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Renal Cell Carcinoma: eMedicine Oncology
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eMedicine Specialties > Oncology > Carcinomas of the Genitourinary Tract
S
Renal Cell Carcinoma
Author: Kush Sachdeva, MD, Private Practice, Southern Oncology and Hematology Associates, South Jersey Hospital System, Fox
Chase Cancer Center
Coauthor(s): Issam Makhoul, MD, Assistant Professor, Department of Medicine, Division of Hematology/Oncology, University of
Arkansas for Medical Sciences; Mansoor Javeed, MD, FACP, Clinical Assistant Professor of Medicine, University of California Davis;
Consulting Staff Sierra Hematology-Oncology Medical Center, California; Brendan Curti, MD, Director, Genitourinary Oncology
Research, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center
Contributor Information and Disclosures
Updated: Jan 7, 2008
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Introduction
Background
Overview
Differential Diagnoses & Workup
Treatment & Medication
Renal cell carcinoma accounts for approximately 3% of adult
malignancies and 90-95% of neoplasms arising from the kidney. It is
Follow-up
characterized by a lack of early warning signs, diverse clinical
References
manifestations, resistance to radiation and chemotherapy, and
Keywords
infrequent but reproducible responses to immunotherapy agents such
as interferon alpha and interleukin (IL)-2. New agents, such as
sorafenib and sunitinib, having anti-angiogenic effects through targeting
multiple receptor kinases, have activity in patients failing immunotherapy. In the past, these tumors were believed to
derive from the adrenal gland; therefore, the term hypernephroma was used often.
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Pathophysiology
The tissue of origin for renal cell carcinoma is the proximal renal tubular epithelium. Renal cancer occurs in both a
sporadic (nonhereditary) and a hereditary form, and both forms are associated with structural alterations of the short
arm of chromosome 3 (3p). Genetic studies of the families at high risk for developing renal cancer led to the cloning of
genes whose alteration results in tumor formation. These genes are either tumor suppressors (VHL, TSC) or
oncogenes (MET).
At least 4 hereditary syndromes associated with renal cell carcinoma are recognized: (1) von Hippel-Lindau (VHL)
syndrome, (2) hereditary papillary renal carcinoma (HPRC), (3) familial renal oncocytoma (FRO) associated with
Birt-Hogg-Dube syndrome (BHDS), and (4) hereditary renal carcinoma (HRC).
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von Hippel-Lindau disease is transmitted in an autosomal dominant familial multiple-cancer syndrome, which confers
predisposition to a variety of neoplasms, including the following:
Renal cell carcinoma with clear cell histologic features
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Pheochromocytoma
Pancreatic cysts and islet cell tumors
Retinal angiomas
Central nervous system hemangioblastomas
Endolymphatic sac tumors
Epididymal cystadenomas
Renal cell carcinoma develops in nearly 40% of patients with von Hippel-Lindau disease and is a major cause of death
among these patients. Deletions of 3p occur commonly in renal cell carcinoma associated with VHL disease. The VHL
gene is mutated in a high percentage of tumors and cell lines from patients with sporadic (nonhereditary) clear cell
renal carcinoma. Several kindreds with familial clear cell carcinoma have a constitutional balanced translocation
between 3p and either chromosome 6 or chromosome 8. Mutations of the VHL gene result in the accumulation of
hypoxia inducible factors (HIFs) that stimulate angiogenesis through vascular endothelial growth factor and its receptor
(VEGF and VEGFR, respectively). VEGF and VEGFR are important new therapeutic targets.
Hereditary papillary renal carcinoma is an inherited disorder with an autosomal dominant inheritance pattern; affected
individuals develop bilateral, multifocal papillary renal carcinoma. Germline mutations in the tyrosine kinase domain of
the MET gene have been identified.
Individuals affected with familial renal oncocytoma can develop bilateral, multifocal oncocytoma or oncocytic
neoplasms in the kidney. Birt-Hogg-Dube syndrome is a hereditary cutaneous syndrome. Patients with Birt-Hogg-Dube
syndrome have a dominantly inherited predisposition to develop benign tumors of the hair follicle (ie, fibrofolliculomas),
predominantly on the face, neck, and upper trunk, and are at risk of developing renal tumors, colonic polyps or tumors,
and pulmonary cysts.
