Applied Radiology

Dr. Babar is an MRI Fellow and Professor and Dr. Reznek is a Professor of Diagnostic Imaging in the Radiology Department at St. Bartholomew's Hospital, West Smithfield, London, UK.

The vast majority of renal lesions can be characterized correctly on computed tomography (CT) into simple cysts, cystic neoplasms, or solid renal cell carcinoma (RCC). However, in about 7% of cases, ¹ CT will fail to establish whether the lesion represents a simple cyst or a cystic neoplasm, and this lesion will then be classified as indeterminate. The vast majority of solid space-occupying lesions of the kidney will prove to be RCC. However, on occasion, some features within this solid mass lesion suggest that the solid mass lesion represents some pathology other than RCC.

Increasingly, small lesions (<1.5 cm) are detected incidentally in patients undergoing routine abdominal CT. Characterization and management of these small lesions is difficult, and these space-occupying lesions can often be regarded as indeterminate.

Thus, three categories of indeterminate lesions will be considered: indeterminate cystic lesions; solid lesions with a feature that suggests pathology other than RCC; and small lesions that are difficult to characterize.

CT technique

Precontrast CT is essential to identify calculi, calcification, and fat within the lesion. The pitch, kV, and mAs should remain constant between pre- and postcontrast scans to allow accurate and reproducible measurement of enhancement of the space-occupying lesion. Although the kidney can be scanned biphasically, scanning both in the corticomedullary and nephrographic phase, lesion detection and characterization is best done in the nephrographic phase. ² In the case of small lesions, an excretory phase may be helpful in surgical planning for nephron-sparing surgery to delineate the relationship of the mass to the renal pelvis. ³ In these circumstances too, CT angiography (performed at 20 to 25 seconds following injection of contrast) may also be useful in planning surgery. ⁴ These two additional phases are important only in planning local resection and not in characterization.

Measurement of the attenuation value

The measurement of attenuation values on spiral CT is slightly less accurate than on conventional axial scans. This has been attributed to partial volume effect secondary to flattening and broadening of the section sensitivity profile, inherent in continuous acquisition techniques. In addition, the decrease in mAs necessary to reduce the heat generated in helical CT results in noisier images, which may affect the reliability of the measurement of the attenuation value. ⁵ Therefore, the attenuation value should be measured on thin collimation scans to reduce partial volume effect, and this measurement should be done in the late nephrographic phase rather than the initial corticomedullary phase (Figure 1).

Indeterminate cystic lesion

Cystic lesions can be indeterminate in three circumstances: 1) the criterion for a benign cyst has not been fulfilled; 2) the cyst occurs in a condition commonly associated with cystic renal cell carcinomas; and 3) the cystic lesion is multiloculated and difficult to evaluate.

Criteria for a simple cyst not fulfilled

Attenuation values-- Computed to-mography attenuation of a simple cyst is that of water. This value varies with different scanners and is influenced by the number of pixels in a region of interest, pixel size, matrix size, and beam-hardening artefacts. ⁶ A reading of up to 20 Hounsfield units (HU) is quite consistent with a benign cyst. A hyperdense cyst may have values between 50 and 90 HU (Figure 2). This is usually seen in hemorrhagic cysts or cysts containing proteinaceous contents. An ultrasound may demonstrate appearances of a simple cyst in about 50% of these cases and can easily differentiate cystic from solid lesions. However, if these lesions are larger than 3 cm and ultrasound does not resolve their nature, surgical exploration may become necessary. ⁷

Enhancement-- Simple cysts should not enhance on postcontrast CT. There is controversy regarding the amount of enhancement that can be accepted as benign and the values beyond which the alarm bells begin to sound. Although the values vary in the literature, the policy at our institute is that a change of <10 HU between pre- and postcontrast scan is regarded as insignificant, a change >20 HU is definite enhancement, and a change between 10 HU and 20 HU is probable enhancement. It is important to remember that enhancement depends not only on the intrinsic nature of the tissue but also on the level of contrast material in the bloodstream and tissue at the time of scanning. This, in turn, will depend on the amount of contrast medium injected, the speed of injection and scanning time.

Septation-- Simple cysts do not usually have septa. If these are present and are few in number, smooth and without nodularity, the cyst is still considered benign. Ultrasound is better than CT in detection of these septa. Features such as septa thicker than 1 mm, associated solid elements, or thickening close to its attachment to the cyst wall makes a lesion very suspicious (Figure 3).

Calcification-- Fine curvilinear calcification in a cyst is considered benign. About 1% to 3% of benign cysts calcify, while 15% of cases of RCC contain calcification. ⁸ Renal cell carcinomas have a different pattern of calcification, which is thick, irregular, and nonperipheral (Figure 4).

