Diagnosis of Renal Mucinous Tubular and Spindle Cell Carcinoma by Virtual Karyotyping with SNP-Arrays Using Formalin-Fixed and Paraffin-Embedded Tissue
SS Shen, HJ Kim, K Alvarez, JY Ro, LD Truong, JH Connelly, AG Ayala, JM Hagenkord, FA Monzon. The Methodist Hospital and Research Institute, Houston; Inje University College of Medicine, Seoul, Korea; St. Luke's Episcopal Hospital, Houston; University of Pittsburgh, Pittsburgh
Background: Mucinous tubular and spindle cell carcinoma (MTSCC) was listed as a histologic variant of renal cell carcinoma (RCC) in the 2004 WHO classification based on it unique morphologic and cytogenetic abberrations. Most studies have shown that MTSCC has an indolent behavior and favorable prognosis. However, there are significant problems in its differential diagnosis from RCC with sarcomatoid component or papillary RCC due to overlapping morphologic features or immunophenotypic profiles. This study evaluates the utility of virtual-karyotyping with single nucleotide polymorphism (SNP) arrays as a diagnostic modality for MTSCC.
Design: Six morphologically well-characterized MTSCCs, 3 sarcomatoid RCCs and 3 papillary RCCs with spindle cell areas were selected from three participating institutions for this study. The cases were reviewed by three genitourinary pathologists to verify the diagnosis and for selection of areas to be analyzed. DNA was obtained from 45 10-m formalin-fixed paraffin-embedded (FFPE) sections and analyzed on GeneChip Mapping 10 K 2.0 or 250K Nsp arrays (Affymetrix, Santa Clara, CA).
Results: Four of 6 MTSCCs were composed of typical tubular and spindle cell areas with mucinous stroma; 1 was predominantly made up of spindle cells with scant mucinous stroma; and other one was composed mainly of compressed tubules. Immunostains showed following positive results: RCC marker (6/6), AMACR (5/5), CD10 (2/6), and Ksp-cadherin (0/5). SNP array analysis showed characteristic chromosomal losses (-1, -14, -15) in all 6 cases and additional losses (-4, -6, -9) in 5 of 6 cases. Sarcomatoid and papillary RCCs showed chromosomal imbalances distinct from that of the MTSCC.
Conclusions: Our results show for the first time that chromosome copy number changes typical for MTSCC can be detected by virtual-karyotyping with SNP arrays using FFPE tissue. This approach appears to be highly reliable in the diagnosis of MTSCC and it has the potential to be a significant aid in the differential diagnosis from its morphological mimickers.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 130, Wednesday Afternoon