Frequency
United States
The age-adjusted incidence of renal cell carcinoma has been rising by 3% per year. According to the American Cancer
Society, in 2007 there will be 51,590 cases (31,990 in males and 19,600 in females) of malignant tumors of the kidney
diagnosed in the United States with 12,890 deaths (8,080 in males and 4,810 in females); renal cell cancer accounted
for 80% of this incidence and mortality.1 The greatest increase in incidence currently is observed in African Americans.
International
Number of deaths worldwide from kidney cancer exceeded 100,000 in 2001.
Mortality/Morbidity
Renal cell carcinoma is the eighth or ninth leading cause of cancer death in the United States. The 5-year survival rates
initially reported by Robson in 1969 were 66% for stage I renal carcinoma, 64% for stage II, 42% for stage III, and only
11% for stage IV.2 Except for stage I, these survival statistics have remained essentially unchanged for several
decades.
Race
Renal cell carcinoma is more common in people of Northern European ancestry (Scandinavians) and North Americans
than in those of Asian or African descent. In the United States, its incidence has been equivalent among whites and
African Americans, but incidence among African Americans is increasing rapidly.
Sex
Renal cell carcinoma has a male-to-female preponderance of 1.6:1.
Age
This condition occurs most commonly in the fourth to sixth decades of life, but the disease has been reported in
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younger people who belong to family clusters.
Clinical
History
Renal cell carcinoma may remain clinically occult for most of its course. The classic triad of flank pain, hematuria, and
flank mass is uncommon (10%) and is indicative of advanced disease. Twenty-five to thirty percent of patients are
asymptomatic, and their renal cell carcinomas are found on incidental radiologic study.
Most common presentations
Hematuria (40%)
Flank pain (40%)
Palpable mass in the flank or abdomen (25%)
Other signs and symptoms
Weight loss (33%)
Fever (20%)
Hypertension (20%)
Hypercalcemia (5%)
Night sweats
Malaise
Varicocele, usually left sided, due to obstruction of the testicular vein (2% of males)
Renal cell carcinoma is a unique and challenging tumor because of the frequent occurrence of paraneoplastic
syndromes, including hypercalcemia, erythrocytosis, and nonmetastatic hepatic dysfunction (ie, Stauffer
syndrome). Polyneuromyopathy, amyloidosis, anemia, fever, cachexia, weight loss, dermatomyositis, increased
erythrocyte sedimentation rate, and hypertension also are associated with renal cell carcinoma. (For more
information, see Paraneoplastic Syndromes.)
Cytokine release by tumor (eg, IL-6, erythropoietin, nitric oxide) causes these paraneoplastic conditions.
Resolution of symptoms or biochemical abnormalities may follow successful treatment of the primary
tumor or metastatic foci.
Physical
Gross hematuria with vermiform clots suggests upper urinary tract bleeding.
Look for hypertension, supraclavicular adenopathy, and flank or abdominal mass with bruit.
Approximately 30% of patients with renal carcinoma present with metastatic disease. Physical examination
should include thorough evaluation for metastatic disease. Organs involved include:
Lung (75%)
Soft tissues (36%)
Bone (20%)
Liver (18%)
Cutaneous sites (8%)
Central nervous system (8%)
Varicocele and findings of paraneoplastic syndromes raise clinical suspicion for this diagnosis.
Causes
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A number of environmental and genetic factors have been studied as possible causes for renal cell carcinoma.
Cigarette smoking doubles the risk of renal cell carcinoma and contributes to as many as one third of all cases.
The risk appears to increase with the amount of cigarette smoking in a dose-dependent fashion.
Obesity is another risk factor, particularly in women; increasing body weight has a linear relationship with
increasing risk.
Hypertension may be associated with an increased incidence of renal cell carcinoma.
Phenacetin-containing analgesia taken in large amounts may be associated with increased incidence of renal
cell carcinoma.
There is an increased incidence of acquired cystic disease of the kidney in patients undergoing long-term renal
dialysis; this predisposes to renal cell cancer.
Tuberous sclerosis
Renal transplantation: Acquired renal cystic disease of the native kidney also predisposes to renal cell cancer in
renal transplant recipients.
VHL disease: This inherited disease is associated with renal cell carcinoma.
More on Renal Cell Carcinoma
Overview: Renal Cell Carcinoma
Differential Diagnoses & Workup: Renal Cell Carcinoma
Treatment & Medication: Renal Cell Carcinoma
Follow-up: Renal Cell Carcinoma
References
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