Oncocytic and chromophobe renal tumors
2023-02-16 Paola Dal Cin, PhD , Michelle S. Hirsch, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Classification
Definition
Genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. 1 However, both tumors are thought to be derived from the intercalated cells of the distal convoluted tubules in the renal cortex. 2,3 The only genetic alteration shared by chromophobe RCC and RO is loss of chromosome 1. Additional heterogeneous groups of oncocytic tumors have recently been described showing overlapping or intermediate (borderline) features between oncocytoma and eosinophilic ChRCC. Some of these tumors may be one of three emerging entities: low grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT) or eosinophilic solid and cystic renal cell carcinoma (ESC-RCC). 4,5 LOTs and EVTS are benign, solitary lesions and are rarely found in patients with tuberous sclerosis complex. ESC is also associated with TSC mutations, and may rarely show more aggressive behavior. 6 Other oncocytic tumors which do not fit into one of these classification subtypes should be referred to as “low grade oncocytic tumor/carcinoma, not otherwise specified”. The latter term can be used to define sporadic tumors and “hybrid oncocytic tumors”. 6
| Oncocytic and chromophobe tumors | Genetic marker(s) |
|---|---|
| Renal oncocytoma (RO) | Loss of chromosomes 1 and/or 14 , 21 and one sex chromosome (most often the Y chromosome). 7,8 |
| Rearrangement of 11q13, with t(9;11)(p23;q12) and t(5;11)(q35;q13) being the most frequent translocations observed 9, with increased expression of cyclinD1, demonstrated by immunohistochemistry. 8,10 A t(6;9)(p21;p23) was reported in 3 cases. 11 | |
| Chromphobe renal cell carcinoma (ChRCC) | Historically , a very unique and characteristic genotype with combination of monosomies, especially of chromosomes 1, 2, 6, 10, 13, 17, 21 and sex chromosome in 86% of tumours and additional losses of chromosomes 3, 5, 8, 9, 11 and 18, and chromosome arm 21q in 12–58% of tumors. 12,13 It has demonstrate that such unique genetic pattern is significantly more frequent in the classic form than in the eosinophilic variant, with chromosome 1 loss, as early event in ChRCC tumorigenesis. 1,14,15 |
| Significantly lower rate of somatic gene mutations, with TP53 and PTEN as the two most frequently mutated genes, esspecially with sarcomatoid differentiation or metastatic disease. Loss of CDKN2A or its expression, by either deletion of 9p21.3 or hypermethylation been associated with short overall survival and were independent predictors of prognosis.16 Addtional alterations in PI3K–AKT–mTOR pathway genes, including PTEN, TSC1, TSC2 and MTOR. 13,14 | |
| Somatic mitochondrial DNA mutations 17 and Increased TERT expression as consequences of known C228T TERT gene promoter mutation or rearrangement e.g. intrachromosomal or with chr. 13 .13,14 | |
| Emerging oncocytic tumors of the kidney | Eosinophilic vacuolated tumor (EVT): often incidental, more frequently in women and typically indolent behavior. Variable copy number variation (CNV) , but loss of chromosome 1 was commonly reported, as well as losses of chromosome 19p or 19q, 18 and loss of heterozygosity at 16p11 and 7q31. Loss of chromosome 1, along with concurrent TSC/mTOR pathway mutations, seem to be the key molecular genetic findings in EVT 19-21 |
| Low-grade oncocytic tumor (LOT): typically detected incidentally and with indole behavior. Single, relatively small tumor, found in a non-syndromic setting, but rare examples of multiple LOTs or admixed with other tumors in patients with tuberous sclerosis complex (TSC) OMIM:191100. Frequent deletions at 19p13 , 1p36 , and 19q13, 18 but not complete chromosomal losses or gains. Involvement of TSC/mTOR pathway genes. 22-25 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 33183792 | 2021 | Chromophobe renal cell carcinoma: current and controversial issues. | Moch H et al |
| 2 | 27256309 | 2016 | DNA Methylation Signature Reveals Cell Ontogeny of Renal Cell Carcinomas. | Malouf GG et al |
| 3 | 30093597 | 2018 | Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. | Young MD et al |
| 4 | 36344185 | 2022 | Kidney Tumors: New and Emerging Kidney Tumor Entities. | Siadat F et al |
| 5 | 33526874 | 2021 | Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. | Trpkov K et al |
| 6 | 35273336 | 2022 | Do we need an updated classification of oncocytic renal tumors? : Emergence of low-grade oncocytic tumor (LOT) and eosinophilic vacuolated tumor (EVT) as novel renal entities. | Hes O et al |
| 7 | 20590944 | 2010 | Molecular pathology of renal oncocytoma: a review. | Yusenko MV et al |
| 8 | 26655904 | 2015 | The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis. | Joshi S et al |
| 9 | 31112346 | 2020 | Cytogenetic analysis of 130 renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations. | Anderson CB et al |
| 10 | 19386349 | 2009 | CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma. | Sukov WR et al |
| 11 | 20952287 | 2011 | A new translocation between chromosomes 6 and 9 helps to establish diagnosis of renal oncocytoma. | Hudacko R et al |
| 12 | 29617669 | 2018 | The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. | Ricketts CJ et al |
| 13 | 31278395 | 2019 | The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications. | Linehan WM et al |
| 14 | 25155756 | 2014 | The somatic genomic landscape of chromophobe renal cell carcinoma. | Davis CF et al |
| 15 | 30787564 | 2019 | Chromosomal aberrations in renal cell carcinoma: An overview with implications for clinical practice. | Quddus MB et al |
| 16 | 32079343 | 2020 | Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients. | Ohashi R et al |
| 17 | 12353267 | 2002 | Somatic mitochondrial DNA mutations in human chromophobe renal cell carcinomas. | Nagy A et al |
| 18 | 30895640 | 2019 | Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity? | Trpkov K et al |
| 19 | 34009776 | 2021 | Eosinophilic Vacuolated Tumor of the Kidney: A Review of Evolving Concepts in This Novel Subtype With Additional Insights From a Case With MTOR Mutation and Concomitant Chromosome 1 Loss. | Kapur P et al |
| 20 | 34521993 | 2022 | Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases. | Farcaş M et al |
| 21 | 34728788 | 2022 | Correction to: Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases. | Farcaş M et al |
| 22 | 34538873 | 2022 | Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney. | Kapur P et al |
| 23 | 35156688 | 2022 | Low-grade oncocytic tumor (LOT) - a new renal entity ready for a prime time: An updated review. | Mansoor M et al |
| 24 | 35980750 | 2022 | TSC/MTOR -associated Eosinophilic Renal Tumors Exhibit a Heterogeneous Clinicopathologic Spectrum : A Targeted Next-generation Sequencing and Gene Expression Profiling Study. | Xia QY et al |
| 25 | 36208048 | 2023 | Low-grade oncocytic tumour of the kidney is characterised by genetic alterations of TSC1, TSC2, MTOR or PIK3CA and consistent GATA3 positivity. | Williamson SR et al |
Citation
Paola Dal Cin, PhD ; Michelle S. Hirsch, MD
Oncocytic and chromophobe renal tumors
Atlas Genet Cytogenet Oncol Haematol. 2023-02-16
Online version: http://atlasgeneticsoncology.org/solid-tumor/209008/oncocytic-and-chromophobe-renal-tumors
