LabMed

Transitional Cell Carcinoma

At a Glance

More than 70,000 cases of bladder cancer are diagnosed annually in the United States. Transitional cell carcinoma arises from the epithelial layer found in the renal pelvis, ureter, or bladder. They are noted for being either solitary or multifocal in nature. Workers exposed to aniline dyes have a higher incidence. People working in chemical, rubber, or plastic manufacturing have a higher incidence as well. Agents, such as 2-naphthylamine, have been identified as the prime offending agent. Other risk factors are phenacetin abuse, heavy smoking, calculi, and bladder schistosomiasis.

Ninety percent of bladder cancers are transitional cell carcinomas. Other types are squamous cell carcinoma, adenocarcinoma, and sarcoma. Typically, carcinoma of the bladders occurs after 50 years of age and in males more than females, with typical ratios of 3:1 or 4:1.

The most common presenting symptom is hematuria, which can be gross in amount. Of course, it might not appear until late in the disease. About 14-37% of patients report pain, either dull or with renal colic, sometimes with the passage of clots.

Ten to fifteen percent of patients experience other bladder symptoms, such as dysuria and frequency. These symptoms often appear late in the disease and are caused by tumor invasion of the muscular wall. Invasion of the trigone or extension outside the bladder may lead to bilateral ureteral obstruction, hydronephrosis, and, eventually, renal failure. Fifty percent of patients who present with invasive bladder cancer have muscle-invasion and a rather poor prognosis.

About 10% of transitional cell carcinomas of the ureteral tract arise in the renal pelvis. Tumors arising in the renal pelvis may seed the ureters.

Pelvic renal transitional cell carcinoma represents about 10% of all renal carcinomas.

Rarely, patients present with peripheral neuropathy or amyloidosis. For the most part, paraneoplastic syndromes are not observed.

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

Bladder tumors typically produce painless hematuria. Thus, one should perform a urinalysis with microscopic examination to quantify the amount of hematuria and to rule out other diseases, such as infection (leukocytes and bacteria) or primary renal disease (casts). Gross hematuria occurs in 75-95% of patients, whereas microscopic hematuria occurs in 3-11% of patients. About 1-2% of patients are completely asymptomatic.

One should send a urine sample for cytological examination and perform imaging studies. Fluoroscopically guided brush biopsy improves diagnostic accuracy.

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 important laboratory medicine test, and knowledge of its differential diagnosis is important. Pseudohematuria can by 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, will also appear as hematuria. The latter usually results from intravascular hemolysis.

In the renal parenchyma, postinfectious glomerulonephritis, thin basement membrane disease, IgA nephropathy, membranoproliferative glomerulonephritis, focal glomerulosclerosis, and cresentic glomerulonephritis all represent primary glomerular causes of hematuria. Diabetes mellitus, lupus erythematosus, Goodpasture syndrome, polyarteritis nodosa, and endocarditis represent systemic causes of hematruia, as do hemolytic-uremic syndrome, throbotic thrombocytopenic purpura, Henoch-Schonlein purpura, malignant hypertension, polycystic kidney disease, hereditary nephritis, and Fabry disease.

Other causes of hematuria are acute pyelonephritis, nephrolithiasis, renal cyst, renal trauma, other renal neoplasms, 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. Nonurinary 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 and with white cell casts and are accompanied with 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?

Although transitional cell carcinomas may be observed by imaging studies, diagnosis rests on histopathological examination.

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

Pathologic stage is the most important predictor of survival. The 5-year survival rate is 75%, if no more than the lamina propria is invaded at the time of cystectomy. The 5-year survival rate is 40% for tumors infiltrating the muscularis propria and 20% for tumors infiltrating the pervesical fat. In earlier stages, tumors tend to be of lower grade, but tumors advance in grade in later stages.

There are emerging molecular tests that may help differentiate low grade from high grade tumors. Low grade tumors tend to be superficial in their pathogenesis and demonstrate alteration in tyrosine kinase receptor FGFR3 and HRAS ongene. Alterations on chromosome 9 can be detected using FISH on cytological specimens, showing gains in 3q, 7p, and 17q and deletions of 9p21 (p16 locus). Muscle-invasive urothelial carcinomas may demonstrate HER2 overexpression/amplification, TSP1 overexpression.

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