldevelopment of the contralateral lung. In ourcase, not only was there hypoplasia of the lungon the opposite side, but of the other lobes of theipsilateral lung. As in previously reported caseswe found no congenital abnormality in any otherpart of the body.The diagnosis of this condition is not without

difficulty, but, in the present case, foetal abnormalitywas first considered when hydramnios developedin the 27th week of pregnancy. This is a commonfeature of cystic disease of the lung, but is uniquein that hydrops foetalis was diagnosed by a maternalpelvic radiograph during pregnancy. Ch'in andTang (1949) and Gottschalk and Abramson (1957)

suggest that the hydramnios is due to cardiovasculardisturbance in the foetus following mediastinal andvena caval displacement by the tumour. This ispostulated to produce an increase in systemicvenous pressure resulting in not only hydrops foetalisbut hydramnios. There seems to be little evidencethat the oedema is the result of cardiac failure.Generalized anasarca is less common in foetuseswith this malformation delivered at term or ininfants who live for some time after birth (Craiget al., 1956).

Children suffering from this disease are usuallypremature; presumably the early labour results fromhydramnios. Ch'in and Tang's series consistedmainly of premature and stillborn foetuses, andother cases reported up to 1943 were either stillbornor died in early neonatal life. The mother of ourcase went into labour at 28 weeks and spontaneouslydelivered a moderately oedematous and cyanosedinfant. Oedema is not unusual in this condition(Grawitz, 1880; Ch'in and Tang, 1949; Craig et al.,1956) and, as mentioned above, is probably dueto vena caval distortion. Thus hamartoma of thelung should be borne in mind in the differentialdiagnosis of cyanosis and oedema in a prematureinfant.

Tension pneumothorax may result from thismalformation (Herrmann et al., 1959), although thevast majority of cases result from rupture of anemphysematous bulla on the surface of the lung or(in slightly older infants) staphylococcal broncho-pneumonia. Our case was unusual in that ruptureof an air-containing cyst had occurred followingattempts at resuscitation.The cases of Fischer, Tropea and Bailey (1943),

of Graham and Singleton (1955), the four cases ofCraig et al. (1956) and the four cases of Herrmannet al. (1959) were all diagnosed during life by radio-logical examination. This investigation should beperformed in all cases in which pulmonary hamar-toma is considered as a possible diagnosis.

In retrospect, it seems evident that the loculatedappearance in the radiograph of our case was due toair in the superficial cystic parts of the tumour andthat a marginal rupture had occurred leading to thepneumothorax. Whilst the limits of part of thetumour were surely outlined, it was not possibleto differentiate between the tumour and the atelec-tatic right lung.

Treatment of this condition is removal of theaffected tissue. As the child continues to breathethe cysts in the malformed lung increase in sizeand progressive displacement of the mediastinumwith compression of the contralateral lung occurs.Thus early treatment is imperative, and this, in

5

479by copyright.

on Novem

ber 29, 2021 by guest. Protected

http://adc.bmj.com

/A

rch Dis C

hild: first published as 10.1136/adc.35.183.475 on 1 October 1960. D

ownloaded from

480 ARCHIVES OF DISEASE IN CHILDHOOD

turn, depends on early radiological diagnosis of thedisease. Our case was complicated by a tensionpneumothorax and hypoplasia of all the lung tissuenot involved in the hamartoma. The period ofsurvival was insufficient to permit surgical inter-vention.

SummaryA case of hamartoma of the lung is described

in an infant who survived for 10 minutes afterdelivery. The remaining lung tissue was hypoplastic.A tension pneumothorax was present on the sameside as the lesion.

Foetal abnormality was suspected during preg-nancy on account of hydramnios. Radiologicalexamination revealed a hydropic foetus. At nec-ropsy a large mass was found replacing the upperlobe of the right lung. On histological examinationthe mass was found to be composed of multiplesmall cysts and spaces lined by respiratory typeepithelium.The relationship between congenital cystic disease

of the lung and truepulmonary neoplasm is discussed.

