Renal cell carcinoma#Classification

Historically, medical practitioners expected a person to present with three findings. This classic triad is 1: haematuria, which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger. It is now known that this classic triad of symptoms only occurs in 10–15% of cases, and is usually indicative that the renal cell carcinoma (RCC) is in an advanced stage. Today, renal cell carcinoma (RCC) is often asymptomatic, meaning it presents no symptoms, and is commonly detected incidentally during examinations for unrelated medical conditions. The percentage of asymptomatic and incidentally diagnosed RCC cases, particularly smaller tumors, has continued to rise in recent years.{{Cite journal |last1=Almdalal |first1=Tarik |last2=Sundqvist |first2=Pernilla |last3=Harmenberg |first3=Ulrika |last4=Hellström |first4=Mikael |last5=Lindskog |first5=Magnus |last6=Lindblad |first6=Per |last7=Lundstam |first7=Svan |last8=Ljungberg |first8=Börje |date=2022-05-01 |title=Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease—A National Register Study |journal=European Urology Open Science |volume=39 |pages=22–28 |doi=10.1016/j.euros.2022.03.005 |issn=2666-1683 |pmc=9068725 |pmid=35528783}}

Other signs and symptom may include haematuria; loin pain; abdominal mass; malaise, which is a general feeling of unwellness; weight loss and/or loss of appetite; anaemia resulting from depression of erythropoietin; erythrocytosis (increased production of red blood cells) due to increased erythropoietin secretion; varicocele, which is seen in males as an enlargement of the pampiniform plexus of veins draining the testis (more often the left testis) hypertension (high blood pressure) resulting from secretion of renin by the tumour; hypercalcemia, which is elevation of calcium levels in the blood; sleep disturbance or night sweats; recurrent fevers; and chronic fatigue.

The greatest risk factors for RCC are lifestyle-related: smoking, obesity and hypertension (high blood pressure) have been estimated to account for up to 50% of cases.{{cite journal|doi=10.1371/journal.pone.0057475|title=Metabolic Factors Associated with Risk of Renal Cell Carcinoma|year=2013|editor1-last=Miller|editor1-first=Todd W|last1=Häggström|first1=Christel|last2=Rapp|first2=Kilian|last3=Stocks|first3=Tanja|last4=Manjer|first4=Jonas|last5=Bjørge|first5=Tone|last6=Ulmer|first6=Hanno|last7=Engeland|first7=Anders|last8=Almqvist|first8=Martin|last9=Concin|first9=Hans|journal=PLOS ONE|volume=8|issue=2|pages=e57475|pmid=23468995|pmc=3585341|last10=Selmer|first10=R|last11=Ljungberg|first11=B|last12=Tretli|first12=S|last13=Nagel|first13=G|last14=Hallmans|first14=G|last15=Jonsson|first15=H|last16=Stattin|first16=P|bibcode=2013PLoSO...857475H|doi-access=free}}

Occupational exposure to some chemicals such as asbestos, cadmium, lead, chlorinated solvents, petrochemicals and PAH (polycyclic aromatic hydrocarbon) has been examined by multiple studies with inconclusive results.{{cite journal|doi=10.1046/j.1464-410x.2000.00708.x|title=Risk factors for adult renal cell carcinoma: A systematic review and implications for prevention|year=2007|last1=Dhôte|first1=R.|last2=Pellicer-Coeuret|first2=M.|last3=Thiounn|first3=N.|last4=Debré|first4=B.|last5=Vidal-Trecan|first5=G.|journal=BJU International|volume=86|pages=20–7|pmid=10886077|issue=1|s2cid=21271953}}{{cite journal|doi=10.1136/oem.2010.056341|title=Occupational exposure to arsenic, cadmium, chromium, lead and nickel, and renal cell carcinoma: A case-control study from Central and Eastern Europe|year=2011|last1=Boffetta|first1=P.|last2=Fontana|first2=L.|last3=Stewart|first3=P.|last4=Zaridze|first4=D.|last5=Szeszenia-Dabrowska|first5=N.|last6=Janout|first6=V.|last7=Bencko|first7=V.|last8=Foretova|first8=L.|last9=Jinga|first9=V.|journal=Occupational and Environmental Medicine|volume=68|issue=10|pages=723–8|pmid=21217163|last10=Matveev|first10=V.|last11=Kollarova|first11=H.|last12=Ferro|first12=G.|last13=Chow|first13=W.-H.|last14=Rothman|first14=N.|last15=Van Bemmel|first15=D.|last16=Karami|first16=S.|last17=Brennan|first17=P.|last18=Moore|first18=L. E.|hdl=11585/682305 |s2cid=29328889|hdl-access=free}}

Another suspected risk factor is the long term use of non-steroidal anti-inflammatory drugs (NSAIDS).{{cite journal|doi=10.1001/archinternmed.2011.356|title=Prospective Evaluation of Analgesic Use and Risk of Renal Cell Cancer|year=2011|last1=Cho|first1=Eunyoung|journal=Archives of Internal Medicine|volume=171|issue=16|pages=1487–93|pmid=21911634|last2=Curhan|first2=G|last3=Hankinson|first3=SE|last4=Kantoff|first4=P|last5=Atkins|first5=MB|last6=Stampfer|first6=M|last7=Choueiri|first7=TK|pmc=3691864}}

Finally, studies have found that women who have had a hysterectomy are at more than double the risk of developing RCC than those who have not.{{cite journal|doi=10.1002/ijc.23750|title=Reproductive, menstrual, and other hormone-related factors and risk of renal cell cancer|year=2008|last1=Zucchetto|first1=Antonella|last2=Talamini|first2=Renato|last3=Dal Maso|first3=Luigino|last4=Negri|first4=Eva|last5=Polesel|first5=Jerry|last6=Ramazzotti|first6=Valerio|last7=Montella|first7=Maurizio|last8=Canzonieri|first8=Vincenzo|last9=Serraino|first9=Diego|journal=International Journal of Cancer|volume=123|issue=9|pages=2213–6|pmid=18711701|last10=La Vecchia|first10=Carlo|last11=Franceschi|first11=Silvia|doi-access=free}} Moderate alcohol consumption, on the other hand, has been shown to have a protective effect.{{Cite journal|last1=Bellocco|first1=R.|last2=Pasquali|first2=E.|last3=Rota|first3=M.|last4=Bagnardi|first4=V.|last5=Tramacere|first5=I.|last6=Scotti|first6=L.|last7=Pelucchi|first7=C.|last8=Boffetta|first8=P.|last9=Corrao|first9=G.|date=2012-09-01|title=Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis|journal=Annals of Oncology|volume=23|issue=9|pages=2235–2244|doi=10.1093/annonc/mds022|issn=1569-8041|pmid=22398178|doi-access=free}}

Hereditary factors have a minor impact on individual susceptibility with immediate relatives of people with RCC having a two to fourfold increased risk of developing the condition. Other genetically linked conditions also increase the risk of RCC, including hereditary papillary renal carcinoma, hereditary leiomyomatosis, Birt–Hogg–Dube syndrome, hyperparathyroidism-jaw tumor syndrome, familial papillary thyroid carcinoma, von Hippel–Lindau disease and sickle cell disease.

The most significant disease affecting risk however is not genetically linked – patients with acquired cystic disease of the kidney requiring dialysis are 30 times more likely than the general population to develop RCC.

The tumour arises from the cells of the proximal renal tubular epithelium. It is considered an adenocarcinoma.{{cite web|title=Renal Cell Carcinoma|website=Merck Manual Professional|publisher=Merck Sharp & Dohme Corp.|date=November 2013|access-date=7 March 2014|url=http://www.merckmanuals.com/professional/genitourinary_disorders/genitourinary_cancer/renal_cell_carcinoma.html|author=Master, VA|url-status=live|archive-url=https://web.archive.org/web/20140307051746/http://www.merckmanuals.com/professional/genitourinary_disorders/genitourinary_cancer/renal_cell_carcinoma.html|archive-date=7 March 2014}} There are two subtypes: sporadic (that is, non-hereditary) and hereditary. Both such subtypes are associated with mutations in the short-arm of chromosome 3, with the implicated genes being either tumour suppressor genes (VHL and TSC) or oncogenes (like c-Met).

The first steps taken to diagnose this condition are consideration of the signs and symptoms, and a medical history (the detailed medical review of past health state) to evaluate any risk factors. Based on the symptoms presented, a range of biochemical tests (using blood and/or urine samples) may also be considered as part of the screening process to provide sufficient quantitative analysis of any differences in electrolytes, kidney and liver function, and blood clotting times. Upon physical examination, palpation of the abdomen may reveal the presence of a mass or an organ enlargement.{{cite journal |doi=10.1016/S1015-9584(11)60019-5 |title=Reactive Hypertrophy of an Accessory Spleen Mimicking Tumour Recurrence of Metastatic Renal Cell Carcinoma |year=2011 |last1=Tjaden |first1=Christin |last2=Werner |first2=Jens |last3=Buechler |first3=Markus W. |last4=Hackert |first4=Thilo |journal=Asian Journal of Surgery |volume=34 |pages=50–2 |pmid=21515214 |issue=1|doi-access=free }}

Although this disease lacks characterization in the early stages of tumor development, considerations based on diverse clinical manifestations, as well as resistance to radiation and chemotherapy are important. The main diagnostic tools for detecting renal cell carcinoma are ultrasound, computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the kidneys.{{cite book |author1=Elizabeth D Agabegi |author2=Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |isbn=978-0-7817-7153-5 |url-access=registration |url=https://archive.org/details/stepuptomedicine0000agab }}

Renal cell carcinoma (RCC) is not a single entity, but rather a collection of different types of tumours, each derived from the various parts of the nephron (epithelium or renal tubules) and possessing distinct genetic characteristics, histological features, and, to some extent, clinical phenotypes.

