J Clin Pathol 1987;40:612-614

Epithelial hyperplasia and malignant change incongenital lung cysts

E A SHEFFIELD, B J ADDIS, B CORRIN, MARY M McCABE

From the Departments of Histopathology, Brompton Hospital, London, and St Vincent's Hospital, Dublin

SUMMARY Patients with congenital lung cysts are at increased risk of developing carcinoma, but themechanisms concerned are not clear. The case of a young adult who developed a bronchioloalveolarcarcinoma associated with a cystic congenital adenomatoid malformation is reported. The adjacentlung showed an unusual intra-alveolar hyperplasia ofmucous cells. Two further cases of congenitaladenomatoid malformation are also described; both patients presented in infancy and showedsimilar mucous cell hyperplasia in alveoli surrounding the cysts. In all three cases the stainingcharacteristic of the mucus was identical with that of normal bronchial mucous glands. It is sug-

gested that the benign proliferation represents a premalignant lesion. Its presence in infants showsthat it may occur at an early age and reinforces the need for early removal of congenital lung cysts.

A number of reports have described the developmentof malignancy in association with congenital lungcysts.I -'8 Adenocarcinoma is the most common typeof tumour, often of bronchioloalveolar pattem, butsquamous cell carcinoma has also been reported.7'8Squamous metaplasia of the lining epithelium of con-genital cysts has been implicated as the precursorlesion in the development of squamous cell carcinomain some cases,9 but the mechanisms implicated in thedevelopment of other tumour types are not clear.We describe two cases of congenital adenomatoid

malformation in children in which mucinous epi-thelium lining parts of the cysts showed hyperplasiaand intra-alveolar extension. These cases are com-pared with a case of bronchioloalveolar carcinoma inan adult associated with a long standing pulmonarycyst and similar mucous cell hyperplasia. We discussthe possible importance of this unusual hyperplasia.

Case reports

CASE 2A 3 year old girl presented with recurrent respiratoryinfections. A chest radiograph showed left sided pul-monary cysts and mediastinal compression. A leftlower lobectomy was performed. Multilocular cystsmeasuring up to 5 cm in diameter and communicatingwith the bronchi were present in the resected lobe.The remaining lung parenchyma was consolidated.

CASE 3An 18 year old male athlete presented with slight hae-moptysis and impairment of his exercise tolerance. Achest radiograph showed a left sided apical cyst,which was excised with a wedge of surrounding lung.Examination of the resected specimen showed a6-5 cm diameter cyst with a trabeculated inner sur-face; white nodules, measuring up to 04 cm indiameter, were found in the adjacent lung.

Material and methods

CASE 1During investigation for isolated pulmonary valvestenosis a 6 month old boy was found to have mul-tiple cysts within the right lower lobe, which com-pressed the mediastinum. A right lower lobectomywas performed. Examination of the resected lobeshowed that it was largely replaced by multiloculatedcysts, measuring from 0 5 to 4cm in diameter, whichcommunicated with the bronchi. There was a thinperipheral rim of unaffected lung.

Accepted br publication 22 December 1986

All the specimens were fixed in formalin, those fromcases 1 and 2 being inflated through the lobar bron-chus. Representative blocks were taken from thespecimens, and sections were stained by haematoxylinand eosin and elastic van Gieson. Mucin wasidentified by periodic acid Schiff and alcian blue highiron diamine stains.

Histological findings

CASES I AND 2The walls of the cysts were formed by smooth muscle

612

copyright. on S

eptember 8, 2021 by guest. P

rotected byhttp://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.40.6.612 on 1 June 1987. Dow

nloaded from

Epithelial hyperplasia and malignant change in congenital lung cysts

and elastic tissue, generally lined by bronchiolar typepseudostratified ciliated columnar and cuboidal epi-thelium. Direct communication with bronchioles andalveolar ducts was shown, the number of bronchiolesappearing to be increased. Cartilage was not presentin the cyst walls.

