congenital pulmonary airway malformation

Digital cases (Digital slides)

 HPC:104 : CPAM type 2
 HPC:370 : Cystic congenital adenomatoid malformation in extrapulmonary sequestration.
 JRC:6291 : Lung cystic adenomatoid transformation.
 JRC:6292 : Lung cystic adenomatoid transformation.
 JRC:6298 : Lung cystic adenomatoid transformation.

Definition: CPAM is a hamartomatous lesion of the lung, with an incidence of about 1 in 5,000 live births, that can be separated into five major types based on clinical and pathologic fea-tures.

it has been proposed that the former designation of this lesion as “CCAM” be changed to “CPAM” to reflect the fact that the lesions as described below are “cystic” in only three of the five types and “adenomatoid” in only one type (type 3).

CPAM more accurately encompasses all five types in this classification.

Epidemiology

 25% of all congenital lung lesions
 4-26% of cases can be associated with other congenital abnormalities.
 estimated incidence: 1 case per 25,000-35,000 pregnancies.

Subtypes

 CPAM type O - CCAM type O (acinar dysplasia)
 CPAM type 1 - CCAM type 1 (bronchial/bronchiolar)
 CPAM type 2 - CCAM type 2 (bronchiolar)
 CPAM type 3 - CCAM type 3 (bronchiolar/alveolar duct)
 CPAM type 4 - CCAM type 4 (peripheral)
 CPAM type 5 - CCAM type 5

CCAM type 0 (congenital acinar dysplasia, congenital acinar aplasia) (1-3%) (neonates, other malformations, poor prognosis)

 solid appearance
 small and firm lungs
 bronchial-type airways with cartilage, smooth muscle and glands separated by abundant mesenchymal tissue

CCAM type 1 (60-70%) (bronchial) (neonates and infants, resectable, good prognosis, possible carcinomatous change)

 1 or more large cysts measuring 2-10 cm in diameter. Larger cysts are often accompanied by smaller cysts, and their walls contain muscle, elastic, or fibrous tissue.
 cartilaginous plates (12%) (12883247)
 Cysts are frequently lined by pseudostratified columnar epithelial cells often interspersed with rows of mucous cells
 focal mucous cell hyperplasia (12 to 25% of type 1 CCAM)
 microscopic foci of bronchioloalveolar carcinoma (1 to 31% of type 1 CCAM) (12883247)

CCAM type 2 (10-15%) (bronchial/bronchiolar) (neonates, other malformation, poor prognosis)

 sponge-like appearance
 multiple small cysts (0.5 to 2 cm)
 small relatively uniform cysts resembling bronchioles separated by normal alveoli
 cysts are lined by cuboid-to-columnar epithelium and have a thin fibromuscular wall.
 solid pale tumor-like tissue
 striated muscle in 5%

CCAM type 3 (5%) (bronchiolar) (neonates, poor prognosis)

 solid appearance
 excess of bronchiolar structure separated by small air spaces, with cuboidal lining, resembling late fetal lung
 grossly a solid mass without obvious cyst formation
 microscopic adenomatoid cysts

CCAM type 4 (28%) (peripheral) (neonates and infants, good prognosis)

 large cysts (up to 10 cm)
 cysts lined by a flattened epithelium (type 1 and 2 pneumocytes) resting on loose mesenchymal tissue
 focal stromal hypercellularity (50%) (12883247)
 focal immature cartilage (12883247)
 associated pleuropulmonary blastoma (bilateral type 4 CCAM with stromal cellularity) (14%) (12883247)

Associations (mostly with type 2)

Anomalies are noted in 15% to 20% of all cases of CPAM, particularly in association with the type 2 lesion.

CPAM is a unilateral lesion in about 95% of cases and involves a single lobe in 80% to 90% of cases.

The right and left sides of the lung are nearly equally involved, with the lower lobes affected in about 60% of cases.

Type 2 CPAM has been noted in nearly 50% of cases of extralobar sequestrations.

An association of CPAM with the later development of a bronchioloalveolar carcinoma has been established.

Variants of CPAM exist as unique entities or are the result of alteration by associated anomalies.

