Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, 17, and this pattern of genetic abnormality is not present in renal oncocytoma

Department of Pathology and Laboratory Medicine, Universitá di Verona, Verona, Italy.
Modern Pathology (Impact Factor: 6.19). 03/2005; 18(2):161-9. DOI: 10.1038/modpathol.3800286
Source: PubMed


That chromophobe renal cell carcinoma has an uncommon eosinophilic variant has been recognized for more than a decade. In sections stained with hematoxylin and eosin, the eosinophilic variant of chromophobe renal cell carcinoma and renal oncocytoma are similar in appearance. While it is well established that chromophobe renal cell carcinoma and renal oncocytoma have different patterns of genetic anomalies, little is known of the genetics of the eosinophilic variant of chromophobe renal cell carcinoma. This study was undertaken to elucidate the genetic lesions of eosinophilic chromophobe renal cell carcinoma and to compare them with those found in classic chromophobe renal cell carcinoma and in renal oncocytoma. A total of 29 renal neoplasms--nine eosinophilic chromophobe renal cell carcinomas, 10 classic chromophobe renal cell carcinomas, and 10 oncocytomas--were investigated by fluorescence in situ hybridization on 5 microm paraffin-embedded tissue sections with centromeric probes for chromosomes 1, 2, 6, 10, and 17. Signals were counted in 100-200 neoplastic nuclei from each tumor. Chromophobe renal cell carcinomas frequently showed loss of chromosomes 1 (70% of classic, 67% of eosinophilic), 2 (90% classic, 56% eosinophilic), 6 (80% classic, 56% eosinophilic), 10 (60% classic, 44% eosinophilic), and 17 (90% classic, 78% eosinophilic); Among the classic chromophobe renal cell carcinomas, only one had no loss of any of the chromosomes, while 50% had loss of all five chromosomes. Among the eosinophilic chromophobe renal cell carcinomas, one of nine had no loss and 44% had loss of all five chromosomes. One oncocytoma had loss of chromosome 1. No other chromosomal loss was detected in the oncocytomas. In conclusion, losses of chromosomes 1, 2, 6, 10, and 17 are frequent in both eosinophilic and classic chromophobe renal cell carcinomas. Loss of chromosome 1 occurs occasionally in oncocytoma but losses of chromosomes 2, 6, 10, and 17 are not found in oncocytomas. When the differential diagnostic problem is oncocytoma vs eosinophilic chromophobe renal cell carcinoma, detection of losses of chromosomes 2, 6, 10, or 17 effectively excludes the diagnosis of oncocytoma and supports the diagnosis of chromophobe renal cell carcinoma.