In both cases tufts ofmucous cells lined parts of thecysts and extended outside the cysts to line adjacentalveoli (figs 1 and 2). Mucin stains showed that thebronchiolar type epithelium lining much of the cystsincluded some goblet cells containing sialomucin. Thepapillary tufts and intra-alveolar collections ofmucous cells contained moderate amounts of bothsialomucin and sulphomucin.

CASE 3The cyst was lined by bronchiolar type epitheliumwith occasional mucous cell tufts similar to those seenin cases 1 and 2. Adjacent to the cyst there were col-lections of benign hyperplastic intra-alveolar mucouscells with small regular basal nuclei and a prominent

Fig 3 Case 3: benign mucous cells lining alveolarepithelium. (Haematoxylin and eosin.)

Fig 4 Case 3: close association exists between tumour (left)and benign hyperplastic mucous cells. (Haematoxylin andeosin.)

,_ ,;^YL'. R B-

Fig I Case 2: tufts ofmucous cells can be seen withinalveolar spaces some distancefrom cyst. Note bronchiolartype ofepithelium lining cyst. (Haematoxylin and eosin.)

*-g ;>-|(' "O>ej' t- ,_ s

Fig 5 Case 3: bronchioloalveolar carcinoma; tumour cellsreplace alveolar epithelium. (Haematoxylin and eosin.)

Fig 2 Case 1: higher magnification showing nests ofcolumnar mucous cellsfilling alveoli. (Haematoxylin andeosin.)

pale cytoplasm. These contained large amounts ofsialomucin and small amounts of sulphomucin (figs 3and 4). Similar mucin was identified in the mucouscells in the cyst.

In addition, an adenocarcinoma of bronchiolo-alveolar type with a multifocal distribution was foundin the lung surrounding the cyst (figs 4 and 5).

613

copyright. on S

eptember 8, 2021 by guest. P

rotected byhttp://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.40.6.612 on 1 June 1987. Dow

nloaded from

614 Sheffield, Addis, Corrin, McCabeTumour cells were columnar with large uniformhyperchromatic basal nuclei and eosinophilic cyto-plasm. Mucin stains showed small amounts of intra-cellular sialomucin close to the apical surface.

Discussion

Congenital cystic adenomatoid malformation isthought to edult from failure of proximal airways tocommunicate normally with alveoli.10 Three typeshave been described.1' The three cases described hereconform to the definition of cystic adenomatoid mal-formation type I. Type II consists of multiple smallcysts lined b'y bronchiolar epithelium and interspersedwith relatively normal alveolar structures. Type IIIappears solid owing to a complex of non-aeratedflattened bronchiole like structures- Types II and IIIare usually associated with respiratory distress at orsoon after birth.The main features of cystic adenomatoid mal-

formation type I are the presence of single or multiplecysts and bronchiole like structures lined by pseudo-stratified ciliated columnar and cuboidal epitheliuminterspersed by rows of goblet cells.'2-6 Hyper-plastic smooth muscle may be present in the cyst wall,but cartilage and inflammatory changes are absent.There may be other associated congenital abnormal-ities, as in our first patient, who also had pulmonarystenosis. Although most patients present in infancy,in some cases symptoms become apparent only inlater life.'7

In case 3 the cyst appeared to be long standing andthe appearances did not suggest cystic change in acarcinoma.'8 '9 The mucous cells seen in cysticadenomatoid malformation are similar to those ofnormal bronchial glands and surface epithelium20;our mucin studies confirm this similarity. The mucouscells may have either a metaplastic or hamartomatousorigin.21 Our cases are unusual in that the mucouscells extended beyond the cysts to line adjacent alve-oli. In cases 1 and 2 the hyperplasia was similar tothat in case 3 but less florid. The intra-alveolar spreadhad a pattern similar to bronchioloalveolar car-cinoma, but the malignant component could be dis-tinguished from the hyperplasia morphologically andby mucin staining.The implication of this finding is that the adeno-

matous component seen in case 3 represents a pre-malignant lesion. The presence of similar, thoughmuch less florid, hyperplasia in the other cases sug-gests that this change may begin at an early age. Wehave recently noted extensive areas of squamousepithelium in ,.iother case of Qystic adenomatoidmalformation iype I, showing that other forms ofmetaplasia can occur in these cysts and supportingthe suggestion that it represents a possible origin for

squamous cell carcinoma.9 These observations sug-gest that cystic adenomatoid malformation carries arisk of malignant change and that early removal ofsuch lesions is advisable.

