Renal Transitional Cell Carcinoma Workup

Urinalysis and urine culture are indicated. The presence of microscopic hematuria suggests urinary tract tumors, which must be ruled out even if the hematuria resolves. The presence of more than 2-5 red blood cells (RBCs) per high-power field (HPF) is considered sufficient to warrant further investigation to rule out upper urinary tract renal transitional cell carcinoma (TCC). Evaluate for urinary tract infections.

Cytologic studies may be helpful. Voided-urine cytology is a convenient and noninvasive method of diagnosis, but it is subjective and lacks the necessary sensitivity for diagnosing upper urinary tract urothelial tumors, especially low-grade neoplasms. Fluoroscopically guided brush biopsy increases the diagnostic accuracy to 80-90%.

In the past, intravenous urography (IVU) was the most commonly used diagnostic method for the evaluation of patients with hematuria in the past. In current practice, however, it is increasingly being replaced by computed tomography (CT) urography.^[8]

Filling defects in the upper urinary tract can be demonstrated in 50-75% of patients. Other common causes of filling defects (eg, nonopaque stones, blood clots, papillary necrosis with sloughing, and fungus balls) should be ruled out. In 13-31% of cases, the affected kidney may not be adequately visualizable.

CT scanning is useful in the diagnosis and staging of renal urothelial tumors (see the images below). It can distinguish between radiolucent renal stones and upper urinary tract urothelial tumors, in that stones appear opaque on CT scans (>200 Hounsfield units [HU] for uric acid stones versus 60-80 HU for tumors).^[9]

CT scanning also can be used for determining the local extent the tumor and the presence of distant metastases, but it is of limited value in predicting the pathologic stage of upper urinary tract urothelial tumors (it is accurate in 43-77% of cases).

Cystoscopy may help to localize bleeding site (left or right) and rule out or confirm concomitant bladder lesions. Retrograde pyelography (RPG) is especially useful when the kidney cannot be visualized by means of IVU or when renal insufficiency or severe contrast allergy prevents the performance of IVU. A properly performed RPG is confirmatory in approximately 85% of cases (see the images below).

Ureteroscopy is routinely used in the diagnosis of renal pelvic tumors. The correct diagnosis can be achieved in 80-90% of cases. The gross appearance usually suffices for the diagnosis of upper urinary tract urothelial carcinoma (UC); however, a biopsy should be obtained if necessary.

Most TCCs are papillary. They may be single or multiple. See image below.

Flat carcinoma in situ (CIS) also may develop in the renal pelvis. CIS may be found in the distal ureter of 20-35% of patients who undergo cystectomy for bladder cancer. The presence of CIS warrants further resection of the ureter until a healthy ureteral segment is reached.

UCs can be characterized according to the degree of nuclear anaplasia. Low-grade tumors may have a thin fibrovascular core that is covered by several layers of cytologically benign urothelium, or they may be more broad-based, with hyperplastic urothelium. High-grade tumors usually are solid masses of large cells with irregular nuclei. Tumor grade is an important predictor of prognosis.

The TNM staging system of the International Union Against Cancer (UICC) is used to stage upper urinary tract carcinomas.

Primary tumor (T) classifications include the following:

• TX – Primary tumor is occult and cannot be assessed
• T0 – No evidence of primary tumor
• Ta – Papillary noninvasive carcinoma
• Tis – Carcinoma in situ
• T1 – Carcinoma involves subepithelial connective tissue
• T2 – Carcinoma invades the muscularis
• T3 – Carcinoma invades beyond muscularis into periureteric or peripelvic fat or into renal parenchyma
• T4 – Carcinoma invades adjacent organs or extends through the kidney into perinephric fat

Regional lymph node (N) classifications include the following:

• NX – Regional lymph nodes cannot be assessed
• N0 – No regional lymph node metastasis
• N1 – Metastasis in a single lymph node, 2 cm or less in greatest dimension
• N2 – Metastasis in a single lymph node 2-5 cm in greatest dimension; or multiple metastatic lymph nodes, none more than 5 cm in greatest dimension
• N3 – Metastasis in a lymph node more than 5 cm in greatest dimension

Distant metastasis (M) classifications include the following:

• MX – Presence of distant metastasis cannot be assessed
• M0 – No distant metastasis
• M1 – Distant metastasis