Download full-text


Available from: Liang Cheng, Mar 26, 2014
  • Source
    • "There were no focal copy-number events by GISTIC analysis (Mermel et al., 2011), suggestive of a simpler chromosomal landscape for ChRCC in comparison with that of other cancers, including the more common clear cell type RCC (ccRCC). We subdivided our ChRCC cases according to previously defined histologic categories of ''classic'' (n = 47), which demonstrate the classical pale cytoplasmic features for which the disease was named, and ''eosinophilic'' (n = 19), based on abundant, eosinophilic cytoplasm and densely packed mitochondria, by expert consensus pathology review (Brunelli et al., 2005). Although all classic cases showed the characteristic ChRCC copy-number pattern, only about half of the eosinophilic cases (10 of 19) showed the same, with four eosinophilic cases showing no copy-number alterations. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
    Cancer Cell 09/2014; 26:319-330. · 23.52 Impact Factor
  • Source
    • "An IHC panel including CD10, parvalbumin, AMACR, CK7, and S100A1 seems the most promising. Fluorescence in situ hybridization analysis using centromeric probes to evaluate the gains of chromosomes 7 and 17 and the losses of chromosomes 1, 2, 3p, 6, 10, 17, and Y can be helpful in selected cases (Fig. 1 and Table 2) [23] [24] [25] [26] [27] [28] [29]. Patients with low-grade tumors (grades 1–2) who are elderly or unfit for surgery can be considered candidates for cryotherapy, RFA, or surveillance programs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last few years, the treatment of renal cell carcinoma (RCC) has progressed significantly, and some histopathologic issues have become important for selection and follow-up after medical and surgical therapies. The aim of this collaborative article is to review the most recent literature on the role of traditional histopathologic features obtained from renal core biopsy or nephrectomy specimens in the management of confined, locally advanced, and metastatic RCC. A nonsystematic review of the literature was performed in April 2010 using the Medline database. Multiple free-text searches were performed for the following items: renal cell carcinoma, clear cell, papillary, chromophobe, histologic* subtype*, histotype*, nuclear grade*, necrosis, sarcomatoid differentiation, biopsy, molecular marker*, and cytogenetic marker*. A total of 2369 records were retrieved from Medline, and 263 full-text studies were considered and partially included in the present review. A panel of experts reached consensus on the main subheadings of this paper. Core needle biopsies can provide important information that is useful to avoid the overtreatment of benign tumors and to help plan watchful waiting or minimally invasive treatments in selected patients. Tumor histotype is fundamental in the pathologic report. In the context of integrated prognostic systems, the combination of the most important clinical and pathologic factors (TNM stage, Fuhrman nuclear grade, presence of necrosis, microvascular invasion, and sarcomatoid dedifferentiation) allows us to reach a high prognostic accuracy. These models can be used to select patients suitable for adjuvant protocols, to design an appropriate follow-up schedule, and to provide careful patient counseling. Molecular and cytogenetic markers should be further evaluated. The histopathologic definition of parenchymal epithelial renal tumors is fundamental to plan the management and follow-up of patients with locally confined, locally advanced, and metastatic RCC.
    European Urology 11/2010; 58(5):655-68. DOI:10.1016/j.eururo.2010.08.001 · 13.94 Impact Factor
  • Source
    • "The apparent complexity of these karyotypes is partially explained by the ploidy of the tumor, as relative gains may result from the presence of two copies of some chromosomes in a hyper-haploid tumor or from four copies of those same chromosomes after polyploidization (hyper-triploidy) (Gerharz et al., 1995; Bugert et al., 1997). Two cases displayed small and atypical alterations and the remaining three showed no copy number changes, as has been reported in a minority of the cases in the literature (Speicher et al., 1994; Iqbal et al., 1996; Brunelli et al., 2005). Finally, only two out of eight oncocytomas were genetically abnormal by CGH, showing the typical 1p loss and 11q gain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The association of a genetic analysis that could improve the diagnostic accuracy of renal cell tumors in biopsy samples would allow better-informed therapeutic decisions. We performed comparative genomic hybridization (CGH) on an ex vivo fine-needle aspiration (FNA) biopsy and a tumor fragment obtained from 75 patients consecutively diagnosed with renal tumors and subjected to radical nephrectomy. The pattern of genomic changes by CGH was used blindly to classify the renal tumors and the genetic findings were subsequently compared with the histopathologic diagnosis. In particular cases, including in two carcinomas with morphologically distinct tumor areas, we performed FISH with several locus-specific probes, and looked for VHL point mutations, exonic rearrangements, or promoter methylation. CGH was successful in 82.7% FNA biopsies and in 96% tumor fragments, with the former allowing genetic diagnosis in 75% of renal cell tumors. The genetic and the initial histological classification differed in two renal neoplasias, but the genetic diagnosis was confirmed after review. The genetic pattern correctly diagnosed 93.5% of clear cell renal cell carcinomas (RCC), 61.5% of chromophobe RCC, 100% of papillary RCC, and 14.3% of oncocytomas, with the negative predictive value being 93.9, 90.7, 100, and 90.2%, respectively. The positive predictive value and specificity of copy number profiles was 100%. We demonstrate that genetic diagnosis by CGH on FNA biopsies can improve differential diagnosis in patients with kidney tumors.
    Genes Chromosomes and Cancer 10/2010; 49(10):935-47. DOI:10.1002/gcc.20805 · 4.04 Impact Factor
Show more