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.{{cite journal |doi=10.1186/1746-1596-3-44 |title=Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors |year=2008 |last1=Hagenkord |first1=Jill M |last2=Parwani |first2=Anil V |last3=Lyons-Weiler |first3=Maureen A |last4=Alvarez |first4=Karla |last5=Amato |first5=Robert |last6=Gatalica |first6=Zoran |last7=Gonzalez-Berjon |first7=Jose M |last8=Peterson |first8=Leif |last9=Dhir |first9=Rajiv |last10=Monzon |first10=Federico A |journal=Diagnostic Pathology |volume=3 |pages=44 |pmid=18990225 |pmc=2588560 |doi-access=free }}{{cite journal |doi=10.1038/modpathol.2008.20 |title=Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors |year=2008 |last1=Monzon |first1=Federico A |last2=Hagenkord |first2=Jill M |last3=Lyons-Weiler |first3=Maureen A |last4=Balani |first4=Jyoti P |last5=Parwani |first5=Anil V |last6=Sciulli |first6=Christin M |last7=Li |first7=Jia |last8=Chandran |first8=Uma R |last9=Bastacky |first9=Sheldon I |last10=Dhir |first10=Rajiv |journal=Modern Pathology |volume=21 |issue=5 |pages=599–608 |pmid=18246049|doi-access=free }} Array-based karyotyping performs well on paraffin embedded tumours{{cite journal |vauthors=Lyons-Weiler M, Hagenkord J, Sciulli C, Dhir R, Monzon FA |title=Optimization of the Affymetrix GeneChip Mapping 10K 2.0 Assay for routine clinical use on formalin-fixed paraffin-embedded tissues |journal=Diagn. Mol. Pathol. |volume=17 |issue=1 |pages=3–13 |year=2008 |pmid=18303412 |doi=10.1097/PDM.0b013e31815aca30 |s2cid=24420204 }} and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumours.

The 2004 World Health Organization (WHO) classification of genitourinary tumours recognizes over 40 subtypes of renal neoplasms. Since the publication of the latest iteration of the WHO classification in 2004, several novel renal tumour subtypes have been described:{{Cite journal | pmid = 24364021| year = 2013| last1 = Crumley| first1 = S. M.| title = Renal cell carcinoma: Evolving and emerging subtypes| journal = World Journal of Clinical Cases| volume = 1| issue = 9| pages = 262–275| last2 = Divatia| first2 = M| last3 = Truong| first3 = L| last4 = Shen| first4 = S| last5 = Ayala| first5 = A. G.| last6 = Ro| first6 = J. Y.| pmc = 3868710 | doi=10.12998/wjcc.v1.i9.262| doi-access = free}}

• Clear cell papillary renal cell carcinoma and clear cell renal cell carcinoma with smooth muscle stroma{{Cite journal | pmid = 21602815| year = 2011| last1 = Rohan| first1 = S. M.| title = Clear-cell papillary renal cell carcinoma: Molecular and immunohistochemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins| journal = Modern Pathology| volume = 24| issue = 9| pages = 1207–20| last2 = Xiao| first2 = Y| last3 = Liang| first3 = Y| last4 = Dudas| first4 = M. E.| last5 = Al-Ahmadie| first5 = H. A.| last6 = Fine| first6 = S. W.| last7 = Gopalan| first7 = A| last8 = Reuter| first8 = V. E.| last9 = Rosenblum| first9 = M. K.| last10 = Russo| first10 = P| last11 = Tickoo| first11 = S. K.| doi = 10.1038/modpathol.2011.80| doi-access = free}}
• Mucinous tubular and spindle cell carcinoma (MTSCC)
• Multilocular cystic clear cell renal cell carcinoma
• Tubulocystic renal cell carcinoma
• Thyroid-like follicular renal cell carcinoma
• Acquired cystic kidney disease-associated renal cell carcinoma
• Renal cell carcinoma with t(6;11) translocation (TFEB)
• Hybrid oncocytoma/chromophobe renal cell carcinoma
• Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)

Laboratory tests are generally conducted when the patient presents with signs and symptoms that may be characteristic of kidney impairment. They are not primarily used to diagnose kidney cancer, due to its asymptomatic nature and are generally found incidentally during tests for other illnesses such as gallbladder disease.{{cite journal|last=Wood|first=Laura S.|title=Renal Cell Carcinoma|journal=Clinical Journal of Oncology Nursing|date=30 November 2009|volume=13|pages=3–7|doi=10.1188/09.CJON.S2.3-7|pmid=19948453}} In other words, these cancers are not detected usually because they do not cause pain or discomfort when they are discovered. Laboratory analysis can provide an assessment on the overall health of the patient and can provide information in determining the staging and degree of metastasis to other parts of the body (if a renal lesion has been identified) before treatment is given.{{citation needed|date=April 2021}}

The presence of blood in urine is a common presumptive sign of renal cell carcinoma. The haemoglobin of the blood causes the urine to be rusty, brown or red in colour. Alternatively, urinalysis can test for sugar, protein and bacteria which can also serve as indicators for cancer. A complete blood cell count can also provide additional information regarding the severity and spreading of the cancer.{{cite journal|last=Bonn|first=Dorothy|title=Urine test for renal-cell carcinoma|journal=The Lancet Oncology|date=31 Jan 2004|volume=5|issue=2|pages=72|doi=10.1016/S1470-2045(04)01368-3|pmid=14974475}}

The CBC provides a quantified measure of the different cells in the whole blood sample from the patient. Such cells examined for in this test include red blood cells (erythrocytes), white blood cells (leukocytes) and platelets (thrombocytes). A common sign of renal cell carcinoma is anaemia whereby the patient exhibits deficiency in red blood cells.{{cite journal |doi=10.1021/ac902204k |title=Combined Blood/Tissue Analysis for Cancer Biomarker Discovery: Application to Renal Cell Carcinoma |year=2010 |last1=Johann |first1=Donald J. |last2=Wei |first2=Bih-Rong |last3=Prieto |first3=Darue A. |last4=Chan |first4=King C. |last5=Ye |first5=Xiaying |last6=Valera |first6=Vladimir A. |last7=Simpson |first7=R. Mark |last8=Rudnick |first8=Paul A. |last9=Xiao |first9=Zhen |last10=Issaq |first10=Haleem J. |last11=Linehan |first11=W. Marston |last12=Stein |first12=Stephen E. |last13=Veenstra |first13=Timothy D. |last14=Blonder |first14=Josip |journal=Analytical Chemistry |volume=82 |issue=5 |pages=1584–8 |pmid=20121140 |pmc=3251958}} CBC tests are vital as a screening tool for examination the health of patient prior to surgery. Inconsistencies with platelet counts are also common amongst these cancer patients and further coagulation tests, including erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT) should be considered.{{citation needed|date=April 2021}}

Blood chemistry tests are conducted if renal cell carcinoma is suspected as cancer has the potential to elevate levels of particular chemicals in blood. For example, liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are found to be at abnormally high levels.{{cite journal |doi=10.1111/j.1477-2574.2012.00495.x |title=A multi-institution analysis of outcomes of liver-directed surgery for metastatic renal cell cancer |year=2012 |last1=Hatzaras |first1=Ioannis |last2=Gleisner |first2=Ana L. |last3=Pulitano |first3=Carlo |last4=Sandroussi |first4=Charbel |last5=Hirose |first5=Kenzo |last6=Hyder |first6=Omar |last7=Wolfgang |first7=Christopher L. |last8=Aldrighetti |first8=Luca |last9=Crawford |first9=Michael |last10=Choti |first10=Michael A. |last11=Pawlik |first11=Timothy M. |journal=HPB |volume=14 |issue=8 |pages=532–8 |pmid=22762401 |pmc=3406350}} The staging of the cancer can also be determined by abnormal elevated levels of calcium, which suggests that the cancer may have metastasised to the bones.{{cite journal|last=Motzer|first=RJ|title=Renal cell carcinoma: a priority malignancy for development and study of novel therapies|journal=Journal of Clinical Oncology|date=Apr 1, 2003|volume=21|issue=7|pages=1193–4|pmid=12663704|doi=10.1200/JCO.2003.12.072}} In this case, a doctor should be prompted for a CT scan. Blood chemistry tests also assess the overall function of the kidneys and can allow the doctor to decide upon further radiological tests.{{citation needed|date=April 2021}}

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin and may be seen as a lump on the lower pelvic or abdomen region. Traditionally, 85 to 90% of solid renal masses will turn out to be RCC but cystic renal masses may also be due to RCC.{{cite journal|last=Sahni|first=V.A.|title=REVIEW: Biopsy of renal masses: when and why|journal=Cancer Imaging|date=1 January 2009|volume=9|issue=1|pages=44–55|doi=10.1102/1470-7330.2009.0005|pmid=19602467|pmc=2739685}} However, the advances of diagnostic modalities are able to incidentally diagnose a great proportion of patients with renal lesions that may appear to be small in size and of benign state. Ten percent of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat).{{cite journal |pmid=6675440 |year=1983 |last1=Nakada |first1=G |last2=Machida |first2=T |last3=Masuda |first3=F |last4=Onishi |first4=T |last5=Yamazaki |first5=H |last6=Kiyota |first6=H |last7=Suzuki |first7=M |last8=Goto |first8=H |title=A case of arteriovenous fistulae secondary to renal cell carcinoma accompanied by congestive heart failure |volume=29 |issue=8 |pages=901–5 |journal=Hinyokika Kiyo. Acta Urologica Japonica}}

Deciding on the benign or malignant nature of the renal mass on the basis of its localized size is an issue as renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, haemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one.{{cite journal |doi=10.1055/s-0031-1293492 |title=Tuberculosis Arthritis and Tenosynovitis |year=2011 |last1=Pattamapaspong |first1=Nuttaya |last2=Muttarak |first2=Malai |last3=Sivasomboon |first3=Chate |journal=Seminars in Musculoskeletal Radiology |volume=15 |issue=5 |pages=459–69 |pmid=22081281|s2cid=260321430 |doi-access=free }} The Bosniak classification system for cystic renal lesions classifies them into groups that are benign and those that need surgical resection, based on specific imaging features.{{cite journal |doi=10.1148/radiol.2362040218 |title=How I Do It: Evaluating Renal Masses1 |year=2005 |last1=Israel |first1=Gary M. |last2=Bosniak |first2=Morton A. |journal=Radiology |volume=236 |issue=2 |pages=441–50 |pmid=16040900|s2cid=1916092 }}

