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What Is Clear Cell Carcinoma Of The Kidney

Looking For More Of An Introduction

Clear Cell and Chromophobe Renal Cell Carcinoma

If you would like more of an introduction, explore these related items. Please note that these links will take you to other sections on Cancer.Net:

  • ASCO Answers Fact Sheet:Read a 1-page fact sheet that offers an introduction to kidney cancer. This free fact sheet is available as a PDF, so it is easy to print.

What Is The Prognosis For People With Ccrcc

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as

  • Where the tumor is in your body
  • If the cancer has spread to other parts of your body
  • How much of the tumor was taken out during surgery

If you want information on your prognosis, it is important to talk to your doctor. NCI also has resources to help you understand cancer prognosis.

Doctors estimate ccRCC survival rates by how groups of people with ccRCC have done in the past. Because there are so few pediatric ccRCC patients, these rates may not be very accurate. They also dont take into account newer treatments being developed.

With this in mind, ccRCC patients with smaller tumors have a better chance of survival than patients with larger tumors. The 5-year survival rate for patients with ccRCC is 50-69%. When ccRCC is already large or has spread to other parts of the body, treatment is more difficult and the 5-year survival rate is about 10%.

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Localtherapy Of Metastases In Metastatic Rcc

A systematic review of the local treatment of metastases from RCC in anyorgan was undertaken . Interventions included metastasectomy,various radiotherapy modalities, and no local treatment. The outcomes assessed were OS, CSSand PFS, local symptom control and adverse events. A risk-of-bias assessment was conducted. Of the 2,235 studies identified only sixteen non-randomisedcomparative studies were included.

Eight studies reported on local therapies of RCC-metastases in variousorgans . This included metastases to any single organor multiple organs. Three studies reported on local therapies of RCC metastases in bone,including the spine , two in the brain and one each in the liver lung and pancreas . Three studies were published as abstracts only . Datawere too heterogeneous to meta-analyse. There was considerable variation in the type anddistribution of systemic therapies and in reporting theresults. versus no/incompletemetastasectomy

Three studies reported on treatment of RCC metastases inthe lung , liver , and pancreas, respectively. The lung study reported a significantly highermedian OS for metastasectomy vs. medical therapy only for both targeted therapy andimmunotherapy. Similarly, the liver and pancreas study reported a significantly highermedian OS and 5-year OS for metastasectomy vs. no metastasectomy. therapies for RCC bonemetastases therapies for RCC brainmetastases of metastases

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Clinical Application Of Mirnas As Markers For Diagnosis And Prognosis

In this review, we included only the most convincing results obtained from studies featuring large sample sizes and detailed statistical evaluations. Initially, we examined the features of miRNAs that are relevant concerning their diagnostic potential. These features are summarized in Table 2.

Table 2. Non-invasive markers suggested for use in ccRCC diagnosis: miRNA level and diagnostic value.

The diagnostic value of elevated miR-210 levels is well established. This may be due to chronic hypoxia observed in ccRCC . However, no correlation of miR-210 expression with tumor stage has been reported . The expression of miR-1233 in RCC cell lines is also stimulated by hypoxia .

The target of miR-451 is an mRNA encoding the PSMB8 protein, which has a pro-inflammatory function, and which is presumably significant in RCC . In RCC, miR-193a-3p affects the PI3K/AKT pathway . miR-28-5p is associated with chromosomal instability . In addition, its target is Ras-related small GTP-binding oncoprotein RAP1B . miR-141 is involved in the suppression of EMT .

The genes discussed above, including some with inconsistent features , have been suggested for the diagnosis of ccRCC . Thus, the methods of ccRCC diagnosis need further verification.

Table 3. Prognostic markers for poor survival and metastasis in ccRCC: miRNA level and predictive value.

Emerging And New Entities

Clear Cell Renal Cell Carcinoma Metastasis To Thyroid

The first three tumors take part in the differential diagnosis of oncocytic tumors and their main distinctive features are reviewed in Table .

