Gliosarcoma arising from an oligodendroglioma (oligosarcoma).

Gliosarcoma, a biphasic tumor with both mesenchymal and glial elements, is typically considered a variant of astrocytoma (glioblastoma), WHO Grade IV. A 57-year-old man presented with altered mental status and was found to have a large right frontal mass. Biopsy and subsequent subtotal resection revealed a WHO Grade II oligodendroglioma with classic histological features, expression of IDH1 R132H mutant protein, and chromosome 1p19q co-deletion. Fifteen months later, the patient developed recurrent tumor composed of intersecting fascicles of spindled cells with necrosis and a high mitotic index. The recurrent tumor stained for both mesenchymal and glial elements, consistent with the diagnosis of gliosarcoma, and showed retained IDH1 R132H expression. By FISH analysis, the gliosarcoma showed no evidence of 1p19q co-deletion. We performed SNP arrays and detailed SNP analysis of both the oligodendroglioma and the gliosarcoma. This demonstrated loss of heterozygosity (LOH) of chromosomes 1 and 19 in the gliosarcoma with retention of the same full-length chromosomes 1 and 19 found intact in the oligodendroglioma. Not surprisingly, the gliosarcoma harbored multiple additional alterations, consistent with clonal evolution. There have been only rare reports of sarcomatous transformation of oligodendroglioma ("oligosarcoma") and most were published prior to the development of modern genetic modalities. Here we present a case with detailed genetic evidence that suggests that mesenchymal metaplasia sarcomatous transformation is possible in classic oligodendrogliomas with 1p19q codeletions.

A common 8q (MYC) amplification detected in a multifocal anaplastic astrocytoma by SNP array karyotyping.

The distinction of multifocal versus multicentric gliomas can conceivably have important therapeutic implications. We present a 27-year-old man with two radiologically distinct non-enhancing infiltrative masses in the anterior frontal lobe and the posterior temporoparietal region. No intervening disease was evident on MRI modalities; the lesions were stable over a period of many months. He underwent two separate resections a few months apart. Given the question of whether his tumors represented two de novo primary multicentric tumors or one multifocal tumor, single nucleotide polymorphism (SNP) array karyotyping and in situ hybridization studies were performed on both tumors. The two tumor profiles looked remarkably similar, histologically and genetically: both were anaplastic astrocytomas with a common 33Mb gain/ amplification of 8q23.3-q24.3, including MYC amplification, suggesting a monoclonal origin. The temporoparietal neoplasm showed several additional genetic alterations. This case illustrates that even with today's advanced neuroimaging modalities, extensive radiologically invisible tumor may be present between seemingly separate sites of glioma involvement. Thus modern global genomic studies of such tumors may help distinguish whether multiple tumors represent one extensive neoplasm with microscopically invasive disease or multiple genetically distinct tumors.

Sarcoma arising as a distinct nodule within glioblastoma: a morphological and molecular perspective on gliosarcoma.

Gliosarcoma is a variant of glioblastoma and is characterized by distinct glial and sarcomatous components. Typically, there is no macroscopic boundary between the components and special stains are often required to distinguish the glial and sarcomatous elements. Some studies suggest similar genetic alterations in both components pointing to a common origin. We present an extreme case of gliosarcoma arising as a discrete fibrous nodule adjacent to a typical glioblastoma. A 65 year-old woman presented with progressive weakness, seizures and right-sided hemiparesis. CT scan demonstrated an irregular enhancing left frontal lobe mass and an adjacent discrete nodule with different imaging characteristics. The unique nature of this macroscopically biphasic neoplasm allowed us to compare the molecular characteristics of glial and sarcomatous elements which were strikingly similar except for small losses and gains in Chr 3. Studies are under way to determine the significance of chromosome 3 alterations in gliosarcomas.

Papillary renal cell-like carcinoma in a retroperitoneal teratoma.

