15 March 2006 Case of the Week #40


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We thank Dr. Ihab Hosny, Robinson Memorial Hospital, Ravenna, Ohio (USA), for contributing this case. We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.


Case of the Week #40


Clinical history


A 56 year old man had a history of CD20+ (B cell) CLL since 2002. He received Rituxan (anti-CD20) and Fludarabine and went into remission. In 2005, he relapsed, and his CLL was now CD20 negative, but CD19+, CD23+ and CD5+. He was treated with Campath (anti-CD52), and went into remission again. He later developed dysuria and hematuria. Cystoscopy showed an erythematous bladder. Multiple biopsies were obtained.


Microscopic images: image1, image2, image3


What is your diagnosis?


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Hemorrhagic cystitis with BK polyoma viral inclusions




The diagnosis was confirmed by an immunostain for SV40 T antigen, which was strongly immunoreactive.


The polyoma viruses are nonenveloped double-stranded DNA viruses (Stanford University website). The polyoma BK virus is widely present in healthy individuals, and may be latent in the kidney, central nervous system and B cells. Other polyoma viruses are JC, which causes progressive multifocal leukoencephalopathy, and SV40, which causes only subclinical infections. The antigens of these polyoma viruses cross-react serologically and functionally, although they are distinct.


Immunosuppression may reactivate the latent virus, and cause hemorrhagic cystitis with the presence of decoy cells, particularly in bone marrow transplant patients. Urine cytology shows cells with enlarged nuclear and homogenized chromatin due to viral inclusions (image). These cells have the same appearance as in our case, and are similarly immunoreactive for SV40 (image). Electron microscopy shows 40 nm sized particles (image). A recent study has found an association of BK virus in immunocompetent patients with bladder carcinoma, with a 3.4 odds ratio (Diagn Cytopathol 2006;34:201).



Nat Pernick, M.D.
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