The main imaging tests performed in order to identify renal cell carcinoma are pelvic and abdominal CT scans, ultrasound tests of the kidneys (ultrasonography), MRI scans, intravenous pyelogram (IVP) or renal angiography.{{cite journal |pmid=8421912 |year=1993 |last1=Jubelirer |first1=SJ |last2=Rubin |first2=M |title=The use of modern radiologic methods in identifying incidental renal cell carcinoma |volume=89 |issue=1 |pages=21–3 |journal=The West Virginia Medical Journal}} Among these main diagnostic tests, other radiologic tests such as excretory urography, positron-emission tomography (PET) scanning, ultrasonography, arteriography, venography, and bone scanning can also be used to aid in the evaluation of staging renal masses and to differentiate non-malignant tumours from malignant tumours.{{citation needed|date=April 2021}}

Contrast-enhanced computed tomography (CT) scanning is routinely used to determine the stage of the renal cell carcinoma in the abdominal and pelvic regions. CT scans have the potential to distinguish solid masses from cystic masses and may provide information on the localization, stage or spread of the cancer to other organs of the patient. Key parts of the human body which are examined for metastatic involvement of renal cell carcinoma may include the renal vein, lymph node and the involvement of the inferior vena cava.{{cite journal|last=Beck|first=AD|title=Renal cell carcinoma involving the inferior vena cava: radiologic evaluation and surgical management|journal=The Journal of Urology|date=Oct 1997|volume=118|issue=4|pages=533–7|pmid=916043|doi=10.1016/S0022-5347(17)58098-2}} According to a study conducted by Sauk et al., multidetector CT imaging characteristics have applications in diagnosing patients with clear renal cell carcinoma by depicting the differences of these cells at the cytogenic level.{{cite journal |doi=10.1148/radiol.11101508 |title=Clear Cell Renal Cell Carcinoma: Multiphasic Multidetector CT Imaging Features Help Predict Genetic Karyotypes |year=2011 |last1=Sauk |first1=Steven C. |last2=Hsu |first2=Margaret S. |last3=Margolis |first3=Daniel J. A. |last4=Lu |first4=David S. K. |last5=Rao |first5=Nagesh P. |last6=Belldegrun |first6=Arie S. |last7=Pantuck |first7=Allan J. |last8=Raman |first8=Steven S. |journal=Radiology |volume=261 |issue=3 |pages=854–62 |pmid=22025734}}

Ultrasonographic examination can be useful in evaluating questionable asymptomatic kidney tumours and cystic renal lesions if computed tomography imaging is inconclusive. This safe and non-invasive radiologic procedure uses high frequency sound waves to generate an interior image of the body on a computer monitor. The image generated by the ultrasound can help diagnose renal cell carcinoma based on the differences of sound reflections on the surface of organs and the abnormal tissue masses. Essentially, ultrasound tests can determine whether the composition of the kidney mass is mainly solid or filled with fluid.

A percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumour for the purpose of diagnosis by pathology. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient may make it unfavourable from a risk-benefit perspective.{{cite journal |doi=10.1016/j.juro.2007.08.124 |title=Renal Mass Biopsy—A Renaissance? |year=2008 |last1=Lane |first1=Brian R. |last2=Samplaski |first2=Mary K. |last3=Herts |first3=Brian R. |last4=Zhou |first4=Ming |last5=Novick |first5=Andrew C. |last6=Campbell |first6=Steven C. |journal=The Journal of Urology |volume=179 |pages=20–7 |pmid=17997455 |issue=1}} However, biopsy tests for molecular analysis to distinguish benign from malignant renal tumours is of investigative interest.

Magnetic resonance imaging (MRI) scans provide an image of the soft tissues in the body using radio waves and strong magnets. MRI can be used instead of CT if the patient exhibits an allergy to the contrast media administered for the test.{{cite journal |doi=10.1148/radiology.154.3.3969475 |pmid=3969475 |year=1985 |last1=Hricak |first1=H |last2=Demas |first2=BE |last3=Williams |first3=RD |last4=McNamara |first4=MT |last5=Hedgcock |first5=MW |last6=Amparo |first6=EG |last7=Tanagho |first7=EA |title=Magnetic resonance imaging in the diagnosis and staging of renal and perirenal neoplasms |volume=154 |issue=3 |pages=709–15 |journal=Radiology}}{{cite journal |pmid=1863349 |year=1991 |last1=Janus |first1=CL |last2=Mendelson |first2=DS |title=Comparison of MRI and CT for study of renal and perirenal masses |volume=32 |issue=2 |pages=69–118 |journal=Critical Reviews in Diagnostic Imaging}} Sometimes prior to the MRI scan, an intravenous injection of a contrasting material called gadolinium is given to allow for a more detailed image. Patients on dialysis or those who have renal insufficiency should avoid this contrasting material as it may induce a rare, yet severe, side effect known as nephrogenic systemic fibrosis.{{cite journal |hdl=2433/119684 |pmid=3195400 |year=1988 |last1=Nishimura |first1=Kazuo |last2=Hida |first2=Shuichi |last3=Okada |first3=Kenichiro |last4=Yoshida |first4=Osamu |last5=Nishimuara |first5=Kazumasa |title=Staging and differential diagnosis of renal cell carcinoma: A comparison of magnetic resonance imaging (MRI) and computed tomography (CT) |volume=34 |issue=8 |pages=1323–31 |journal=Acta Urologica Japonica}} A bone scan or brain imaging is not routinely performed unless signs or symptoms suggest potential metastatic involvement of these areas.

MRI scans should also be considered to evaluate tumour extension which has grown in major blood vessels, including the vena cava, in the abdomen. MRI can be used to observe the possible spread of cancer to the brain or spinal cord should the patient present symptoms that suggest this might be the case.{{citation needed|date=April 2021}}

Intravenous pyelogram (IVP) is a useful procedure in detecting the presence of abnormal renal mass in the urinary tract. This procedure involves the injection of a contrasting dye into the arm of the patient. The dye travels from the blood stream and into the kidneys which in time, passes into the kidneys and bladder. This test is not necessary if a CT or MRI scan has been conducted.{{cite journal|last=Reznek|first=RH|title=CT/MRI in staging renal cell carcinoma|journal=Cancer Imaging|date=Feb 14, 2004|volume=4 Spec No A|pages=S25–32|pmid=18215972|doi=10.1102/1470-7330.2004.0012|pmc=1435344|issue=Spec No A}}

Renal angiography uses the same principle as IVP, as this type of X-ray also uses a contrasting dye. This radiologic test is important in diagnosing renal cell carcinoma as an aid for examining blood vessels in the kidneys. This diagnostic test relies on the contrasting agent which is injected in the renal artery to be absorbed by the cancerous cells.{{cite journal |doi=10.2214/ajr.177.3.1770659 |title=Using MR Angiography for Surgical Planning in Pelvic Kidney Renal Cell Carcinoma |year=2001 |last1=Kocak |first1=Mehmet |last2=Sudakoff |first2=Gary S. |last3=Erickson |first3=Scott |last4=Begun |first4=Frank |last5=Datta |first5=Milton |journal=American Journal of Roentgenology |volume=177 |issue=3 |pages=659–60 |pmid=11517066}} The contrasting dye provides a clearer outline of abnormally-oriented blood vessels believed to be involved with the tumour. This is imperative for surgeons as it allows the patient's blood vessels to be mapped prior to operation.

The staging of renal cell carcinoma is the most important factor in predicting its prognosis.[http://www.cornellurology.com/kidney/gi/rcc.shtml Kidney Cancer / General Information] {{webarchive|url=https://web.archive.org/web/20111101172045/http://www.cornellurology.com/kidney/gi/rcc.shtml |date=2011-11-01 }} at Weill Cornell Medical College, James Buchanan Brady Foundation, Department of Urology Staging can follow the TNM staging system, where the size and extent of the tumour (T), involvement of lymph nodes (N) and metastases (M) are classified separately. Also, it can use overall stage grouping into stage I–IV, with the 1997 revision of AJCC described below:

At diagnosis, 30% of renal cell carcinomas have spread to the ipsilateral renal vein, and 5–10% have continued into the inferior vena cava.{{cite journal |doi=10.2214/ajr.171.6.9843299 |title=Inferior vena cava tumor thrombus in renal cell carcinoma: Staging by MR imaging and impact on surgical treatment |year=1998 |last1=Oto |first1=A |last2=Herts |first2=B R |last3=Remer |first3=E M |last4=Novick |first4=A C |journal=American Journal of Roentgenology |volume=171 |issue=6 |pages=1619–24 |pmid=9843299}}

Image:Renal cell carcinoma.jpg

File:Renal tumors by relative incidence and prognosis.png and prognoses, including renal cell carcinoma and its subtypes]]

Image:Kidney cancer.jpg

The gross and microscopic appearance of renal cell carcinomas is highly variable. The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids.{{cite web |url=http://www.britannica.com/EBchecked/topic/497921/renal-carcinoma |title=Clear-cell Carcinoma, Hypernephroid Tumour, or Hypernephroma |access-date=2010-03-31 |url-status=live |archive-url=https://web.archive.org/web/20100507015655/http://www.britannica.com/EBchecked/topic/497921/renal-carcinoma |archive-date=2010-05-07 }} The body of the tumour shows large blood vessels that have walls composed of cancerous cells.