We report a case of somatic type malignancy with papillary renal cell carcinoma differentiation arising in a retroperitoneal mixed germ cell tumor. The patient was a 36-year-old man with a synchronous mediastinal teratoma. The somatic type malignancy in the retroperitoneal tumor was composed of papillary structures covered by atypical epithelial cells with eosinophilic cytoplasm, prominent nucleoli and pseudostratified nuclei. Papillary cores contained numerous aggregates of foamy macrophages, typical of type I papillary renal cell carcinomas. The immunohistochemical profile was consistent with papillary renal cell carcinoma, including positive reactions for cytokeratin 7 and alpha-methyl acyl CoA racemase. There was no somatic type malignancy component in the synchronous mediastinal teratoma. Both the retroperitoneal and the mediastinal tumor showed gains of 12p and chromosome 17 material. There was no c-MET mutation in the somatic type malignancy. To our knowledge, this is the first report of a somatic type malignancy with features of papillary renal cell carcinoma arising in a germ cell tumor. It is important not to confuse such a retroperitoneal tumor with a conventional papillary renal cell carcinoma, because presence of other malignant histologies within the germ cell tumor may warrant different treatment. In such cases, the presence of isochromosome 12p can be helpful to the diagnosis.

Interlaboratory performance of a microarray-based gene expression test to determine tissue of origin in poorly differentiated and undifferentiated cancers.

Clinical workup of metastatic malignancies of unknown origin is often arduous and expensive and is reported to be unsuccessful in 30 to 60% of cases. Accurate classification of uncertain primary cancers may improve with microarray-based gene expression testing. We evaluated the analytical performance characteristics of the Pathwork tissue of origin test, which uses expression signals from 1668 probe sets in a gene expression microarray, to quantify the similarity of tumor specimens to 15 known tissues of origin. Sixty archived tissue specimens from poorly and undifferentiated tumors (metastatic and primary) were analyzed at four laboratories representing a wide range of preanalytical conditions (eg, personnel, reagents, instrumentation, and protocols). Cross-laboratory comparisons showed highly reproducible results between laboratories, with correlation coefficients between 0.95 to 0.97 for measurements of similarity scores, and an average 93.8% overall concordance between laboratories in terms of final tissue calls. Bland-Altman plots (mean coefficients of reproducibility of 32.48+/-3.97) and kappa statistics (kappa >0.86) also indicated a high level of agreement between laboratories. We conclude that the Pathwork tissue of origin test is a robust assay that produces consistent results in diverse laboratory conditions reflecting the preanalytical variations found in the everyday clinical practice of molecular diagnostics laboratories.

A multicenter, cross-platform clinical validation study of cancer cytogenomic arrays.

Cytogenomic microarray analysis (CMA) offers high resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multiplatform, multicenter clinical validation project to compare the reliability and inter- and intralaboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms-from Affymetrix, Agilent, and Illumina. Each microarray platform was employed at two independent test sites. The results were compared in a blinded manner with current standard methods, including karyotype, FISH, or morphology. Twenty-nine chronic lymphocytic leukemia blood, 34 myelodysplastic syndrome bone marrow, and 30 fresh frozen renal epithelial tumor samples were assessed by all six laboratories. Thirty formalin fixed paraffin embedded renal tumor samples were analyzed at the Affymetrix and Agilent test sites only. All study samples were initial diagnostic samples. Array data were analyzed at each participating site and were submitted to caArray for central analysis. Laboratory interpretive results were submitted to the central analysis team for comparison with the standard-of-care assays and for calculation of intraplatform reproducibility and cross-platform concordance. The results demonstrated that the three microarray platforms 1) detect clinically actionable genomic changes in cancer compatible to standard-of-care methods; 2) further define cytogenetic aberrations; 3) identify submicroscopic alterations and loss of heterozygosity (LOH); and 4) yield consistent results within and between laboratories. Based on this study, the CGC concludes that CMA is a sensitive and reliable technique for copy number and LOH assessment that may be used for clinical oncology genomic analysis.

Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas.

