Pathological changes in ureterovesical and ureteropelvic junction obstruction explained by fetal ureter histology

The etiology of ureterovesical junction obstruction (UVJO) and ureteropelvic junction obstruction (UPJO) is obscure with an adynamic narrow segment causing the obstruction. In this study, the authors compared interstitial cells of Cajal (ICC) and collagen-to-muscle ratio (CM ratio) between UVJO, UPJO, and fetal ureters to investigate whether a maturational arrest of the fetal ureter could explain both clinical pathologies.

Group 1 (control) involved specimens of the normal ureter (nephrectomy for trauma/tumor; n = 20), while group 2, specimens of UVJO (n = 14); group 2 was further divided into group 2a, the dilated megaureter above UVJO, and group 2b, UVJO narrow segment; group 3, UPJO narrow segment excised during pyeloplasty (n = 31); and group 4, normal fetal ureters (n = 12). The specimens were analyzed for ICC using immunohistochemistry and CM ratio on Masson's trichrome (stains collagen in blue and muscle in red).

The median ICC/10 high-power field was 16.1 (8.3) in the normal and 17.3 (7.9) in the dilated segment of the megaureter, with no significant difference, but was significantly less in the narrow segment of UVJO at 4.5 (2.0), narrow segment of UPJO at 5.1 (2.3), and fetal ureter at 5.0 (2.3). The median CM ratio was 0.75 (0.29) in the normal and 0.65 (0.2) in the dilated segment of the megaureter, with no significant difference between them (figure), but was significantly higher in the narrow segment of UVJO at 3.0 (0.8), narrow segment of UPJO at 2.5 (0.71), and fetal ureter at 3.1 (0.61). Overall UVJO, UPJO, and fetal ureter segment had significantly less ICC density and more collagen compared with the normal ureter (P < 0.001 by Mann-Whitney U test).

There are conflicting reports on the etiopathogenesis of UVJO and UPJO, with several authors showing decreased ICC and increased collagen in the narrow segment. In this study, the authors found that the pathological changes at UVJ and UPJ segments resemble fetal ureter morphology. We also found that in fetal ureters, as the gestation progressed, there was an increase in the ICC density/smooth muscle, whereas the collagen content decreased. While the entire ureter has uniform embryological origin, it essentially remains an epithelial tube until the late gestation. The maturational process involves differentiation of smooth muscles cells/ICC to establish the peristaltic machinery required to functionally connect the ureter at both ends. This process, probably, starts at the mid ureter during fetal life and extends toward the UPJ and UVJ, and its failure, probably, results in UPJO or UVJO. The study's limitations are small numbers, and further larger studies are required to validate this hypothesis.