Gross examination often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, haemorrhage and scarring. In a microscopic context, there are four major histologic subtypes of renal cell cancer: clear cell (conventional RCC, 75%), papillary (15%), chromophobic (5%), and collecting duct (2%). Sarcomatoid changes (morphology and patterns of IHC that mimic sarcoma, spindle cells) can be observed within any RCC subtype and are associated with more aggressive clinical course and worse prognosis. Under light microscopy, these tumour cells can exhibit papillae, tubules or nests, and are quite large, atypical, and polygonal.{{citation needed|date=April 2021}}

Recent studies have brought attention to the close association of the type of cancerous cells to the aggressiveness of the condition. Some studies suggest that these cancerous cells accumulate glycogen and lipids, their cytoplasm appear "clear", the nuclei remain in the middle of the cells, and the cellular membrane is evident.{{cite journal |pmid=1016084 |year=1976 |last1=Vasil'Eva |first1=NN |last2=Koriakina |first2=RF |title=Morphological diagnosis of renal cell carcinoma. Histo-cytological parallels |volume=38 |issue=12 |pages=12–7 |journal=Arkhiv Patologii}} Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularised. The tumour compresses the surrounding parenchyma, producing a pseudocapsule.{{cite web |url=http://www.pathologyatlas.ro/renal-cell-carcinoma-grawitz-tumor-kidney-pathology.php |title=Renal clear cell carcinoma (Grawitz tumor) |date=January 30, 2009 |website=Atlas of Pathology |url-status=live |archive-url=https://web.archive.org/web/20090310101234/http://www.pathologyatlas.ro/renal-cell-carcinoma-grawitz-tumor-kidney-pathology.php |archive-date=March 10, 2009 }}

The most common cell type exhibited by renal cell carcinoma is the clear cell, which is named by the dissolving of the cells' high lipid content in the cytoplasm. The clear cells are thought to be the least likely to spread and usually respond more favourably to treatment. However, most of the tumours contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumour is mixed, containing both clear and granular cells.{{cite journal|last=López|first=JI|title=Renal tumors with clear cells. A review|journal=Pathology, Research and Practice|date=Mar 2013|volume=209|issue=3|pages=137–46|pmid=23433880|doi=10.1016/j.prp.2013.01.007}}

The recommended histologic grading schema for RCC is the Fuhrman system (1982), which is an assessment based on the microscopic morphology of a neoplasm with haematoxylin and eosin (H&E staining). This system categorises renal cell carcinoma with grades 1, 2, 3, 4 based on nuclear characteristics. The details of the Fuhrman grading system for RCC are shown below:{{cite journal |id={{INIST|18271804}} |last=Rioux-Leclercq |first=Nathalie |title=Le grade nucléaire de fuhrman, facteur pronostique du cancer du rein depuis 25 ans |trans-title=The Fuhrman grading system for kidney cancer prognosis |language=fr |journal=Progrès en Urologie |date=November 2006 |volume=16 |issue=4 |pages=5–8 |pmid=17183964}}

Nuclear grade is believed to be one of the most imperative prognostic factors in patients with renal cell carcinoma. However, a study by Delahunt et al. (2007) has shown that the Fuhrman grading is ideal for clear cell carcinoma but may not be appropriate for chromophobe renal cell carcinomas and that the staging of cancer (accomplished by CT scan) is a more favourable predictor of the prognosis of this disease.{{cite journal |last1=Delahunt |first1=Brett |last2=Sika-Paotonu |first2=Dianne |author-link2=Dianne Sika-Paotonu |last3=Bethwaite |first3=Peter B. |last4=McCredie |first4=Margaret R. E. |last5=Martignoni |first5=Guido |last6=Eble |first6=John N. |last7=Jordan |first7=T. |year=2007 |title=Fuhrman Grading is not Appropriate for Chromophobe Renal Cell Carcinoma |journal=The American Journal of Surgical Pathology |volume=31 |issue=6 |pages=957–60 |doi=10.1097/01.pas.0000249446.28713.53 |pmid=17527087 |s2cid=27154220}} In relation to renal cancer staging, the Heidelberg classification system of renal tumours was introduced in 1976 as a means of more completely correlating the histopathological features with the identified genetic defects.{{cite journal |doi=10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G |title=The Heidelberg classification of renal cell tumours |year=1997 |last1=Kovacs |first1=Gyula |last2=Akhtar |first2=Mohammed |last3=Beckwith |first3=Bruce J. |last4=Bugert |first4=Peter |last5=Cooper |first5=Colin S. |last6=Delahunt |first6=Brett |last7=Eble |first7=John N. |last8=Fleming |first8=Stewart |last9=Ljungberg |first9=Börje |last10=Medeiros |first10=L. Jeffrey |last11=Moch |first11=Holger |last12=Reuter |first12=Victor E. |last13=Ritz |first13=Eberhard |last14=Roos |first14=Göran |last15=Schmidt |first15=Dietmar |last16=Srigley |first16=John R. |last17=Störkel |first17=Stephan |last18=Van Den Berg |first18=Eva |last19=Zbar |first19=Bert |journal=The Journal of Pathology |volume=183 |issue=2 |pages=131–3 |pmid=9390023|s2cid=34796951 |doi-access=free }}

The risk of renal cell carcinoma can be reduced by maintaining a normal body weight.{{cite journal|last1=Lauby-Secretan|first1=B|last2=Scoccianti|first2=C|last3=Loomis|first3=D|last4=Grosse|first4=Y|last5=Bianchini|first5=F|last6=Straif|first6=K|title=Body Fatness and Cancer—Viewpoint of the IARC Working Group|journal=The New England Journal of Medicine|date=25 August 2016|volume=375|issue=8|pages=794–798|pmid=27557308|pmc=6754861|doi=10.1056/nejmsr1606602|url=https://discovery.dundee.ac.uk/en/publications/81847828-6457-4530-99ed-7b3c639705fb}}

Image:Embolization kidney.jpg of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.]]

The type of treatment depends on multiple factors and the individual, some of which include the stage of renal cell carcinoma (organs and parts of the body affected/unaffected), type of renal cell carcinoma, pre-existing or comorbid conditions and overall health and age of the person.{{cite book|title=Renal Cell Carcinoma Clinical Management|publisher=Humana Pr Inc.|isbn=978-1-62703-061-8|pages=105–118|author=Simmons|author2=Campbell|chapter=Assessment of Oncologic Risk for Clinical Stage T1 Renal Tumours|date=2012-09-26}}

Every form of treatment has both risks and benefits; a health care professional will provide the best options that suit the individual circumstances.

If it has spread outside of the kidneys, often into the lymph nodes, the lungs or the main vein of the kidney, then multiple therapies are used including surgery and medications. RCC is resistant to chemotherapy and radiotherapy in most cases but does respond well to immunotherapy with interleukin-2 or interferon-alpha, biologic, or targeted therapy. In early-stage cases, cryotherapy and surgery are the preferred options.

Active surveillance or "watchful waiting" is becoming more common as small renal masses or tumours are being detected and also within the older generation when surgery is not always suitable. Active surveillance involves completing various diagnostic procedures, tests and imaging to monitor the progression of the RCC before embarking on a more high risk treatment option like surgery.{{cite book |doi=10.1007/978-1-62703-062-5_10 |chapter=Active Surveillance of the Small Renal Mass |title=Renal Cell Carcinoma |year=2013 |last1=Smaldone |first1=Marc C. |last2=Canter |first2=Daniel |last3=Kutikov |first3=Alexander |last4=Uzzo |first4=Robert G. |isbn=978-1-62703-061-8 |pages=167–94}} In the elderly, patients with co-morbidities, and in poor surgical candidates, this is especially useful.

Different procedures may be most appropriate, depending on circumstances.

The recommended treatment for renal cell cancer may be nephrectomy or partial nephrectomy, surgical removal of all or part of the kidney. This may include some of the surrounding organs or tissues or lymph nodes. If cancer is only in the kidneys, which is about 60% of cases, it can be cured roughly 90% of the time with surgery.

Small renal tumors (< 4 cm) are treated increasingly by partial nephrectomy when possible.{{cite journal |author=Novick AC |title=Nephron-sparing surgery for renal cell carcinoma |journal=Br J Urol |volume=82 |issue=3 |pages=321–4 |date=September 1998 |pmid=9772865 |doi=10.1046/j.1464-410X.1998.00751.x|doi-access=free }}{{cite journal |author=Herr HW |title=Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10-year followup |journal=J. Urol. |volume=161 |issue=1 |pages=33–4; discussion 34–5 |date=January 1999 |pmid=10037361 |doi=10.1016/S0022-5347(01)62052-4}}{{cite journal |vauthors=Van Poppel H, Bamelis B, Oyen R, Baert L |title=Partial nephrectomy for renal cell carcinoma can achieve long-term tumor control |journal=J. Urol. |volume=160 |issue=3 Pt 1 |pages=674–8 |date=September 1998 |pmid=9720519 |doi=10.1016/S0022-5347(01)62751-4}} Most of these small renal masses manifest indolent biological behavior with excellent prognosis.{{cite journal |vauthors=Mattar K, Jewett MA |title=Watchful waiting for small renal masses |journal=Curr Urol Rep |volume=9 |issue=1 |pages=22–5 |date=January 2008 |pmid=18366970 |doi=10.1007/s11934-008-0006-3|s2cid=26763264 }} Nephron-sparing partial nephrectomy is used when the tumor is small (less than 4 cm in diameter) or when the patient has other medical concerns such as diabetes or hypertension. The partial nephrectomy involves the removal of the affected tissue only, sparing the rest of the kidney, Gerota's fascia and the regional lymph nodes. This allows for more renal preservation as compared to the radical nephrectomy, and this can have positive long-term health benefits.{{cite journal |doi=10.1016/j.juro.2009.12.030 |title=Nephrectomy Induced Chronic Renal Insufficiency is Associated with Increased Risk of Cardiovascular Death and Death from Any Cause in Patients with Localized cT1b Renal Masses |year=2010 |last1=Weight |first1=Christopher J. |last2=Larson |first2=Benjamin T. |last3=Fergany |first3=Amr F. |last4=Gao |first4=Tianming |last5=Lane |first5=Brian R. |last6=Campbell |first6=Steven C. |last7=Kaouk |first7=Jihad H. |last8=Klein |first8=Eric A. |last9=Novick |first9=Andrew C.|journal=The Journal of Urology |volume=183 |issue=4 |pages=1317–23 |pmid=20171688 }} Larger and more complex tumors can also be treated with partial nephrectomy by surgeons with a lot of kidney surgery experience.{{cite journal |doi=10.1111/j.1464-410X.2012.11112.x |title=Practice-setting and surgeon characteristics heavily influence the decision to perform partial nephrectomy among American Urologic Association surgeons |year=2013 |last1=Weight |first1=Christopher J. |last2=Crispen |first2=Paul L. |last3=Breau |first3=Rodney H. |last4=Kim |first4=Simon P. |last5=Lohse |first5=Christine M. |last6=Boorjian |first6=Stephen A. |last7=Thompson |first7=R. Houston |last8=Leibovich |first8=Bradley C. |journal=BJU International |volume=111 |issue=5 |pages=731–8 |pmid=22502641|s2cid=829345 }}

