How is clear cell renal cell carcinoma (CCRCC) graded based on nuclear characteristics?

Updated: Mar 11, 2019
  • Author: Ronald J Cohen, MB, BCh, PhD, FRCPA, FFPATH; Chief Editor: Liang Cheng, MD  more...
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Nuclear characteristics form the basis of the Fuhrman nuclear grading system and are currently used for grading CCRCC, as follows [44] :

  • Grade 1: Nuclei are small (< 10µm) and round, with dense chromatin and inconspicuous nucleoli

  • Grade 2: Nuclei are slightly larger (15 µm), with finely granular chromatin and small nucleoli

  • Grade 3: The nuclei are 20 µm in size and may be oval in shape, with coarsely granular chromatin and prominent nucleoli

  • Grade 4: The nuclei are pleomorphic, with open chromatin and single or multiple macronucleoli

Increasing nuclear grade is associated with several histologic tumor characteristics, including an increasing proportion of eosinophilic cells [43, 44] and hyaline globules, which are often associated with granular cytoplasm. These can be identified either intracellularly or extracellularly in 17% of CCRCCs as bright eosinophilic globules that stain positively with PAS stain or red with the Masson trichrome stain. [43, 45]

Histologic coagulative necrosis occurs in 28-37% of CCRCCs, most commonly in those with high nuclear grade. [39, 46, 47] Other variations associated with a high grade include cells with sarcomatoid or rhabdoid differentiation. Sarcomatoid differentiation is seen in 5-25% of CCRCCs and is identified as focal to extensive regions of malignant spindled cells growing as whorled or intersecting fascicles, or in a storiform pattern.

Association with histologic necrosis is particularly common. Tumors are usually classified as Fuhrman grade 4 based on the presence of these sarcomatoid elements. [48, 49, 50]

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