Diagnosis and Staging

Histological diagnosis

This information has been reproduced with the  permission of the EAU Guidelines Office.

The histological diagnosis in RCC is established after surgical removal of renal tumours or after biopsy specimen examinations1-3. The Fuhrman classification system for nuclear grade (grade 1, 2, 3 and 4) in RCC4,5 has been the most generally accepted classification, and is an important, independent prognostic factor for RCC (level of evidence: 3).

According to the WHO6 there are at least three major histological subtypes of RCC:

  • clear cell (cRCC, 80-90%)
  • papillary (pRCC, 10-15%)
  • chromophobe (chRCC, 4-5%) (level of evidence 3).

These RCC types can be differentiated by histological and molecular genetic changes (level of evidence 3) (Table 5). Papillary RCC can further be divided into two different subtypes, type 1 and type 2 with an adverse clinical course (Table 5)7,8 (level of evidence 3).

Histological subtype Percentage of RCC Histological description Associated molecular genetic changes
Clear cell (cRCC) 80-90% Most cRCC are composed predominantly of cells containing clear cytoplasm, although eosinophilic cytoplasm predominates in some cells. The growth pattern may be solid tubular and cystic Identified by the specific deletion of chromosome 3p and mutation of the VHL gene. Other changes are duplication of the chromosome band 5q22, deletion of chromosome 6q, 8p, 9p and 14q
Papillary (pRCC) 10-15% Most pRCCs have small cells with scanty cytoplasm, but also basophilic, eosinophilic or pail-staining characteristics. A papillary growth pattern predominates, although there may be tubular papillary and solid architectures. Necrotic areas are common. Papillary RCC can be divided into two different subtypes type 1 with small cells and pale cytoplasm and type 2 with large cells and eosinophilic cytoplasm, the latter having a worse prognosis The most consistent genetic alterations are trisomies of chromosomes 3q, 7, 8, 12, 16, 17 and loss of the y chromosome
Chromophobe (chRCC) 4-5% The cells of chRCC may have pail or eosinophilic granular cytoplasm. Growth usually occur in solid sheets The genetic characteristic is a combination of loss of chromosomes 1, 2, 6, 10, 13, and 17

Table 5: Major histological subtypes of RCC.

References:
1. Brierly RD, Thomas PJ, Harrison NW, Fletcher MS, Nawrocki JD, Ashton-Key M. Evaluation of fine needle aspiration cytology for renal masses. BJU Int 2000;85(1):14-8. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/10619937
2. Dechet CB, Zincke H, Sebo TJ, King BF, LeRoy AJ, Farrow GM, Blute ML. Prospective analysis of computerized tomography and needle biopsy with permanent sectioning to determine the nature of solid renal masses in adults. J Urol 2003;169(1):71-4. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/12478106
3. Remzi M, Marberger M. Renal tumor biopsies for evaluation of small renal tumors: why, in whom and how? Eur Urol 2009 Feb;55: 359-67.
http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/18849108
4. Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6(7):655-63.
http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/7180965
5.Lang H, Lindner V, de Fromont M, Molinie V, Letourneux H, Meyer N, Martin M, Jacqmin D. Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: assessment of 241 patients with > 15-year follow-up. Cancer 2005;103(3):625-9. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/15611969
6.Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds). In: Pathology and genetics of tumours of the urinary system and male genital organs. World Health Organization Classification of Tumours. Lyons: IARC Press, 2004: p. 7.
7.Delahunt B, Eble JN, McCredie MR, Bethwaite PB, Stewart JH, Bilous AM. Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases. Hum Pathol 2001 Jun;32(6):590-5. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/pubmed/11431713
8. Pignot G, Elie C, Conquy S, Vieillefond A, Flam T, Zerbib M, Debré B, Amsellem-Ouazana D. Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. Urology 2007 Feb;69(2):230-5.