Low-grade oncocytic tumor of the kidney shares with oncocytomas the predominant solid and nested growth pattern and the oncocytic cytoplasm. However, they show a distinct immunophenotype of c-KIT/CD117 negative and cytokeratin 7 positive. The typical microscopic picture is of solid sheets and compact nests, with gradual transition to trabecular areas, sharply delineated edematous stromal areas with loose cell growth. These loose irregular areas of growth differ from the islands of oncocytic cells in hypocellular areas of oncocytoma. Genomic findings are shared with oncocytomas such as loss of 1p36 and diploid pattern, while gains and losses that are common in chromophobe RCC are not seen. They exhibit uniformly an indolent course . Although the authors advocate that low-grade oncocytic tumor of the kidney may be readily recognized in HE stain, we recommend that this diagnosis should be considered in tumors with compatible findings in the context of cKIT/CD117 negative, cytokeratin 7 positive findings when the common differential diagnosis of oncocytoma and chromophobe carcinoma is being evaluated. The importance of recognizing this tumor is to avoid labeling such indolent tumors as unclassified RCC.

Fig. 7Fig. 8

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Other Types With Predominant Eosinophilic Cells

Tubulocystic carcinoma is a rare subtype of renal cell carcinoma. The gross appearance is typically of multicystic mass. At microscopy, the tumor is formed by small and medium sized tubules with occasional cystic dilated tubules. The tumor cells have eosinophilic/oncocytic cytoplasm and nuclei show a typical prominent nucleolus . Recognition of this tumor is of relevance to acknowledge that, even though the nuclear grade is high, the expected clinical behavior is of an indolent neoplasm. This tumor is typically positive for cytokeratin 7 and AMARC, however, the diagnosis is mostly based on morphology and immunohistochemistry is usually not required. However, attention should be given to grossing, with wide sampling, since Tubulocystic carcinomas with poorly differentiated areas have been associated with FH-deficiency and shown to behave aggressively . Therefore, poorly differentiated adenocarcinoma areas should be reported and immunohistochemistry with FH and 2SC, along with clinical investigation, are recommended in this scenario . Poorly differentiated foci exclude the diagnosis of tubulocystic carcinoma, and the evaluation of FH deficiency will allow documentation of FH-deficient RCC.

Table reviews key recommendations on the differential diagnosis of these tumors.

Mesenchymal Tumors That May Be Considered In Differential Diagnosis

Angiomyolipomas comprise 0.72.0% of all renal tumors and about 20% of them area associated with tuberous sclerosis . As a consequence, germline mutations of TSC1 gene and the TSC2 gene are recommended. The pathological diagnosis is usually straightforward due to characteristic combination of bland morphologies of adipose tissue, smooth muscle tissue and large vessels with thickened walls. The clinical behavior is benign in the absence of epithelioid morphology. The diagnosis of epithelioid angiomyolipomas requires more than 80% of epithelioid cells. Epithelioid angiomyolipoma has metastatic potential may also be associated with tuberous sclerosis. Metastatic behavior is predicted by larger size , carcinoma-like atypia, involvement of perinephric tissues, renal vein invasion and necrosis. Those aggressive epithelioid angiomyolipoma may mimic high-grade eosinophilic renal cell carcinomas .

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Role Oflymph Node Invasion In Locally Advanced Rcc

In locally advanced RCC, the role of LND is still controversial. The onlyavailable RCT demonstrated no survival benefit for patients undergoing LND but this trialmainly included organ-confined disease cases . In the settingof locally advanced disease, several papers addressed the topic with contradictory results,as did several systematic reviews. Bhindi et al. couldnot confirm any survival benefit in patients at high risk of progression treated with LND. More recently, Luo etal. reported a systematic review and meta-analyses showing a survival benefit inpatients with locally advanced disease treated with LND . Morespecifically, thirteen studies on patients with LND and non-LND were identified and includedin the analysis. In the subgroup of locally advanced RCC , LND showed asignificantly better OS rate in patients who had undergone LND compared to those without LND. of clinically negativelymph nodes in locally advanced RCC

In case of cN-, the probability of finding pathologically confirmed LNmetastases ranges between 0 and 25%, depending mainly on primary tumour size and thepresence of distant metastases . In case of clinically negativeLNs at imaging, removal of LNs is justified only if visible or palpable during surgery, at least for staging, prognosis and follow-up implicationsalthough a benefit in terms of cancer control has not yet been demonstrated . Whether to extend the LND also toretroperitoneal areas without cN+ remains controversial .

Assessment Of The Performance Of Different Models

Clear Cell Renal Cell Carcinoma – Histopathology

The predictive accuracy of the clinical factors model, radiomics signature, and radiomics nomogram for differentiating aggressive ccRCC from non-aggressive ccRCC was quantified by the area under the receiver operating characteristics curve in both the training and validation sets. Decision curve analysis was used to calculate the net benefits for a range of threshold probabilities in the whole cohort to assess the clinical usefulness of the nomogram.

