Renal cell carcinoma: Radiological diagnosis and staging

Renal Cell Carcinoma: Radiological Diagnosis and Staging By Errol Levine

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ADIOLOGY plays an important role in the detection, diagnosis, and staging of renal cell carcinoma. Current imaging techniques have had a notable effect on tumor detection. Small low-stage carcinomas are now commonly identified during abdominal sonography or computed tomography (CT) performed for nonrenal complaints. Indeed, almost as many new renal cell carcinomas are currently being detected incidentally as are being found in patients investigated because of hematuria or flank pain.’ Renal cell carcinoma presents radiologically as a renal mass. Diagnosis is dependent on differentiation from other causes of a renal mass, including benign cyst; pseudoneoplasms such as a prominent column of Bertin, abscess, or hematoma; and neoplasm, of other histology, such as lymphoma, renal metastasis, oncocytoma, or angiomyolipoma, all of which require different therapy.* If a radiologic test finding raises the likelihood of renal cell carcinoma, the neoplasm should then be staged. Renal cell carcinoma is usually staged according to the classification of Robson et al.3 In stage I the neoplasm is confined within the renal capsule; in stage II perinephric extension has occurred but is contained by the renal fascia; in stage IIIA venous invasion (renal vein invasion that may extend into the inferior vena cava) is present; in stage IIIB regional lymph node metastasis has developed; in stage IIIC both venous and lymph node invoIvement are present; in stage IVA an adjacent organ (excluding the ipsilateral adrenal gland) is invaded; and in stage IVB there are distant metastases. EXCRETORY

UROGRAPHY

Excretory urography cannot usually determine the nature of a renal mass. However, there From the Department of Diagnostic Radiology. University of Kansas Medical Center, Kansas Citv. Errol Levine: Professor OfDiagnostic Radiology. Address reprint requests to Errol Levine, MD. PhD. Department of Diagnostic Radiology, University of Kansas Medical Center, Rainbow Boulevard at 39th St, Kansas City. KS 66103. o 1987 by Grune & Stratton, Inc. 0037-198X/87/2204-0004%05.00/0 248

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are several urographic signs that suggest renal cell carcinoma. One such sign is calcification, which occurs in about 13% of renal cell carcinomas and which is usually amorphous and centrally located (Fig l).2*4 However, a carcinoma may show a curvilinear or annular type of calcification (Fig 2) which may cause it to be mistaken for a calcified simple renal cyst.’ Renal cell carcinoma sometimes invades a calyx or the renal pelvis and causes a smooth or irregular filling defect (Fig 1). It may also obstruct the collecting system and cause localized hydrocalyces or hydronephrosis. Pelvic and ureteral notching may occur from peripelvic and periureteric collateral veins formed because of invasion of the renal vein. The absence of contrast medium excretion by a kidney containing a carcinoma usually indicates renal vein occlusion by the neoplasm. COMPUTED

TOMOGRAPHY

CT Diagnosis

Since a tissue-specific diagnosis is not possible by CT, differentiation between renal cell carcinoma and other malignant renal tumors such as solitary lymphoma, metastasis, and invasive renal pelvic carcinoma is often not possible. However, renal cell carcinoma is a much more common cause of a solitary renal mass than the other neoplasms and may be suspected from a variety of CT findings6s7 Renal cell carcinomas are usually isodense with normal renal parenchyma on precontrast images.* Accordingly, a small tumor may not be visible on an unenhanced CT scan. Larger neoplasms usually produce a mass effect. CT often shows amorphous central calcification, but it is particularly helpful in evaluating a renal mass with annular or curvilinear calcification.5 Demonstration of a soft tissue mass extending beyond the calcification clearly indicates the neoplastic nature of the lesion (Fig 2B).5 After intravenous contrast medium administration, the renal cell carcinoma is enhanced, but usually to a lesser extent than normal renal parenchyma. Enhancement is usually inhomogeneous because of tumor hemorrhage and necrosis (Figs 3 and 4). The in Roentgenology,

Vol XXII,

No 4 (October),

1987:

pp 248-259

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mass usually shows an indistinct interface with the surrounding parenchyma and often has a lobulated or irregular outer margin (Fig 3). By using these CT criteria, a diagnostic accuracy >95% can be reached.’ Abdominal

CT Staging

CT has an overall accuracy of about 91% in staging renal cell carcinoma.’ In stage I neoplasm, the perinephric fat and renal fascia are normal (Fig 4). Stage II is characterized by tumor extension into the perinephric fat and thickening of the renal fascia.6 The tumor extension may be manifested as perinephric strands of soft tissue density. However, since such strands may also result from resolving perinephric hematoma, fat necrosis, dilated collateral blood vessels, or edema of connective tissue septa,9 the tumor should not be assigned to stage II unless there is a soft tissue mass at least 1 cm in diameter in the perinephric space (Fig 5).’ Sometimes tumor extension beyond the renal

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capsule is evident only on microscopic examination; this results in incorrect CT tumor stagCT may reveal invasion of the renal vein or inferior vena cava, which indicates a stage IIIA tumor.6v8*9Tumor invasion of a renal vein may be suspected if the vein is enlarged or shows an abrupt change in caliber, or if intraluminal areas of decreased density are evident on contrastenhanced scans (Fig 6). A large right-sided tumor may obscure the right renal vein.6p8 An enlarged renal vein may not contain tumor**’ but may be the result of increased blood flow from a hypervascular neoplasm.**’ Errors of interpretation may be avoided by using bolus, dynamic, and thin-section collimation scanning. Vena caval extension may be suspected if there is an intraluminal area of decreased density on contrast scans, sometimes with caval enlargement.6.8pgCT also helps determine proximal caval tumor extent (Fig 7). Particularly on the right side, it may be impossible to distinguish between intraluminal tumor thrombus and extrinsic caval

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Fig 2. Renal call carcinoma with curvilinear calcification. (Al Upper pole mass (arrowheads) with dense annular calcification. (6) CT shows a low-density soft tissue mass (arrows) extending posteriorly beyond the calcification (arrowheads). (Courtesy of Dr G. David Dixon, St Luke’s Hospital, Kansas City, MO.)

compression caused by a large primary tumor or enlarged lymph nodes. Metastases to regional lymph nodes indicate a stage IIIB tumor. Nodes exceeding 2 cm in diameter on CT almost always contain tumor (Fig 5). Nodes in the 1- to 2-cm range, especially if numerous at the renal hilar level, should be regarded with suspicion but are considered indeterminate by size criteria alone.* Enlarged nodes resulting from reactive hyperplasia and normal-

sized nodes containing microscopic neoplastic foci are common causes of false-positive and false-negative interpretation, respectively.6*8*9 CT may show direct invasion of adjacent muscles, such as the diaphragm, psoas, quadratus lumborum, or erector spinae (Fig 8), as well as invasion of adjacent viscera, such as the liver, colon, pancreas, or spleen.6*8 Loss of fat planes between the tumor and adjacent structures such as the liver is not necessarily a sign of organ

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Fig 3. Small neoplasm (arrow) with ric extension (open arrow). Note the appearance and slightly irregular tumor

early perinephinhomogeneous margin.

invasion. Such invasion should be suggested only when there is enlargement or density change in the adjacent structure (Fig S).* Abdominal CT is also useful for showing hematogenous metastases to the liver, contralateral adrenal gland (Fig 9) or kidney, and lumbar vertebrae.* Bilateral synchronous renal cell carcinoma is also readily detected by CT.* SONOGRAPHY

Renal cell carcinoma presents on sonography as a solid mass that usually transmits sound poorly so that the acoustic transmission is either

unchanged or decreased when compared with that of normal renal parenchyma. The mass may be hypoechoic, isoechoic, or hyperechoic (Fig 10) compared with normal renal cortex. Most are isoechoic.“,” The lesion often shows an inhomogeneous echo pattern owing to hemorrhage and necrosis.” Calcification produces high-amplitude echoes with acoustic shadowing.” Sonography is distinctly inferior to CT for staging because bowel gas often precludes adequate ultrasound evaluation of the renal veins and regional lymph nodes.‘* However, sonography is useful for showing proximal caval and right atria1 tumor extension (Fig 7). MAGNETIC

Fig 4. Stage I renal renal fascia (arrow) are

cell carcinoma. normal.

