MSCT assists in renal cell cancer workup

April 14, 2006

Renal cell cancer is the most frequently encountered malignant tumor in the kidney. Over 30,000 new cases are diagnosed annually in the U.S. Many cases are now detected incidentally, as a result of the widespread use of multislice CT. MSCT usage is also redefining diagnostic workup of renal lesions and facilitating renal cell cancer staging.

Renal cell cancer is the most frequently encountered malignant tumor in the kidney. Over 30,000 new cases are diagnosed annually in the U.S. Many cases are now detected incidentally, as a result of the widespread use of multislice CT. MSCT usage is also redefining diagnostic workup of renal lesions and facilitating renal cell cancer staging.

Multiphasic CT acquisitions should be performed after injection of a single contrast bolus to achieve the highest staging accuracy and permit differential diagnosis. Single-phase acquisition after injection of a split contrast agent bolus is also possible. An MSCT protocol for evaluating renal masses should contain unenhanced images of the kidneys, followed by contrast-enhanced scans through the entire abdomen in nephrographic and delayed phases. The nephrographic phase is most effective in tumor localization and staging.1-4 Low-dose excretory phase scans enable assessment of the renal pelvis and ureters.5 The accuracy of CT for staging renal masses can reach 91%, with most staging errors related to diagnoses of tumoral perinephric extension.1,2,4,6,7

The relative newness of MSCT technology has limited published experience of its protocols used on patients with renal disorders. Various authors have explored the improved temporal and spatial resolution that MSCT has brought to the kidneys and urinary tract. Others, however, caution against the escalation of patients' radiation exposure in this manner.

EARLY DETECTION

Increasing use of ultrasound and MSCT for clinical diagnoses has led to an increase in the detection of renal masses.8 The earlier a malignant mass is detected on imaging, the greater the chance of it being an early-stage tumor of low grade. This finding will make the tumor amenable to nephron-sparing surgery as opposed to total nephrectomy.9 Options for treating localized renal cell carcinoma include nephrectomy (open or laparoscopic, total or partial), laparoscopic and percutaneous ablation (for example, radiofrequency ablation, cryotherapy), and minimally invasive catheter techniques such as superselective chemoembolization. Imaging can play an important role in choosing the most appropriate therapeutic strategy.

Prognosis and outcome of renal cell carcinoma are influenced by tumor stage and grade at the time of diagnosis. MSCT can be used both for primary diagnosis and for definitive differentiation of renal masses that are indeterminate or suspicious on intravenous urography (IVU) or ultrasound. CT is more widely available than MRI, scan times are shorter, and costs are lower. MRI, however, offers a wider range of soft-tissue contrasts, radiation-free examination, and imaging across virtually any cross-sectional plane. Patients with impaired renal function and documented allergic reaction to iodinated contrast agents can undergo a complete diagnostic kidney workup on MRI.

PROTOCOL CONSIDERATIONS

MSCT can detect, characterize, and stage renal tumors in one fast, high-resolution examination, assuming that a tailored multiphasic protocol is followed. A narrow detector collimation should be employed to allow for multiplanar reformatting. This could be 4 x 1 mm, 16 x 0.75 mm, or 64 x 0.6 mm, depending on scanner configuration. Scanning should be done in the unenhanced and nephrographic phases and possibly also the delayed phase. Radiation exposure can be kept to a minimum using low-dose techniques for unenhanced and delayed phases. Further reductions are possible if scanners are equipped with dose modulation algorithms. These tailor x-ray tube current to patients' anatomy along the x-, y-, and z-axes.

Delivery of multiple boluses means that patients' kidneys process several phases of contrast in just one CT scan. This is an elegant method of limiting radiation dose, although it decreases contrast between renal arteries, parenchyma, and renal pelvis when compared with multiphasic imaging. Difficulties may also arise with image interpretation if renal function deviates from the expected normal range, or when the two kidneys differ functionally.

State-of-the-art MSCT scanners provide isotropic volume elements (voxels), which make it possible to generate high-quality sagittal and coronal multiplanar reformatted images and to use 3D volume rendering techniques. These displays are an efficient way to handle large volumes of data and facilitate communication with urologists.

We obtain coronal MPR views routinely when assessing renal pathologies on MSCT. We find that volume-rendered views help evaluate renal vasculature, detect extrarenal tumor spread, and visualize the relationship between a tumor and the renal vessels and pelvis. Suspicion of renal vein invasion can be clarified by loading the thin-slice data set into dedicated 3D viewing software. Delayed-phase (excretory phase) scans can be displayed using maximum intensity projection techniques at reconstructed slice thicknesses of 10 to 30 mm. This display does not help find small lesions within the renal pelvis and ureters, because these can be masked by bright contrast within the renal collecting system.

