This case report describes a 60-year-old male presenting with a suspicious bladder mass obstructing the right ureteric orifice, leading to right-sided hydronephrosis. Histopathology of the resection revealed cystitis glandularis with intestinal metaplasia. This is on a background of high-grade prostate cancer managed with radical prostatectomy and radiation therapy.
This case is unique, given the behaviour of the cystitis glandularis with intestinal metaplasia leading to obstruction of the ureteric orifice and subsequent hydronephrosis. Previously, there have been few case reports of hydronephrosis and acute renal failure resulting from cystitis glandularis.8–10 In particular, the history of high-grade prostatic cancer poses an additional layer of complexity in differentiating between benign changes, precursory changes to a bladder adenocarcinoma, or a local recurrence of the prostatic adenocarcinoma.
There has been conflicting evidence regarding the premalignant potential of cystitis glandularis with intestinal metaplasia. Some retrospective studies have found that no patients with cystitis glandularis (including cystitis glandularis with intestinal metaplasia) progressed to adenocarcinoma.11, 12 However, an association between intestinal metaplasia with dysplasia and concurrent carcinoma (including adenocarcinoma and urothelial carcinoma) has been identified.13 This is supported by a recent study, which found that intestinal metaplasia with high-grade dysplasia contains oncogenic genetic variants associated with bladder adenocarcinoma and urothelial carcinoma.14 Additionally, significant telomere shortening in intestinal metaplasia of the bladder has been demonstrated, a phenomenon commonly observed in precursors of epithelial cancer.15 A recent study has also found that a minority of cases with intestinal metaplasia without dysplasia demonstrate mutations in the genes commonly associated with colonic adenocarcinoma.16
Aside from the concerns and debates regarding whether cystitis glandularis with intestinal metaplasia is premalignant, the differential diagnoses of cystitis glandularis versus primary bladder adenocarcinoma are worth highlighting given their similar clinical presentation. This is particularly relevant as there may be a greater clinical suspicion of bladder adenocarcinoma in this patient given his history of high-grade prostatic adenocarcinoma and previous radiation therapy. Furthermore, a previous study has demonstrated that, after correcting for diagnostic bias, the rate of bladder cancer in patients with prostate cancer is 18-times higher than the expected rates in the general population.17 Patients with cystitis glandularis may present with haematuria and evidence of diffuse bladder wall thickening or nodules on imaging, which can mimic a bladder malignancy. The only differentiating radiological factors may be extramural infiltration and lymph node metastasis, which occur exclusively in bladder cancer. Hence, the gold standard for diagnosing cystitis glandularis is through cystoscopy and biopsy.18 Intestinal metaplasia and adenocarcinoma of the bladder share overlapping features on histopathology, including dissecting mucin, muscularis propria infiltration, atypia, and mitoses. However, the degree of mucin extravasation, muscle invasion, cytological atypia, frequency of mitoses, as well as presence of signet cells and necrosis are different, which may assist diagnosis.19
This patient was managed with a transurethral resection of the bladder tissue, and repeat cystoscopies were planned for surveillance. This is in line with recommendations by the literature, although there are limited therapeutic advances in the management of cystitis glandularis with intestinal metaplasia. The mainstay treatment is surgical resection of the affected tissue, with the most common approach being a transurethral resection.18 One case report has described the use of aggressive surgical management of florid cystitis glandularis refractory to standard treatment, consisting of a cystoprostatectomy with cavernosal nerve sparing and neobladder construction.20 The use of intravesical perfusion therapy post-operatively is controversial, with agents such as immunosuppressants and anthracyclines being used.18 Other unique treatments include oral steroid therapy21 and intravesical curcumin.22 In addition, some suggestions in the literature include reducing causes of inflammation and undergoing long-term endoscopic surveillance.15 Cystoscopy surveillance is important given the evidence of cystitis glandularis recurrence, and it is recommended especially in patients displaying dysplastic changes due to the potential higher risk of malignancy.23 As an alternative to repeated cystoscopies, a paper has explored the use of a nomogram to predict the risk of recurrence of cystitis glandularis in individuals.24
Regarding this patient’s presentation with right-sided hydronephrosis, a study has found that cystitis glandularis with and without obstruction of the upper urinary tract demonstrated the same histopathological features and immunohistochemistry.25 Hence, although unusual, this clinical presentation presents the same theoretical level of premalignant risk as a patient without upper urinary tract obstruction. A protective factor is the absence of dysplasia on histopathology; however, this patient should be monitored closely for recurrence of his cystitis glandularis and any other changes. With regards to additional risk factors, this patient was treated with EBRT for a possible recurrence of his prostatic adenocarcinoma. A retrospective study of 84,397 individuals has found that patients treated with EBRT compared to a prostatectomy have an increased risk of developing bladder cancer.26 Further research may be indicated into the association between radiotherapy and cystitis glandularis with intestinal metaplasia, and ultimately whether this increases the risk of primary bladder adenocarcinoma.
In conclusion, this case report presents a case of cystitis glandularis with intestinal metaplasia, on a background of radiation therapy for high-grade prostate cancer. This case is interesting from several aspects, and we examine these in relation to the risk of developing primary bladder adenocarcinoma. Intestinal metaplasia has demonstrated changes such as telomere shortening and mutations which may suggest premalignant potential. Although unusual, the upper urinary tract obstruction in this patient may not pose an additional risk. Additionally, the patient did not demonstrate dysplastic features, and dysplasia has been suggested to confer additional risk. However, both a history of prostatic adenocarcinoma, and the use of EBRT may be associated with higher rates of bladder adenocarcinoma. Additionally, even though complete transurethral resection of abnormal appearing areas has been performed, cystoscopic surveillance is important for possible recurrence of cystitis glandularis with metaplasia or occurrence of bladder adenocarcinoma.