Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma

Ruíz-Cordero, Roberto; Rao, Priya; Li, Lerong; Qi, Yuan; Atherton, Daniel S.; Peng, Bo; Singh, Rajesh; Kim, Tae Beom; Kawakami, Fumi; Routbort, Mark J.; Alouch, Nail; Chow, Chi Wan; Tang, Ximing; Lü, Wei; Brimo, Fadi; Matin, Surena F.; Wood, Christopher G.; Tannir, Nizar M.; Wistuba, Ignacio I.; Chen, Ken; Wang, Jing; Medeiros, L. Jeffrey; Karam, Jose A.; Tamboli, Pheroze; Sircar, Kanishka

doi:10.1038/s41379-019-0304-y

Cited by 42 publications

(47 citation statements)

References 27 publications

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“…60,61 A very recent and comprehensive study by Ruiz-Cordero et al studied hybrid oncocytic and chromophobe tumour by gene expression profiling and targeted NGS and compared the results with chromophobe RCC and renal oncocytoma. 62 Hybrid oncocytic and chromophobe tumours were more frequently multifocal and did not exhibit mutations in genes that are recurrently mutated in renal oncocytoma or chromophobe RCC, but they showed copy number alterations primarily involving losses in chromosomes 1 and X/Y. mRNA transcript data separated hybrid oncocytic and chromophobe tumour from renal oncocytoma and chromophobe RCC.…”

Section: Hybrid Oncocytic and Chromophobe Tumoursmentioning

confidence: 98%

“…Therefore, the term 'hybrid oncocytic and chromophobe tumour' was proposed 20 and is now variably used in several scenarios, including tumours in BHD syndrome, oncocytomatosis and for sporadic cases. [60][61][62] Unfortunately, the morphological criteria are not exactly defined. Some hybrid oncocytic and chromophobe tumours show a mosaic pattern with defined renal oncocytoma-like zones with solid nests/alveoli in close contact to chromophobe RCC-like zones (Fig.…”

Section: Hybrid Oncocytic and Chromophobe Tumoursmentioning

confidence: 99%

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Chromophobe renal cell carcinoma: current and controversial issues

Moch

Ohashi

2021

Pathology

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It has been 35 years since Professor Thoenes and his colleagues discovered chromophobe renal cell carcinoma (RCC). Since then, our knowledge about this tumour entity has changed and novel tumour entities have been discovered. The aim of this review is to discuss recent molecular findings and open questions in diagnosing chromophobe-like/oncocytic neoplasms. The broader differential diagnosis of chromophobe-like and oncocytomalike neoplasms includes SDH-deficient renal cell carcinoma, fumarate hydratase (FH) deficient RCC, epitheloid angiomyolipoma ('oncocytoma like'), MiT family translocation RCC and the emerging entity of eosinophilic solid and cystic renal cell carcinoma. After separation of these tumours from chromophobe RCC, it becomes evident that chromophobe RCC are low malignant tumours with a 5-6% risk of metastasis. Recent next generation sequencing (NGS) and DNA methylation profiling studies have confirmed Thoenes' theory of a distal tubule derived origin of chromophobe RCC and renal oncocytomas. Comprehensive genomic analyses of chromophobe RCC have demonstrated a low somatic mutation rate and identified TP53 and PTEN as the most frequently mutated genes, whereas 'unclassified' RCC with oncocytic or chromophobe-like features can show somatic inactivating mutations of TSC2 or activating mutations of MTOR as the primary molecular alterations. For the future, it would be desirable to create a category of 'oncocytic/chromophobe RCC, NOS' with the potential of further molecular studies for identification of TSC1/2 mutations in these rare tumours.

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Section: Hybrid Oncocytic and Chromophobe Tumoursmentioning

confidence: 98%

Section: Hybrid Oncocytic and Chromophobe Tumoursmentioning

confidence: 99%

Chromophobe renal cell carcinoma: current and controversial issues

Moch

Ohashi

2021

Pathology

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“…Therefore, this study clearly showed that BHD-related renal cancer lacks the mutations in driver genes, such as TP53, CDKN2A, RB1, PTEN, and mTOR , typically observed in CHRCC. It is of interest to note that at molecular level BHD-related hybrid oncocytic/chromophobe tumors can be differentiated from the sporadic counterpart of these tumors in that these last tumors have copy number losses in chromosomes 1 and XY, but lacks recurrent mutations [ 101 ].…”