Fisher et al. described a type 1 CPAM with large cysts filled with large papillary projections that consisted of delicately branching fibrovascular stalks covered with cuboidal to columnar epithelial cells.

 pulmonary malformations

• extralobar sequestration (CCAM type 2 and CCAM type 3) with systemic arterial supply
• controlateral extralobar pulmonary sequestration (15300558)
• bronchial atresia (7298053)
• polyalveolar lobe

 epithelial hyperplasias

• atypical goblet cell hyperplasia
• nonmucinous atypical adenomatous hyperplasia
• focal mucous cell hyperplasia (25% of type 1 CCAM)

 renal malformations

• cystic renal disease
• ipsilateral multicystic renal dysplasia (15630540)
• bilateral renal agenesis
• contralateral renal agenesis (15630540)

 ovarian germ cell hypoplasia (15630540)

 malignant tumors

• pleuropulmonary blastoma (bilateral type 4 CCAM with stromal cellularity) (14%) (12883247)
• rhabdomyosarcoma (16007610, 11431779, 9314270)
• malignant mesenchyma
• bronchioloalveolar carcinoma (31% of type 1 CCAM) (12883247, 9475333)
• atypical goblet cell hyperplasia ((15138930)

 chromosomal anomalies

• trisomy 13 (12673637)
• trisomy 18 (11173951)
• chromosme 18 rearrangement (partial deletion of 18p and partial duplication of 18q) (11173951)

 miscellaneous

• aneurysm of the vein of Galen (15022074)
• sirenomelia
• intestinal atresia
• skeletal malformations
• cleft palate
• hydranencephaly
• hydrocephalus
• diaphragmatic hernia
• Bilateral renal agenesis/dysgenesis
• Extralobar pulmonary sequestration
• Cardiovascular malformation
• Diaphragmatic hernia
• Hydrocephalus and macrocephaly
• MyelomeningoceleJejunal atresia
• Prune-belly syndrome
• Sirenomelia
• Bilateral nephromegaly
• Pierre Robin syndrome
• Pulmonary hypoplasia
• Skeletal malformation
• Bile duct hypoplasia
• Left heart hypoplasia
• Polycytosis of a solitary medial kidney

Differential diagnosis

 stromal cellularity in a type 4 CCAM should raise the possibility of blastomatous transformation.

See also

 congenital pulmonary cysts
 pulmonary malformative cysts
 pulmonary cystic malformations
 pulmonary cyst lesions

References

 Riedlinger WF, Vargas SO, Jennings RW, Estroff JA, Barnewolt CE, Lillehei CW, Wilson JM, Colin AA, Reid LM, Kozakewich HP. Bronchial atresia is common to extralobar sequestration, intralobar sequestration, congenital cystic adenomatoid malformation, and lobar emphysema. Pediatr Dev Pathol. 2006 Sep-Oct;9(5):361-73. PMID: 16953677

 Vargas SO, Korpershoek E, Kozakewich HP, de Krijger RR, Fletcher JA, Perez-Atayde AR. Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation: insights into its relationship with pleuropulmonary blastoma. Pediatr Dev Pathol. 2006 May-Jun;9(3):190-5. PMID: 16944975

 Wilson RD, Hedrick HL, Liechty KW, Flake AW, Johnson MP, Bebbington M, Adzick NS. Cystic adenomatoid malformation of the lung: Review of genetics, prenatal diagnosis, and in utero treatment. Am J Med Genet A. 2006 Jan 15;140(2):151-5. PMID: 16353256

 MacSweeney F, Papagiannopoulos K, Goldstraw P, Sheppard MN, Corrin B, Nicholson AG. An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol. 2003 Aug;27(8):1139-46. PMID: 12883247

 Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol. 1977 Mar;8(2):155-71. PMID: 856714

 Cha I, Adzick NS, Harrison MR, Finkbeiner WE. Fetal congenital cystic adenomatoid malformations of the lung: a clinicopathologic study of eleven cases. Am J Surg Pathol. 1997 May;21(5):537-44. PMID: 9158677

 Cangiarella J, Greco MA, Askin F, et al. 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; 8:913-8.