Cystitis Cystica and Cystitis Glandularis of the Urinary Bladder: A Review and Update

Cystitis glandularis is a proliferative disorder of the urinary bladder which has tended to be associated with glandular metaplasia of the transitional cells that line the urinary bladder. Cystitis glandularis tends to be closely related to cystitis cystica with which it commonly does exist. Cystitis cystica represents a proliferative or reactive changes which tend to occur within von Brunn nests which do acquire luminal spaces and become cystically dilated, and cystitis may undergo glandular metaplasia which does represent cystitis glandularis or the cystitis may undergo intestinal type of metaplasia which is referred to as intestinal type of cystitis. Cystitis cystica and cystitis glandularis is a very common incidental finding. Cystitis cystica and glandularis tend to develop I the setting of chronic irritation or inflammation of the urinary bladder mucosa. Cystitis cystica and glandularis tend to be frequently found in co-existence with interrelated lesions and they represent benign simulators of invasive carcinoma of the urinary bladder. With regard to mode of manifestation and diagnosis, cystitis cystica and cystitis glandularis tend to be diagnosed incidentally based upon: findings of urinary bladder lesions at cystoscopy undertaken for some other reason or upon incidental finding of a urinary bladder lesion following the undertaking of radiology imaging (ultra-sound scan, or computed tomography (CT) scan or magnetic resonance imaging (MRI) scan undertaken for something else. The patient may also manifest with lower urinary tract symptoms of urinary frequency, urgency, urge incontinence or poor flow of urine or difficulty in initiating urine. On rare occasions when the ureteric orifices are involved the patient may manifest with one sided loin pain or bilateral loin pain if both ureteric orifices are obstructed by the urinary bladder lesion. In severe cases of bilateral ureteric obstruction there may be evidence of impairment of renal function. Haematuria could also be a mode of presentation. Ultrasound scan of renal tract could demonstrate a polypoidal thickening of the wall of the urinary bladder usually in the trigone of the bladder but in extensive cases the thickening could be all over the urinary bladder and in cases where the ureteric orifices are obstructed there may be evidence of hydroureter and hydronephrosis. CT scan may show hyper-vascular polypoid mass within the urinary bladder, and MRI scan could demonstrate a hyperintense vascular core with encompassing low-intensity signal. These radiology imaging features are non-specific and would differentiate the urinary bladder lesion from invasive urothelial carcinoma. Diagnosis of the cystitis tends to be made based upon histopathology examination and immunohistochemistry staining studies of biopsy specimens or the trans-urethral resection specimens of the urinary bladder lesions. Microscopy pathology examination of the specimens tend to demonstrate: (a) abundant urothelial von Brunn nests which often tend to exhibit a vaguely lobular distribution of invaginations as well evidence of non-infiltrative growth as well as growth and variable connection to surface, (b) Gland-like lumina with columnar or cuboidal cells with regard to cases of cystitis glandularis, (c) Cystically dilated lumina or cystic cavities which are filled with eosinophilic fluid in the scenario of cystitis cystica, (d) Majority of cases of cystitis tend to demonstrate coexistence of both patterns, (e) Cells lack significant atypia, mitotic activity, stromal reaction and muscular invasion and degenerative atypia tends to be occasionally present. Immunofluorescence studies in cases of cystitis glandularis tend to demonstrate uniform membranous expression of beta catenin without cytoplasmic or nuclear localization. Cases of cystitis cystica and cystitis glandularis tend to exhibit positive immunohistochemistry staining for various markers as follows: GATA3, CK7, (full thickness), CK20 (umbrella cells), p63 (basal cell layer), uroplakin II/III, thrombomodulin, beta catenin, (membranous), and E-cadherin. Cases of cystitis cystica and cystitis glandularis tend to exhibit negative immunohistochemistry staining for the following immunohistochemistry staining agents: CDX2, Villin, MUC2, MUC5AC, and beta catenin, (nuclear). Some of the differential diagnoses of cystitis cystica and cystitis glandularis include: von Brunn nest hyperplasia, Urothelial carcinoma in situ, Inverted Urothelial papilloma, Nested variant of invasive urothelial carcinoma, and Microcystic variant of urothelial carcinoma. On rare occasions cystitis cystica and cystitis glandularis could be found contemporaneously in association with a urothelial carcinoma and hence every pathologist who examines specimens of cystitis cystica and cystitis glandularis needs to undertake a thorough examination of various areas of the bladder lesion to be absolutely sure there is no synchronous malignancy in the urinary bladder lesion. The treatment of cystitis cystica does entail removal of the source of irritation or source of the bladder inflammation including foreign bodies, long-term urinary catheter, vesical calculus and others as well as trans-urethral resection of the urinary bladder lesion or lesions. On very rare occasions cystectomy had been undertaken. Individuals who have vesical-ureteric obstruction may require insertion of nephrostomy on the side of the obstruction followed by insertion of antegrade or retrograde ureteric stents due to scarring at the site of obstruction or when the scar is too dense then excision of the lesion and re-implantation of the ureter may be required. In cases of severe impairment of renal function, on very rare occasions dialysis may be required as supportive care. But for majority of patients, trans-urethral resection of the bladder lesion would tend to be enough.