The Intravesical Ureter in Children With Vesicoureteral Reflux: A Morphological and Immunohistochemical Characterization

Abstract

We investigated intravesical ureteral endings using immunohistochemical methods to study general morphology, smooth muscle architecture and collagen composition in children with vesicoureteral reflux. Samples were obtained from 29 ureterorenal units in children with a mean age of 52.3 months undergoing reflux surgery. Routine histological paraffin embedded sections were stained with hematoxylin and eosin, and Masson trichrome to assess general morphology. Staining for actin, myosin and desmin was performed to evaluate the presence, allocation and architecture of the ureteral smooth muscle wrap. In addition, indirect immunohistochemical methods were used to study the collagen composition of the ureteral wall and CD68 was used for macrophage labeling as a marker of tissue remnant scavenging. All investigations were done using high power field magnification for quantification. In addition, age matched, nonrefluxing ureteral specimens served as controls. Smooth muscle alpha-actin, myosin and desmin expression were extensively decreased in all specimens pertaining to the ureteral ending. This distal part showed a high degree of muscle atrophy and degeneration as well as a disordered fiber arrangement associated with increased extracellular matrix collagen accumulation. In addition, CD68 positive macrophages were significantly increased. In contrast to these observations, the proximal intravesical portion of the ureter showed intact morphology and arrangement of the muscular coat. Refluxing intravesical ureteral endings showed dysplasia, atrophy and architectural derangement of smooth muscle fibers. Consequently symmetrical contraction of the distal ureteral smooth muscle coat creating the active valve mechanism to protect reflux is not achievable.