Bilateral hydronephrosis secondary to diffuse intestinal metaplasia of the bladder

A 78-year-old male presented following a fall. He had a 48-hour history of macroscopic haematuria and lower urinary tract symptoms. His comorbidities included asthma, PEs, hypertension and CKD. His medications included apixaban, antihypertensives and finasteride. He was fully independent in ADLs. Physical examination revealed a tender lower abdomen and stable observations.

Bilateral hydroureteronephrosis best appreciated on the axial and coronal portal venous phase CT AP images. The urinary bladder is grossly abnormal with a thickened/irregular wall with multiple diverticula (some containing wall calcification). Further suspicious, bilateral iliac chain nodes measuring up to 12mm in short axis noted. Prostate is not significantly enlarged.

Transabdominal ultrasound again highlights the grossly abnormal and thickened bladder wall with multiple diverticula and catheter in situ. The bladder is noted to contain 310mls despite catheterisation (and the bladder was not clamped). Bilateral hydronephrosis and hydroureter noted with multiple simple renal cysts.

Subsequent MRI pelvis was performed secondary to ongoing, nephrostomy dependent, right obstructive uropathy and consideration for right nephrectomy. This demonstrated nonspecific thickening of the entire visible distal right ureter (possibly due to recent stent placement); however no clear obstructing mass lesion at the right VUJ. Multiple bladder diverticula were again noted containing multiple, small dependent calculi.

Intestinal metaplasia (IM) of the bladder is characterised by benign, glandular proliferation whereby urothelium becomes lined by intestinal type epithelium.[1]  It can be focal or diffuse.[2]  Its aetiology is not well understood however is thought to occur from a reactive process.[3]  IM of the bladder is rare (ranges from 0.1-0.9%). [1][3] This is a florid example of a rare case. 

Histologically, IM of the bladder closely resembles intestinal epithelium with the presence of glands lined by mucin-producing columnar epithelial cells. The glands tend to have minimal atypia with no involvement of the muscularis propria.[4] Adenocarcinomas of the bladder, however, are heavily mucin-producing and usually deeply invade the muscularis propria. Microscopically, positive staining to nuclear beta-catenin suggests there is potential for IM to progress to malignancy with a similar signalling mechanism identified in oesophageal adenocarcinoma and Barrett’s oesophagus.[5]

There is conflicting evidence as to whether IM is a premalignant lesion to adenocarcinoma. Morten et al. recognised telomere shortening, a feature implicated in epithelial carcinogenesis, and cytogenic abnormalities in cases of IM, suggesting IM is a precursor lesion in adenocarcinoma.[6]

Acosta et al. investigated the presence of potential oncogenic genetic variants in cases of IM with and without dysplasia.[7] Oncogenic genetic variants, including mutations commonly seen in adenocarcinoma and TCC of the bladder were found in IM, supporting the view that it may represent a cancer precursor.[7]

Longterm clinicopathological studies have failed to demonstrate the development of adenocarcinoma in patients with IM. [6][8] Smith et al. evaluated 136 patients over a 24-year period, with florid cystitis cystica et glandularis or intestinal metaplasia. The study concluded that although IM can be associated with the concurrent diagnosis of carcinoma, there was no evidence to suggest that it increases the risk of malignancy.[8]  Likewise, Corica et al. followed-up 53 IM patients for 10 years and concluded IM was not a risk factor for adenocarcinoma. [5]

Take Home Points:

• Highlights the difficulty in macroscopically diagnosing IM compared to malignant neoplasms and their similar CT and sonographic appearance. Low threshold to perform biopsies/regular cystoscopic surveillance is paramount and important to consider IM in cases of obstructive uropathy.
• Mindful of the associated complications of IM of the bladder. This case demonstrates complications due to its extensive nature including obstructive uropathy.

Ongoing debate if IM of the bladder has malignant potential. Further, larger-scale epidemiological and clinical studies are now required to evaluate this further.

Differential Diagnosis:

• Differentials include multiple bladder diverticula seen in cases of bladder outflow obstruction. In this particular case, with a florid picture of innumerable bladder diverticula and prostate gland of relatively normal volume, this differential is less likely.
• Bladder cancer could not be excluded on imaging alone and thus necessitated TURBT and histopathological diagnosis. Patriarca et al. demonstrated florid von Brunn nests can mimic the nested variant of TCC, the most common form of bladder cancer. [9] The characterising difference of histologically of the von Brunn nests featured in TCC was the variable spacing between the nests and an infiltrative base. [9]
• Other important, perhaps less recognised differential diagnoses involve conditions in which there are proliferative or reactive changes occurring within von Brunn nests (a histological hallmark of IM). Examples include cystitis cystica and cystitis glandularis, whereby the von Brunn nests undergo cystic dilatation and glandular metaplasia respectively. These conditions are frequently coexisting, interrelated lesions developing in the setting of chronic mucosal irritation or inflammation.