Renal cell carcinoma: Clinical aspects, imaging diagnosis, and staging

Renal Cell Carcinoma: Clinical Aspects, Imaging Diagnosis, and Staging By Errol Levine

ENAL CELL carcinoma comprises 80% to

R 90% of primary malignant renal neoplasms in the adult age group and accounts for about 3% of adult malignancies. 1,2 The tumor occurs about twice as commonly in men as in women. 1 Although renal cell carcinoma may occur at any age including childhood, the median age at diagnosis is about 57 years5 ,2 The cause of renal cell carcinoma remains unknown, and most renal cell carcinomas occur sporadically. However, causative factors can sometimes be identified. The tumor occurs in about 36% of patients with von Hippel-Lindau disease, 3 and the incidence of invasive renal cell carcinoma is about 3 to 6 times greater among long-term dialysis patients than in the general population. 4 PATHOLOGY

Renal cell carcinomas vary in their gross pathology from cystic lesions lined by a thin layer of tumor cells to completely solid masses. 1 Cystic neoplasms may develop because of extensive hemorrhage or necrosis, or they may have an inherently cystic growth pattern. Solid tumors _<3 cm in size are often homogeneous in appearance and show smooth, rounded contours, and may therefore be indistinguishable from benign renal neoplasms such as oncocytomas. s As the tumors enlarge, they frequently develop irregular, lobulated margins and show variegated appearances caused by old or recent hemorrhage and necrosis. Many tumors are

ABBREVIATIONS CT, computed tomography; MR, magnetic resonance; MRI, magnetic resonance imaging; IV, intravenous; SE, spin echo; FLASH, fast low-angleshot,

From the Department of Radiology, University of Kansas Medical Center, Kansas City, Kansas. Address reprint requests to Errol Levine, MD, PhD, Department of Radiology, 2169 KU Hospital, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 661607234. Copyright © 1995 by W..B. Saunders Company 0037-198X/95/3002-000455.00/0 128

surrounded by pseudocapsules composed of atrophied renal parenchyma and connective tissue, the latter merging with dense fibrous septa that course through the tumor and that may contain foci of calcification.1 Microscopically, most renal cell carcinomas grow as tubules, cords, or sheets of cells in a highly vascular stroma) Some tumors show a papillary growth pattern with multiple papillae containing delicate connective tissue cores lined by epithelial cells. Based on cytoplasmic criteria, four types of renal cell carcinoma are recognized: clear cell, granular cell, mixed clear and granular cell, and sarcomatoid carcinoma. In sarcomatoid tumors, the tumor cells resemble mesenchymal cells but originate from tubular epithelium. Sarcomatoid tumors are associated with poor patient survival. NATURAL HISTORY AND PATTERNS OF SPREAD

Renal cell carcinoma has a predominantly expansile growth pattern. Once the renal capsule is breached, direct tumor extension occurs in the perinephric fat and may involve the ipsilateral adrenal gland.2 At first the tumor remains confined by the surrounding renal fascia. However, eventually the renal fascia is breached, and direct invasion of posterior abdominal muscles and of adjacent viscera may occur6,7 (Fig 1). Metastases may develop in the regional lymph nodes, particularly the paraaortic and paracaval lymph nodes located above and below the renal vessels. 2 The tumor may later extend via the cysterna chyli and thoracic duct. Retrograde tumor extension into the tributaries of the thoracic duct may cause metastases in hilar, mediastinal, and supraclavicular lymph nodes.S,9 Renal cell carcinomas sometimes extend into the main renal vein and may eventually involve the inferior vena eava 1° (Fig 1). Vena caval involvement occurs more commonly with rightsided tumors than with those on the left, presumably because of the shorter length of the right renal vein. 11Most often the tumor extends 1 or 2 cm into the middle third of the vena cava, but Seminars in Roentfitenology. Vol XXX, No 2 (April), 1995: pp 128-148

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STAGING OF RENAL CELL C A R C I N O M A

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STAGE I

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TUMOR WITHIN CAPSULE

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STAGE II TUMOR INVASION OF PERINEPHRIC FAT (CONFINED TO RENAL FASCIA)

STAGE III TUMOR INVOLVEMENT OF REGIONAL LYMPH NODES AND/OR RENAL VEIN AND CAVA

STAGE IV ADJACENT ORGANS OR DISTANT METASTASES

Fig 1. Staging of renal cell carcinoma according to the system of Robson et al. 8 (Reprinted with permission, 7)

sometimes tumor extends into the retrohepatic part of the cava. 12,13 Proximal tumor propagation within the cava may cause involvement of the hepatic veins, and the tumor may eventually extend into the right atrium, right ventricle, and pulmonary artery. 12,~3 Usually the tumor remains unattached to the venous wall and floats freely within the lumen except at the site of initial invasion. ~2J3 Addition of clotted blood around the tumor core may increase the size of the tumor thrombus to a diameter equal to or greater than that of the inferior vena cava. The lungs are the most frequent site for metastases in renal cell carcinoma, and cells passing through the pulmonary capillaries may reach multiple sites via the arterial circulation, accounting for other common sites of metastases including the liver, bone, adrenal, opposite kidney, and brain. 2 Metastases from renal cell carcinoma may be multiple, although, not uncommonly, solitary metastases may be encountered in the lungs or in bone.