Wall thickness-- The walls of a simple cyst are typically imperceptible. Any thickening, especially if it is irregular or focal, is considered suspicious (Figure 5). Such thickening may be seen in cystic carcinomas, or infected or hemorrhagic cysts.

Cystic disease associated with renal cancer

In some conditions, renal cystic disease is so frequently associated with RCC that it is difficult to characterize these lesions with certainty. Such conditions include von Hipple-Lindau disease (VHL) and acquired cystic disease of dialysis.

Von Hipple-Lindau disease-- Renal cell carcinomas occur in 38% to 55% of patients with VHL, but benign cysts also occur in 85% of patients. ⁹ It is essential to note that even cysts that appear benign on CT may contain malignant cells. Therefore, under no circumstances can cysts, irrespective of their appearance, be entirely dismissed as benign (Figure 6). CT is the modality of choice for follow-up.

Acquired cystic disease of dialysis (ACKD)-- Renal cell carcinomas occur in about 17% of patients (Figure 7) and here, too, care is essential in evaluating these lesions. ¹⁰

Multiloculated lesion

Multiloculated appearance of a cyst is seen in multiloculated cystic nephroma (MCN) and also in localized cystic disease.

Multiloculated cystic nephroma -- Multiloculated cystic nephroma is a rare benign neoplasm that is usually unilateral, solitary, and sharply demarcated, with a tendency to herniate into the renal pelvis. ¹¹ It is not possible to definitely distinguish MCN from RCC on radiological grounds, but extensive calcification, hemorrhagic cystic content, solid regions, and hypervascularity favor a diagnosis of RCC over MCN. On CT, MCN appears as multiple, fluid-filled cysts separated by thick septa (Figure 8). Peripheral or central calcification is present in 10% to 15% of cases, in which the calcification may have a circular, stellate, flocculent, or granular pattern.

Localized cystic disease-- Localized cystic disease is an entity where multiple benign cysts are localized to one part of the kidney. This is not a forme fruste of adult polycystic disease of the kidney, as was previously considered to be the case. ¹² Cystic neoplasms can be confused with localized cystic disease when this cluster of cysts appears poorly defined from the adjacent renal parenchyma.

In practice, there is a spectrum of appearances for cystic lesions ranging from those typical of a simple cyst to that of a cystic neoplasm. Bosniak ⁷ has classified this spectrum into four groups, as delineated below.

Class I: This class includes simple renal cysts with no unusual features, and the attenuation value of the cyst's contents is <20 HU. These cysts do not require any further evaluation or follow-up.

Class II: These are benign lesions that are minimally complicated in that they have some imaging finding of concern. Such findings include: internal septa, which are thin (¾ 1 mm), smooth, and attached to the wall without any associated thickening; fine calcification that lies peripherally in the wall of the cyst or within a septum; a cluster of cysts; and "hyperdense cysts" that have an attenuation value of 60 to100 HU prior to administration of contrast medium. The increased density of hyperdense cysts is due to a high protein content or breakdown products of blood. ¹³

In order to evaluate these Class II cystic lesions completely, at least 25% of their circumference should project outside the renal contour. No follow-up is required.

Class IIF: This class was later added to the original Bosniak classification. These are minimally complicated cysts that nevertheless have "somewhat suspicious" features that do not require surgical exploration but do require follow-up to establish stability of the lesion. Bosniak recommends follow-up at 3-, 6-, and 12-month intervals. This class includes cystic lesions with more calcium in the wall or slightly more complicated appearances than can be accepted for Class II.

Class III: These are more complicated cysts that require surgery because it is not possible to characterize these lesions with certainty by imaging findings alone. These lesions usually have irregular margins, thick irregular calcification, thick or enhancing septa, multiloculated appearance, uniform wall thickening, or small nonenhancing areas of nodularity. Some of these lesions are benign, such as hemorrhagic cysts, complex septated cysts, multiloculated cysts, multilocular cystic nephroma, and densely calcified cysts. Approximately 50% of these cysts will prove to be malignant. A cyst that protrudes from the surface of the kidney can be encircled on its periphery by an effaced wedge of renal parenchyma. This is the so-called "beak" or "claw" sign and must be differentiated from the thick wall of a cystic neoplasm. ¹⁴

Class IV: These are clearly cystic/ necrotic malignant neoplasms and have nonhomogenous contents, nonuniform wall thickening/enhancement, and may also contain solid enhancing nodules. Class IV lesions need to be staged and treated accordingly.

Although the Bosniak classification has proved to be quite robust, there are problems with the system, and small indeterminate lesions are difficult to categorize into one class or another. This is particularly the case between the differentiation of Class II (nonsurgical) and Class III (surgical) lesions. Personal experience of the observer may play a role at this stage.

