Figure 1. Gross Appearance
This image from another patient shows multiple cystic spaces up to 3 cm occupying the whole lobe.
The pulmonary artery supplied the lesion.
Find the undulating cartilage plates lining the cyst at the top.
Find the small central bronchus.
Find a collection of alveolar structures.
Find a normal membranous bronchiole.
Find a pulmonary artery.
At the left and blending in without a capsule, back-to-back cystic spaces and dilated alveolar structures form the lesion. Collateral ventilation via pores of Kohn can occur from the normal lung.
What is the diagnosis? Answer
Scroll down after answering the questions.
Congenital Pulmonary Airway Malformation (CPAM) (formerly, congenital cystic adenomatoid malformation, CCAM)
Definition: CPAM refers to architecturally abnormal pulmonary tissue with or without cyst formation. CPAMs are malformations of lung parenchyma involving airway branching, epithelial maturation, and vessel development . Absence of a bronchial connection has been described in some of the lesions: collateral ventilation occurs via surrounding normal lung, giving rise to air trapping and expansion of the lesion after birth [2,3]. Vascular supply is via the pulmonary artery and vein . The new name reflects the fact that not all lesions are cystic or have adenomatoid (glandular) features .
Classification: CPAMs have been classified into 5 types, based on resemblance to different levels of normal airway structures from bronchi (type 0) to alveoli (type 5) . Only types 1-3 are discussed here.
Clinical Presentation: CPAMs may be diagnosed in utero, occasionally being detected incidentally on routine prenatal screening sonography. In such cases, serial sonograms may show regression of the lesion. CPAMs in the neonatal period present with worsening respiratory difficulty. Patients with CPAMs beyond the age of 1 month may present with cough and fever, reflecting infection.
In a series of 47 CPAMs diagnosed in utero, 42% occurred in the lower lobes, and the others occurred in upper or middle lobes or, rarely, some combination. Lesions were present in the right lung more frequently than the left, 2.4:1. Macrocystic CPAMs predominated over solid forms, 1.4:1 .
In a review of the literature, males and females were equally represented. Lower lobe lesions predominated (44%) with the rest scattered in other lobes . Stillborns comprised 14% (n=120); infants from birth to 1 mo, 62%; those from 1 mo to 2 y 11%; and children 2 to 14 y (13%) of the cases. In contrast to the fetuses reviewed by Adzick , et al, lesions predominated on the left, 1.4:1. After birth, patients presented with respiratory distress (68%) or signs of infection (16%) . However, a diagnosis of CPAM should not be made in the presence of chronic inflammation, which may mimic the histologic changes of CPAM .
Imaging Manifestations of CPAMs: Chest radiographs in patients with CPAMs, regardless of the presence or absence of cystic components, show mass effect within the affected hemithorax, producing shift of the cardiomediastinal structures to the contralateral side. Radiographs taken shortly after birth, before appreciable air accumulates within the cysts, may show a unilateral soft-tissue opacity associated with mediastinal shift. CPAMs often become air-filled within a few days after birth, and chest radiographs may then show a cystic mass producing contralateral cardiomediastinal shift. Air-fluid levels may occasionally be encountered .
Thoracic CT is more effective than chest radiography in demonstrating the morphology of CPAMs. Thoracic CT in patients with cystic CPAMs shows multiple, variably-sized, thin-walled cysts associated with areas of pulmonary hyperlucency that displace the pulmonary vasculature and interlobar fissures. Areas of disorganized pulmonary parenchyma may also be encountered .
Lucent and Solid Lesions: Occasionally, one cyst may be dominant, and CPAM may then present as an entirely lucent lesion. Completely solid lesions with little accumulated air present as a soft tissue mass within the chest. CPAMs show a slight upper lobe predominance; 15% may show multilobar involvement. Most CPAMs derive their blood supply via the pulmonary circulation, and this feature allows cross-sectional imaging to distinguish CPAMs from sequestrations. In adults, CPAMs may present as solid and/or thin-walled cystic lesions .