PRECISE TIMING

MSCT scanning requires precise timing for contrast bolus injection and image acquisition. We generally use a power injector to deliver 100 to 150 mL nonionic iodinated contrast into a large antecubital vein as a single bolus. The amount of contrast agent depends on patient weight; 0.5 g iodine per kg body weight is usually injected. The delivery rate is typically set to 2 to 5 mL/sec. Radiopaque contrast media then passes through the three renal compartments: blood vessels, interstitium, and tubules. The small size of renal interstitial space means that contrast in the kidney at each time point after bolus injection is primarily a function of renal perfusion and renal excretion.

Protocols concentrating on macroscopic renal arteries will commence scanning shortly after contrast injection. These include examinations to rule out renovascular disorders in patients with arterial hypertension or to check for variants in the renovascular anatomy of living kidney donors. Peak renal enhancement depends on several parameters, including circulation time, heart rate, ejection volume, and circulating blood volume. It often occurs 10 to 25 seconds after injection. It may be necessary, however, to inject a test bolus covering the abdominal aorta at the level of the renal artery takeoffs to determine the most appropriate delay for CT angiography.

The renal cortex enhances strongly 40 to 70 seconds after intravenous contrast administration, whereas enhancement of the renal medulla usually trails behind (corticomedullary phase). Contrast equilibrium between cortex and medulla can be expected 80 to 100 seconds after bolus injection (nephrographic phase).

Bright contrast from excreted contrast shows first in excretory tubules within the renal medulla (excretory phase). The renal calices and pelvis start to fill with excreted contrast after approximately 120 seconds. Contrast in the renal collecting system is, as in IVU, usually strongest three to five minutes after bolus injection, assuming renal excretory function is normal and postrenal transport of excretory products is unimpeded. Ureters may be best visualized after seven to 10 minutes, whereas it may take up to 20 minutes for the bladder to opacify fully. A 250-mL saline flush after acquisition of nephrographic phase images can improve delineation of the ureters.10

Contrast-enhanced images should be obtained in the parenchymal and excretory phases for most imaging purposes other than CT angiography. It may be more difficult to recognize parenchymal lesions when contrast is strong between renal cortex and medulla in the early phase of parenchymal enhancement. Preference should thus be given to imaging in the nephrographic phase, with a delay of 80 to 100 seconds. Imaging of lesions arising from, or extending into, renal calices and the pelvis may benefit from strong contrast between soft tissue and excretory products. A delay of three to five minutes may be chosen for this application.

Complete kidney evaluation requires both pre- and postcontrast CT. Exact delineation of calcifications and recognition of small amounts of fat or blood within parenchymal lesions may provide important diagnostic clues that help determine patient management.

DIFFERENTIAL DIAGNOSES

Renal cell carcinoma accounts for about 3% of all adult neoplasms.11 Patients with stage T1 or T2 cancer at the time of treatment have an excellent chance of survival. Once malignancy extends beyond the kidney, however, survival depends on whether the tumor progresses by direct extension or at distant metastatic sites. Survival of patients with extensive renal cell carcinoma is closely related to tumor grade and degree of malignancy.12,13

Asymptomatic tumors that are confined within the renal capsule are now discovered more frequently and treated surgically, because of the increased use of ultrasound and abdominal CT. Angiomyolipoma is usually recognized, but differentiation of rarer benign lesions such as adenoma or oncocytoma from renal cell carcinoma is not usually possible (Figure 1).14 Surgery remains the only successful curative treatment of renal adenocarcinoma. This makes early tumor detection and accurate radiological assessment of tumor extent crucial during pretherapy staging.

Both contrast-enhanced CT and multiplanar MRI can demonstrate regional lymph nodes, vascular extension, and distant metastasis.15,16 MRI has been suggested as the imaging method of choice for cases of vascular tumor extension.15,17 Other authors have shown that MSCT with MPR and MRI perform equally well in the assessment of tumor thrombus.18 The difference between contrast-enhanced MRI and triphasic MSCT for overall staging accuracy of renal cell cancer has also been questioned.15 Most centers have opted for CT as the standard imaging modality for complete diagnostic workup of renal masses.

Various authors have emphasized the importance of CT during the nephrographic phase. Significantly more renal lesions are detected during this phase than during the corticomedullary phase.2 This is particularly true for lesions that are smaller than 3 cm4 and for those that are hypovascular.1 Combining corticomedullary and nephrographic phase images reveals even more lesions than using nephrographic phase images alone.2 Corticomedullary phase examinations are associated with false-positive findings, however.2,4 CT in the corticomedullary phase is recommended when information about renal vasculature is desired or when a renal lesion may represent an aneurysm, arteriovenous malformation, or fistula.19,20

CYST CHARACTERIZATION

Angiomyolipoma may be best characterized on unenhanced CT. Renal cysts, on the other hand, are detected and characterized equally well during the nephrographic and excretory phases of imaging.21 A study of 173 renal lesions (90 malignant) in 96 patients showed that sensitivity for renal lesions was significantly higher in the nephrographic phase of spiral CT than in the corticomedullary phase (97% versus 84%). Specificity and accuracy were higher when both phases were combined, compared with either phase evaluated alone.3 Staging accuracy improved significantly when unenhanced CT images were combined with contrast-enhanced images from the corticomedullary and nephrographic phase. With the three phases combined, staging accuracy was 91%, compared with 82% for unenhanced and corticomedullary phase CT, and 86% for unenhanced and nephrographic phase CT (p< 0.05).