Perinephric

fat and

RESONANCE

IMAGING

On spin-echo (SE) images, renal cell carcinoma varies from hypointense to hyperintense in appearance compared with surrounding renal parenchyma. This depends to some extent on the pulse sequence used.13*14The lesion often has irregular margins and shows an inhomogeneous appearance from hemorrhage and necrosis (Fig 11). Calcium deposits emit little or no signal and are therefore usually inconspicuous. This limits the usefulness of magnetic resonance (MR) imaging in evaluating renal masses.13 MR imaging is accurate in staging renal cell carcinoma and is particularly useful in detecting venous tumor extension (Fig 12).14 Normally flowing blood in the renal veins and inferior vena cava does not usually produce a detectable MR

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Fig 5. Carcinoma extends through the renal capsule and causes a mass (white arrow) in the perinephric space. The left renal fascia (arrowheads) is thickened (compare with the normal right side). Note the metastatic enlargement of the paraaortic lymph node (black arrow).

signal. Venous tumor thrombus causes an intraluminal signal and exhibits intensity changes with variation in pulse repetition interval and echo delay time that are similar to the intensity changes of the main tumor mass.14 Direct sagittal MR imaging is particularly helpful in evaluating the superior extent of caval tumor thrombus relative to the diaphragm, hepatic veins, and right atrium (Fig 12B). ANGIOGRAPHY

Arteriography

Most renal cell carcinomas show increased vascularity and are therefore readily diagnosed by selective renal arteriography. The most characteristic angiographic finding is the presence of “tumor” vessels. These are irregular in outline, tortuous with an absence of normal tapering, randomly distributed, variable in size, and unpredictable in branching (Fig 13). In hypervascular neoplasms, the tumor vessels are often dilated and the main renal artery enlarged. Arteriovenous communications often cause early opacification of the renal vein (Fig 14). Angiography may also help in tumor staging. Renal vein tumor extension may be suspected if the vein shows a filling defect (Fig 14), if it fails to opacify after selective injection of a large volume of contrast material (30 mL) into the renal artery, or if vascularized tumor thrombus is demonstrated (Fig 6).” Arteriography has proved of limited value in detecting extrarenal spread. ‘*r6~r7A carcinoma may extend into the perinephric tissues without angiographic evi-

dence. Furthermore, noninvasive intracapsular tumors may have an extensive blood supply from capsular, lumbar, adrenal, phrenic, hepatic, and even mesenteric arteries.17 However, arteriography can accurately identify a small metastasis in the adrenal glands, liver, or opposite kidney. INFERIOR VENA CAVOGRAPHY PHLEBOGRAPHY

AND RENAL

Inferior vena cavography and renal phlebography are rarely required nowadays for evaluating renal cell carcinoma since venous extension can usually be accurately assessed by noninvasive techniques such as sonography, CT, or MR imaging. INTRAVENOUS DIGITAL SUBTRACTION ANGIOGRAPHY

Renal cell carcinoma may be evaluated by intravenous (IV) digital subtraction angiography (DSA) with a contrast bolus administered via a catheter placed in the distal inferior vena cava.‘* The first phase of the examination provides a conventional inferior vena cavogram. In the second phase, the origin of the renal arteries from the aorta and the vascularity of the renal tumor are evaluated. The examination is continued into the third phase when recirculation of contrast material produces opacification of the renal veins. The renal vein draining the affected kidney is judged to be patent if it is shown simultaneously with the renal vein on the normal side. Criteria for renal vein extension include nondemonstration of the renal vein, the presence of an

