Renal cell carcinoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2]
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Overview
Historical Perspective
Renal cell carcinoma was first described in 1826. Following contradictory hypotheses regarding the origin of renal tumors, it was not until 1960 that Oberling and colleagues showed that renal carcinomas originate from renal cells.
Classification
Classification of renal cell carcinomas according to histopathological subtypes is based on the 1997 classification by Heidelberg and colleagues. Classification may also be according to the stage of renal cell carcinoma, which often is based on Robson classification system or the tumor-lymph node-metastasis (TNM) system.
Pathophysiology
The pathophysiology of renal cell carcinomas plays an important role in differentiating different types of renal cell carcinomas and in choosing appropriate targeted medical therapies. Sporadic forms of clear cell renal carcinomas, the most common form of renal cell carcinomas, have similar pathophysiological mechanisms to those of von Hippel Lindau (VHL) disease. On the other hand, MET proto-oncogene seems to play a role in the disease pathogenesis of papillary forms of renal cell carcinoma. Uniquely also, oncocytomas are benign tumors that arise from type A intercalated cells, whereas chromophobe renal cell carcinoma arises from type B intercalated cells.
Causes
Most renal cell carcinomas develop sporadically. Only a few have genetic predisposition and are associated with known syndromes, such as von Hippel Lindau (VHL), hereditary paragangliomas, leiomyomatosis, and Birt-Hogg-Dube (BHD) syndrome, among several others.
Differentiating Renal cell carcinoma from other Diseases
The differential diagnosis of renal cell carcinomas includes metastastic disease, cysts, abscesses, lymphomas, and other benign and malignant tumors, and associated syndromes.
Epidemiology and Demographics
Renal cell carcinoma is considered the 7th most common cancer in men and 9th most common cancer in women, accounting for approximately 2-3% of malignant tumors in adults. Men are twice more likely to be affected than women with an mean age of presentation at 60 years. Most renal cell carcinomas develop sporadically, while only a small number of cases are of genetic diseases. Clear cell carcinomas are the most common renal cell carcinomas and collecting-duct carcinomas are the least common. Renal cell carcinomas are mostly found incidentally during radiological abdominal work-up.
Risk Factors
Established risk factors for renal cell carcinoma include cigarette smoking, hypertension, end-stage renal failure, analgesic drug use, environmental exposure to carcinogens, and some genetic syndromes.
Screening
There are currently no guidelines for screening for renal cell carcinoma.
Natural History, Complications and Prognosis
The projected 5-year survival is significantly associated with the stage of the tumor at diagnosis. Stage I tumors are associated with more than 90% 5-year survival vs. less than 20% survival for tumors of stage IV. The potential aggression of a tumor has been shown to be associated with tumor size, grade of tumor, and histopathological subtype. High grade tumors greater than 7 cm of clear cell type generally have a higher aggressive potential than low grade tumors smaller than 3 cm of papillary type. Finally, complications vary according to the local extension of the tumor, and the presence of paraneoplastic syndromes and/or metastases.
Diagnosis
Diagnostic study of choice
A needle biopsy should always be performed when the finding of a renal mass is detected on imaging.
History and Symptoms
Common symptoms of renal cell carcinoma include hematuria, flank pain, palpable abdominal mass,weight loss and anorexia.
Physical Examination
Common physical examination findings of renal cell carcinoma include low body mass index, high blood pressure, palpation of abdominal mass, auscultation of abdominal bruit, varicocele, muscle atrophy, skin pallor, facial flushing, and supraclavicular lymphadenopathy.
Laboratory Findings
Laboratory findings of renal cell carcinoma include anemia, polycythemia, hypercalcemia, elevated ESR, elevated liver function tests, elevated alkaline phosphatase, elevated lactate dehydrogenase, elevated serum creatinine, hematuria, and cancer cells on urine cytology.
Electrocardiogram
There are no ECG findings associated with renal cell carcinoma.
X-ray
There are no x-ray findings associated with renal cell carcinoma. However, an x-ray may be helpful in the diagnosis of pulmonary metastasis of renal cell carcinoma.
Ultrasound
Ultrasound may be helpful in the diagnosis of renal cell carcinoma. Ultrasound may be helpful when CT scan results are equivocal.
CT scan
Renal CT scan may be helpful in the diagnosis of renal cell carcinoma. CT may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of primary cancer.
MRI
Other Imaging Findings
Other Diagnostic Studies
Most patients are diagnosed with renal cell carcinoma following the incidental finding of the tumor during abdominal radiological work-up. The gold standard of diagnosis is percutaneous needle biopsy of the involved kidney, with or without imaging-guidance. The most common symptom associated with the disease is hematuria. Physical exam may be unrevealing, or may be positive for signs of local tumor extension, paraneoplastic syndromes, or metastases, such as a palpable abdominal mass, high blood pressure, facial flushing, skin pallor, or other neurological, pulmonary, or musculoskeletal abnormalities. Common laboratory findings may show anemia or polycythemia, hypercalcemia, elevated serum creatinine, elevated liver function tests, ESR, ALP, and LDH. Imaging is an important diagnostic and follow-up procedure in renal cell carcinoma. The use of CT, MRI, CXR, and ultrasound are all feasible options in the work-up, according to the 2013 American Urological Association (AUA) guidelines.
Treatment
Medical treatment
The medical therapies of renal cell carcinoma include chemotherapy, hormone treatment, immunotherapy, and targeted therapy.
Surgery
Surgery is the mainstay of treatment for renal cell carcinoma. Partial nephrectomy and ablation are recommended for patients who develop small renal masses. For patients with locally advanced renal tumors, radical nephrectomy is recommended. Moreover, radical nephrectomy or organ sparing treatment, along with the use of interferon alfa, is also used as part of a more aggressive management plan in cases with metastatic renal tumors.
Primary prevention
Primary prevention strategies include early screening, changing lifestyle, decreasing exposure to occupational risk factors, and controlling of hypertension.
Secondary prevention
There are no established measures for the secondary prevention of renal cell carcinoma.