Urothelial Carcinoma with Prominent Squamous Differentiation in the Setting of Neurogenic Bladder – Role of HPV Infection
Elen B Blochin, Kay J Park, Satish K Tickoo, Victor E Reuter, Hikmat Al-Ahmadie. Memorial Sloan-Kettering Cancer Center, New York, NY; Ackerman Academy of Dermatopathology, New York, NY
Background: Squamous cell carcinoma (SCC) of the urinary bladder (UB) is rare; even more rare is its association with human papillomavirus (HPV). We report on two cases of HPV-positive urothelial carcinoma (UC) of the UB with predominant squamous differentiation (SQ) arising in patients with neurogenic bladder (NB) and long standing history of self catheterization (CATH).
Design: Two cases of apparent SCC of UB with basaloid appearance occurring in patients with neurogenic bladders were identified prospectively. p16 immunohistochemistry and HPV in situ hybridization (ISH) were performed. A retrospective institutional database review of SCC arising in NB was also performed and slides assessed for morphologic features.
Results: Patient 1 was a 44 year old female with h/o lipomeningomyelocele and laminectomy at age 5, using clean intermittent (CI) CATH 20x/ day from a young age. Patient 2 was a 48 year old who was paraplegic at T8 from a motor vehicle accident (MVA) at 23. In 2000 she underwent bladder-intestinal augmentation cystoplasty and was using CICATH. Neither had significant gynecologic histories. Tumors from both patients had a basaloid appearance with diffuse, strong p16 and punctate nuclear staining by HPV-ISH. One was almost entirely composed of SCC with in situ SCC in the surface urothelium resembling high grade dysplasia of the uterine cervix. The other showed a combination of SQ and glandular features as well as SCC in situ arising at the junction of native bladder and small intestine. Retrospective analysis of 250 cases of UC with SQ or pure SCC of the UB revealed 4 patients with a history of NB. Two used CICATH (one since 1985 after MVA; one since 1986 for multiple sclerosis). One patient used self CATH 2-3x a day since 1998 after surgery for endometriosis, and one had NB of uncertain etiology not requiring CATH. Microscopically, the tumors were either pure SCC or exhibited prominent SCC component in an otherwise usual UC. All 4 cases showed prominent keratinization. p16 was patchy in 1 case where it focally labeled UC in situ and invasive SCC. HPV ISH in this case was negative.
Conclusions: This is the first report of HPV-associated UC of the bladder with prominent squamous differentiation arising in patients with neurogenic bladder and self CATH. These 2 cases demonstrate that HPV-induced urothelial carcinoma may develop from physical trauma, SQ metaplasia, viral inoculation and stepwise carcinogenesis similar to that seen in uterine cervical cancers.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 98, Tuesday Afternoon