Renal cell carcinoma

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A review of renal cell carcinoma was published in BMJ in November 2014.[1]

Although lumped together as a single entity for convenience, it is best regarded as a number of different tumours, derived from different parts of the nephron (insofar as any tumour can be thought to be specifically derived from cell). Each variant has different molecular, histomorphological and, unsurprisingly, clinical characteristics.

For instance, classical clear cell renal carcinoma is associated with loss of the VHL gene, both in sporadic cases and also in von Hippel-Lindau disease. The VHL protein, amongst other functions, controls hypoxia inducible factors and VEGF, targets for targetted therapies.



  • Commonest primary kidney tumour in adults[2].
  • 1-3% of visceral tumours.
  • Males>females

See this BMJ "infographic" to compare the incidence of renal cell carcinoma in different populations.

Clinical Features

Classically presents with triad of:

  1. Flank pain
  2. Haematuria
  3. Palpable abdominal mass.

This triad is less commonly (around 5-10% of presentation) seen nowadays as it implies late-stage disease.


Risk factors

Histological Features

Clear cell variant of renal cell carcinoma.
Chromophobe variant of renal cell carcinoma.
Papillary variant of renal cell carcinoma.

Histological sub-types:

  • Clear cell, of which there are further sub-types:
    • eosinophilic variant (can be confused with chromophobe on needle biopsy)
    • multilocular cystic variant (better prognosis than standard clear cell)
  • Chromophobe (better prognosis than standard clear cell)
  • Xp11 translocation associated RCC.
  • Papillary: type 1 and type 2

Medullary and collecting duct carcinoma are usually considered separately (aggressive tumours).


Clear cell variant graded using the Fuhrman grading.

Extrapolation of Fuhrman grading to other variants has been unreliable.[3] Alternatives have been suggested for other variants, e.g. chromophobe RCC[4] and papillary[5] (see also review [6]).


This sections refers to conventional clear cell variant. Relatively poor due to late presentation (although this may change with increasing incidental diagnoses found on scans for other purposes).

  • 5 year survival up to 70% if no evidence of metastasis.
    • For tumors less than 5 cm in diameter 10-year cancer-specific mortality rate after open partial nephrectomy is 5.5%[7].
  • If renal vein involved or extension into perinephric fat year survival 15-20%


  • Incidental small renal mass less than 1cm diameter active surveillance (care with radiation exposure !)[8]
  • If fit and no metastatic disease:
    • Tumour < 5cm diameter open or laparoscopic partial nephrectomy
    • Thermal ablation is option in selected cases
    • Otherwise radical nephrectomy
  • Metastatic & advanced disease
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  1. Jonasch E, Gao J, Rathmell WK. Renal cell carcinoma. BMJ (Clinical research ed.). 2014; 349:g4797.(Epub)
  2. General and Systematic Pathology. Underwood JCE. Churchill Livingstone 2000.ISBN 0-443-06285-4
  3. Delahunt B, Sika-Paotonu D, Bethwaite PB, McCredie MR, Martignoni G, Eble JN, Jordan TW. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. The American journal of surgical pathology. 2007 Jun; 31(6):957-60.(Link to article – subscription may be required.)
  4. Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, Lyles RH. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. The American journal of surgical pathology. 2010 Sep; 34(9):1233-40.(Link to article – subscription may be required.)
  5. Sika-Paotonu D, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. The American journal of surgical pathology. 2006 Sep; 30(9):1091-6.(Link to article – subscription may be required.)
  6. Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2009 Jun; 22 Suppl 2:S24-36.(Link to article – subscription may be required.)
  7. Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: indications, techniques and outcomes. The Journal of urology. 2001 Jul; 166(1):6-18.
  8. Gill IS, Aron M, Gervais DA, Jewett MA. Small renal mass. The New England journal of medicine. 2010 Feb 18; 362(7):624-34.(Link to article – subscription may be required.)