Surgical nephrectomy may be "radical" if the procedure removes the entire affected kidney including Gerota's fascia, the adrenal gland which is on the same side as the affected kidney, and the regional retroperitoneal lymph nodes, all at the same time. This method, although severe, is effective. But it is not always appropriate, as it is a major surgery that contains the risk of complication both during and after the surgery and can have a longer recovery time.{{cite journal |doi=10.1016/j.surge.2013.02.007 |title=Renal cell carcinoma with IVC and atrial thrombus: A single centre's 10 year surgical experience |year=2013 |last1=Casey |first1=R.G. |last2=Raheem |first2=O.A. |last3=Elmusharaf |first3=E. |last4=Madhavan |first4=P. |last5=Tolan |first5=M. |last6=Lynch |first6=T.H. |journal=The Surgeon |volume=11 |issue=6 |pages=295–9 |pmid=23510704}} It is important to note that the other kidney must be fully functional, and this technique is most often used when there is a large tumour present in only one kidney.

File:Large left renal tumor with tumor thrombus all the way to the heart.jpg

In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium, this portion of the tumor can be surgically removed, as well. When the tumor involved the inferior vena cava, it is important to classify which parts of the vena cava are involved and to plan accordingly, as sometimes complete resection will involve an incision into the chest with increased morbidity. For this reason, Dr. Gaetano Ciancio adapted liver mobilization techniques from liver transplant to address retrohepatic or even suprahepatic inferior vena caval thrombus associated with renal tumors.{{cite journal | last1=Ciancio | first1=Gaetano | last2=Livingstone | first2=Alan S. | last3=Soloway | first3=Mark | title=Surgical Management of Renal Cell Carcinoma with Tumor Thrombus in the Renal and Inferior Vena Cava: The University of Miami Experience in Using Liver Transplantation Techniques | journal=European Urology | publisher=Elsevier BV | volume=51 | issue=4 | year=2007 | issn=0302-2838 | doi=10.1016/j.eururo.2006.11.055 | pages=988–995| pmid=17175095 }} With this technique, the whole abdominal inferior vena cava is able to be mobilized. This facilitates milking of the tumor down below the major hepatic veins by the surgeon's fingers, bypassing the need for a thoracoabdominal incision or cardiopulmonary bypass.{{cite journal | last1=Ciancio | first1=Gaetano | last2=Soloway | first2=Mark S. | title=Renal cell carcinoma with tumor thrombus extending above diaphragm: Avoiding cardiopulmonary bypass | journal=Urology | publisher=Elsevier BV | volume=66 | issue=2 | year=2005 | issn=0090-4295 | doi=10.1016/j.urology.2005.03.039 | pages=266–270| pmid=16098354 }} In cases of known metastases, surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival,{{cite journal |vauthors=Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED |title=Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis |journal=J. Urol. |volume=171 |issue=3 |pages=1071–6 |date=March 2004 |pmid=14767273 |doi=10.1097/01.ju.0000110610.61545.ae |citeseerx=10.1.1.469.2497 }} as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss.{{cite journal | vauthors = Mulders PF, Brouwers AH, Hulsbergen-van der Kaa CA, van Lin EN, Osanto S, de Mulder PH | title = [Guideline 'Renal cell carcinoma'] | language = nl| journal = Nederlands Tijdschrift voor Geneeskunde | volume = 152 | issue = 7 | pages = 376–80 | date = February 2008 | pmid = 18380384 }}

Surgery is increasingly performed via laparoscopic techniques. Commonly referred to as key hole surgery, this surgery does not have the large incisions seen in a classically performed radical or partial nephrectomy, but still successfully removes either all or part of the kidney. Laparoscopic surgery is associated with shorter stays in the hospital and quicker recovery time but there are still risks associated with the surgical procedure. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery. For small exophytic lesions that do not extensively involve the major vessels or urinary collecting system, a partial nephrectomy (also referred to as "nephron sparing surgery") can be performed. This may involve temporarily stopping blood flow to the kidney while the mass is removed as well as renal cooling with an ice slush. Mannitol can also be administered to help limit damage to the kidney. This is usually done through an open incision although smaller lesions can be done laparoscopically with or without robotic assistance.

Laparoscopic cryotherapy can also be done on smaller lesions. Typically a biopsy is taken at the time of treatment. Intraoperative ultrasound may be used to help guide placement of the freezing probes. Two freeze/thaw cycles are then performed to kill the tumor cells. As the tumor is not removed followup is more complicated (see below) and overall disease-free rates are not as good as those obtained with surgical removal.

Surgery for metastatic disease: If metastatic disease is present surgical treatment may still a viable option. Radical and partial nephrectomy can still occur, and in some cases, if the metastasis is small this can also be surgically removed. This depends on what stage of growth and how far the disease has spread.

Percutaneous ablation therapies use image-guidance by radiologists to treat localized tumors if a surgical procedure is not a good option. Although the use of laparoscopic surgical techniques for complete nephrectomies has reduced some of the risks associated with surgery, surgery of any sort in some cases will still not be feasible. For example, the elderly, people who already have severe renal dysfunction, or people who have several comorbidities, surgery of any sort is not warranted.

A probe is placed through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.{{cite journal |vauthors=Mogami T, Harada J, Kishimoto K, Sumida S |title=Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell carcinoma |journal=Int. J. Clin. Oncol. |volume=12 |issue=2 |pages=79–84 |date=April 2007 |pmid=17443274 |doi=10.1007/s10147-006-0654-6|s2cid=5743758 }}{{cite journal |vauthors=Boss A, Clasen S, Kuczyk M, Schick F, Pereira PL |title=Image-guided radiofrequency ablation of renal cell carcinoma |journal=Eur Radiol |volume=17 |issue=3 |pages=725–33 |date=March 2007 |pmid=17021704 |doi=10.1007/s00330-006-0415-y|s2cid=12651841 }} Ideally, percutaneous ablation is restricted to tumours smaller than 3.5 cm and to guide the treatment. However, there are some cases where ablation can be used on tumors that are larger.

The two main types of ablation techniques that are used for renal cell carcinoma are radio frequency ablation and cryoablation.

Radio frequency ablation uses an electrode probe which is inserted into the affected tissue, to send radio frequencies to the tissue to generate heat through the friction of water molecules. The heat destroys the tumor tissue. Cell death will generally occur within minutes of being exposed to temperatures above 50 °C.

Cryoablation also involves the insertion of a probe into the affected area, however, cold is used to kill the tumor instead of heat. The probe is cooled with chemical fluids which are very cold. The freezing temperatures cause the tumor cells to die by causing osmotic dehydration, which pulls the water out of the cell destroying the enzyme, organelles, cell membrane and freezing the cytoplasm.

Cancers often grow in an unbridled fashion because they are able to evade the immune system. Immunotherapy is a method that activates the person's immune system and uses it to their own advantage. It was developed after observing that in some cases there was spontaneous regression.{{cite book|title=Renal Cell Carcinoma Clinical Management|year=2013|publisher=Humana |isbn=978-1-62703-061-8|pages=279–302|author=Davar|author2=Fenton|author3=Appleman|chapter=Immunotherapy for Renal Cell Carcinoma}} Immunotherapy capitalises on this phenomenon and aims to build up a person's immune response to cancer cells. Other targeted therapy medications inhibit growth factors that have been shown to promote the growth and spread of tumours.{{cite journal|last1=Santoni|first1=M|last2=De Tursi|first2=M|last3=Felici|first3=A|last4=Lo Re|first4=G|last5=Ricotta|first5=R|last6=Ruggeri|first6=EM |last7=Sabbatini|first7=R|last8=Santini|first8=D|last9=Vaccaro|first9=V|last10=Milella|first10=M|title=Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives|journal=Expert Review of Anticancer Therapy|date=June 2013|volume=13|issue=6|pages=697–709|doi=10.1586/era.13.52|pmid=23773104|s2cid=36871651}}{{cite book|title=Renal Cell Carcinoma Clinical Management|year=2013|publisher=Humana |isbn=978-1-62703-061-8|pages=219–230|author=Stroup|chapter=Neoadjuvant Targeted Therapy and Consolidative Surgery}} Most of these medications were approved within the past ten years.{{cite journal|last1=Shoji|first1=S|last2=Nakano|first2= M|last3= Sato|first3= H|last4= Tang|first4= XY|last5= Osamura|first5= YR|last6= Terachi|first6= T|last7= Uchida|first7= T|last8= Takeya|first8= K|title=The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma|journal=Clinical & Experimental Metastasis|date=January 2014|volume=31|issue=1|pages=111–34|doi=10.1007/s10585-013-9612-7|pmid=23959576|s2cid=15100003}} These treatments are:{{cite journal|last1=Jonasch|first1=E|last2=Futreal|first2= PA|last3= Davis|first3= IJ|last4= Bailey|first4= ST|last5= Kim|first5= WY|last6= Brugarolas|first6= J|last7= Giaccia|first7= AJ|last8= Kurban|first8= G|last9= Pause|first9= A|last10= Frydman|first10= J|last11= Zurita|first11= AJ|last12= Rini|first12= BI|last13= Sharma|first13= P|last14= Atkins|first14= MB|last15= Walker|first15= CL|last16= Rathmell|first16= WK|title=State of the science: an update on renal cell carcinoma|journal=Molecular Cancer Research|date=July 2012|volume=10|issue=7|pages=859–80|doi=10.1158/1541-7786.MCR-12-0117|pmid=22638109|pmc=3399969}}

