DISTINCTIVE ULTRASTRUCTURAL PATHOLOGY OF NONULCERATIVE INTERSTITIAL CYSTITIS - NEW OBSERVATIONS AND THEIR POTENTIAL SIGNIFICANCE IN PATHOGENESIS

Ultrastructural study of the bladder in interstitial cystitis has, so far, been limited, mainly to the urothelium. The present study was con ducted first to study in detail the ultrastructural features of all ti ssue components of the bladder wall in nonulcerative interstitial cyst itis and second to derive clues from the observed changes to pathogene sis of the disease. Endoscopic biopsies of urothelium with attached su burothelium, and muscularis, were obtained from both lesional and nonl esional areas in 5 female patients with unequivocal clinical diagnosis of interstitial cystitis. The specimens were processed for electron m icroscopic study by standard methods and subjected to comprehensive ul trastructural study of urothelium, suburothelium, detrusor muscle cell s, intrinsic blood vessels, and intrinsic nerves. A distinctive combin ation of peculiar muscle cell profiles, injury of intrinsic vessels an d nerves in muscularis and suburothelium, and discohesive urothelium w as observed in lesional and less markedly in nonlesional samples of al l specimens. Marked edema of various tissue elements and cells appeare d to be a common denominator of many observed changes. Edema of muscle cells resulted in characteristic querciphylloid profiles, so designat ed because of peripheral bosselation of cell sarcoplasm with a lobed p erimeter resembling that of an oak leaf Urothelial changes disrupted t he true permeability barrier, consisting of asymmetric unit membrane a nd triple epithelial junctions of surface (umbrella) cells. Vascular l esions included endothelial cell injury and suggested sluggishness of intrinsic microcirculation. Neural changes included a combination of d egenerative and regenerative features, some expressing neural plastici ty. The observed ultrastructural changes appear to be sufficiently dis tinctive to be diagnostic in specimens submitted for pathologic confir mation of nonulcerative interstitial cystitis. The changes do not supp ort a primary pathogenetic role of mast cells or a selectively deficie nt glycosaminoglycan layer. They do suggest, however, a pathogenesis b ased on a potentially self-perpetuating process of neurogenic inflamma tion that can trigger a biologically potent cascade of events, includi ng a leaky urothelium and mast cell activation. As proposed, neurogeni c inflammation consolidates various proposals advanced as the pathogen esis of interstitial cystitis and can readily accommodate infectious, immunologic, and autoimmunologic mechanisms as factors that contribute to development or chronicity of the disease.