Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

Abstract

Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of selfcatheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common welldifferentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation. Modern Pathology (2012) 25, 1534-1542; doi:10.1038/modpathol.2012.112; published online 6 July 2012 Keywords: HPV; neurogenic bladder; squamous cell carcinoma; urothelial cancerThe human papillomavirus (HPV) has an important role as a human carcinogen, with an estimated 10% of cancers worldwide attributed to it. 1 HPV is a small circular double-stranded DNA virus with more than 100 different types described to date. 2 The potential of the virus to cause malignant or benign lesions dictates its classification into low-risk (6,11,40,42, and so on) or high-risk (16,18,31,33,45,51, and so on) types. The prototypical model for carcinogenesis is squamous cell carcinoma of the uterine cervix, in which nearly all such carcinomas are associated with HPV infection. 3,4 The oncogenic role of HPV is also well established for a subset of squamous cell carcinomas in the vulva, 5 penis, 6 anus, 7 and oropharynx. 8 The possible role of HPV infection in bladder tumors has not been completely elucidated as HPV detection rates vary widely from 0 to 100%, depending on the study. 9,10 An intriguing issue has been the possible association of the virus with bladder squamous cell carcinoma. The few published studies 11-14 on this relationship have shown a low frequency of HPV detection, implying that HPV is not likely to have a major role in the development of bladd...

Human Papillomavirus is Not an Etiologic Agent of Urothelial Inverted Papillomas

“…21 The presence of HPV infection in 2 cases of urothelial carcinoma with prominent squamous differentiation has recently been reported in the particular setting of neurogenic bladder. 25 HPV has also been associated with urothelial carcinoma in renal transplant recipients. 26 Considering these findings, it appears that any link between HPV and bladder neoplasia is more directly associated with particular clinical circumstances than as a general etiologic agent in the majority of bladder cancers.…”

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

“…Squamous cell carcinoma is defined by the presence of intercellular bridges or keratinization and may be present in up to 40% of invasive urothelial carcinomas [63][64][65][66]. It is almost never associated with human papillomavirus infection, with the rare exception of some cases with a basaloid morphology [67,68]. Interestingly, recent genomic data have described a basal/squamous-like molecular subtype that has squamoid morphology and immunophenotype and is associated with poor survival and poor response to systemic therapy [69,70].…”

Current and Proposed Molecular Diagnostics in a Genitourinary Service Line Laboratory at a Tertiary Clinical Institution

“…Finally, a recent study identified a subset of urothelial carcinomas with coinfection of high-risk human papillomavirus (HPV) strains. 63 These tumors had a unique histomorphology, with prominent basaloid squamous-type differentiation, and commonly occurred in patients with neurogenic bladder. In situ hybridization for highrisk HPV strains can confirm coinfection in suspected cases (Fig.…”