BRAF rearrangements and BRAF V600E point mutations are recurring events in pediatric low-grade gliomas. However, their clinical significance, including possible interactions between these markers and other glioma biomarkers, is unclear. In this study a retrospective cohort of 198 pediatric low-grade gliomas (including 40 treated with adjuvant therapy) was analyzed for BRAF rearrangements, BRAF V600E, p16/CDKN2A deletion, p53 expression, and MIB1 proliferation index. In tumors with BRAF rearrangement, homozygous p16 deletion correlated with shorter progression-free survival (P = .04). A high MIB1 proliferation index trended toward worse response to adjuvant radiotherapy compared to BRAF-rearranged, p16-intact tumors (P = .08). On multivariate analysis, the 2 most consistently powerful independent adverse prognostic markers were midline location (P = .0001) and p16 deletion (P = .03). Tumors with BRAF V600E had a strong trend toward an increased risk for progression (hazard ratio = 2.48, P = .07), whereas those with BRAF rearrangement had a milder trend toward reduced risk (hazard ratio = .54, P = .15). These data suggest that p16 deletion adversely impacts the outcomes of BRAF-driven gliomas, that high proliferation index may be a better marker of progression risk than BRAF, that BRAF rearrangement and BRAF V600E might not necessarily produce comparable outcomes, and that none of these markers is stronger than tumor location in determining prognosis in pediatric low-grade gliomas.

Clinical genomics of renal epithelial tumors.

Kidney and upper urinary tract cancers account for approximately 54,000 cases every year in the United States, and represent about 3.7% of adult malignancies, with more than 13,000 annual deaths. Classification of renal tumors is typically based on histomorphologic characteristics but, on occasion, morphologic characteristics are not sufficient. Each of the most common histologic subtypes harbors specific recurrent genetic abnormalities, such as deletion of 3p in conventional clear cell carcinoma, trisomy 7 and 17 in papillary renal cell carcinoma, multiple monosomies in chromophobe renal cell carcinoma, and a nearly diploid genome in benign oncocytomas. Knowledge of this information can provide diagnostic support and prognostic refinement in renal epithelial tumors. Identification of the specific subtype of a renal tumor is critical in guiding surveillance for recurrence and the appropriate use of targeted therapies. Cytogenomic arrays are increasingly being used as a clinical tool for genome-wide assessment of copy number and loss of heterozygosity in renal tumors. In addition, the improved understanding of the hereditary causes of renal tumors and their role in sporadic malignancies has led to the development of more effective targeted therapies. This review summarizes the genetic and genomic changes in the most common types of renal epithelial tumors and highlights the clinical implications of these aberrations.

Abnormal villous morphology associated with triple trisomy of paternal origin.

The vast majority of trisomies in spontaneous abortions (SAB) are single and of maternal origin, most frequently due to meiosis I errors. Triple trisomies are exceedingly rare (approximately 0.05% of spontaneous abortions), most often of maternal origin, and associated with increased maternal age. Some trisomic SAB specimens can exhibit abnormal villous morphology simulating a partial hydatidiform mole, a distinct form of hydatidiform mole characterized by diandric triploidy. A SAB specimen from a 27-year-old woman, G1P0 at 8 weeks gestational age, was reviewed in consultation to address the finding of morphological features suggestive of a partial hydatidiform mole but DNA ploidy analysis yielding a diploid result. The villi were irregularly shaped and hydropic but lacked trophoblastic hyperplasia; p57 expression was retained. Since fully developed features of a partial hydatidiform mole were lacking, additional analysis was performed. Molecular genotyping and single nucleotide polymorphism array analysis demonstrated biparental diploidy with trisomy of chromosomes 7, 13, and 20, all of paternal origin. The three trisomies may have originated from paternal meiosis II errors, or from mitotic nondisjunction. We believe this to be the first report of triple trisomy in a SAB confirmed to be of paternal origin.

Array-based karyotyping for prognostic assessment in chronic lymphocytic leukemia: performance comparison of Affymetrix 10K2.0, 250K Nsp, and SNP6.0 arrays.