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• Nivolumab{{cite journal |vauthors=Quinn DI, Lara PN |title=Renal-Cell Cancer – Targeting an Immune Checkpoint or Multiple Kinases |journal=N. Engl. J. Med. |volume=373 |issue=19 |pages=1872–4 |year=2015 |pmid=26406149 |doi=10.1056/NEJMe1511252 |pmc=7526749 }}
• Axitinib{{cite journal|last1=Dranitsaris|first1=G|last2=Schmitz|first2=S|last3=Broom|first3=RJ|title=Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy|journal=Journal of Cancer Research and Clinical Oncology|date=November 2013|volume=139|issue=11|pages=1917–26|doi=10.1007/s00432-013-1510-5|pmid=24037486|s2cid=27524034}}
• Sunitinib{{cite journal|last1=Motzer|first1=Robert J.|last2=Hutson|first2=Thomas E.|last3=Tomczak|first3=Piotr|last4=Michaelson|first4=M. Dror|last5=Bukowski|first5=Ronald M.|last6=Rixe|first6=Olivier|last7=Oudard|first7=Stéphane|last8=Negrier|first8=Sylvie|last9=Szczylik|first9=Cezary|last10=Kim|first10=Sindy T.|last11=Chen|first11=Isan|last12=Bycott|first12=Paul W.|last13=Baum|first13=Charles M.|last14=Figlin|first14=Robert A.|title=Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma|journal=New England Journal of Medicine|volume=356|issue=2|year=2007|pages=115–124|issn=0028-4793|doi=10.1056/NEJMoa065044|pmid=17215529|doi-access=free}}
• Cabozantinib
• Everolimus
• Lenvatinib
• Pazopanib
• Bevacizumab
• Sorafenib
• Tivozanib
• Temsirolimus{{cite web|url=http://www.torisel.com/|title=TORISEL® (temsirolimus) -Safety Info- Renal Cell Carcinoma Treatment|website=www.torisel.com|access-date=19 March 2018|url-status=live|archive-url=https://web.archive.org/web/20180413191552/http://www.torisel.com/|archive-date=13 April 2018}}
• Interleukin-2 (IL-2) has produced "durable remissions" in a small number of patients, but with substantial toxicity.[https://www.nlm.nih.gov/medlineplus/ency/article/000516.htm/ Renal Cell Carcinoma] {{webarchive|url=https://web.archive.org/web/20160705053508/https://www.nlm.nih.gov/medlineplus/ency/article/000516.htm |date=2016-07-05 }} MedlinePlus Medical Encyclopedia. Retrieved on 2010-09-10
• Interferon-α

{{div col end}}

For patients with metastatic cancer, sunitinib probably results in more progression of the cancer than pembrolizumab, axitinib and avelumab.{{Cite journal|last1=Hofmann|first1=Fabian|last2=Hwang|first2=Eu Chang|last3=Lam|first3=Thomas BL|last4=Bex|first4=Axel|last5=Yuan|first5=Yuhong|last6=Marconi|first6=Lorenzo SO|last7=Ljungberg|first7=Börje|date=2020-10-14|title=Targeted therapy for metastatic renal cell carcinoma|url=https://doi.org/10.1002/14651858.CD012796.pub2|journal=Cochrane Database of Systematic Reviews|volume=2020|issue=10|pages=CD012796|doi=10.1002/14651858.cd012796.pub2|pmid=33058158|pmc=8094280|issn=1465-1858|hdl=2164/11109|hdl-access=free}} In comparison to pembrolizumab and axitinib, it probably results in more death, but it may slightly reduce serious unwanted effects. When compared with combinations of immunotherapy (nivolumab and ipilimumab), sunitinib may lead to more progression and serious effects. There may be little to no difference in progression, survival and serious effects between pazopanib and sunitib.

Activity has also been reported for ipilimumab{{cite journal |vauthors=Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, Suri KB, Levy C, Allen T, Mavroukakis S, Lowy I, White DE, Rosenberg SA |title=Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis |journal=J. Immunother. |volume=30 |issue=8 |pages=825–30 |year=2007 |pmid=18049334 |pmc=2134980 |doi=10.1097/CJI.0b013e318156e47e }} but it is not an approved medication for renal cancer.{{cite web |url=http://packageinserts.bms.com/pi/pi_yervoy.pdf |title=Archived copy |access-date=2014-10-29 |url-status=live |archive-url=https://web.archive.org/web/20150206103033/http://packageinserts.bms.com/pi/pi_yervoy.pdf |archive-date=2015-02-06 }}

More medications are expected to become available in the near future as several clinical trials are currently being conducted for new targeted treatments,{{cite web|url=https://www.cancerresearch.org/scientists/science-of-immunotherapy/cancer-types/kidney-cancer|title=Kidney Cancer|website=Cancer Research Institute|access-date=19 March 2018|url-status=live|archive-url=https://web.archive.org/web/20171224042416/https://www.cancerresearch.org/scientists/science-of-immunotherapy/cancer-types/kidney-cancer|archive-date=24 December 2017}} including: atezolizumab, varlilumab, durvalumab, avelumab, LAG525, MBG453, TRC105, and savolitinib.

Chemotherapy and radiotherapy are not as successful in the case of RCC. RCC is resistant in most cases but there is about a 4–5% success rate, but this is often short-lived with more tumours and growths developing later.

Adjuvant therapy, which refers to therapy given after a primary surgery, had for a long time not been found to be beneficial in renal cell cancer. However in 2021 Pembrolizumab was approved for adjuvant treatment after showing promising disease-free survival improvements.{{cite journal | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma | title=FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma | journal=FDA | date=17 November 2021 }}

Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed. This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.

Metastatic renal cell carcinoma (mRCC) is the spread of the primary renal cell carcinoma from the kidney to other organs. Approximately 25–30% of people have this metastatic spread by the time they are diagnosed with renal cell carcinoma.{{cite journal|doi=10.1007/s00345-004-0466-0|title=Novel approaches in the therapy of metastatic renal cell carcinoma|year=2005|last1=Lam|first1=John S.|last2=Leppert|first2=John T.|last3=Belldegrun|first3=Arie S.|last4=Figlin|first4=Robert A.|journal=World Journal of Urology|volume=23|issue=3|pages=202–12|pmid=15812574|s2cid=12091991}} This high proportion is explained by the fact that clinical signs are generally mild until the disease progresses to a more severe state.{{cite journal|doi=10.1016/j.eururo.2007.03.035|title=Renal Cell Carcinoma Guideline|year=2007|last1=Ljungberg|first1=Börje|last2=Hanbury|first2=Damian C.|last3=Kuczyk|first3=Marcus A.|last4=Merseburger|first4=Axel S.|last5=Mulders|first5=Peter F.A.|last6=Patard|first6=Jean-Jacques|last7=Sinescu|first7=Ioanel C.|journal=European Urology|volume=51|issue=6|pages=1502–10|pmid=17408850|author8=European Association of Urology Guideline Group for renal cell carcinoma}} The most common sites for metastasis are the lymph nodes, lung, bones, liver and brain. How this spread affects the staging of the disease and hence prognosis is discussed in the "Diagnosis" and "Prognosis" sections.

MRCC has a poor prognosis compared to other cancers, although average survival times have increased in the last few years due to treatment advances. Average survival time in 2008 for the metastatic form of the disease was under a year, and by 2013 this improved to an average of 22 months.{{cite journal|doi=10.1097/CAD.0b013e3283609ec1|pmid=23552469|title=Chemotherapy in metastatic renal cell carcinoma today? A systematic review|year=2013|last1=Buti|first1=Sebastiano|last2=Bersanelli|first2=Melissa|last3=Sikokis|first3=Angelica|last4=Maines|first4=Francesca|last5=Facchinetti|first5=Francesco|last6=Bria|first6=Emilio|last7=Ardizzoni|first7=Andrea|last8=Tortora|first8=Giampaolo|last9=Massari|first9=Francesco|journal=Anti-Cancer Drugs|volume=24|issue=6|pages=535–54|s2cid=205529087}} Despite this improvement the five-year survival rate for mRCC remains under 10%{{cite journal|doi=10.1016/j.juro.2012.08.026|title=Improvement in Overall Survival of Patients with Advanced Renal Cell Carcinoma: Prognostic Factor Trend Analysis from an International Data Set of Clinical Trials|year=2012|last1=Patil|first1=Sujata|last2=Manola|first2=Judith|last3=Elson|first3=Paul|last4=Negrier|first4=Sylvie|last5=Escudier|first5=Bernard|last6=Eisen|first6=Tim|last7=Atkins|first7=Michael|last8=Bukowski|first8=Ronald|last9=Motzer|first9=Robert J.|journal=The Journal of Urology|volume=188|issue=6|pages=2095–100|pmid=23083849}} and 20–25% of patients remain unresponsive to all treatments and in these cases, the disease has a rapid progression.