Section: Birt-hogg-dubé (Bhd) Syndromementioning

confidence: 99%

Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets

Testa

Castelli

2020

Medicines

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Renal cell cancer (RCC) involves three most recurrent sporadic types: clear-cell RCC (70–75%, CCRCC), papillary RCCC (10–15%, PRCC), and chromophobe RCC (5%, CHRCC). Hereditary cases account for about 5% of all cases of RCC and are caused by germline pathogenic variants. Herein, we review how a better understanding of the molecular biology of RCCs has driven the inception of new diagnostic and therapeutic approaches. Genomic research has identified relevant genetic alterations associated with each RCC subtype. Molecular studies have clearly shown that CCRCC is universally initiated by Von Hippel Lindau (VHL) gene dysregulation, followed by different types of additional genetic events involving epigenetic regulatory genes, dictating disease progression, aggressiveness, and differential response to treatments. The understanding of the molecular mechanisms that underlie the development and progression of RCC has considerably expanded treatment options; genomic data might guide treatment options by enabling patients to be matched with therapeutics that specifically target the genetic alterations present in their tumors. These new targeted treatments have led to a moderate improvement of the survival of metastatic RCC patients. Ongoing studies based on the combination of immunotherapeutic agents (immune check inhibitors) with VEGF inhibitors are expected to further improve the survival of these patients.

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“…The histopathological and molecular characterisation of renal neoplasms is continuously evolving, as re ected in the 2016 World Health Organization (WHO) classi cation, and in the introduction of potentially new and emerging renal entities in the post-WHO era [10,11]. For example, clear cell papillary RCC (ccpRCC), a tumour of low malignant potential, is now classi ed as a separate entity [12], while the so called "hybrid chromophobe oncocytic tumour" (HOCT), showing features that overlap between RO and chromophobe renal cell carcinoma (chRCC), considered a subtype of chRCC in the 2016 WHO classi cation, has been found to demonstrate molecularly distinct pro le, with genomic features intermediate between those of RO and chRCC [13,14]. Other entities, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Other entities, e.g. fumarate hydrase (FH)-de cient RCCs, as well as emerging entities, such low grade-oncocytic tumours (LOT) and high grade-oncocytic tumours [14][15][16][17] are also expanding the spectrum of renal oncocytic neoplasia [11].…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Renal Oncocytoma From Renal Cell Carcinoma Using 99mTc-Sestamibi SPECT/CT.

Tzortzakakis

Papathomas

Gustafsson

et al. 2021

Preprint

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Background: 99mTc-Sestamibi Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) contributes to the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC). We investigated whether standard uptake value (SUV) SPECT, has a beneficial role in differentiating renal oncocytoma (RO) from renal cell carcinoma (RCC) besides visual assessment. As a secondary aim, we evaluated the mitochondrial content of 19 oncocytic tumours arranged in a tissue microarray, by immunohistochemistry, using succinate dehydrogenase complex subunit B (SDHB) protein expression. In addition to visual evaluation of 99mTc-Sestamibi uptake by characterizing renal tumours as Sestamibi positive or Sestamibi negative regarding their uptake compared to the non-tumoral renal parenchyma, SUVmean and SUVmax measurements were performed in the renal tumour and the non-tumoral renal parenchyma. Intra Class Correlation calculated to assess the intra-reader reliability of SUV measurements. ROC-analysis demonstrated an optimal cut off SUV value that differentiates RO from RCC. SDHB score was analysed using Cochran–Armitage test for trend.Results: 57 renal tumours from 52 patients were evaluated. Visual evaluation of 99mTc-Sestamibi SPECT/CT examination resulted in a sensitivity of 83%, whereas quantitative evaluation showed a sensitivity of 64% regarding the differential of RO from RCC. A significant trend (p=0,0328) of increased SDHB score found in the Sestamibi positive group.Conclusion: Quantitative evaluation with SUV SPECT measurements did not improve the performance of 99mTc-Sestamibi SPECT/CT in differentiating RO from RCC. 99mTc- Sestamibi SPECT/CT identified a larger Sestamibi-positive tumour group containing RO, Hybrid Oncocytic Chromophobe Tumours and the majority of chromophobe RCCs. Thus, Sestamibi-negative renal tumours, that are possibly malignant, should be considered for surgery. Patients with Sestamibi-positive tumours can be suited for biopsy and follow up according to active surveillance protocols. Low Grade Oncoytic Tumour, a provisional renal entity with no proven recurrence or metastatic potential, appears to be positive on 99mTc- Sestamibi SPECT/CT examination.

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Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma

Cited by 42 publications

References 27 publications

Chromophobe renal cell carcinoma: current and controversial issues

Chromophobe renal cell carcinoma: current and controversial issues

Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets

Differentiation of Renal Oncocytoma From Renal Cell Carcinoma Using 99mTc-Sestamibi SPECT/CT.

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