Brief review about Cystitis Cystica and Glandularis. Is it a benign of a malignant condition?

1. Mahmoud Alameddine, MBBS
Urology Associate Consultant
International Medical Center

2.  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.

3. Von Brunn’s Nests
Submucocal formation and proliferation of transitional cells foci

4. Cystitis Cystica:
Central degeneration of the
epithelial foci

5. Cystitis Glandularis:
More degeneration in the center with
metaplasia of the epithelial cells into a
cuboidal/columnar cells
Cuboidal/
Columnar
Cells

6. Intestinal Metaplasia
Goblet cells

7.  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 :–

8.  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

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

10.  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

11.  Irritative voiding symptoms:
 Frequency
 Dysuria
 Urgency
 Bacteruria
 Gross hematuria
 Chronic UTI
 They may complain of voiding mucus
 Less frequently: ureteral obstruction and
subsequently hydronephrosis.

12. 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.

13.  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.

15. 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)

16.  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.

17.  Squamous metaplasia
 Fibroepithelial Polyps
 GU Tuberculousis
 Transitional cell carcinoma
 Squamous cell carcinoma
 Adenocarcinoma
 Metastatic disease

19.  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.

20.  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. UROLOGY :–

21.  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. UROLOGY :–

22.  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