| Abstract|| |
Cystitis cystica and cystitis glandularis (CG) are relatively common appearances in the urinary bladder though CG may occasionally mimic a neoplasm. Microscopically, two types of CG are recognized, the usual type and intestinal type. This study was undertaken to study the morphology of CG and to highlight the differences in morphology between CG and adenocarcinoma. Eleven cases of CG were seen, of which 3 cases showed predominantly CG, usual type and eight cases showed CG of intestinal type. One case of primary adenocarcinoma was included in this study, where the adjacent bladder mucosa showed CG. Evaluation of the histological features of CG, especially intestinal type helps in correct categorization of this lesion and differentiation from adenocarcinoma of the bladder.
Keywords: Cystitis glandularis, intestinal variant, urinary bladder
|How to cite this article:|
Rau AR, Kini H, Pai RR. Morphological evaluation of cystitis glandularis. Indian J Pathol Microbiol 2009;52:203-5
| Introduction|| |
Cystitis cystica (CC) and cystitis glandularis (CG) are relatively common appearances in the urinary bladder and are reported in 60%-70% of cases in various autopsy studies. , They are usually asymptomatic lesions, being incidental findings in biopsies done for other lesions. CG may occasionally appear as nodular, irregular masses on cystoscopic examination, mimicking a neoplasm. , Microscopically, two types are recognized, the usual type and intestinal type.  Some of these lesions, especially the intestinal type, when widespread may mimic adenocarcinoma.  In addition, the prognosis of CG is undetermined, with cases of widespread CG progressing to adenocarcinoma having been reported. , This study was undertaken to evaluate the morphology of CG and to highlight the difference in morphology between CG and adenocarcinoma.
| Materials and Methods|| |
All patients in whom a diagnosis of CG of the urinary bladder was made between 2001 and 2006 were identified from the records of this department. All available material was retrieved and reviewed by the authors. The clinical records were reviewed wherever available.
| Results|| |
Eleven cases of CG were studied, one of which also showed primary adenocarcinoma bladder. The clinical and microscopic features are summarized in [Table 1].
The gross features were similar in 10 transurethral resection specimens, which consisted of multiple small irregularly shaped fragments of tissue without specific features. A cystectomy specimen was received in the case of primary adenocarcinoma, where a mucosa-based nodular lesion was seen in the fundus of the bladder measuring 3 × 1 × 0.5cm. It was solid grey-white and friable on cut section.
Eleven cases of CG were seen, where 3 cases showed predominantly CG, usual type characterized by glands in the lamina propria lined by cuboidal to tall columnar epithelial cells surrounded by layers of transitional epithelium. Eight cases of CG of intestinal type (CGIT) were seen, where the majority of the glands in the lamina propria were lined by tall columnar epithelium with abundant mucin and basally placed uniform nuclei without a surrounding layer of transitional epithelium [Figure 1]. A smaller component of usual cystitis glandularis was present in these cases. In 3 cases of CGIT, extravasated mucin was seen in the stroma with compression of the adjacent connective tissue, mild edema and focal hyalinization [Figure 2]. No atypical cells or significant inflammatory cell infiltrate was present in the mucin in any of these cases. The lining epithelium of the bladder was transitional in all the cases with focal mucinous metaplasia present in two cases. No muscularis propria invasion, signet ring cells or necrosis was seen in any of the cases. One case of primary adenocarcinoma was included in this study, which was composed of glandular elements with no recognizable urothelial elements. Colonic type glands lined by atypical cells invading the muscularis propria with desmoplastic response and extravasated mucin containing malignant cells was seen. The adjacent bladder mucosa showed CC and CGIT with atypia of the lining epithelium.