Specific chromosomal alterations are recognized as important prognostic factors in chronic lymphocytic leukemia (CLL). Array-based karyotyping is gaining acceptance as an alternative to the standard fluorescence in situ hybridization (FISH) panel for detecting these aberrations. This study explores the optimum single nucleotide polymorphism (SNP) array probe density for routine clinical use, presents clinical validation results for the 250K Nsp Affymetrix SNP array, and highlights clinically actionable genetic lesions missed by FISH and conventional cytogenetics. CLL samples were processed on low (10K2.0), medium (250K Nsp), and high (SNP6.0) probe density Affymetrix SNP arrays. Break point definition and detection rates for clinically relevant genetic lesions were compared. The 250K Nsp array was subsequently validated for routine clinical use and demonstrated 98.5% concordance with the standard CLL FISH panel. SNP array karyotyping detected genomic complexity and/or acquired uniparental disomy not detected by the FISH panel. In particular, a region of acquired uniparental disomy on 17p was shown to harbor two mutated copies of TP53 that would have gone undetected by FISH, conventional cytogenetics, or array comparative genomic hybridization. SNP array karyotyping allows genome-wide, high resolution detection of copy number and uniparental disomy at genomic regions with established prognostic significance in CLL, detects lesions missed by FISH, and provides insight into gene dosage at these loci.

Reproducibility and performance of virtual karyotyping with SNP microarrays for the detection of chromosomal imbalances in formalin-fixed paraffin-embedded tissues.

BACKGROUND: Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues. Here, we report the performance and reproducibility of virtual karyotyping of FFPE tissues with Affymetrix SNP arrays. METHODS: Virtual karyotypes from 442 FFPE tumor samples were generated using the Affymetrix GeneChip Mapping 10K Xba 2.0 and/or 250K Nsp SNP mapping arrays. Samples ranged from a few weeks to 17 years in archival storage. Virtual karyotypes were assessed for copy number changes, loss of heterozygosity, and acquired uniparental disomy. RESULTS: Overall, 75.3% of samples produced interpretable virtual karyotypes with the 10K arrays and 76.7% in the 250K arrays. Parameters for the selection of samples for hybridization were determined, which increased the success rate in both platforms to 81.3 and 92.6%, respectively. FFPE virtual karyotypes generated with both 10K Xba 2.0 and 250K Nsp arrays showed 100% concordance in intralaboratory and interlaboratory reproducibility studies. Samples older than 7 years showed decreased performance. CONCLUSIONS: SNP arrays are a reliable, reproducible, and robust platform for the virtual karyotyping of FFPE tumor tissues with performance characteristics adequate for clinical application. Parameters that most significantly affected sample performance were sample age and storage conditions.

Residency training in pathology informatics: a virtual rotation solution.

Efforts are being made to provide informatics training in residency programs. However, various factors limit this process: (1) limited access to pathology informatics expertise and resources, (2) crowded rotation schedules, and (3) incompatible rotation structures at different institutions. We devised a novel e-learning solution (located at https://secure. opi.upmc.edu/VRPI/index.cfm) that circumvents these limitations. The course includes didactic lectures given by experts in the field and video-recorded hands-on laboratories. The lectures are supplemented by readings from a textbook. Because it is self-paced, it can accommodate various rotation structures. Module topics and depth of coverage are directed to the level of general practicing pathologists, with quizzes provided for each module. Course progress can be tracked on the Web site by an administrator. The experience so far with this resource has been positive, and it seems to be effective in improving resident competency in pathology informatics and basic computer skills.

Detection of chromosomal aberrations in renal tumors: a comparative study of conventional cytogenetics and virtual karyotyping with single-nucleotide polymorphism microarrays.

CONTEXT: -Renal epithelial neoplasms have characteristic chromosomal imbalances, and we have shown previously that virtual karyotypes derived from single-nucleotide polymorphism microarrays can be performed on formalin-fixed, paraffin-embedded tissue. OBJECTIVE: -To perform a direct comparison of virtual and conventional karyotypes to evaluate concordance of results. DESIGN: -Twenty archival formalin-fixed, paraffin-embedded tumor samples with preexisting, conventional cytogenetic results were analyzed with Affymetrix 10K 2.0 or 250K Nsp single-nucleotide polymorphism microarrays. RESULTS: -Nineteen samples yielded adequate virtual karyotypes for interpretation. Eight samples showed complete agreement between the 2 techniques, and 8 samples showed partial agreement. The disease-defining lesions (eg, loss of 3p for clear cell carcinoma) were identified in all 19 cases by virtual karyotypes and in 15 cases by conventional karyotypes. Virtual and conventional karyotypic findings were concordant in the identification of these disease-defining lesions in 86% (13 of 15) of cases. In 3 cases, virtual karyotypes identified lesions consistent with the morphologic diagnosis, whereas the conventional karyotypes were unsuccessful because of insufficient tumor representation or stromal overgrowth. Two cases with acquired uniparental disomy were identified by single-nucleotide polymorphism arrays, and 5 cases with translocations were identified by conventional karyotype. CONCLUSIONS: -Our results show that both techniques are able to identify the characteristic chromosomal abnormality for renal tumor subtypes in most cases. Discrepancies can be explained by inherent limitations of each technique, inadequate tumor sampling, and tumor heterogeneity. We conclude that virtual karyotyping is a robust alternative to conventional cytogenetics for the evaluation of chromosomal anomalies in formalin-fixed, paraffin-embedded tissues from renal epithelial neoplasms.