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Clear Cell Renal Cell Carcinoma

Some clear cell renal cell carcinomas demonstrate a focal pseudopapillary growth pattern secondary to tumor cell dropout sparing the cells at the periphery of blood vessels.

In , 2016

Gross Features

Gross features of chromophobe renal cell carcinoma vary according to the cell type. This example of a tumor with classical histology shows a yellow-tan cut surface. A macroscopic central scar is observed in 15% of Ch-RCCs. Such a scar is indicative of a slowly growing tumor scars are also seen in some renal oncocytomas and low-grade clear cell RCCs.

Microscopic Features

The nuclei in Ch-RCC are typically hyperchromatic, with markedly irregular nuclear membranes , as seen in this classical histology of the tumor.

Abundant pale cytoplasm simulating low-grade clear cell renal cell carcinoma

Usually in small flat groups

No vacuolated cytoplasm or branching vessels

Papillary Renal Cell Carcinoma

Abundant papillary structures with foamy macrophages

Usually low-grade atypia, lack of branching vessels

Usually CK7, AMACR, and CA9

Chromophobe Renal Cell Carcinoma

Pronounced irregular nuclei with perinuclear haloes

Hale colloidal iron stain , CK7, CD117, vimentin

Translocation-Associated Renal Cell Carcinoma

Prominent papillary architecture and high-grade clear cells

Strong nuclear stain for TFE3 or TFEB AE1/AE3

Adrenal Cortical Tumors

Metastatic Tumors

Ruth L. Katz, Savitri Krishnamurthy, in, 2008

Living With Clear Cell Renal Cell Carcinoma

Your medical team will develop a treatment plan to help you fight ccRCC, but there are some very important parts of your care that cant happen in an operating room.

Managing your everyday life with ccRCC can feel like a huge challenge. But there are some simple steps you can take at home, with friends, and with other healthcare professionals. Great ways to take care of yourself during treatment include:

  • Eating healthier. There isnt a set diet plan for ccRCC, but eating healthy can help you feel better during treatments and recovery. Talk with your doctor before making any major changes to your diet.
  • Taking time for mental health. It can be hard to talk about a cancer diagnosis, even with family and friends. Mental health professionals such as counselors and psychologists can help you sort through the stress and emotions of managing ccRCC.
  • Asking for help. Its a good idea to turn to friends, family, loved ones, or other supportive people when youre managing ccRCC. Local charities and cancer support groups can help you find support if youre in need.

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Which Imaging Investigations For Whichpatients And When

  • The sensitivity of chest radiography and US for detection of small RCC metastases ispoor. The sensitivity of chest radiography is significantly lower than CT-scans, asproven in comparative studies including histological evaluation . Therefore, follow-up for recurrence detectionwith chest radiography and US are less sensitive .
  • Positron-emission tomography and PET-CT as well as bone scintigraphy should not be usedroutinely in RCC follow-up, due to their limited specificity and sensitivity .
  • Surveillance should also include evaluation of renal function and cardiovascular riskfactors .
  • Outside the scope of regular follow-up imaging of the chest and abdomen, targetedimaging should be considered in patients with organ-specific symptoms, e.g. CT or MRIimaging of the brain in patients experiencing neurological symptoms .

A follow-up algorithm for monitoring patients aftertreatment for RCC is needed, recognising not only the patients risk of recurrenceprofile, but also the efficacy of the treatment given . These prognostic systemscan be used to adapt the follow-up schedule according to predicted risk of recurrence.Ancillary to the above, life-expectancy calculations based on comorbidity and age atdiagnosis may be useful in counselling patients on duration of follow-up .

Table 8.1: Proposed follow-up schedule following treatment forlocalised RCC, taking into account patient risk of recurrence profile and treatment efficacy

Risk profile

CT once yr

CT once every two yrs

Summary Ofevidence And Recommendation For Epidemiology Aetiology And Pathology

Clear cell renal cell carcinoma

Summary of evidence

Several verified risk factors have been identifiedincluding smoking, obesity and hypertension. These are considered definite riskfactors for RCC.


Strength rating

Increase physical activity, eliminate cigarettesmoking and in obese patients reduce weight are the primary preventativemeasures to decrease risk of RCC.


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The Radiomics Nomogram Establishment And Assessment Of The Performance Of Different Models

Figure 6 Radiomics nomogram developed with receiver operating characteristic curves and calibration curves. The radiomics nomogram, combining sex, tumor maximum diameter, neutrophils, albumin, and Rad-score, developed in the training set. The nomogram calibration curves in the training and validation sets. Calibration curves indicate the goodness-of-fit of the model. The closer the pink line approaches the gray line, the better agreement between the predictive probabilities and the observed probabilities.

