Renal Cell Carcinoma with Leiomyomatous Stroma Lacks VHL Alteration: A Further Feature Differentiating It from Clear Cell Renal Cell Carcinoma
Guido Martignoni, Matteo Brunelli, Diego Segala, Ioana Borze, Lilit Atanesya, Suvi Savola, Luisa Barzon, Giulia Masi, Regina Tardanico, John Nelson Eble, Marco Chilosi, Tom Bohling, Liang Cheng, Brett Delahunt, Stefano Gobbo, Sakari Knuutila. University of Verona, Verona, Italy; Hartmann Institute and HUSLab, University of Helsinki, Helsinki, Finland; MRC-Holland, Amsterdam, Netherlands; University of Padua, Padua, Italy; Spedali Civili, Brescia, Italy; Indiana University School of Medicine, Indianapolis, IN; Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
Background: Renal cell carcinoma (RCC) with leiomyomatous stroma is a rare tumor composed of admixture of epithelial clear cell component arranged in small nest and tubular structures intermixed with a prominent leiomyomatous stroma. Controversies on the presence of loss of chromosome 3p detected by FISH has been reported and therefore it has been considered a clear cell RCC. In this study we have evaluated the chromosome 3 and VHL status of three of such tumors using Fluorescence In Situ Hybridization (FISH), array Comparative Genomic Hybridization (CGH), gene sequencing analysis and Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS–MLPA) analysis.
Design: Three RCCs with leiomyomatous stroma were recruited on the basis of their morphological features. We performed FISH analysis by using probes for the chromosome 3 and 3p25, array CGH, VHL sequencing analysis and MS–MLPA analysis.
Results: RCCs with leiomyomatous stroma displayed an admixture of two distinct components: the epithelial cells with clear cytoplasm and hyperchromatic irregular low grade nuclei, arranged in tubules, cords and nests and a stromal proliferation composed of mature smooth muscle cells, organized in bundles sometimes in conjunction to the peripheral discontinuous pseudocapsule. Deletion of chromosome 3p, VHL mutation and significant VHL methylation or changes in copy number were not detected in any cases and a flat-profile was demonstrated at CGH analysis.
Conclusions: RCCs with leiomyomatous stroma do not show 3p deletion, VHL mutation and methylation abnormalities that are frequent in clear cell RCC. Overall, this kind of tumor shows a genomic stability after wide whole genomic CGH analysis. On the basis of aforementioned characteristics, RCC with leiomyomatous stroma should not be considered a clear cell RCC.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 173, Monday Afternoon