We thank Mr P Goldstraw, Mr JCR Lincoln, Mr VLynch, and Professor MX Fitzgerald for permissionto publish clinical details of these patients andRhodabe Khambatta for typing the manuscript.

References

1 Bauer S. Carcinoma arising in a congenital lung cyst. Diseases ofthe Chest 1961;40:552-5.

2 Korol E. The correlation of carcinoma and congenital cysticemphysema of the lungs. Report of ten cases. Diseases of theChest 1953;23:403-1 1.

3 Huntington HW, Poppe JK, Goodman MJ. Carcinoma arising ina congenital cyst of the lung. Report of a case. Diseases of theChest 1963;44:329-32.

4 Larkin JC, Phillips S. Carcinoma complicating cyst of lung.Diseases of the Chest 1955;27:453-7.

5 Bass HE, Singer E. Co-existing lobar adenocarcinoma and cysticdisease of the lung. Ann Intern Med 1951;34:498-507.

6 Moersch HJ, Clagett OT. Pulmonary cysts. Journal of ThorackSurgery 1947;16: 179-94.

7 Hurley P, Corbishley C, Pepper J. Bronchioloalveolar carcinomaarising in longstanding lung cysts. Thorax 1985;40:960.

8 Prichard MG, Brown PJE, Sterrett GF. Bronchioloalveolar car-cinoma arising in longstanding lung cysts. Thorax 1984;39:545-9.

9 Womack NA, Graham EA. Epithelial metaplasia in congenitalcystic disease of the lung. Am J Pathol 1941;17:645-53.

10 Spencer H. Pathology of the lung. 4th ed. London: PergamonPress, 1985:79-130.

11 Stocker JT, Madewell JE, Drake RM, Congenital cystic adeno-matoid malformation of the lung. Classification and morpho-logic spectrum. Hum Pathol 1977;8:155-71.

12 Landing BH, Dixon LG. Congenital malformations and geneticdisorders of the respiratory tract. (Larynx, trachea, bronchiand lungs). Am Rev Resp Dis 1979;120:151-80.

13 Belanger R, La Fleche LR, Picard J-L. Congenital cystic ade-nomatoid malformation of the lung. Thorax 1964;19:1-1 1.

14 Kwittken J, Reiner L. Congenital cystic adenomatoid mal-formation of the lung. Pediatrics 1962;30:759-68.

15 Moncrieff MW, Cameron AH, Astley R, Roberts KD, AbramsLD, Mann JR. Congenital cystic adenomatoid malformationof the lung. Thorax 1969;24:476-87.

16 Miller RK, Sieber WK, Yunis EJ. Congenital adenomatoid mal-formation of the lung. A report of 17 cases and review of theliterature. Pathol Annu 1980;15:387-407.

17 Avitabile AM, Hulnick DH, Greco MA, Feiner HD. Congenitalcystic adenomatoid malformation of the lung in adults. Am JSurg Pathol 1984;8:193-202.

18 Anderson HJ, Pierce JW. Carcinoma of the bronchus presentingas thin-walled cysts. Thorax 1954;9:100-5.

19 Peabody JW, Rupnik EJ, Hanner JM. Bronchial carcinoma mas-querading as a thin-walled cyst. American Journal of Roent-genology 1957;77: 1051-4.

20 Lamb D, Reid L. Histochemical types of acidic glycoprotein pro-duced by mucous cells of the tracheobronchial glands in man.J Pathol 1969;98:213-28.

21 Daroca PJ. Mucogenic cells of congenital adenomatoid mal-formation of lung. Arch Pathol Lab Med 1979;103:258-60.

Requests for reprints to: Dr BJ Addis, Department of Histo-pathology, Brompton Hospital, Fulham Road, LondonSW3 6HP, England.

copyright. on S

eptember 8, 2021 by guest. P

rotected byhttp://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.40.6.612 on 1 June 1987. Dow

nloaded from