| Discussion|| |
Cystitis cystica and CG refers to invagination of the urothelium into the underlying lamina propria that have undergone cystic change or glandular metaplasia respectively., They are common lesions, considered as anatomic variants, being reported in 60%-70% of autopsy cases , and 0.1%-1.9% in clinical setting. , They are commonest in the trigone region of the bladder, but may be extensive.  CG may cause irritative symptoms, hematuria and rarely hydronephrosis. Though CG is usually a microscopic feature, nodular rounded or irregular elevations of the mucosa resembling neoplasia on cystoscopy are sometimes seen, , as in the three cases in this study. CG may be associated with chronic irritation of the bladder, following catheterization, stones or inflammation.  Widespread CG is seen in bladder extrophy,  neurogenic bladder  and in association with pelvic lipomatosis.  CG is present in 14%-67% of patients with nonurachal adenocarcinoma bladder,  while the presence of CG with atypia in a fundal-based adenocarcinoma excludes the diagnosis of urachal adenocarcinoma. 
On microscopy, CG is histologically divided into two types, the typical and CGIT. , Both usual and CGIT may co-exist, though one type may predominate over the other in a given case.  CGIT is less common, though this is the type that may resemble neoplasia grossly  or microscopically. The typical form of CG is usually superficial in location and characterized by glands in the lamina propria lined by cuboidal or columnar epithelium surrounded by several layers of urothelial cells. In CGIT, the lining cells resemble intestinal epithelium and are tall columnar with abundant mucin and often interspersed with goblet cells not associated with transitional cells.  Extravasated mucin, dissecting through the stroma may be seen in CGIT, causing diagnostic difficulties.  Histochemically, the mucin in CGIT is similar to colonic mucin.  In this study, 8/11 (73%) cases had CGIT, compared to 18/38 (47%) cases reported by Jacobs et al .  In the literature, though the incidence of CGIT is reported to be less than CG usual type,  the relatively high incidence of CGIT in this and other studies  is probably due to the likelihood of pathologists to document CGIT as compared to the usual type, which is considered a normal variant. In this study, extravasated mucin was seen in 3/11 (27%) cases, while Jacobs et al ,  reported it in 4/9 (44%) of the cases in their study and Young and Bostwick  noted that extravasated mucin was not an uncommon finding in CGIT.
The differential diagnosis of CG includes adenocarcinoma and endocervicosis.  CGIT, especially when extensive may present as exophytic masses and may morphologically mimic well differentiated adenocarcinoma. In CG usual type, peripheral transitional cells are seen, suggesting their benign nature. However, in CGIT, the glands lack these peripheral transitional cells and are lined by tall columnar mucin-secreting cells that may mimic well differentiated adenocarcinoma. The glands in CGIT are usually limited to the lamina propria. Though rarely, superficial and limited invasion may be identified in CG,  desmoplasia and deep muscle invasion are absent. Architecturally, the glands in CG are uniform and cytologically bland, with rare mitosis as compared to the complex glands, cytologically atypical cells and frequent mitosis seen in adenocarcinoma.  Extravasation of mucin may be seen in adenocarcinoma and CG,  as seen in the three cases in the present study. However, in adenocarcinoma, tumor cells are seen within or around the mucin pools, while in CG, the mucin is not associated with malignant cells.  Endocervicosis is a benign glandular lesion of the urinary bladder seen in women of the reproductive age group, where haphazard proliferation of irregularly shaped endocervical type mucinous gland is seen in the bladder wall. The glands in endocervicosis are typically deeply situated, involving the deep muscularis propria and lamina propria, in contrast to the superficially situated glands in CG. The lining epithelium is columnar and mucin secreting but ciliated cells are often interspersed among them, helping in the differentiation. Extravasated mucin with inflammatory response may be seen in endocervicosis, while in CGIT, it is usually in the lamina propria with minimal inflammatory response. ,,
The relationship of CGIT with subsequent adenocarcinoma is unresolved, with cases of progress of widespread CGIT to adenocarcinoma being documented. , Recent studies suggest that CGIT, which expresses β-catenin in the nucleus has a malignant potential compared to CG usual type, which expresses β-catenin on the membrane.  However, the significance of localized CG has not been determined and probably does not have the same association. 