The available treatments for RCC discussed in the "Treatment" section are also relevant for the metastatic form of the disease. Options include interleukin-2, which is a standard therapy for advanced renal cell carcinoma. From 2007 to 2013, seven new treatments have been approved specifically for mRCC (sunitinib, temsirolimus, bevacizumab, sorafenib, everolimus, pazopanib and axitinib). These new treatments are based on the fact that renal cell carcinomas are very vascular tumours – they contain a large number of blood vessels. The drugs aim to inhibit the growth of new blood vessels in the tumours, hence slowing growth and in some cases, reducing the size of the tumours.{{cite journal|doi=10.1016/j.ctrv.2012.06.010|title=What is the optimal therapy for patients with metastatic renal cell carcinoma who progress on an initial VEGFr-TKI?|year=2013|last1=Calvo|first1=Emiliano|last2=Ravaud|first2=Alain|last3=Bellmunt|first3=Joaquim|journal=Cancer Treatment Reviews|volume=39|issue=4|pages=366–74|pmid=22832091}}

Side effects unfortunately are quite common with these treatments and include:{{cite journal|doi=10.1016/j.ctrv.2012.12.006|title=A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma|year=2013|last1=Alasker|first1=Ahmed|last2=Meskawi|first2=Malek|last3=Sun|first3=Maxine|last4=Ismail|first4=Salima|last5=Hanna|first5=Nawar|last6=Hansen|first6=Jens|last7=Tian|first7=Zhe|last8=Bianchi|first8=Marco|last9=Perrotte|first9=Paul|journal=Cancer Treatment Reviews|volume=39|issue=4|pages=388–401|pmid=23317510|last10=Karakiewicz|first10=Pierre I.}}

• Gastrointestinal effects – nausea, vomiting, diarrhea, anorexia
• Respiratory effects – coughing, dyspnea (difficulty breathing)
• Cardiovascular effects – hypertension (high blood pressure)
• Neurological effects – intracranial hemorrhage (bleeding into the brain), thrombosis (blood clots) in the brain
• Effects on the skin and mucous membranes – rashes, hand-foot syndrome, stomatitis
• Bone marrow suppression – resulting in reduced white blood cells, increasing the risk of infections plus anemia and reduced platelets
• Renal effects – impaired kidney function
• Fatigue

Radiotherapy and chemotherapy are more commonly used in the metastatic form of RCC to target the secondary tumours in the bones, liver, brain and other organs. While not curative, these treatments do provide relief for symptoms associated with the spread of tumours.

The prognosis is influenced by several factors, including tumour size, degree of invasion and metastasis, histologic type, and nuclear grade. Staging is the most important factor in the outcome of renal cell cancer. The following numbers are based on patients first diagnosed in 2001 and 2002 by the National Cancer Data Base:[http://www.cancer.org/acs/groups/cid/documents/webcontent/003107-pdf.pdf/ Kidney Cancer (Adult) – Renal Cell Carcinoma] {{webarchive|url=https://web.archive.org/web/20160405223318/http://www.cancer.org/acs/groups/cid/documents/webcontent/003107-pdf.pdf |date=2016-04-05 }} American Cancer Society. Retrieved on 2010-09-10

A Korean study estimated a disease-specific overall five-year survival rate of 85%.{{cite journal|title=IN THIS ISSUE|journal=Japanese Journal of Clinical Oncology|volume=41|issue=1|year=2010|pages=NP|issn=0368-2811|doi=10.1093/jjco/hyq238|doi-access=free}} Taken as a whole, if the disease is limited to the kidney, only 20–30% develop metastatic disease after nephrectomy.[http://www.emedicinehealth.com/renal_cell_cancer/page11_em.htm#Outlook/] {{webarchive|url=https://web.archive.org/web/20151205085643/http://www.emedicinehealth.com/renal_cell_cancer/page11_em.htm|date=2015-12-05}} Renal Cancer Causes, Symptoms, Treatment. eMedicine Health. Retrieved on 2010-09-10 More specific subsets show a five-year survival rate of around 90–95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80–85%.{{Citation needed|date=October 2008}} For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%.{{Citation needed|date=October 2008}} Factors as general health and fitness or the severity of their symptoms impact the survival rates. For instance, younger people (among 20–40 years old) have a better outcome despite having more symptoms at presentation, possibly due to lower rates spread of cancer to the lymph nodes (stage III).

Histological grade is related to the aggressiveness of the cancer, and it is classified in 4 grades, with 1 having the best prognosis (five-year survival over 89%), and 4 with the worst prognosis (46% of five-year survival).

Some people have the renal cell cancer detected before they have symptoms (incidentally) because of the CT scan (Computed Tomography Imaging) or ultrasound. Incidentally diagnosed renal cell cancer (no symptoms) differs in outlook from those diagnosed after presenting symptoms of renal cell carcinoma or metastasis. The five-year survival rate was higher for incidental than for symptomatic tumours: 85.3% versus 62.5%. Incidental lesions were significantly lower stage than those that cause symptoms, since 62.1% patients with incidental renal cell carcinoma were observed with Stage I lesions, against 23% were found with symptomatic renal cell carcinoma.{{cite journal | vauthors = Tsui KH, Shvarts O, Smith RB, Figlin R, de Kernion JB, Belldegrun A | title = Renal cell carcinoma: prognostic significance of incidentally detected tumors | journal = The Journal of Urology | volume = 163 | issue = 2 | pages = 426–30 | date = February 2000 | pmid = 10647646 | doi = 10.1016/s0022-5347(05)67892-5}}

If it has metastasized to the lymph nodes, the five-year survival is around 5% to 15%. For metastatic renal cell carcinoma, factors which may present a poor prognosis include a low Karnofsky performance-status score (a standard way of measuring functional impairment in patients with cancer), a low haemoglobin level, a high level of serum lactate dehydrogenase, and a high corrected level of serum calcium.{{cite journal |doi=10.1200/JCO.2004.06.132 |title=Prognostic Factors for Survival in Previously Treated Patients with Metastatic Renal Cell Carcinoma |year=2003 |last1=Motzer |first1=R. J. |journal=Journal of Clinical Oncology |volume=22 |issue=3 |pages=454–63 |pmid=14752067 |last2=Bacik |first2=J |last3=Schwartz |first3=LH |last4=Reuter |first4=V |last5=Russo |first5=P |last6=Marion |first6=S |last7=Mazumdar |first7=M|doi-access=free }}{{cite journal |pmid=10561319 |year=1999 |last1=Motzer |first1=RJ |last2=Mazumdar |first2=M |last3=Bacik |first3=J |last4=Berg |first4=W |last5=Amsterdam |first5=A |last6=Ferrara |first6=J |title=Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma |volume=17 |issue=8 |pages=2530–40 |journal=Journal of Clinical Oncology |doi=10.1200/jco.1999.17.8.2530}} For non-metastatic cases, the Leibovich scoring algorithm may be used to predict post-operative disease progression.{{cite journal |doi=10.1002/cncr.11234 |title=Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma |year=2003 |last1=Leibovich |first1=Bradley C. |last2=Blute |first2=Michael L. |last3=Cheville |first3=John C. |last4=Lohse |first4=Christine M. |last5=Frank |first5=Igor |last6=Kwon |first6=Eugene D. |last7=Weaver |first7=Amy L. |last8=Parker |first8=Alexander S. |last9=Zincke |first9=Horst |journal=Cancer |volume=97 |issue=7 |pages=1663–71 |pmid=12655523 |doi-access=free }}

Renal cell carcinoma is one of the cancers most strongly associated with paraneoplastic syndromes, most often due to ectopic hormone production by the tumour. The treatment for these complications of RCC is generally limited beyond treating the underlying cancer.

The incidence of the disease varies according to geographic, demographic and, to a lesser extent, hereditary factors. There are some known risk factors, however the significance of other potential risk factors remains more controversial. The incidence of the cancer has been increasing in frequency worldwide at a rate of approximately 2–3% per decade{{cite journal|doi=10.1016/j.ctrv.2007.12.001|title=Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review|year=2008|last1=Gupta|first1=Kiran|last2=Miller|first2=Jeffrey D.|last3=Li|first3=Jim Z.|last4=Russell|first4=Mason W.|last5=Charbonneau|first5=Claudie|journal=Cancer Treatment Reviews|volume=34|issue=3|pages=193–205|pmid=18313224}} until the last few years where the number of new cases has stabilised.{{cite journal|doi=10.1016/j.eururo.2011.06.049|title=The Epidemiology of Renal Cell Carcinoma|year=2011|last1=Ljungberg|first1=Börje|last2=Campbell|first2=Steven C.|last3=Choi|first3=Han Yong|last4=Jacqmin|first4=Didier|last5=Lee|first5=Jung Eun|last6=Weikert|first6=Steffen|last7=Kiemeney|first7=Lambertus A.|journal=European Urology|volume=60|issue=4|pages=615–21|pmid=21741761}}

The incidence of RCC varies between sexes, ages, races and geographic location around the world. Men have a higher incidence than women (approximately 1.6:1){{cite journal|doi=10.1056/NEJMra043172|title=Renal-Cell Carcinoma|year=2005|last1=Cohen|first1=Herbert T.|last2=McGovern|first2=Francis J.|journal=New England Journal of Medicine|volume=353|issue=23|pages=2477–90|pmid=16339096|url=https://semanticscholar.org/paper/55f232dcc1c38655f4215c2fd9cefaf4775eff29}}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }} and the vast majority are diagnosed after 65 years of age. Asians reportedly have a significantly lower incidence of RCC than whites and while African countries have the lowest reported incidences, African Americans have the highest incidence of the population in the United States. Developed countries have a higher incidence than developing countries, with the highest rates found in North America, Europe and Australia / New Zealand.{{cite book |doi=10.1007/978-1-62703-062-5_1 |chapter=Etiology of Renal Cell Carcinoma: Incidence, Demographics, and Environmental Factors |title=Renal Cell Carcinoma |year=2013 |last1=Birkhäuser |first1=Frédéric D. |last2=Kroeger |first2=Nils |last3=Pantuck |first3=Allan J. |isbn=978-1-62703-061-8 |pages=3–22}}

Daniel Sennert made the first reference suggesting a tumour arising in the kidney in his text Practicae Medicinae, first published in 1613.{{cite journal|last=Delahunt|first=Brett|title=History of Renal Neoplasia|journal=United States and Canadian Academy of Pathology 2009 Annual Meeting|date=March 8, 2009|url=http://www.uscap.org/site~/98th/pdf/companion09h02.pdf|access-date=April 27, 2013|archive-date=March 29, 2020|archive-url=https://web.archive.org/web/20200329054018/http://www.uscap.org/site~/98th/pdf/companion09h02.pdf|url-status=dead}}

Miril published the earliest unequivocal case of renal carcinoma in 1810.{{cite journal|last=Delahunt|first=Brett|author2=Thornton A|title=Renal cell carcinoma. A historical perspective|journal=J Urol Pathol|year=1996|volume=4|pages=31–49}} He described the case of Françoise Levelly, a 35-year-old woman, who presented to Brest Civic Hospital on April 6, 1809, supposedly in the late stages of pregnancy.

