Chromophobe Renal Cell Carcinoma: Results From a Large Single-Institution Series

Casuscelli, Jozefina; Becerra, Maria F.; Seier, Kenneth; Manley, Brandon; Benfante, Nicole; Redzematovic, Almedina; Stief, Christian G.; Hsieh, James J.; Tickoo, Satish K.; Reuter, Victor E.; Coleman, Jonathan; Russo, Paul; Ostrovnaya, Irina; Hakimi, A. Ari

doi:10.1016/j.clgc.2019.06.011

Cited by 44 publications

(36 citation statements)

References 20 publications

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“…Overall, the most common histology seen with sarcomatoid features is ccRCC, which comprises ~80% of all RCC cases 54 . Reports have suggested that chromophobe RCCs, which comprise ~5–10% of all RCC cases 55 , might harbour a higher rate of sarcomatoid dedifferentiation than ccRCCs 10 , 56 , although the higher prevalence of ccRCCs made it difficult to validate this finding. Sarcomatoid change has also been reported in acquired cystic disease RCCs 57 and hereditary leiomyomatosis RCC syndrome-associated RCCs 58 , 59 .…”

Section: Pathologymentioning

confidence: 99%

Sarcomatoid renal cell carcinoma: biology, natural history and management

et al. 2020

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Renal cancers are estimated to be diagnosed in 73,750 people in the USA in 2020, and to contribute to 14,830 deaths 1. The 2018 GLOBOCAN report on the global incidence of renal cancers has described 403,262 patients with renal cancer, and 175,098 deaths caused by renal cancers worldwide 2,3. Approximately 90% of all diagnosed renal parenchymal malignancies are renal cell carcinomas (RCCs) 4. A rare transformation called sarcomatoid dedifferentiation can occur in most RCC histological subtypes and portends an especially poor prognosis. RCCs in which sarcomatoid dedifferentiation has occurred are commonly referred to as sarcomatoid RCCs (sRCCs), and patients with sRCCs often present with advanced or metastatic disease and rarely survive >1 year 5-7. Sarcomatoid features are present in approximately 4-5% of all RCCs 8-11. However, this proportion can range from 1 to 29% depending on the primary histology and the reporting study 7,9-13. Although infrequently diagnosed in the localized setting (~20-40% of all sRCCs) 14,15 , approximately 20% of patients with metastatic RCC harbour sarcomatoid dedifferentiation 15. Patients commonly present with an sRCC at between 54 and 63 years of age 6,7,13,14,16,17 , and the male-to-female ratio ranges from 1.3:1 to 2:1 (refs 6,13,14,18,19). Similar to all other RCCs, the mechanisms underlying this gender difference remain unclear. However, possibilities include historical gender differences in occupational exposure or smoking habits, or the influence of sex hormones on tumour biology 20. The natural history and prognosis of sRCCs are poor, as approximately 60-80% of patients present with advanced or late-stage disease 14,15. Median survival is approximately 6-13 months and a higher percentage of sarcomatoid dedifferentiation on histology has been reported to confer a worse prognosis 6,7,11,21,22. Retrospective reports have shown reduced overall survival and cancer-specific survival in patients with increased sarcomatoid features 11,21. Compared with patients without sarcomatoid features, patients with ≥25% sarcomatoid features had ~30% increased overall risk of dying of any cause (HR 2.07, P = 0.048) 11 and those with ≥30% sarcomatoid features had a 52% increased risk of

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Section: Pathologymentioning

confidence: 99%

Sarcomatoid renal cell carcinoma: biology, natural history and management

et al. 2020

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“…Since the first description by Thoenes et al, epidemiology and pathological features of chromophobe RCC have been extensively studied. [18][19][20][21][22][23] Chromophobe RCC accounts for approximately 5-7% of RCC. Most tumours are sporadic.…”

Section: Epidemiology Macroscopy Histopathologymentioning

confidence: 99%

“…Numerous studies have confirmed that tumour size and the presence of sarcomatoid morphology indicates poor prognosis and increased risk of metastatic development for chromophobe RCC. 23,28,[85][86][87][88] Tumour grade is also important, but the four tiered nuclear grading system proposed by ISUP could not be validated for chromophobe RCC, because they have an innate constitutive atypia including prominent nucleoli, nuclear irregularities and bi-nucleation. 89 In the past, there have been several attempts to develop a grading system for chromophobe RCC, [20][21][22]27,85,86,90,91 considering the inherent geographic nuclear crowding and presence of anaplasia.…”

Section: Prognosis and Grading Of Chromophobe Rccmentioning

confidence: 99%

“…Patients with high grade tumours (sarcomatoid differentiation and/or tumour necrosis) should have a stringent follow-up because of their increased risk of metastasis. 23 Because metastasis of chromophobe RCC is very rare, dedicated prospective clinical trials for metastatic chromophobe RCC are not available and patients are treated as non-clear cell RCC. Favourable responses to VGF-tyrosine kinase inhibitor agent, mTOR inhibitors and immune checkpoint inhibitors have been reported.…”

Section: Treatment Of Metastatic Chromophobe Rccmentioning

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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“…Finally and importantly, median overall survival was clearly inferior for patients with sarcomatoid differentiation compared to those without this differentiation properties (7.5 months vs. 38 months) [ 143 ]. Recently, Casuscelli et al have reported a survey on a very large cohort of 496 CHRCC patients diagnosed and surgically treated at Memorial Sloan Kettering Cancer Center [ 144 ]. This study definitely confirmed the findings observed in previous studies, showing that: at 10 years, the relapse-free survival was 91.7% and the overall survival 82.1% for CHRCC patients, compared to 79.4% and 63.6% for CCRCC patients; patients with CHRCC displayed less frequently sarcomatoid differentiation compared to CCRCC patients (1.2% vs. 4%); larger tumor size, sarcomatoid differentiation, and higher tumor-stage are significantly associated with adverse RFS and OS in CCRCCs [ 144 ].…”

Section: Chromophobe Renal Cancermentioning

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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Chromophobe Renal Cell Carcinoma: Results From a Large Single-Institution Series

Cited by 44 publications

References 20 publications

Sarcomatoid renal cell carcinoma: biology, natural history and management

Sarcomatoid renal cell carcinoma: biology, natural history and management

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

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