Clinical Conditions

Renal Cell Carcinoma (RCC)

RCC is the most common type of kidney cancer. RCC begins small and grows larger over time, like many other cancers. Based on limited observations, renal cancers appear to grow approximately 1 cm (1/2 inch) in diameter per year. RCC usually grows as a single mass. Sometimes, a kidney may contain more than one tumor or tumors may be found in both kidneys at the same time. Patients with bilateral tumors, early onset of disease, or multiple tumors may suggest a genetic predisposition to form RCC as occurs in patients with Von Hippel-Lindau disease. In the past, RCCs were diagnosed only after they have become quite large or symptoms of flank pain, blood in the urine, or palpable mass in the abdomen developed. But fortunately, most RCC are now found incidentally (during evaluation of unrelated medical problems) by imaging studies such as ultrasound, CAT scan, or MRI. The recently observed rising incidence of RCC may not be solely due to increased use of imaging studies but a trend toward increased detection of small lesions that are surgically curable has been noted. RCC is difficult to treat and rarely cured once it has spread beyond the kidney and current therapies have limited efficacy. Researchers are beginning to understand ways that cause these kidney cells become cancerous. Much research is now focused on how mutations of genes on chromosome 3, 7, 17 result in kidney tumors. Other researchers are studying how different genetic changes seen in RCC affect how the cancer looks under the microscope and how likely it is to grow and spread aggressively. Doctors hope to use this information to treat RCC more effectively in new ways that cause fewer side effects.

Types

Recent advances in understanding genetic changes associated in kidney tumor formation have led a new pathologic classification of RCC into 5 different types:

  1. Clear cell type (65% of RCC)
    Cell origin: proximal tubule
    Cytogenetic abnormalities: chromosome 3p deletions, mutations of VHL gene (tumor suppressor gene)
  2. Papillary cell type (Chromophil) (15% of RCC)
    Cell origin: proximal tubule
    Cytogenetic abnormalities: trisomies of chromosomes 3q, 7, 12, 16, 17, 20; loss of Y chromosome
  3. Chromophobe cell type (10% of RCC)
    Cell origin: intercalated cell of cortical collecting duct
    Cytogenetic abnormalities: monosomies of chromosomes 1, 2, 6, 10, 13, 17, and 21; hypodiploidy
  4. Oncocytoma (5% of RCC)
    Cell origin: Intercalated cell of cortical collecting duct
    Cytogenetic abnormalities: loss of chromosomes 1 and Y
  5. Unclassified cell type (5% of RCC): Sarcomas, collecting duct tumors, etc.

Recent data suggest that clear cell RCC has a slightly worse prognosis as compared to papillary or chromophobe cell RCC, however, the majority of low stage tumors, regardless of its cell type, can be cured with surgical resection. Oncocytoma is usually a benign lesion with an extremely low chance of spreading. Spindle cell types or sarcomas tend to grow and spread more quickly than the other kinds of RCCs. It can be associated with any of subtype mentioned and this subtype portends poor prognosis.

Grade

Tumor grade is an important prognostic factor. Grading refers to how closely the cancer cells look like normal kidney cells under the microscope. Fuhrman grading system has a scale of 1 through 4 with grade 1 tumor being a very little different from normal kidney cells. These cancers usually are slow to grow and spread and tend to have a good prognosis. On the other extreme, grade 4 tumors look quite different from normal kidney cells and have a worse prognosis. Therefore, grading of tumor cells is an important factor in assessing prognosis except in papillary RCC type where grading seems to have a minimal prognostic value.

Staging

The most important factor in predicting prognosis is the stage. The stage describes the cancer's size and how deeply it has spread beyond the kidney. The Staging System of the American Joint Committee on Cancer (AJCC) is sometimes known as TNM system. The letter T followed by a number from 1 to 3 describes the tumor's size and spread to nearby tissues. Higher T numbers indicate a larger tumor and/or more extensive spread to tissues near the kidney. The letter N followed by a number from 0 to 2 indicates whether the cancer has spread to lymph nodes near the kidney and, if so, how many are affected. Lymph nodes are bean-sized collections of immune system cells that help fight infections and cancers. The letter M followed by a 0 or 1 indicates whether or not the cancer has spread to distant organs (for example, the lungs or bones) or to lymph nodes that are not near to the kidneys. The next section summarizes features of the 1997 revision of AJCC stages for cancer.

Summary of renal cell cancer AJCC (TNM) stages

Stage I: The tumor is 7 cm (about 2 3/4 inches) or smaller, and limited to the kidney. There is no spread to lymph nodes or distant organs.

Stage II: The tumor is larger than 7.0 cm but still limited to the kidney. There is no spread to lymph nodes or distant organs.

Stage III: There are several combinations of T and N categories that are included in this stage. These include tumors of any size, with or without spread to fatty tissue around the kidney, with or without spread into the large veins leading from the kidney to the heart, with spread to one nearby lymph node, but without spread to distant lymph node or other organs. Stage III also includes tumors with spread to fatty tissue around the kidney and/or spread into the large veins leading from the kidney to the heart, that have not spread to any lymph nodes or other organs.

Stage IV: There are several combinations of T, N, and M categories that included in this stage. This stage includes any cancers that have spread directly through the fatty tissue and the fascia ligament-like tissue that surrounds the kidney. Stage IV also includes any cancer that has spread to more than one lymph node near the kidney, to any lymph node not near the kidney, or to any other organs such as the lungs, bone, or brain.

Detailed definitions of renal cell cancer T, N, M categories and stage groupings

Primary tumor (T):

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor 7 cm or less, limited to kidney
T2: Tumor greater than 7 cm, limited to kidney
T3: Tumor extends into major veins/adrenal/ perinephric tissue; not beyond Gerota's fascia
T3a: Tumor invades adrenal/perinephric fat
T3b: Tumor extends into renal vein(s) or vena cava below diaphragm
T3c: Tumor extends into vena cava above diaphragm
T4: Tumor invades beyond Gerota's fascia

N - Regional lymph nodes
NX: Regional nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single regional lymph node
N2: Metastasis in more than one regional lymph node

M - Distant metastasis
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis