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At a Glance

Renal cell carcinoma, also known as the hypernephroma, clear cell carcinoma, adenocarcinoma, or the Grawitz tumor, is a tumor of the kidney and accounts for 85% of primary renal malignancies in adults. Most commonly, it is found in patients older than 40 years of age with a 2:1 male predominance. It is more prevalent in patients with von Hippel-Lindau disease (70%) and patients with horseshoe kidneys or polycystic kidney disease.

Hematuria is the most common presenting sign, but is found in only 50-60% of cases. One-third of tumors are palpable at the time of diagnosis, and one-third present with abdominal or flank pain. The classic triad of hematuria, renal mass, and flank pain is present in only 10-15% of patients at the time of diagnosis. The diagnosis of renal carcinoma may be late, often occurring due to a metastasis or at autopsy.

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Patients often present with constitutional symptoms or paraneoplastic syndromes. Common among these are fever, which may be low grade or intermittent. Others presentations are benign hepatomegaly without liver dysfunction, with 10% developing a syndrome of non-metastatic hepatic dysfunction manifested by hepatomegaly, elevated plasma, or serum alkaline phosphatase and bilirubin, along with hyperglobulinemia and hypoalbuminemia.

Rarely, 1-3% of patients develop polycythemia, but anemia is present in 30-40% of cases.

Other symptoms and signs are the development of anorexia, weight loss, feminization or masculinization, Cushing syndrome, and hypertension.

A few patients develop massive leukocytosis, eosinophilia, and hypercalcemia, which may be accompanied by metastases, thrombophlebitis, varicocele, endocrine syndromes, or amyloidosis.

Signs of tumor extension are renal vein occlusion of the vena cava, potentially up to the right atrium, or spontaneous rupture of the kidney with retroperitoneal hemorrhage.

Twenty to twenty-five percent of tumors have metastasized by the time of diagnosis.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Renal cell carcinomas often produce painless hematuria (50-60% of cases). Thus, one should perform a urinalysis with microscope to quantify the amount of hematuria and to rule out other diseases, such as infection (leukocytes and bacteria) or primary renal disease (casts).

Urine cultures are useful in establishing the presence of infection, as well as ruling it out.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Evaluation of hematuria is the most common laboratory test, and its knowledge of its differential diagnosis is important. Pseudohematuria can be caused by food, such as beets, or food dyes. It may be caused by certain medications, such as phenytoin, rifampin, or pyridium. Pigments, such as porphyria, myoglobin, or hemoglobin, also appear as hematuria. The latter usually results from intravascular hemolysis.

In the renal parenchyma, post-infectious glomerulonephritis, thin basement membrane disease, IgA nephropathy, membranoproliferative glomerulonephritis, focal glomerulosclerosis, and crescentic glomerulonephritis all represent primary glomerular causes of hematuria.

Diabetes mellitus, lupus erythematosus, Goodpasture’s syndrome, polyarteritis nodosa, and endocarditis represent systemic causes of hematuria, as do hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, Henoch-Schonlein purpura, malignant hypertension, polycystic kidney disease, hereditary nephritis, and Fabry’s disease. Other causes of hematuria are acute pyelonephritis, nephrolithiasis, renal cyst, renal trauma, other urinary tract neoplasms, such as transitional cell carcinoma of the renal pelvis, ureters, or bladder, low clotting factors, thrombocytopenia, acute interstitial nephritis, analgesic nephropathy, sickle cell trait or disease, medullary sponge kidney, malaria, papillary necrosis, and renal infarction.

Lower urinary tract abnormalities cause hematuria, such as cystitis, prostatitis, urethritis, trauma, foreign body, calculi, varices, radiation cystitis, cyclophosphamide, anticoagulants, schistosomiasis, and tuberculosis. Non-urinary tract causes of hematuria include appendicitis, pelvic inflammatory disease, diverticulitis, and neoplasms of adjacent organs.

Interstitial nephritis can be caused by penicillins and cephalosporins, sulfonamides, sulfonamide-containing diuretics, NSAIDs, rifampin, phenytoin, and allopurinol. Although 95% of cases of interstitial nephritis present with hematuria, they also present with white cells in the urine, with white cell casts, and are accompanied by fever, rash, arthralgias, and peripheral eosinophilia.

Proteinuria and protein casts suggest a renal origin. Bacteria in the urine and positive urine cultures suggest infectious causes. Further evaluation includes cytology, upper tract imaging, and cystoscopy.

What Lab Results Are Absolutely Confirmatory?

There is no specific laboratory medicine test that absolutely confirms the diagnosis of renal cell carcinoma. Localization of the tumor relies on imaging studies, and confirmation of the diagnosis depends on histopathological identification of tissue.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Other useful tests include:

IL-2R: Serum levels increase with the stage of the tumor; preoperative level remains elevated for at least 3 months

bFGF, ICAM-1, IL-6, and TNF-alpha: These markers can be used as prognostic factors prior to treatment. Only TNF-alpha is also an independent prognostic indicator. A normal plasma TNF-alpha is highly predictive of a good prognosis in patients with untreated renal cell carcinoma.

c-erbB-2: Pretreated serum levels of the ectodomain are inversely related to disease stage and tumor grade. Survival time for patients with serum levels above median level is significantly longer than for patients with lower levels.

E-selectin: High concentrations in patient sera correlate with low incidence of metastasis and, consequently, correlate with good prognosis. Expression of elevated E-selectin facilitates metastasis. However, excessive production of E-selectin in the serum is said to have an inhibitory effect against metastasis.

TNF-alpha, IL-1beta, and IL-6: TNF-alpha and IL-1beta are significantly higher in the advanced stage of renal cell carcinoma. All three are also significantly higher in C-reactive protein (CRP)-positive patients.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Many of the follow-up tests may be affected by other conditions. Because these tests, such as IL-6, TNF-alpha, and IL2-R, are markers of the inflammation, conditions related to infection or other causes of inflammation may affect the results.