Fetal Pulmonary Malformations: Defining Histopathology

Abstract

Although classification schemes have sought to categorize congenital cystic lung malformations, studies including the pathology of pulmonary malformations occurring specifically during the fetal period are limited. To better characterize such histopathology, we reviewed a total of 23 fetal lung malformations seen at the Children's Hospital of Philadelphia from 1996 to 2004. Twenty-one of the 23 fetal pulmonary malformations could be categorized into 1 of 3 groups based upon the predominant histologic features present within each lesion. Group 1 (9/21) demonstrated tubular airspaces lined by columnar epithelium. Group 2 (6/21) contained airspaces lined by cuboidal epithelium and surrounded by smooth muscle with abundant interstitial mesenchyme. Group 3 (6/21) showed a mixture of relatively mature-appearing airspaces lined by flattened epithelium and scattered dilated bronchiole-like structures. Cysts were of variable size but in all cases showed a respiratory-type lining. Gestational ages ranged from 21 5/7 to 38 2/7 weeks. Patients in groups 1 and 2 were generally younger than those in group 3; however, morphology did not seem to correlate entirely with normal stages of fetal lung development, and group 2 lesions in particular were the least akin to normal fetal lung. In 4 cases a systemic vascular supply to a lobe of lung was identified, providing evidence that such vasculature is embryonic in origin. The histopathology of fetal lung malformations highlights the variability seen in such lesions at all ages, and it is hoped that continued investigations will provide further insight into these enigmatic lesions.

Congenital cystic lung disease: contemporary antenatal and postnatal management

“…Based on a study of 11 fetal resections (gestational ages 21-27 weeks), Cha and colleagues [39] identified two primary patterns: pseudoglandular and canalicular. More recently, results of a study reported by Kreiger et al [34] described 23 resected fetal CCAMs (gestational ages ranging from approximately 21-38 weeks) indicated three groups, based upon the predominant histologic features seen within the parenchyma between cysts. Group 1 lesions contained tubular airspaces lined by columnar epithelium.…”

“…Also, Stocker later proposed that the designation of CCAM be changed to CPAM to reflect the fact that lesions are cystic in only three of the five types and adenomatoid in only one type (type 3) [18]. Important to note, reported descriptions of Stocker's classifications vary in the literature, as does the reported prevalence of CPAM subtypes [2,5,18,30,34]. Moreover, it appears that the expanded classification and nomenclature have not yet been widely adopted by pediatric surgeons.…”

“…Technologic advances in antenatal ultrasonography (US) and the advent of fetal surgery have enabled histologic investigations of antenatally resected specimens [34,39]. These studies have shown that the Stocker classification has limited applicability to pulmonary lesions resected during fetal life.…”

A Novel In Vitro Model to Study Alveologenesis

“…These diseases include bronchopulmonary dysplasia, congenital pulmonary airway malformations, and the lung hypoplasia associated with congenital diaphragmatic hernia (1)(2)(3). Nevertheless, there is a deficit of model systems that can be used to examine mechanisms that control this last stage of lung development.…”

Laser microdissection allows detection of abnormal gene expression in cystic adenomatoid malformation of the lung

“…Microarray is relatively insensitive to subtle differences in expression compared with reverse transcriptase polymerase chain reaction (RT-PCR) and can produce bias through nonlinear amplification of RNA. In addition, tissue heterogeneity is a confounding factor in the study of CCAM, and histology is highly variable from lesion to lesion [11]. Therefore, we used laser capture microdissection (LMD) to isolate the predominant epithelium in CCAM specimens, as well as its underlying mesenchyme, and performed careful analysis of gene expression on those cells.…”