We are indebted to Mr. E. Clark of the BernhardBaron Memorial Research Laboratories, Queen Char-lotte's Hospital, for the photograph and photom.cro-graphs.

REFERENCES

Bain, G. 0. (1959). Congenital adenomatoid malformation of thelung. Dis. Chest, 36, 430.

Ch'in, K. Y. and Tang, M. Y. (1949). Congenital adenomatoidmalformation of one lobe of a lung with general anasarca.Arch. Path., 48, 221.

Coffee, H. L. (1956). Congenital lung cysts; a review of the literatureand case report. J. med. Ass. Ga. 45, 199.

Conway, D. J. (1951). The origin of lung cysts in childhoodArch. Dis. Childh., 26, 504.

Cornma, P., Dichter, I., Gamentay, E. and Mindru, M. (1959).Un cas d'hamertome pulmonaire. Sem. Hdp. Paris, 35, 1029.

Craig, J. M., Kirkpatrick, J. and Neuhauser, E. B. D. (1956). Con-genital cystic adenomatoid malformation of the lung in infants.Amer. J. Roentgenol., 76, 516.

Fischer, C. C., Tropea, F., Jr. and Bailey, C. P. (1943). Congenitalpulmonary cysts; report of an infant treated by lobectomy withrecovery. J. Pediat., 23, 219.

Galvez Fermin, N. (1958). Consideraciones sobre un caso dehamartoma del pulmon. Arch. cuban. Cancer., 17, 143.

Goodyear, J. E. and Shillitoe, A. J. (1959). Adenomatoid hamartomaof the lung in a newborn infant. J. clin. Path., 12, 172.

Gottschalk, W. and Abramson, D. (1957). Placental edema andfetal hydrops: a case of congenital cystic and adenomatoidmalformation of the lung. Obstet. and Gynec., 10, 626.

Graham, G. G. and Singleton, J. W. (1955). Diffuse hamartomaof the upper lobe in infant: Report of successful surgical removal.Amer. J. Dis. Child., 89, 609.

Grawitz, P. (1880). Ueber angeborne Bronchiectasie. VirchowsArch. path. Anat., 82, 217.

Harris, W. H. and Schattenberg, H. J. (1942). Anlagen and resttumors of the lung inclusive of 'mixed tumours' (Womack andGraham). Amer. J. Path., 18, 955.

Herrmann, J. W., Jewett, T. C., Jr. and Galletti, G. (1959). Broncho-genic cysts in infants and children. J. thorac. Surg., 37, 242.

Huickel, R. (1927). Beitiage zur angeborenen Wabenlunge.Frankfurt. Z. Path., 35, 320.

Jones, C. J. (1949). Unusual hamartoma of the lung in a newborninfant. Arch. Path. (Chicago), 48, 150.

Klosk, E., Bernstein, A. and Parsoanet, A. E. (1946). Cystic diseaseof the lung. Ann. intern. Med., 24, 217.

Koboth, I. (1936). Geschwulstartige Fehlbildungen eines Lungen-lappens bei einer Fruhgeburt. Frankfurt. Z. Path., 50, 10.

Koontz, A. R. (1925). Congenital cysts of the lung. Bull. JohnsHopk. Hosp., 37, 340.

Levine, R. M. (1950). Congenital cystic disease of the lung. Canad.med. Ass. J., 62, 181.

Lima, M. L. M. T. de. Zerbini, E. J. and Bittencourt, D. (1955).Hamartomas do pulmao. Rev. paul. Med., 47, 143.

Thomas, M. R. (1949). A cystic hamartoma of the lung in a new-born infant. J. Path. Bact., 61, 599.

Timossi, C. (1955). Su di un caso di amartoma polmonare. Arch.Radiol. (Napoli), n.s. 4, 355.

Willis, R. A (1958). The Borderland of Embryology and Pathology.Butterworth, London.

Wolman, 1. J. (1930). A case of congenital cystic lung in a stillbornfetus. Bull. Ayer. clin. Lab., 2, No. 12, p. 49.

by copyright. on N

ovember 29, 2021 by guest. P

rotectedhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.35.183.475 on 1 O

ctober 1960. Dow

nloaded from