Complete hydatidiform mole with retained maternal chromosomes 6 and 11.

Distinction of hydatidiform moles from nonmolar specimens and their subclassification as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies to refine ascertainment of risk of persistent gestational trophoblastic disease which differs among these entities. Immunohistochemical analysis of p57 expression, a paternally imprinted maternally expressed gene on 11p15.5, and molecular genotyping are useful for improving diagnosis. CHMs are characterized by androgenetic diploidy, with the loss of p57 expression owing to lack of maternal DNA. Loss of p57 expression distinguishes CHMs from both PHMs (diandric triploidy) and nonmolar specimens (biparental diploidy) which retain expression. In the process of evaluating molar specimens in our laboratory with p57 immunohistochemistry and molecular genotyping, we identified a morphologically typical androgenetic diploid CHM with aberrant diffuse p57 expression. Molecular genotyping by short tandem repeat markers and genome-wide copy number analysis by single nucleotide polymorphism array established androgenetic diploidy with retained maternal copies of chromosomes 6 and 11, with aberrant p57 expression attributable to the latter. This case, only the second reported to date, illustrates the value of combined traditional pathologic and ancillary molecular techniques for refined diagnosis of molar specimens. Specimens with morphologic features suggestive of CHM yet retaining p57 expression should be subjected to molecular genotyping to establish a definitive diagnosis because misclassification as PHM underestimates the risk of persistent gestational trophoblastic disease. We recommend use of p57 immunohistochemistry and molecular genotyping to evaluate all products of conception specimens for which there is any consideration of a diagnosis of hydatidiform mole. Genome-wide analysis has the potential to assist in localizing imprinted genes critical for determining the morphologic and behavioral phenotypes of hydatidiform moles.

Multiple distinct clones may co-exist in different lineages in myelodysplastic syndromes.

Using single nucleotide polymorphism (SNP) microarray with unfractionized bone marrow specimens, recent studies have demonstrated that multiple cytogenetically cryptic genomic aberrations, uniparental disomy (UPD) and/or copy number (CN) aberration, are present in patients with myelodysplastic syndromes (MDS). We hypothesize that various hematopoietic lineages in MDS may carry different cytogenetically cryptic genomic aberrations leading to lineage-specific manifestations of MDS. Flow cytometry sorting was performed to sort 12 MDS marrow samples into blastic, erythroid, immature myeloid and lymphoid fractions. The fractions with enough DNA underwent 250K SNP microarray analysis. Of importance, different chromosomal regions of UPD, deletions and/or gains were present in different fractions of same patients in all samples. Only small percentages (6.7%) of genomic aberrations were present in all fractions from same patients. These results suggest that multiple distinct clones may co-exist in different lineages in MDS and may contribute to cytopenias in specific lineages and the significant clinical heterogeneity observed in these patients. Further studies are warranted to confirm our findings and to investigate the lineage specific genomic lesions in MDS.

Virtual-karyotyping with SNP microarrays in morphologically challenging renal cell neoplasms: a practical and useful diagnostic modality.

