Decreased Interstitial Cells of Cajal-like Cells, Possible Cause of Congenital Refluxing Megaureters: Histopathologic Differences in Refluxing and Obstructive Megaureters

Objectives: To evaluate the location of interstitial cells of Cajal-like cells and the ureteral aspect using histopathologic studies of obstructive and refluxing megaureters to reveal the different pathogenesis of megaureters in the human urinary tract. The underlying pathophysiology of obstructive megaureter and refluxing megaureter is poorly understood. Methods: The data from 14 patients with obstructive megaureter (7 boys and 7 girls), with a mean age of 12 months (range 2-84), and 9 patients with refluxing megaureter (7 boys and 2 girls), with a mean age of 11 months (range 4-24), were compared. We investigated the difference in the histopathologic aspects using Masson's trichrome, terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (for apoptosis), and human c-kit antibody (CD117 for interstitial cells of Cajal-like cells) between the obstructive and refluxing megaureters. Results: The proportion of smooth muscle was significantly lower in segments of refluxing megaureter (32.04% ± 4.96%) than in the segments of obstructive megaureter (52.48% ± 3.46%; P < .01). The number of apoptotic cells was significantly increased in the obstructive megaureter (mean 1661 ± 135.1 cells) compared with the refluxing megaureter (mean 375.2 ± 65.14 cells; P < .0001). The number of c-kit positive cells was significantly lower in the refluxing megaureter (mean 83.60 ± 48.84 cells) than in the obstructive megaureter (mean 463.6 ± 100.4 cells; P < .05). Conclusions: The differences in the histopathologic aspects can provide information on the possible pathophysiology of obstructive and refluxing megaureters. Ureteral peristalsis can be affected by the increased myocyte apoptosis in the obstructive megaureter and by the decreased number of interstitial cells of Cajal-like cells and smooth muscle content in refluxing megaureters. Additional research is warranted to elucidate the exact pathophysiology.