Microscopic description:

On low power, fragmented and scattered bladder tissue with cystic areas and areas with glandular/villous (finger-like) formation is seen.

On high power, lamina propria shows cystically dilated nests with central lumen and surrounding abundant macrophages. These nests are well-defined and are lined by benign urothelium. The cells are uniform, small, oval and show no/minimal cytologic atypia, pleomorphism and mitotic activity. The lumen shows eosinophilic fluid. Urothelium overlying these cystic areas is also benign. These features correspond to cystitis cystica of bladder.

On high power, villi-like structures are seen, that are formed due to columnar epithelium being thrown into papillary folds. The lining epithelium resembles intestinal epithelium and shows abundant intracytoplasmic mucin with presence of goblet cells and basally oriented pseudostratified nuclei. The cells do not show high grade dysplastic features like luminal mitoses, atypical mitoses and loss of polarity.

Due to these benign features, urothelial carcinoma and primary and metastatic adenocarcinoma is ruled out. Cystitis glandularis with intestinal metaplasia is similar to cystitis cystica but the nests shows inner intestinal type lining with goblet cells surrounded by outer urothelial cells.

On immunohistochemical staining, the urothelium and areas with cystitis cystica stain positive for CK7 (membranous), GATA3 (nuclear) and negative for CK20, CDX2 and beta-catenin (non-specific); the villous structures stain positive for CK20 (membranous), CDX2 (nuclear) and beta-catenin (strong, membranous) and negative for CK7 and GATA3. These features are consistent with a diagnosis of villous adenoma of bladder with low grade dysplasia arising from intestinal metaplasia and cystitis cystica of the urothelium of the bladder wall.

Discussion:

Villous adenoma is a benign glandular neoplasm most commonly found in the colon.

It rarely arises in the urinary tract, usually in patients >50 years of age, M=F, and the most common reported symptom is hematuria.

The etiology of villous adenoma of the urinary tract is unclear, though it is hypothesized that embryologically the distal colorectal and urinary bladder arise from partitioning the cloaca by the urorectal septum. The remnants of cloaca may exist in the bladder and can cause a glandular epithelial neoplasm. An alternative theory suggests that the neoplasms originate from injured stem cells of urothelium, due to chronic infection or chemical injury, which result in glandular metaplasia.

More than 90% of bladder neoplasms arise from urothelial lining. Villous differentiation is more rare, with varying reports on possible association with malignant tumors. Villous adenoma has been found to rarely progress to villous adenocarcinoma, and has also been found to coexist with urothelial carcinoma. Therefore, the best treatment option is to completely remove the tumor to avoid missing any possible aggressive components.

Prognosis for villous adenoma is excellent when tumor is completely resected, with research showing they rarely recur.

Typically CK20/ CDX2 positivity, CK7 positivity.

Villous adenoma can transform from benign tumor to malignant adenocarcinoma, which appear identical in morphological and immunohistochemical features. Therefore it is critical to make a differential diagnosis between villous adenoma of the urinary tract, and secondary involvement from adjacent metastatic anatomical sites such as the colon.

References:

Wang, Jindong & Manucha, Varsha. (2015). Villous Adenoma of the Urinary Bladder: A Brief Review of the Literature. Archives of pathology & laboratory medicine. 140. 91-93. 10.5858/arpa.2014-0198-RS.

Atik E, Akansu B, Davarci M, Inci M, Yalcinkaya F, Rifaioglu M. Villous adenoma of the urinary bladder: rare location. Contemp Oncol (Pozn). 2012;16(3):276-7. doi: 10.5114/wo.2012.29300. Epub 2012 Jul 6. PMID: 23788894; PMCID: PMC3687408.

Qin LF, Liang Y, Xing XM, Wu H, Yang XC, Niu HT. Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature. World J Clin Cases. 2019 Apr 6;7(7):891-897. doi: 10.12998/wjcc.v7.i7.891. PMID: 31024961; PMCID: PMC6473125.

Hah YS, Jung HJ. Villous adenoma of bladder with uncommon location in a super-aged patient without gross hematuria. IJU Case Rep. 2021 Apr 7;4(4):197-199. doi: 10.1002/iju5.12280. PMID: 34258525; PMCID: PMC8255289.

Kato Y, Konari S, Obara W, Sugai T, Fujioka T. Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature. BMC Urol. 2013 Jul 20;13:36. doi: 10.1186/1471-2490-13-36. PMID: 23870731; PMCID: PMC3726475.

https://www.auanet.org/education/auauniversity/education-products-and-resources/pathology-for-urologists/urinary-bladder/non-neoplastic-lesions/cystitis-glandularis

Mitra S, Ayyanar P, Kaur G. Villous Morphology in Urinary Bladder Biopsy: An Approach to Diagnosis. Int J Surg Pathol. 2020 Feb;28(1):4-12. doi: 10.1177/1066896919868527. Epub 2019 Aug 13. PMID: 31409167.

CASE IMAGES