Evaluation of chromosomal aberrations in patients with benign conditions and reactive changes in urinary cytology

Abstract

BACKGROUND:Fluorescence in situ hybridization (FISH) is routinely used to help clarify atypical urinary cytology. However, to the authors' knowledge, little is known regarding the frequency of chromosomal aberrations in non‐neoplastic conditions that could potentially lead to false‐positive FISH results. The objective of the current study was to evaluate the frequency of chromosomal aberrations in benign cells of the urinary tract using the UroVysion FISH test.METHODS:The authors analyzed 77 Papanicolaou‐stained benign urine cytology specimens with reactive epithelial atypia using a FISH assay detecting the chromosomes 3, 7, and 17 and the gene locus 9p21. A positive test result was defined as an increased copy number of at least 2 chromosomes in ≥ 4 of 25 cells, or > 10 cells with a tetraploid or octaploid pattern, or homozygous or heterozygous deletion of 9p21 (≥ 12cells).RESULTS:FISH was positive in 27 of 77 bladder washings (35.1%) including 25 of 65 bladder washings (40.5%) and 2 of 15 voided urines (13.5%) from patients with irritative bladder (15 of 36 patients), a history of radiotherapy (7 of 12 patients), nonspecific cystitis (3 of 11 patients), hematuria (3 of 8 patients), and lithiasis (1 of 4 patients) . In 7 of 27 FISH‐positive urothelial specimens, the positivity was solely due a polyploid pattern (tetraploid/octaploid pattern) in > 10 of the cells.CONCLUSIONS:Chromosomal aberrations can occur in reactive urothelial cells, with a tetraploid pattern being the most common. Even an aneuploid pattern of FISH signals does not always prove malignancy because it rarely occurs in reactive urothelial cells. Correlation of FISH results with cytomorphology and patient history is crucial to avoid false‐positive diagnoses. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

The value of the UroVysion® FISH assay in the risk‐stratification of patients with “atypical urothelial cells” in urinary cytology specimens

“…41 Previously documented reasons for false-positive U-FISH test results include chromosomal aberrations in urothelial cells in benign conditions, including the presence of polyomavirus infection, 42,43 urolithiasis-related changes, and changes induced by chemotherapy or radiation therapy, 44 or even the presence of numerous umbrella cells. This suggests that U-FISH testing could be used as a tool to triage patients with AUC, defining a group of patients at higher risk of developing UC, who need closer clinical followup and additional or more frequent cystoscopy and/or imaging workup.…”

The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology

“…The UroVysion FISH test can increase the sensitivity of cytology for the detection of LGUC from 25 to 60 to 75%, but usually low-grade neoplasms are clearly visible by cystoscopy and the FISH result will not impact the clinical management. Conversely, in the setting of atypia with negative or inconclusive findings on cystoscopy, a negative UroVysion FISH test makes it very unlikely that these abnormal cells derive from a HGUC and this additional information will help the urologist in further management of the patient [59]. …”

Targeted multiprobe fluorescence in situ hybridization analysis for elucidation of inconclusive pancreatobiliary cytology

“…The relevance of 9p21 deletion has already been reported in 1994. 41 The 9p21 deletion has frequently been observed in different cancer types, but never in benign cells . However, one must keep in mind that chromosomal aberrations are not restricted to overtly malignant tumors but also occur, though to a lesser degree, in preneoplastic lesions .…”

“…In addition, cytological sampling errors due to absence of tumor cells in the specimens, inflammatory changes with reactive cells obscuring tumor cells, or the inability to retrace cytologically identified rare tumor cells in paucicellular specimens after hybridization can explain false‐negative results . We minimized the latter 2 scenarios by relocating the tumor cells seen in the original Papanicolaou slide for subsequent targeted FISH analysis using a computer‐controlled automated stage, as previously described . This has become a convenient routine procedure in our FISH laboratory.…”