Prenatal sonography: CPAMs often present as echogenic masses on sonography. Occasionally multiple small cysts or a single dominant cyst may be encountered. Lesions with a dominant cyst may be drained in utero via thoracostomy tube, whereas large lesions without a dominant cyst may require fetal surgery to prevent fetal hydrops (pleural effusion, ascites, skin thickening), which can also be diagnosed by sonography .
In the prenatal period, sonography and, more recently, MRI are very useful for detecting thoracic mass lesions and for distinguishing among the various causes of such lesions. Fetal MRI is increasingly used to characterize masses discovered on prenatal sonography or for potential fetal lesions in a complicated pregnancy. MRI may effectively show feeding vasculature in a pulmonary sequestration or liver or stomach within the chest in patients with congenital diaphragmatic hernia.
Postnatally, thoracic CT is most commonly used to detect and diagnose neonatal thoracic mass lesions. Diaphragmatic hernias will show viscera within the thorax. Sequestrations (see below) present as mass lesions within the thorax.
Histology: Lesions are not encapsulated and occupy part or all of a lobe. Type 1 lesions have large, intercommunicating, back-to-back cystic spaces lined by pseudostratified, ciliated, columnar epithelium, as well as smaller cystic spaces lined by ciliated columnar to cuboid (bronchiolar) epithelium. Smooth muscle without glands surrounds these structures. Sometimes, portions of cartilage may be found. Almost half of cases contain proliferations of tall-columnar, mucinous cells resembling pyloric mucinous epithelium . Type 2 lesions have smaller back-to-back cystic spaces lined by bronchiolar epithelium and surrounded by smooth muscle. Cartilage and glands are absent, but occasionally, random bundles of skeletal muscle may be present in the interstitium. Dilated alveolar ducts and alveolar spaces lined by flat epithelium are present in both types 1 and 2. Type 3 lesions are composed of microscopic cystic spaces lined by ciliated, columnar epithelium and alveolar spaces lined by cuboid cells resembling those present in the pseudoglandular stage of early fetal development . For classification purposes, the presence or absence of a connection to the normal tracheobronchial tree and the type of blood supply should be determined.
Differential diagnosis: The major diagnoses to be considered include infantile lobar hyperinflation (overinflation of an entire lobe caused by intrinsic or extrinsic narrowing of the bronchus); congenital segmental bronchial atresia; previous infection with cysts and chronic inflammation, which mimic CPAM; and sequestration. Segmental bronchial atresia usually occurs in an upper lobe and has a proximal mucocele at the site of the atresia. The normal-appearing distal lung is overinflated . Sequestrations are characterized by a systemic blood supply and absent bronchial connection. Histologic features of CPAMs are sometimes found in sequestrations [4,12].
Natural history and treatment of CPAMs: In utero, large masses, often of the solid variety (type 3) of CPAM, are likely to be associated with mediastinal shift, lung hypoplasia, polyhydramnios, and fetal hydrops. On serial ultrasound examinations, some large lesions, especially the cystic ones, partially regress, and hydrops can disappear spontaneously [8,13]. In some cases, in utero placement of a thoracoamniotic catheter shunt to drain cystic structures or, alternatively, fetal lobectomy has been performed with survival of the infant . If hydrops and severe extrapulmonary malformations are absent, symptomatic newborn infants usually survive early neonatal surgery . In one report, 3 fetuses with CPAM and hydrops showed resolution of the hydrops after prenatal steroid therapy . Surgical resection is advised in asymptomatic patients to prevent infection and to permit normal lung growth .
Associations: Besides in utero complications, and postnatal infection, CPAMs have been associated with the rare development of neoplasms (see above for Type 4 CPAM). Mucinous bronchioloalveolar carcinoma (BAC) has been described adjacent to type 1 CPAMs or may develop years after removal of the lesion. However, recurrence after removal of the tumor is rare [4,7]. The mucinous cells have immunohistochemical staining resembling both ordinary mucinous BACs of the lung and gastric pyloric glands . Type 2 CPAMs are associated with other congenital anomalies more frequently than are the other types.
