CYSTITIS CYSTICA

AND GLANDULARIS

Mahmoud Alameddine, MBBS

Urology Associate Consultant

International Medical Center

DEFINITION Cystitis cystica and glandularis is a rare

proliferative disease of mucus-producing glands within the mucosa and submucosa of the bladder epithelium.

It is characterized by foci of transitional cells that underwent glandular metaplasia.

METAPLASTIC THEORY

Von Brunn’s NestsSubmucocal formation and proliferation of transitional cells

foci

Cystitis Cystica:

Central degeneration of the epithelial foci

Cystitis Glandularis: More degeneration in the center with metaplasia of the epithelial cells into a cuboidal/columnar cells

Cuboidal/Columna

r Cells

IS IT TRASNFORMED FROM CYSTITIS GLANDULARIS OR ASSOCIATED WITH

IT???

Intestinal Metaplasia

Goblet cells

PREVALENCE The prevalence of symptomatic cystitis glandularis

with a gross lesion in the US is 0.9–1.9%.¹

Autopsy series that looked for von Brunn nests, cystitis cystica and cystitis glandularis in asymptomatic people, found that 50–100% of samples have these histologic changes with no gross lesion²

Which led to the belief that cystitis cystica and glandularis may be an incidental histologic finding rather than a precursor to bladder cancer.

1. Lin JI et al. (1980) Diffuse cystitis glandularis. Associated with adeno- carcinomatous change. Urology 15: 411–415

2. Andersen JA and Hansen BF (1972) The incidence of cell nests, cystitis cystica and cystitis glandularis in the lower urinary tract revealed by autopsies. J Urol 108: 421–424

RISK FACTORS Chronic bladder inflammation caused by:

Stones Bladder outflow obstruction Long-term indwelling catheter i.e spinal injury

Pelvic Lipomatosis: Rare proliferative disorder that causes increase

deposition of fat around the bladder, rectum and prostate.

Cystitis glandularis is found in 75% of those patients¹

No clear risk factors.

1. Heyns CF et al. (1991) Pelvic lipomatosis associated with cystitis glandularis and adenocarcinoma of the bladder. J Urol 145: 364–366

PELVIC LIPOMATOSIS

CT scan view of Pelvic Lipomatosis: Pear shape bladder and deposition of fat around the bladder and rectum.

PATHOGENESIS OF CYSTITIS CYSTICA AND GLANDULARIS IN PELVIC

LIPOMATOSIS Venous and lymphatic stasis due to perivesical

fat compression and chronic inflammation.

Leads to mucosal edema and proliferation of blood vessels within the stroma.

The damaged epithelium sloughs off and regenerates with hyperplasia and subsequent glandular metaplasia.

Tong RSK et al. (2002) Pelvic lipomatosis associated with proliferative cystitis occurring in two brothers. Urology 59 (Suppl): 602

CLINICAL PICTURE Irritative voiding symptoms:

Frequency Dysuria Urgency

Bacteruria Gross hematuria Chronic UTI They may complain of voiding mucus Less frequently: ureteral obstruction and

subsequently hydronephrosis.

Coelho RF et al Cystoprostatectomy with ileal neobladder for treatment of severe cystitis glandularis in an AIDS patient. Clinics (Sao Paulo). 2008 Oct;63(5):713-6.

CYSTOSCOPIC FINDINGS

A gross appearance looks like cobblestone pattern.

The bladder neck and trigone are the areas most frequently involved.

Followed by the lateral walls and the dome of the bladder.

It shows a cobblestone appearance of the mucosa

with a focal polypoid mass 

cystitis glandularis forming a mass with blueberry spots

in the urinary bladder.¹

1. Shigehara K et al. Cystitis glandularis forming a tumorous lesion in the urinary bladder: A rare appearance of disease. Indian J Urol (2008)

TREATMENT The first step is to treat the source of chronic bladder

irritation if it is present i.e. treat UTI and stones, replace indwelling catheters with CIC.

Transurethral resection of bladder lesions.

Intravesical steroids injection.

Nephrostomy tubes may be initially necessary for severe ureteral obstruction before definitive therapy.

Bladder augmentation and cystectomy have been described in severe intractable cases who fail initial therapy and progressed into bladder contracture and renal failure.

DIFFERENTIAL DIAGNOSIS Squamous metaplasia Fibroepithelial Polyps GU Tuberculousis Transitional cell carcinoma Squamous cell carcinoma Adenocarcinoma Metastatic disease

IS CYSTITIS GLANDULARIS A BENGNIN

OR A PRE-CANCEROUS LESION?

The first reported study implicating Cystitis Cystica and Glandularis in the development of adenocarcinoma was published in 1950.¹

In 1980, first report of bladder adenocarcinoma in a patient with Cystitis Cystica and Glandularis associated with pelvic lipomatosis.²

1. Immergut S, and Cottler ZR: Mucin producing adenocarcinoma of the bladder associated with cystitis follicularis and glandularis. Urol Cutaneous Rev 54: 531–534, 1950.

2. O’Brien AM, and Urbanski SJ: Papillary adenocarcinoma in situ of bladder. J Urol 134: 544–546, 1985.

Since then, sporadic case reports have associated Cystitis Cystica and Glandularis with bladder cancer.

Around 16 case reports were published.

10 of them, the conclusions were based only on the synchronous presence of cancer with glandular metaplasia in the specimen.

Smith et al. Role of Cystitis Cystica et Glandularis and Intestinal Metaplasia in Development of Bladder Carcinoma. UROLOGY71: 915–918, 2008.

In 2008 a study was published from Cleveland Clinic. They studied 88 patients with cystitis cystica and glandilaris and 15 patients with intestinal metaplasia who underwent interval follow up cystoscopies for a mean period of 4.4 years.

1 patient of the cystitis group developed bladder TCC, and this occurred 3 months after the initial biopsy. To be noted that this patient had a past history of upper tract TCC.

None of the intestinal metaplasia group had subsequent bladder cancer.

Smith et al. Role of Cystitis Cystica et Glandularis and Intestinal Metaplasia in Development of Bladder Carcinoma. UROLOGY71: 915–918, 2008.

TO SUM UP This case reveals the continued challenge to understand this

rare disease and its clinical importance as a precursor to cancer.

It is clearly indicated that cystitis glandularis and intestinal metaplasia can be identified coincidentally with bladder cancer.

However, the long-term outcomes have not supported the role of these lesions as preneoplastic.

Larger series of patients with cystitis glandularis and intestinal metaplasia are needed to delineate the association between these lesions and bladder cancer.

Until then, interval cystoscopy might be of value and for an indefinite time.¹

1. Lin JI et al. (1980) Diffuse cystitis glandularis. Associated with adenocarcinomatous change. Urology 15: 411–415