Koenig published the first classification of renal tumours based on macroscopic morphology in 1826. Koenig divided the tumors into scirrhous, steatomatous, fungoid and medullary forms.{{cite journal |doi=10.1016/j.cll.2005.01.007 |title=History of the Development of the Classification of Renal Cell Neoplasia |year=2005 |last1=Delahunt |first1=Brett |last2=Eble |first2=John N. |journal=Clinics in Laboratory Medicine |volume=25 |issue=2 |pages=231–46, v |pmid=15848734}}

Following the classification of the tumour, researchers attempted to identify the tissue of origin for renal carcinoma.

The pathogenesis of renal epithelial tumours was debated for decades. The debate was initiated by Paul Grawitz when in 1883, he published his observations on the morphology of small, yellow renal tumours. Grawitz concluded that only alveolar tumours were of adrenal origin, whereas papillary tumours were derived from renal tissue.

In 1893, Paul Sudeck challenged the theory postulated by Grawitz by publishing descriptions of renal tumours in which he identified atypical features within renal tubules and noted a gradation of these atypical features between the tubules and neighboring malignant tumour. In 1894, Otto Lubarsch, who supported the theory postulated by Grawitz coined the term hypernephroid tumor, which was amended to hypernephroma by Felix Victor Birch-Hirschfeld to describe these tumours.{{cite journal |doi=10.1001/archinte.1929.00140050123011 |title=Carcinoma of the Renal Cortex with Factors Bearing on Prognosis |year=1929 |last1=Judd |first1=E. Starr |journal=Archives of Internal Medicine |volume=44 |issue=5 |pages=746}}

Vigorous criticism of Grawitz was provided by Oskar Stoerk in 1908, who considered the adrenal origin of renal tumours to be unproved. Despite the compelling arguments against the theory postulated by Grawitz, the term hypernephroma, with its associated adrenal connotation, persisted in the literature.

Foot and Humphreys, and Foote et al. introduced the term Renal Celled Carcinoma to emphasize a renal tubular origin for these tumours. Their designation was slightly altered by Fetter to the now widely accepted term Renal Cell Carcinoma.{{cite journal |pmid=14861941 |year=1951 |last1=Foot |first1=NC |last2=Humphreys |first2=GA |last3=Whitmore |first3=WF |title=Renal tumors: Pathology and prognosis in 295 cases |volume=66 |issue=2 |pages=190–200 |journal=The Journal of Urology|doi=10.1016/S0022-5347(17)74326-1 }}

Convincing evidence to settle the debate was offered by Oberling et al. in 1959 who studied the ultrastructure of clear cells from eight renal carcinomas. They found that the tumour cell cytoplasm contained numerous mitochondria and deposits of glycogen and fat. They identified cytoplasmic membranes inserted perpendicularly onto the basement membrane with occasional cells containing microvilli along the free borders. They concluded that these features indicated that the tumours arose from the epithelial cells of the renal convoluted tubule, thus finally settling one of the most debated issues in tumour pathology.{{cite journal |doi=10.1038/186402a0 |title=Ultrastructure of the Clear Cells in Renal Carcinomas and its Importance for the Demonstration of their Renal Origin |year=1960 |last1=Oberling |first1=CH. |last2=Rivière |first2=M. |last3=Haguenau |first3=FR. |journal=Nature |volume=186 |issue=4722 |pages=402–403|pmid=14428164 |bibcode=1960Natur.186..402O |s2cid=4224899 }}

• Dysuria
• Interferon
• Interleukin-2
• Kidney cancer
• Knudson hypothesis
• Rapamycin
• Stauffer syndrome
• Vinblastine
• Vasculogenic Mimicry

{{Reflist|30em|refs=

{{cite journal|doi=10.1016/j.bbcan.2007.12.002|pmid=18187049|title=Genetics and epigenetics of renal cell cancer|year=2008|last1=Baldewijns|first1=Marcella M.L.|last2=Van Vlodrop|first2=Iris J.H.|last3=Schouten|first3=Leo J.|last4=Soetekouw|first4=Patricia M.M.B.|last5=De Bruïne|first5=Adriaan P.|last6=Van Engeland|first6=Manon|journal=Biochimica et Biophysica Acta (BBA) - Reviews on Cancer|volume=1785|issue=2|pages=133–155}}

{{cite book|title=Renal Cell Carcinoma Clinical Management |year=2013|publisher=Humana Pr Inc.|isbn=978-1-62703-061-8|pages=3–22|author=Birkhauser|last2=Kroeger|first2=Pantuck|chapter=Etiology of Renal Cell Carcinoma: Incidence, Demographics, and Environmental Factors}}

{{cite journal |doi=10.1056/NEJMra043172|pmid=16339096 |title=Renal-Cell Carcinoma |year=2005 |last1=Cohen |first1=Herbert T. |last2=McGovern |first2=Francis J. |journal=New England Journal of Medicine |volume=353 |issue=23 |pages=2477–90|url=https://semanticscholar.org/paper/55f232dcc1c38655f4215c2fd9cefaf4775eff29 }}

{{cite journal |doi=10.1097/01.ju.0000092764.81308.6a |title=Paraneoplastic Signs and Symptoms of Renal Cell Carcinoma: Implications for Prognosis |year=2003 |last1=Kim |first1=Hyung L. |last2=Belldegrun |first2=Arie S. |last3=Freitas |first3=Danielo G. |last4=Bui |first4=Matthew H.T. |last5=Han |first5=KEN-RYU |last6=Dorey |first6=Frederick J. |last7=Figlin |first7=Robert A. |journal=The Journal of Urology |volume=170 |issue=5 |pages=1742–6 |pmid=14532767}}

{{cite book |doi=10.1007/978-1-62703-062-5_5 |chapter=Prognostic Factors for Localized Renal Cell Carcinoma |title=Renal Cell Carcinoma |year=2013 |last1=Lane |first1=Brian R. |isbn=978-1-62703-061-8 |pages=83–102}}

{{cite journal |pmid=20865085 |year=2009 |last1=Lipworth |first1=L |last2=Tarone |first2=RE |last3=Lund |first3=L |last4=McLaughlin |first4=JK |title=Epidemiologic characteristics and risk factors for renal cell cancer |volume=1 |pages=33–43 |pmc=2943168 |journal=Clinical Epidemiology|doi=10.2147/clep.s4759 |doi-access=free }}

{{cite book|title=Renal Cell Carcinoma Clinical Management |year=2013|publisher=Humana |isbn=978-1-62703-061-8|pages=155–166|author=Matin|author2=Ahrar|chapter=Thermal Ablation}}

{{cite book|title=Renal Cell Carcinoma Clinical Management|year=2013|publisher=Humana |isbn=978-1-62703-061-8|pages=339–348|author=Metz|author2=Davis|chapter=Palliative and Supportive Care for Renal Cancer}}

{{cite journal|doi=10.1056/NEJM199609193351207|title=Renal-Cell Carcinoma|year=1996|last1=Motzer|first1=Robert J.|last2=Bander|first2=Neil H.|last3=Nanus|first3=David M.|journal=New England Journal of Medicine|volume=335|issue=12|pages=865–75|pmid=8778606}}

{{cite journal |doi=10.1038/nrc1364 |title=Searching for the hereditary causes of renal-cell carcinoma |year=2004 |last1=Pavlovich |first1=Christian P. |last2=Schmidt |first2=Laura S. |journal=Nature Reviews Cancer |volume=4 |issue=5 |pages=381–93 |pmid=15122209|s2cid=17905393 }}{{cite journal |doi=10.1016/S0140-6736(09)60229-4 |pmid=19269025 |title=Renal cell carcinoma |year=2009 |last1=Rini |first1=Brian I |last2=Campbell |first2=Steven C |last3=Escudier |first3=Bernard |journal=The Lancet |volume=373 |issue=9669 |pages=1119–1132|s2cid=24535138 }}

{{cite book|title=Renal Cell Carcinoma Clinical Management|year=2013|publisher=Humana Pr Inc.|isbn=978-1-62703-061-8|pages=119–132|author=Russo|chapter=Radical Nephrectomy for Localised Renal Tumours: Oncological and Renal Functional Considerations}}

{{cite journal |doi=10.1007/s12094-008-0276-8 |title=Origin of renal cell carcinomas |year=2008 |last1=Valladares Ayerbes |first1=Manuel |last2=Aparicio Gallego |first2=Guadalupe |last3=Díaz Prado |first3=Silvia |last4=Jiménez Fonseca |first4=Paula |last5=García Campelo |first5=Rosario |last6=Antón Aparicio |first6=Luis Miguel |journal=Clinical and Translational Oncology |volume=10 |issue=11 |pages=697–712 |pmid=19015066|hdl=2183/19413 |hdl-access=free }}

}}

{{Medical resources

| ICD10 = {{ICD10|C|64||c|64}}

| ICD9 = {{ICD9|189.0}}

| ICDO = {{ICDO|8312|3}}

| OMIM = 144700

| OMIM_mult = {{OMIM|605074||none}}

| MedlinePlus = 000516

| eMedicineSubj = med

| eMedicineTopic = 2002

| DiseasesDB = 11245

| MeSH1 = D002292

}}

{{Urologic neoplasia}}

{{Tumor morphology}}

{{Authority control}}

{{DEFAULTSORT:Renal Cell Carcinoma}}

Category:Kidney cancer

Category:Medical triads