Each additional phase does, of course, increases patients' exposure to radiation. Renal CT should therefore be limited to the minimum number of scans necessary to characterize a renal lesion or stage renal cancer.

Characterization of renal lesions requires good knowledge of differential diagnoses for solid and cystic masses. Malignant differentials include renal lymphoma, metastasis, sarcoma, and transitional cell cancer (Figure 2). Benign lesions that should be recognized are angiomyolipoma (which do not always contain fat on MSCT), oncocytoma, adenoma (considered a precancerous lesion), renal infarction, and dromedary hump, a normal anatomic variant that frequently mimics tumor on ultrasound. Renal abscesses can also have a masslike appearance on MSCT (Figure 1).

Renal cell cancer itself may present as a solid, uniformly enhancing mass, but it can also appear as infiltrating tumor or as a complex cystic lesion. The latter is typically characterized for potential malignancy with the Bosniak classification system.22 Clear cell renal cell carcinoma enhances more strongly than other histologic subtypes, such as chromophobe, collecting duct, or papillary tumors. Corticomedullary phase imaging is superior to excretory phase imaging when differentiating these tumors.23 Renal cell carcinoma may also enhance more strongly than complex high-attenuation renal cysts.24

STAGING AND CLASSIFICATION

Solid kidney tumors are worked up using the revised TNM system. Primary tumors are classified from T1 to T4:

- T1 tumor is confined to renal parenchyma and measures 0 to 4 cm (T1a, see Figure 3), or 4 to 7 cm (T1b).

- T2 tumor is larger than 7 cm but still confined to the kidney.

- T3 tumor extends beyond kidney but is limited to Gerota's fascia. Extension is into ipsilateral adrenal gland or into perirenal fat (T3a), into renal vein or inferior vena cava below diaphragm (T3b), or into inferior vena cava above the diaphragm (T3c) (Figures 4 and 5).

- T4 is any renal cell cancer extending beyond Gerota's fascia.

Classification of cystic renal lesions into those requiring surgical exploration and those requiring observation remains a difficult task. The value of Bosniak's radiological classification of cystic renal masses has been widely discussed and reviewed in the published literature. Five categories of lesions are distinguished in the revised, extended version of this system:25-28

- Category I lesions are simple benign cysts that demonstrate homogeneous, watery content and a smooth, sharp interface with adjacent renal parenchyma. No wall thickening, calcification, or enhancement is observed.

- Category II lesions show one or two thin septations of no more than 1 mm or fine calcifications within walls or septa. Hyperdense cysts that would otherwise be regarded as category I lesions are also classified as category II. Benign category II lesions measure 3 cm or less in diameter, have one quarter or more of their wall extending outside the kidney, and do not enhance with contrast media. Category II lesions are usually benign but may turn out to be malignant when they are more complex.

- Category IIF describes cystic lesions that are minimally complicated but sufficiently suspicious to require follow-up. This category includes cystic lesions with an increased number of fine septa or increased calcifications that may be thicker or nodular.

- Category III lesions are truly indeterminate cystic masses. A large proportion will turn out to be benign, though the proportion of malignant masses is sufficient to warrant surgical exploration. They are characterized by uniform wall thickening, nodularity, thick or irregular peripheral calcifications, and multilocularity with multiple enhancing septa. Category III also includes hyperdense lesions that do not fit into categories II and IIF.

- Category IV lesions include those with a nonuniform or enhancing thick wall, large or enhancing nodules within the walls, or visibly solid components within a cystic lesion.25-27 They are almost always malignant.

The presence of enhancing soft-tissue elements within a cystic lesion is more important than the presence and degree of calcification, when distinguishing between potentially benign and malignant lesions on CT.26 CT-guided cyst puncture, with aspiration and core biopsy, has been suggested as a useful way of avoiding invasive exploration or surgery in patients with Bosniak IIF and III renal lesions. One study, however, found that eight out of 28 malignancies were either indeterminate or misdiagnosed as benign by aspiration and biopsy.28 Renal cell carcinoma may also metastasize along needle tracks after puncture for biopsy or aspiration. Needle puncture of complex renal cysts and solid lesions remains highly controversial.

MULTIPHASIC PROTOCOL

In summary, MSCT remains the most important imaging modality in preoperative assessment of renal cell cancer. It can detect, classify, and stage renal masses. A multiphasic imaging protocol containing unenhanced, nephrographic, and excretory phases should be used, with radiation dose kept to a minimum. MRI and contrast-enhanced ultrasound offer a viable alternative for patients with known allergies to iodinated contrast agents and can aid evaluation of hypovascularized tumors.

DR. GRASER and DR MUELLER-LISSE are radiologists, and PROF. REISER is department head, all in the department of clinical radiology at Grosshadern Clinic, University of Munich, in Germany. DR. STAEHLER is a urologist at the same institution.

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