Wednesday, September 26, 2012

Renal Cell Carcinoma - A Reappraisal part 5

Classification, Grading, and Staging

Recent advancements in the understanding of the genetics of RCC have led to a new pathological classification of five different subtypes of RCCs: clear cell, papillary, chromophobe, collecting duct carcinoma (Bellini Duct tumor), and renal carcinoma unclassified (renal medullary carcinoma). This classification is primarily based on cytologic appearance and the cell origin in combination with growth pattern and genetic alterations (Campbell & Lane, 2012; Kennedy et al., 1990).
The grading of RCC is based on the morphology of a neoplasm with hematoxylin and eosin (H&E) staining on microscopy. The most popular and widely used system for grading RCC is a nuclear grading system described by Fuhrman, Lasky, and Limas in 1982. This system categorizes RCC into one of four grades based on nuclear characteristics and has been shown to correlate with prognosis (see Table 3).
Table 3. Fuhrman Grading System
Grade 1
Nuclei of the tumor cells are small (< 10 μm), hyperchromatic, and round (resembling mature lymphocytes), with no visible nucleoli and little detail in the chromatin.
Grade 2
Nuclei of the tumor cells are slightly larger (15 μm) with finely granular "open" chromatin but small, inconspicuous nucleoli.
Grade 3
Nuclei of the tumor cells are larger (20 μm in size) and may be oval in shape, with coarsely granular chromatin. The nucleoli are easily recognizable.
Grade 4
The nuclei are pleomorphic with open chromatin or hyperchromatic and single or multiple macronucleoli.
Source: Fuhrman et al., 1982.

The Tumor Node Metastasis (TNM) staging system is used for staging all histologic variants of renal carcinoma. This system assesses the anatomic extent of disease and has been shown to correlate with prognosis. A revision was proposed in 2010 and is supported by the American Joint Committee on Cancer (AJCC) (2010) (see Table 4).
Table 4. Tumor Node Metastasis
Tumor (T) Description
Primary tumor cannot be assessed
No evidence of primary tumor
Tumor 7 cm or less, limited to kidney
Tumor 4 cm or less in greatest dimension, limited to the kidney
Tumor more than 4 cm but not more than 7 cm in greatest dimen-sion, and limited to the kidney
Tumor greater than 7 cm, limited to kidney
Tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney
Tumor more than 10 cm, limited to the kidney
Tumor extends into major veins/adrenal/perinephric tissue; not beyond Gerota's fascia
Tumor invades perinephric tissue, renal sinus or renal vein
Tumor extends into renal vein(s) or vena cava below diaphragm
Tumor extends into vena cava above diaphragm or into wall of vane cava at any level
Tumor invades beyond Gerota's fascia or directly into adrenal gland
Regional lymph nodes
Regional nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single regional lymph node
Metastasis in more than one regional lymph node
Distant metastasis
Distant metastasis cannot be assessed
No distant metastasis
Distant metastasis
Source: Edge et al., 2010.

Another commonly used staging system ranges from Stage I to IV based on anatomic stage and places into a prognostic group (see Table 5).
Table 5. Anatomic Staging System/Prognostic Group
Anatomic Stage
Prognostic Group
Stage 1
T1 N0 M0
Stage 2
T2 N0 M0
Stage 3
T1 or T2, N1 M0
T3 N0 or N1, M0
Stage 4
T4 any N M0
Any T, any N, M1
Source: Edge et al., 2010.

It is hoped that with greater knowledge of tumor genetics and immunohistochemistry, there will be an improved ability to make prognoses and appropriately target therapy to those who would most benefit (Odonez & Hank, 2011).



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