Approximately 7 % of renal cell tumors are reported to be "unclassified" renal cell carcinoma (RCC) under the current (morphology-based) classification. Genetic lesions characteristic for RCC subtypes can be identified by virtual karyotyping with single nucleotide polymorphisms (SNP) microarrays. In this study, we examined whether virtual karyotypes could be used to better classify a cohort of morphologically challenging/unclassified RCC. Tumor resection specimens from 21 patients were profiled by virtual karyotyping with Affymetrix 10K 2.0 or 250K Nsp SNP mapping arrays and were also evaluated independently by a panel of 7 genito-urinary pathologists. Tumors were classified by the established pattern of genomic imbalances based on a reference cohort of 98 cases with classic morphology and compared with the morphologic diagnosis of the pathologist panel. Virtual karyotyping analysis identified recognized patterns of chromosomal imbalances in all but 1 (16/17 or 94%) cases with successful analysis. Four cases failed owing to low DNA quality. All cases with a panel diagnosis of unclassified RCC and cases in which a majority diagnosis was not reached were classified by their virtual karyotypes. In 1 case, the molecular-based diagnosis was in disagreement with the majority diagnosis. One case with a majority diagnosis of oncocytoma showed a novel genomic pattern not previously identified in the classic morphology cohort. We conclude that virtual karyotypes generated by SNP arrays are a valuable tool for increasing diagnostic accuracy in morphologically challenging or unclassified renal neoplasms. We consider that this technique is a feasible and practical approach for resolving difficult-to-diagnose renal tumors in clinical practice.

Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors.

Renal tumors with complex or unusual morphology require extensive workup for accurate classification. Chromosomal aberrations that define subtypes of renal epithelial neoplasms have been reported. We explored if whole-genome chromosome copy number and loss-of-heterozygosity analysis with single nucleotide polymorphism (SNP) arrays can be used to identify these aberrations and classify renal epithelial tumors. We analyzed 20 paraffin-embedded tissues representing clear cell, papillary renal and chromophobe renal cell carcinoma, as well as oncocytoma with Affymetrix GeneChip 10K 2.0 Mapping arrays. SNP array results were in concordance with known genetic aberrations for each renal tumor subtype. Additional chromosomal aberrations were detected in all renal cell tumor types. The unique patterns allowed 19 out of 20 tumors to be readily categorized by their chromosomal copy number aberrations. One papillary renal cell carcinoma type 2 did not show the characteristic 7/17 trisomies. Clustering using the median copy number of each chromosomal arm correlated with histological class when using a restricted set of chromosomes. In addition, three morphologically challenging tumors were analyzed to explore the potential clinical utility of this method. In these cases, the SNP array-based copy number evaluation yielded information with potential clinical value. These results show that SNP arrays can detect characteristic chromosomal aberrations in paraffin-embedded renal tumors, and thus offer a high-resolution, genome-wide method that can be used as an ancillary study for classification and potentially for prognostic stratification of these tumors.

Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors.

BACKGROUND: Renal epithelial tumors are morphologically, biologically, and clinically heterogeneous. Different morphologic subtypes require specific management due to markedly different prognosis and response to therapy. Each common subtype has characteristic chromosomal gains and losses, including some with prognostic value. However, copy number information has not been readily accessible for clinical purposes and thus has not been routinely used in the diagnostic evaluation of these tumors. This information can be useful for classification of tumors with complex or challenging morphology. 'Virtual karyotypes' generated using SNP arrays can readily detect characteristic chromosomal lesions in paraffin embedded renal tumors and can be used to correctly categorize the common subtypes with performance characteristics that are amenable for routine clinical use. METHODS: To investigate the use of virtual karyotypes for diagnostically challenging renal epithelial tumors, we evaluated 25 archived renal neoplasms where sub-classification could not be definitively rendered based on morphology and other ancillary studies. We generated virtual karyotypes with the Affymetrix 10 K 2.0 mapping array platform and identified the presence of genomic lesions across all 22 autosomes. RESULTS: In 91% of challenging cases the virtual karyotype unambiguously detected the presence or absence of chromosomal aberrations characteristic of one of the common subtypes of renal epithelial tumors, while immunohistochemistry and fluorescent in situ hybridization had no or limited utility in the diagnosis of these tumors. CONCLUSION: These results show that virtual karyotypes generated by SNP arrays can be used as a practical ancillary study for the classification of renal epithelial tumors with complex or ambiguous morphology.