In conclusion, CG is a histological entity commonly encountered in urinary bladder biopsies. CGIT is of greater significance since it may mimic adenocarcinoma both cystoscopically and on histopathology, in addition to which, widespread CGIT has uncertain malignant potential. Evaluation of the histological features of CGIT helps in correct categorization of this lesion and differentiating from adenocarcinoma of the bladder.
| References|| |
|1.||Wiener DP, Koss LG, Sablay B, Freed SZ. The prevalence and significance of Brunn's nests, cystitis cystica and squamous metaplasia in normal bladders. J Urol 1979;122:317-21. [PUBMED] |
|2.||Young RH, Elbe JN. Non neoplastic disorders of the urinary bladder. In: Bostwick DG, Elbe JN, editors. Urologic surgical pathology. St Louis: Mosby; 1997. p. 167-212. |
|3.||Murphy WM. Urologic pathology. 2 nd ed. Philadelphia: WB Saunders; 1989. p. 44-62. |
|4.||Young RH, Bostwick DG. Florid cystitis glandularis of intestinal type with mucin extravasation: A mimic of adenocarcinoma. Am J Surg Pathol 1996;20:1462-8. |
|5.||Bullock PS, Thoni DE, Murphy WM. The significance of colonic mucosa (intestinal metaplasia) involving the urinary tract. Cancer 1987;59:2086-90. |
|6.||Heyns CF, De Kock ML, Kirsten PH, Van Velden DJ. Pelvic lipomatosis associated with cysititis glandularis and adenocarcinoma bladder.J Urol 1991;145:364-6. |
|7.||Foster CS, Ross JS. Pathology of the urinary bladder: Major problems in pathology. Philadelphia: Saunders; 2004. |
|8.||Susmano D, Rubenstein AB, Dakin AR, Lloyd FA. Cystitis glandularis and adenocarcinoma of the bladder. J Urol 1971;105:671-4. |
|9.||Mukhopadhyay S, Taylor W. Bladder tumour in a 41 year old man. Arch Pathol Lab Med 2004;128:e89-90. |
|10.||Delnay KM, Stonehill WH, Goldman H, Jukkola AF, Dmochowski RR. Bladder histological changes associated with chronic indwelling urinary catheter. J Urol 1999;161:1106-8. |
|11.||Thomas DG, Ward AM, Williams JL. A study of 52 cases of adenocarcinoma of the bladder. Br J Urol 1971;43:4-15. |
|12.||Grignon DJ. Neoplasms of the urinary bladder. In: Bostwick DG, Elbe JN, editors. Urologic surgical pathology. St Louis: Mosby; 1997. p. 215-305. |
|13.||Jacobs LB, Brooks JD, Epstein JI. Differentiation of colonic metaplasia from adenocarcinoma of urinary bladder. Hum Pathol 1997;28:1152-7. |
|14.||Newbould M, Mc William LJ. A study of vesical adenocarcinoma, intestinal metaplasia and related lesions using mucin histochemistry. Histopathology 1990;17:225-30. |
|15.||Young RH. Pseudoneoplastic lesions of the urinary bladder and urethra: A selective review with emphasis on recent information. Semin Diagn Pathol 1997;14:133-46. |
|16.||Clement PB, Young RH. Endocervicosis of the urinary bladder. A report of six cases of a benign mullerian lesion that may mimic adenocarcinoma. Am J Surg Pathol 1992;16:533-42. |
|17.||Nazeer T, Ro JY, Tornos C, Ordonez NG, Ayala AG. Endocervical type glands in urinary bladder: A clinicopathologic study of six cases. Hum Pathol 1992;16:533-42. |
|18.||Bryan RT, Nicholls JH, Harrison RF, Jankowski JA, Wallace DM. The role of beta-catenin signaling in the malignant potential of cystitis glandularis. J Urol 2003;170:1892-6. |
Aarathi R Rau
7/22 1st Main Road, Ganganagar, Karnataka - 560 032, Bangalore
[Figure 1], [Figure 2]