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Renal cell carcinoma

Last updated: September 7, 2021

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Renal cell carcinoma (RCC), which arises from renal tubular epithelium, is the most common cause of renal malignancy in adults. While a fraction of cases of RCC occur in association with hereditary disorders, most cases are sporadic. Important risk factors for RCC include smoking, acquired cystic disease of the kidney, nephrolithiasis, and chronic acetaminophen use. Clinical features of RCC include hematuria, flank pain, a flank mass, anemia, and weight loss. Patients may also present with paraneoplastic manifestations such as hypercalcemia and hypertension. The most important initial test is a contrast CT of the abdomen. The treatment of choice is surgical resection. RCC is notoriously resistant to classical chemotherapeutic agents. Early stage RCC with tumor growth limited to the kidney has a very good prognosis.

Epidemiological data refers to the US, unless otherwise specified.


  • Most renal cell carcinomas (RCCs) occur sporadically.
  • Approx. 4% of renal cell carcinomas are associated with hereditary factors.
  • Both forms show structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene.

Risk factors for sporadic RCC [2][3]

Hereditary renal cell carcinomas [3]

Hereditary renal cell carcinomas are autosomal dominant and tend to affect patients at a younger age than sporadic renal cell carcinomas.

  • Overview
    • Usually asymptomatic in the early stages
    • Patients become symptomatic when the tumor has reached a large size (usually > 10 cm) and/or if metastases are present.
  • Constitutional symptoms
  • Symptoms caused by primary tumor [5]
    • Hematuria (∼ 60%)
    • Flank pain (∼ 40%)
    • Palpable renal mass (30–40%)
  • Symptoms of local spread and metastatic disease: see “Complications” below

The classical triad of renal cell carcinoma consists of hematuria, flank pain, and a palpable flank mass. However, only 10–15% of patients present with all three components of the triad and > 25% present with one or more atypical symptoms related to paraneoplastic syndromes and/or disseminated disease. [5]

TNM classification (8th Edition, 2017)

Overview of TNM classification
TNM Tissue invasion

AJCC staging (8th Edition, 2017)

Overview of AJCC stages
AJCC stage TNM
Stage I
  • T1; N0
Stage II
  • T2; N0
Stage III
  • T1 or T2; N1
  • T3; N0 or N1
Stage IV
  • T4; Any N; M0
  • Any T; Any N; M1

Imaging [5]

Evaluation of RCC

Evaluation of metastatic disease

Laboratory tests [5]

Blood tests


Renal cell carcinomas are adenocarcinomas that usually arise from the epithelial cells of the proximal convoluted tubule.

Overview of the most important types of renal cell carcinoma [6][7]
Clear cell renal cell carcinoma Non-clear cell renal cell carcinomas
Papillary (chromophilic) RCC Chromophobe RCC Oncocytic RCC Collecting duct carcinoma (Bellini duct carcinoma)
Relative frequency
  • ∼ 70%
  • ∼ 10–15%
  • ∼ 5%
  • ∼ 1%
  • ∼ 1%
Cell of origin
  • Unknown
  • Unknown
Macroscopic appearance
  • Yellow or golden due to high intracellular lipid concentration
Microscopic appearance
  • Clear cells
  • Unifocal, unilateral growth
  • Cuboidal, low columnar cells
  • Cells grow in papillary formations
  • Bilateral, multifocal growth possible
  • Originate from oncocytomas
  • Similar to chromophobic RCC, but without perinuclear halo
  • Cells occur as tumor nests
  • Hobnail pattern: irregularly arranged malignant glandular cells within a fibrous stroma
  • Medullary duct carcinoma: A variant that is associated with sickle cell disease.
  • Excellent prognosis
  • Aggressive tumor with a poor prognosis

Rule of 3: A mutation in the VHL (von Hippel-Lindau) gene on chromosome 3 causes RCC (renal cell carcinoma).

Malignant renal masses

All renal masses > 1 cm in size are presumed to be renal cell carcinoma and treated as such.

Benign renal masses

Angiomyolipoma [8]


  • Definition: benign epithelial tumor arising from the intercalated tubular cells in the collecting duct
  • Clinical features
  • Pathology
    • Macroscopy: smooth, clearly defined brown tumor with central radial scar
    • Microscopy
      • Large acidophilic cells
      • Excessive amount of mitochondria acidophilic, granular cytoplasm without perinuclear clearing (unlike chromophobe RCC)
  • Therapy
    • Often resected in order to exclude RCC
    • Surveillance
    • Nephrectomy in case of incease in tumor size
  • Prognosis: Oncocytomas are not invasive, but they may transform into a malignant oncocytic RCC.

The differential diagnoses listed here are not exhaustive.

Curative approach

Surgical resection [9]

Palliative approach

Targeted therapy [10]

Immunotherapy [11]

Genitourinary intervention

Therapy resistance

  • Radiation therapy is not typically used to treat RCC due to resistance. [12]
  • High resistance rate against chemotherapy because tumor cells express MDR-1 (multidrug resistance protein-1)

Chemotherapy is not used to treat RCC because RCC is highly resistant to chemotherapeutic agents.

Complications caused by paraneoplastic syndromes [5]

Paraneoplastic RCC: Polycythemia (EPO), Renin (hypertension), hyperCalcemia (PTHrP) and hyperCortisolism (ACTH).

