Utilization of FISH To Distinguish Urothelial Carcinoma with Nested Variant Growth Pattern from von Brunn's Nests
TN Oberg, BR Kipp, MB Campion, JS Voss, RE Jimenez, TJ Sebo, JC Cheville, KC Halling, M Zhou, J Zhang. Mayo Clinic, Rochester, MN; Cleveland Clinic, Cleveland, OH
Background: Urothelial carcinoma (UC) with a nested variant (NV) growth pattern is a rare form of UC with an aggressive clinical behavior. The bland morphology of NVUC characterized by large closely packed nests of urothelial cells can make the diagnosis difficult to distinguish from benign von Brunn's nests (VBN). Fluorescence in situ hybridization (FISH) studies have demonstrated that the UroVysion™ probe set (Abbott Molecular Inc., Des Plaines, IL) can detect chromosomal abnormalities in paraffin embedded specimens, not only in typical UC but also rarer histological variants of bladder cancer. The goal of this study was to determine whether FISH could distinguish NVUC from VBN on paraffin-embedded biopsy specimens.
Design: Paraffin-embedded bladder specimens (N=31) were reviewed and identified by pathologists to either contain UC with NV (n=23) or VBN (n=8). Utilizing centromere enumeration probes 3, 7, and 17 and the locus specific 9p21 probe (UroVysion), a cytotechnologist enumerated signal patterns of 50 tumor cells in NVUC or VBN areas identified by a uropathologist. Polysomy was defined as ≥3 signals for ≥2 probes and loss of both 9p21 signals defined homozygous 9p21 loss. Cell counts for each type of FISH abnormality in NVUC and VBN were compared using the Wilcoxon rank sum test.
Results: The mean number of polysomy cells present in NVUC cases was 5 cells (median 2, range 0-30) and the mean number of cells with homozygous 9p21 loss was 21 cells (median 14, range 0-46). VBN cases demonstrated a mean of 0.4 polysomic cells (median 0, range, 0-1) and 11 cells with homozygous 9p21 loss (median 6, range 2-49). A statistically significant difference was found between NVUC and VBN for the number of polysomy cells present (p=0.043) but not for the number of cells present with only homozygous 9p21 loss (p=0.109). Twelve of the 23 (52%) NVUC cases and no VBN cases demonstrated ≥2 polysomic cells. The remaining 11 (48%) NVUC cases and one of the eight (13%) VBN cases had ≥10 cells with homozygous 9p21 loss.
Conclusions: The data from this study suggest that FISH may help distinguish NVUC from VBN on paraffin-embedded biopsy specimens.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 140, Wednesday Afternoon