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Fig 6. Venous extension of renal carcinoma. (Al The tumor (T) has extended into the left renal vein (arrows), which is enlarged and occupied by low-density tissue similar in attenuation value to the primary neoplasm. The inferior vena cava (open arrow) is normal. Note the metastatic involvement of an enlarged regional lymph node farrowhead). (6) Selective renal arteriogram shows a hypovascular mass (arrows). Note the striated appearance in the renal vein (arrowheads) that indicates vascularized tumor thrombus.

intraluminal filling defect, and the presence of collateral veins.18 An important advantage of IV DSA is that it can be performed on outpatients. NEEDLE PUNCTURE

AND ASPIRATION

BIOPSY

Diagnostic aspiration of a solid renal mass is not usually indicated since the technique may sample nonmalignant appearing parts of a carcinoma,” and because it may result in pneumothorax, perinephric hemorrhage,*’ or tumor growth

along the needle track.*’ However, the technique is sometimes indicated in patients with lymphoma or other known neoplasms when there is a renal mass; distinction from renal cell carcinoma has obvious theraneutic considerations. CHEST RADIOGRAPHY

AND CT

The lungs are the most common site for metastasis from renal cell carcinoma. Mediastinal lymph node involvement occurs in about 9% of

Venous extension. (A) A renal carciFig 7. noma (arrowheads) has extended into the infc rior vena cave (arrows), which is enlarged by an inhomogeneous neoplastic thrombus. (B) The CT scan displays extension into the retrohepatic part of the cave (arrowheads). The mass could be seen in the supradiaphragmatic part of the ceva on a more cephalad scan. (C) Longitudinal ultrasound scan shows enlargement of the inferior vena cava (arrowheads) from the inhomogeneous thrombus. Proximally the tumor (arrow) extends into the right atrium (A).

RADIOLOGY

Fig (open spinaf back pfirlllil

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carcinoma 8. Renal call the erector arrow) invading 1 muscle and tis sues of the (arrows). (Rap1 4ntad with 5sion.f)

Fig 9. Right renal call with left adrenal metastasis printed with permission.‘*)

Fig 10. Longitudinal sonogram of right reveals hyparachoic upper pole mass (arrows).

kidney (K) L. liver.

carcinoma (arrowhead).

(ar .row) (Ra-

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patients and often coexists with pulmonary involvement. ** If the conventional chest radiograph shows multiple metastases, no further thoracic evaluation is necessary. However, if the chest radiograph is normal or equivocal, or shows a solitary nodule, thoracic CT should be obtained at the time of the abdominal CT examination, in a search for multiple small metastases. SKELETAL

SCINTIGRAPHY

The frequency of skeletal metastases at the time of diagnosis of renal cell carcinoma is about

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10%.23S25 About 85% of patients with bone metastases have bone pain.25*26 Accordingly, the frequency of asymptomatic bone metastases in patients with renal cell carcinoma is low. Therefore, there may be reason to question the use of skeletal scintigraphy in many centers as a routine staging procedure for renal cell carcinoma.25T26 However, if a patient with suspected renal cell carcinoma complains of bone pain, a skeletal scintigram should be obtained and supplemented, if necessary, by plain films of the affected areas.

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Fig 12. Tumor with vena caval extension. (A) MR (SE BOO/30) shows a tumor (arrows) with a highintensity area (open arrow), representing hemorrhage. Th>ere is extension into an enlarged right renal vein and the inferior vena cava (arrowheads), and into the distal end of the left renal vein (white arrow). Note the extensive retrocaval adenopathy (curved arrow). (B) Sagittal MR (BE 2000/30) displays the intracaval tumor (arrowheads). It extends proximally almost to the diaphragm (open arrow). The retrocaval adenopathy is again shown (arrows).