Complications caused by local spread

Complications caused by metastatic disease

Reactive amyloidosis [14]

We list the most important complications. The selection is not exhaustive.

Survival of kidney cancer patients

  • Overall prognosis is determined by the anatomic extent of the disease (stage of cancer at diagnosis) and the histopathology of the tumor.
  • Targeted therapies have significantly prolonged survival time.
  • Early stage RCC with tumor growth limited to the kidney generally has a good prognosis.
5-year survival of kidney cancer patients [17]
SEER stage Description 5-year survival rate
  • 93%
  • 70%
  • 12%
All stages combined
  • Combination of all three SEER stages
  • 75%

Increased awareness and screening (e.g., ultrasound) of high-risk patients in recent years has led to earlier tumor detection and improved the prognosis of RCC.

Motzer score [18]


  • Used to determine prognosis of patients with stage IV (distant) disease
  • A point is assigned for each of the following criteria.
  • Based on the resulting score, the prognosis of the metastatic RCC patient is estimated.
  • High scores are associated with a poorer prognosis.


Motzer score
Parameter Description
Karnofsky performance status

< 80%

< 80%: 1 point
> 80%: 0 points
Hemoglobin level

< 12.0 g/dL

< 12.0 g/dL: 1 point
> 12.0 g/dL: 0 points
< 13.5 g/dL < 13.5 g/dL: 1 point
> 13.5 g/dL: 0 points
LDH (> 1.5 times the upper normal limit) > 420 U/L > 420 U/L: 1 point
< 420 U/L: 0 point
Serum calcium > 10 mg/dL (> 2.5 mmol/L) > 10 mg/dL (> 2.5 mmol/L): 1 point
< 10 mg/dL (< 2.5 mmol/L): 0 points
Time from diagnosis to systemic treatment < 1 year < 1 year: 1 point
> 1 year: 0 points


Motzer score interpretation
Points Risk Median survival
  • Low
  • 20 months
  • Intermediate
  • 10 months
≥ 3
  • High
  • 4 months
  1. Key Statistics About Kidney Cancer. Updated: February 1, 2020. Accessed: November 16, 2020.
  2. Cheng G, Xie L. Alcohol intake and risk of renal cell carcinoma: a meta-analysis of published case-control studies. Archives of Medical Science. 2011; 4 : p.648-657. doi: 10.5114/aoms.2011.24135 . | Open in Read by QxMD
  3. Risk Factors for Kidney Cancer. Updated: February 1, 2020. Accessed: November 19, 2020.
  4. Acquired Cystic Kidney Disease. Updated: August 1, 2015. Accessed: March 1, 2017.
  5. Renal cell carcinoma. Updated: February 15, 2017. Accessed: February 15, 2017.
  6. Vos N, Oyen R. Renal Angiomyolipoma: The Good, the Bad, and the Ugly. Journal of the Belgian Society of Radiology. 2018; 102 (1). doi: 10.5334/jbsr.1536 . | Open in Read by QxMD
  7. Williams NS, Bulstrode C, O'Connell PR. Bailey & Love's Short Practice of Surgery. CRC Press ; 2013
  8. Targeted Therapy for Kidney Cancer. Updated: February 3, 2020. Accessed: November 19, 2020.
  9. Immunotherapy for Kidney Cancer. Updated: February 1, 2012. Accessed: November 19, 2020.
  10. Tselis N, Chatzikonstantinou G. Treating the Chameleon: Radiotherapy in the management of Renal Cell Cancer. Clinical and Translational Radiation Oncology. 2019; 16 : p.7-14. doi: 10.1016/j.ctro.2019.01.007 . | Open in Read by QxMD
  11. Harrison JW, Cherukuri R, Buchan D. Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive Decline from Limbic Encephalitis. J Gen Intern Med. 2015; 30 (7): p.1037-1040. doi: 10.1007/s11606-014-3172-7 . | Open in Read by QxMD
  12. Babu A, Lachmann H, Pickett T, Boddana P, Ludeman L. Renal cell carcinoma presenting as AA amyloidosis: a case report and review of the literature.. CEN case reports. 2013; 3 (1): p.68-74. doi: 10.1007/s13730-013-0088-8 . | Open in Read by QxMD
  13. Ahmed M, Solangi K, Abbi R, Adler S. Nephrotic syndrome, renal failure, and renal malignancy: an unusual tumor-associated glomerulonephritis. J Am Soc Nephrol. 1997; 8 (5): p.848-852.
  14. Woodrow G, Innes A, Ansell ID, Burden RP. Renal cell carcinoma presenting as nephrotic syndrome. Nephron. 1995; 69 (2): p.166-169.
  15. Survival Rates for Kidney Cancer. Updated: February 1, 2020. Accessed: November 19, 2020.
  16. Robert J. Motzer, Madhu Mazumdar, Jennifer Bacik, William Berg, Alison Amsterdam, Joseph Ferrara. Survival and Prognostic Stratification of 670 Patients With Advanced Renal Cell Carcinoma. Journal of Clinical Oncology. 1999; 17 (8): p.2530-2530. doi: 10.1200/jco.1999.17.8.2530 . | Open in Read by QxMD
  17. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2014
  18. What Is Kidney Cancer?. Updated: May 5, 2020. Accessed: November 19, 2020.