It has been shown that the larger the number of combined noncystic features, the more likely a renal lesion will be malignant. ¹⁵

Indeterminate solid mass

Approximately 85% of solid masses detected on CT will prove to be RCC. ¹⁶ These typically enhance following intravenous injection of contrast, although approximately 20% are hypovascular. ¹⁷ Nevertheless, on occasion, certain features may suggest that the solid lesion represents something other than RCC. These features include the presence of fat, multiplicity, the pattern of enhancement, and location.

Presence of fat

Detection of fat in a solid mass is of great importance, as its presence can reliably make a diagnosis of angiomyo-lipoma. Fat is not usually seen in RCC. However, there have been a few reports in literature in which large RCC lesions have engulfed surrounding perinephric fat or in which cases of RCC have shown osseous metaplasia. ¹⁸ These are isolated case reports and for all practical purposes, presence of fat in a solid mass virtually excludes the diagnosis of renal cell carcinoma. Region-of-interest measurements <­20 HU in a renal mass are diagnostic of an angiomyolipoma in nearly every case. ¹⁹ When the presence of fat is equivocal, thinner collimation and pixel mapping of a region of interest can demonstrate a small focus of fat in a renal tumor. Three contiguous measurements <­20 HU after pixel mapping is diagnostic of fat and thus an angiomyolipoma. ²⁰ Approximately 5% of angiomyolipomas contain no demonstrable fat on CT or MRI and are then indistinguishable from small RCC.

Multiplicity

Multiple lesions point toward an aetiology other than an RCC, as only 5% of RCCs are multiple. ²¹ Lymphoma and metastases are more likely considerations in cases of multiple lesions. Non-Hodgkin's lymphoma is manifested by small, multifocal intrarenal hypo-attenuating solid masses with or without nodal disease. Similarly, in a patient with a known history of malignancy, metastasis to the kidneys are more common than primary RCC. Percutaneous biopsy may be useful in these circumstances.

Pattern of enhancement

Almost all solid renal masses enhance with administration of contrast. Enhancement of RCC and other solid masses is usually >20 HU. Differentiation between RCC and other tumors is not possible on the basis of enhancement characteristics.

Location

Typically, RCC tumors are peripheral within the parenchyma, cause an irregularity of the renal outline, and enhance inhomogeneously following intravenous contrast medium injection. Conversely, transitional cell carcinomas lie centrally within the kidney, the renal outline is maintained, and the carcinomas are either avascular or enhance only slightly after contrast administration. These features should alert the radiologist to the possibility that the solid mass lesion does not represent an RCC.

Indeterminate small lesions

Lesions larger than 1.5 cm are usually easily characterized by imaging. In contrast, lesions smaller than 1.5 cm pose a challenge. The majority of these smaller lesions represent benign cysts. If the lesion is <1.5 cm and has an attenuation value of <20 HU on routine CT performed for a nonrenal indication, it is considered benign and no further imaging is required. If the lesion has an attenuation value of <­20 HU, it is considered an angiomyolipoma and no more imaging is done. Lesions that measure >20 HUs are considered potential neoplasms. An ultrasound is performed first to determine whether it represents a simple benign cyst. If this is the case, no further imaging is required. If the ultrasound is not confirmatory, a dedicated thin-section CT with and without contrast may be performed in an attempt to diminish partial volume effect. If there is no definite enhancement (<10 HU) on postcontrast scans, the lesion is considered a hyperdense cyst.

If there is enhancement, a follow-up CT at 3-, 6-, and 12-month intervals is initially recommended. If the lesion is stable, yearly follow-up is advised. If, on the other hand, the lesion increases to 2 cm in diameter within 1 year, surgery is indicated.

Role of percutaneous biopsy/cytology

Percutaneous fine-needle aspiration biopsy and core biopsy are less accurate than imaging in diagnosis of an indeterminate renal space-occupying lesion. Percutaneous renal biopsy of a focal lesion has been shown to have a sensitivity of 62% to 100% and specificity ranging from 0% to 100%. ²² Treatment decision-making should not be based on needle biopsy results because of significant rate of both false-negative and false-positive results.

The role of biopsy is limited to diagnosis of a relatively large solitary renal mass in patients with a known primary malignancy elsewhere and also in cases of suspected lymphoma.

Conclusion

As CT is used more widely, the incidental space-occupying lesions of the kidney are detected with increasing frequency.
To categorically place these lesions into a definite benign or malignant group is not always possible. It is essential to pay careful attention to imaging techniques in order to evaluate each lesion meticulously, as failure to do so may result in the dismissal of a potentially curable malignant lesion as benign. Conversely, excessive investigation of benign lesions will lead to inappropriate and unnecessary discomfort for the patient. AR