Table 3 Results of radiomics nomogram, radiomics signature, and the clinical model predictive ability for distinguishing between aggressive ccRCC and non-aggressive ccRCC.

Figure 7 Comparison of receiver operating characteristic curves between the radiomics nomogram and clinical model for the prediction of aggressive clear cell renal cell carcinoma in the training and validation cohorts. AUC, area under the receiver operating characteristic curve.

The decision curve analyses for the clinical factor model and radiomics nomogram are presented in Figure 8. It showed that the radiomics nomogram had a higher overall net benefit in differentiating aggressive ccRCC from non-aggressive ccRCC than the clinical factor model across the full range of reasonable threshold probabilities.

Prognosis And Predictive Factors

Patients with clear cell renal cell carcinoma tend to have a worse prognosis than patients with other histologic subtypes of RCC, with 5-year disease-specific survival rates of 50-69%, compared with 67-87% for papillary RCC and 78-87% for chRCC. However, analysis of 1000 patients showed very similar 5-year disease-specific survival rates for CCRCC and papillary RCC once metastatic disease was present.

Multivariate analyses indicate that histologic RCC subtype has no significant independent value for predicting cancer-specific survival because prognosis is primarily dependent upon TNM stage and Fuhrman nuclear grade. Multivariate analysis specifically of CCRCC cases shows that in addition to the 3 separate components of tumor staging , other significant independent predictors of poor prognosis are nuclear grade, tumor size, and the presence of histologic necrosis or sarcomatoid differentiation.

Rhabdoid differentiation is also observed in CCRCC and seems to impart a poor outcome similar to sarcomatoid change however, this factor has not yet been tested in predictive models. Interestingly, histological necrosis is seen more commonly in papillary RCC but is not a significant predictor of poor prognosis for papillary RCC, even in univariate analyses.

  • Delahunt B, Eble JN. History of the development of the classification of renal cell neoplasia. Clin Lab Med. 2005 Jun. 25:231-46, v. .

  • Pascual D, Borque A. Epidemiology of kidney cancer. Adv Urol. 2008. 782381. .

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    Development Of Radiomics Signature And Radiomics Nomogram

    The prevention of the overfitting of the signature can be realized through the conduction of dimension reduction of the features before signature construction. Only were the radiomics chosen to be kept when meeting a criterion of inter- and intra-observer ICCs greater than 0.75, then the minimum-Redundancy Maximum-Relevancy method was performed to eliminate the redundant and irrelated features and kept 30 features. The remaining features were enrolled into the least absolute shrinkage and selection operator regression model to select the most valuable features in the training cohort. Then the radiomics signature was calculated by summing the selected feature values weighted by their corresponding features.

    To provide a more individualized predictive model, a nomogram combining the final radiomics signature and significant clinical variables were built in the training cohort. The calibration of the nomogram was evaluated with a calibration curve. The HosmerLemeshow test was conducted to assess the goodness-of-fit of the nomogram. A radiomics nomogram score for each patient was obtained in the training and validation cohorts.

    Summary Ofevidence And Recommendation On Locally Recurrent Rcc After Treatment Of Localiseddisease

    Biology of Clear Cell Renal Cell Carcinoma

    Summary of evidence

    • recurrence in the contralateral kidney
    • distant metastases
    • cardiovascular events.

    There is no consensus on follow-up strategies after RCC treatment, withlimited evidence suggesting that more frequent post-operative imaging intervals do notprovide any improvement for early detection of recurrence that would lead to improvedsurvival . As such, intensive radiological surveillance may notbe necessary for all patients. Follow-up is also important to assess functional outcomes andto limit long-term sequelae such as renal function impairment, end-stage renal disease andcardiovascular events .

    Currently, the key question is whether any recurrencedetection during follow-up and subsequent treatment will lead to any meaningful change insurvival outcome for these patients.

    In contrast to high-grade and/or locally advanced disease, the outcomeafter surgery for T1a low-grade tumours is almost always excellent. It is thereforereasonable to stratify follow-up, taking into account the risk of each different RCC todevelop a local or distant recurrence. Although there is no randomised evidence, largestudies have examined prognostic factors with long follow-up . One study has shown asurvival benefit in patients who were followed within a structured surveillance protocol vs.patients who were not patients undergoing follow-up seem tohave a longer OS when compared to patients not undergoing routine follow-up .

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