Pathogenesis: Immunohistochemical tests have shown that thyroid transcription factor (one factor that regulates lung development) shows a bronchiolar epithelial distribution in CPAMs 1-3 similar to that of fetal lung in the early pseudoglandular stage, and it has been proposed that CPAMs develop because of hyperplasia of bronchiolar cells arrested at this stage of development [1,15]. Lesions may enlarge after birth as collateral ventilation and air trapping occur .
Final diagnosis: Congenital pulmonary airway malformation, Type 1.
References: To return to reference section after viewing abstract, click here before clicking on "abstract".
1. Cangiarella J, Greco M, Askin F, Perlman E, Goswami S, Jagirdar J. 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. Mod Pathol 1995; 8:913-918. Abstract
2. Moerman P, Fryns J, Vandenberghe K, Devlieger H, Lauweryns J. Pathogenesis of congenital cystic adenomatoid malformation of the lung. Histopathology 1992; 21:315-321. Abstract
3. Miller R, Sieber W, Yunis E. Congenital adenomatoid malformation of the lung. A report of 17 cases and review of the literature. Pathol Annu 1980; 15 (Pt 1):387-407.
4. Stocker J. Congenital pulmonary airway malformation--a new name for and an expanded classificaton of congenital cystic adenomatoid malformation of the lung. Histopathology 2002; 41 (Suppl 2):424-431.
5. Davidson L, Batman P, Fagan D. Congenital acinar dysplasia: a rare cause of pulmonary hypoplasia. Histopathology 1998; 32:57-59. Abstract
6. Ota H, Langston C, Honda T, Katsuyama T, Genta R. Histochemical analysis of mucous cells of congenital adenomatoid malformation of the lung. Insights into the carcinogenesis of pulmonary adenocarcinoma expressing gastric mucins. Am J Clin Pathol 1998; 110:450-455. Abstract
7. MacSweeney F, Papagiannopoulos K, Goldstraw P, Sheppard M, Corrin B, Nicholson A. An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol 2003; 27:1139-1146. Abstract
8. Adzick N, Harrison M. Management of the fetus with a cystic adenomatoid malformation. World J Surg 1993; 17:342-349. Abstract
9. Kim W, Lee K, Kim I, Suh Y, Im J, Yeon K, Chi J, et al. Congenital cystic adenomatoid malformation of the lung: CT-pathologic correlation. AJR 1997; 168:47-53. Abstract
10. Hulnick D, Naidich D, McCauley D, Feiner H, Avitabile A, Greco M, Genieser N. Late presentation of congenital cystic adenomatoid malformation of the lung. Radiology 1984;151:569-573. Abstract
11. Jederlinic P, Sicilian L, Baigelman W, Gaensler E. Congenital bronchial atresia. A report of 4 cases and a review of the literature. Medicine 1986; 65:73-83.
12. Walford N, Htun K, Chen J, Liu Y, Teo H, Yeo G. Intralobar sequestration of the lung is a congenital anomaly: anatomopathological analysis of four cases diagnosed in fetal life. Pediatr Dev Pathol 2003. Abstract
13. MacGillivray T, Harrison M, Goldstein R, Adzick N. Disappearing fetal lung lesions. J Pediatr Surg 1993; 10:1321-1325. Abstract
14. Tsao K, Hawgood S, Vu L, Hirose S, Sydorak R, Albanese C, Farmer D, et al. Resolution of hydrops fetalis in congenital cystic adenomatoid malformation after prenatal steroid therapy. J Pediatr Surg 2003; 38:508-510. Abstract
15. Morotti R, Gutierrez M, Askin F, Profitt S, Wert S, Whitsett J, Greco M. Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of the lung. Pediatr Dev Pathol 2000; 3:455-461. Abstract
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Undulating cartilages in wall of cystic space
Small bronchus with normal-appearing cartilages in wall
Small group of alveoli
Normal membranous bronchiole
Normally-placed pulmonary artery
Congenital pulmonary airway malformation (CPAM), type 1