ALGORITHMIC EVALUATION

APPROACH TO RADIOLOGICAL OF RENAL CELL CARCINOMA

The diagnostic pathway is determined to some extent by how the tumor is first discovered. If discovered incidentally by CT, no further investigation may be necessary. However, in patients complaining of symptoms such as hematuria, excretory urography should be performed first, since hematuria may be caused by several different conditions such as renal calculi and urothelial carcinoma as well as by renal cell carcinoma. It is mandatory to follow the urographic discovery of a renal mass by a more definitive

radiologic study because excretory urography is notoriously unreliable in differentiating between a benign and malignant renal mass. Since sonography is inaccurate in tumor staging,” CT is usually the preferred next procedure in patients with urographic findings suggesting renal cell carcinoma. If CT shows a solid renal mass and clearly demonstrates local tumor extension, radiologic evaluation of the primary tumor may stop at this point. However, sometimes CT fails to provide adequate staging. This occurs particularly with a large tumor that distorts the anatomy and may prevent adequate visualization of the venous structures.@*’ If CT

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hypervascular right kidney. with opacification arrows) and Tumor thrombus cephalic renal

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tumor in the lower pole of the Note the arteriovenous shunting of two renal veins (curved the inferior vena cava (arrows). is present in the larger, more vein.

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fails to demonstrate the proximal extent of a caval tumor thrombus, the cava and right atrium may be evaluated further by sonography or MR imaging with ECG gating. Inferior vena cavography is rarely required. Preoperative routine renal arteriography is no longer considered necessary in patients with renal cell carcinoma.g*27 However, some surgeons require a demonstration of the number and location of renal arteries before surgery. IV DSA is usually adequate for this purpose. However, conventional arteriography is still sometimes required in special situations. It is indicated in patients undergoing tumor angioinfarction and when vascular mapping is needed for surgical planning in a patient with a tumor of a solitary kidney, bilateral primary neoplasms, or a neo-

plasm in a horseshoe kidney.27 Other indications for conventional arteriography include a questionable small contralateral tumor, differentiation of invasive urothelial carcinoma from renal cell carcinoma, an indeterminate renal mass after CT and sonography, cases in which the organ of origin of the neoplasm is obscure (eg, renal v adrenal), and instances when there is suspected renal vascular disease in the opposite kidney. If chest radiographs show pulmonary, pleural, or mediastinal metastases, no further diagnostic procedure is indicated. However, if the chest radiograph is normal, thoracic CT is indicated. Skeletal scintigraphy is preferred to radiography in patients complaining of bone pain.

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14. Hricak H, Amparo E, Fisher MR. et al: Abdominal venous system: Assessment using MR. Radiology 1985;156:415-422 15. Simpson A, Baron MC, Mitty HA: Angiographic patterns of venous extension of hypernephroma. J Vrol 1974;111:441-444 16. Bracken B, Jonsson K: How accurate is angiographic staging of renal cell carcinoma? Urology 1979;14:96-99 17. Buist TAS: Parasitic arterial supply to intracapsular renal cell carcinoma. AJR 1974;120:653-659 18. Ford KK, Braun SD, Miller GA, et al: Intravenous digital subtraction angiography in the preoperative evaluation of renal masses.AJR 1985;145:323-326 19. Sherwood T, Trott PA: Needling renal cysts and tumors: Cytology and radiology. Br Med J 1975;3:755-758 20. Helm CW, Burwood RJ, Harrison NW, et al: Aspiration cytology of solid renal tumors. Br J Ural 1983;55:249253 21. Bush WH, Burnett LL, Gibbons RP: Needle tract seeding of renal cell carcinoma. AJR 1977;129:725-727 22. Latour A, Shulman HS: Thoracic manifestations of renal cell carcinoma. Radiology 1976;121:43-48 23. Forbes GS, McLeod RA, Hattery RR: Radiologic manifestations of bone metastases from renal carcinoma. AJR 1977;129:61-66 24. Swanson DA, Orovan WL, Johnson DE, et al: Osseous metastases secondary to renal cell carcinoma. Urology 1981;18:556-561 25. Rosen PR, Murphy KG: Bone scintigraphy in the initial staging of patients with renal-cell carcinoma: Concise communication. J Nucl h4ed 1984;25:289-291 26. Lindner A, Goldman DC, deKernion JB: Cost-effective analysis of prenephrectomy radioisotope scans in renal cell carcinoma. Urology 1983;22:127-129 27. Mauro MA, Wadsworth DE, Stanley RJ, et al: Renal cell carcinoma: Angiography in the CT era. AJR 1982;139:1135-1138