Polyoma Virus-Associated Cellular Changes in the Urine and Bladder Biopsy Samples

Abstract

Polyoma (BK) virus-type cellular changes are occasionally reported in urine specimens, yet rarely detected in histologic sections of bladder biopsies. A total of 762 predominantly voided urine specimens with a cytologic diagnosis of polyoma virus-type change were retrieved from the cytopathology files of the Johns Hopkins Hospital over a 15-year period (1988-2003). Biopsies were available for 33 cases (29 patients) following or preceding the urinary cytology (mean interval, 210 days). The biopsies originated primarily from bladder (n=31) with one biopsy each from renal pelvis and urethra. Representative paraffin blocks were chosen from each case for immunoperoxidase staining with SV40 large T antigen. There were 22 males and 7 females with an age range of 34 to 79 years (mean, 64.7 years). The histologic diagnoses of the 33 tissue biopsies were: benign urothelium (n=9), urothelial carcinoma (n=21) and 1 case each of dysplasia, small cell carcinoma, and chronic lymphocytic leukemia involving lamina propria of the bladder. Only 3 of 33 biopsies on hematoxylin-stained sections showed morphologic changes of polyoma virus, which lacked sufficient tissue to perform immunohistochemistry for SV40 large T antigen (LTag). Immunohistochemical staining for LTag was positive in 7 cases. Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53. One of these 2 cases was from an organ transplant recipient and the other from a patient with no known immunosuppression. Our data lead to the following conclusions: 1) cytology appears to be more sensitive than histology in detecting cells with polyoma virus; 2) cytohistologic discordance might be due to: a) polyoma (BK) virus infected cells are shed from the tissue and collected in the urine; b) polyoma virus changes may be focal and not sampled in directed tissue biopsies; c) polyoma virus changes may originate from sites in the genitourinary tract other than the bladder; d) the lack of a "gold standard" to confirm the cytologic diagnoses of polyoma virus; and e) the discordance in time between the biopsy and cytology specimens in the current retrospective study. 3) Because some cytologically benign cases of polyoma virus were associated with malignant biopsies, careful morphologic evaluation is required to avoid false-negative urinary cytology samples. This investigation further examined the immunohistochemical staining pattern for SV40 LTag and p53 in noninvasive low-grade papillary urothelial carcinoma using a tissue microarray constructed from bladder biopsies of 79 randomly selected patients. Weak LTag staining was present in occasional neoplastic urothelial cells of 2 patients. The staining was present in only one of four samples from each tumor (0.63%; 2 of 316 tumor spots), which further illustrates the patchy and focal presence of virion containing cells. p53 staining in...

Archetype and Rearranged Non-coding Control Regions in Urothelial Bladder Carcinoma of Immunocompetent Individuals

“…Furthermore, a statistically significant association between urine cytological evidence of PyV infection (decoy cells) and BC was also demonstrated in immunocompetent patients (18). Despite this experimental and epidemiological evidence, clinical cases of PyV-associated urological malignancies are rare and presented mainly as isolated case reports, mostly in transplant recipients or rarely in immunocompetent patients (17,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Evaluation of Renal Biopsies for BK Virus Nephropathy in Non-Renal Transplant Immunosuppressed Patients

“…Preservation of paraffin blocks of renal specimens obtained from the patients made it possible to use this method. Immunohistochemical staining with SV40 in paraffin blocks prepared before have been shown to be efficient in several studies reported so far (21,22). …”

A Potential Linkage Between the JC and BK Polyomaviruses and Brain and Urinary Tract Tumors: A Review of the Literature

“…52 In the studies by Fioriti et al and Monini et al, BKV sequences were found to be present at a high frequency in bladder carcinomas. 78, 79 Weinreb et al reported a significant association between urine cytology suggestive of PyV infection and subsequent diagnosis of bladder carcinoma. 75 Alexiev et al reported two cases of kidney transplant patients who developed PVAN and unspecified BKV infection followed by the development of carcinoma of the urinary bladder several years post transplantation.…”

“…79 concluded that there is evidence for a significant link between BKV expression and prostate cancer development, particularly between BKV infection and cancer risk ( Table 2). 98 …”

“…[82][83][84] The presence of BKV sequences in kidney cancer samples also seems to vary among different cohorts of patients. 50,51,[74][75][76][77][78][79][80][81][82][83][84] Kausman et al reported the case of a 10-year-old child with a carcinoma of the donor renal pelvis following BKV allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of the secondary tumors and a return to health.…”