CLINICAL PRESENTATION

In the past, renal cell carcinoma was most frequently diagnosed late in its course when the tumor had attained a large size. Such patients presented with gross hematuria, flank pain, or flank masses, and many already had metastatic disease. However, the common use of abdominal sonography and computed tomography (CT) in recent years has led to the increasingly frequent discovery of small asymptomatic renal cell carcinomas during examinations performed for reasons other than suspected renal tumor. 14 Such tumors are often smaller than 3 cm in size and are less likely to be locally advanced or to have metastasized, and the chance for surgical cure is thus greater. Patients with renal cell carcinoma sometimes present with systemic symptoms that do not suggest urinary tract disease. 7 Anorexia, lassitude, and weight loss are common, and some patients complain of gastrointestinal symptoms including nausea, vomiting, anorexia, constipation, and abdominal pain. 7 Fever may be the only presenting symptom of renal cell carcinoma, and some patients present with hepatic dysfunction in the absence of liver metastases (Stouffer's syndrome), with the liver function tests returning to normal after tumor resection. 7 Some patients with renal cell carcinoma present with erythrocytosis, presumably caused by excessive erythropoietin secretion. Hypercalcemia may occur in patients with renal cell carcinoma without bone metastases and may be caused by several humoral factors secreted by the tumors. Rarer endocrine syndromes associated with renal cell carcinoma include hypokalemia secondary to ectopic adrenocorticotropic hormone production, galactorrhea caused by ectopic prolactin secretion, gynecomastia and loss of libido secondary to ectopic gonadotropin production, and hypertension caused by renin secretion. 7 Some patients with renal cell carcinoma present with initial symptoms caused by metastases including bone pain, cough, and central nervous system symptoms.7 STAGING

Tumor stage at diagnosis has a most important effect on ultimate patient prognosis6,13,~5 (Fig 2). Several studies have shown that tumor spread to the retroperitoneal lymph nodes or

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renal fascia), stage IIIA of venous invasion (renal vein invasion that may extend into the inferior vena cava), stage IIIB of regional lymph node metastases, and stage IIIC of both venous and lymph node involvement. Stage IVA neoplasms extend through the renal fascia to involve adjacent organs (other than the ipsilateral adrenal), and stage IVB neoplasms have distant metastases. 6 The staging system of the American Joint Committee for Cancer Staging is based on three separate assessments, a8 These are T, which indicates the extent of the primary tumor; N, which indicates the status of the regional lymph nodes; and M, which indicates the presence or absence of metastases. The extent of malignant disease is indicated by numbers added to each of these three categories.18

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THERAPY 10

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t = years after surgery Fig 2. Survival of 499 patients with renal cell carcinoma according to stage. Differences in age existed between patients with stage I and stage II tumors, and with stage III and stage IV tumors. "Expected" curves represent survival of similar populations without tumor. (Reprinted with permission, Is)

beyond the renal fascia markedly reduces patient survival 6,13 (Fig 2). The effect of venous tumor extension on long-term prognosis is more controversial. Various investigators have reported that patients with venous involvement but without lymph node invasion may survive as long as do patients with tumors confined to the kidney. ~3,16However, other reports suggest that venous involvement reduces survival time. 15J7 Multiple metastases have a dismal effect on patient prognosis. 15On the other hand, patients with solitary metastases from renal cell carcinoma have more favorable prognoses. Several staging systems have been described for renal cell carcinoma, but two that are generally used are that of Robson et al6 and the TNM classification of the American Joint Committee for Cancer Staging. 18 In the Robson system (Fig 1), stage I consists of tumor confined within the renal capsule, stage II of perinephric extension (yet contained by the

Appropriate tumor therapy is greatly dependent on imaging findings. Radical nephrectomy, which includes preliminary ligation of the renal artery and vein and en bloc removal of the kidney and ipsilateral adrenal gland within their investing fascia, has been the standard surgical treatment for renal cell carcinoma for many years. 6 In addition, some surgeons include a regional lymphadenectomy as part of the procedure. 6,16 However, metastases may occur in isolated and distant nodes, and there is no convincing evidence that routine lymphadenectomy improves patient survival.19 Recently doubt has been cast on the need for routine radical nephrectomy in all patients with renal cell carcinoma. Some studies have shown that small, round peripheral tumors (3 or 4 cm or smaller) within well-defined fibrous capsules, as shown by imaging, may be appropriately managed by partial nephrectomy.2° The adjacent perinephric fat is excised en bloc with the tumor. Patients treated with this technique show similar 5-year survival rates to those of patients with small low-stage renal cell carcinomas treated with radical nephrectomy, although they occasionally develop tumor recurrence in the kidney remnant. 2° However, many surgeons believe that radical nephrectomy is the treatment of choice for most renal cell carcinomas, regardless of size, if the contralateral kidney is normal. They reserve partial nephrectomy for

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small renal cell carcinomas in patients who have renal functional impairment or a coexisting contralateral disorder (such as chronic pyelonephritis, hydronephrosis, or renal arterial disease) that may cause progressive renal functional impairment in the future. 21 Partial nephrectomy is also performed for small renal neoplasms occurring in a solitary kidney or in patients with bilateral small neoplasms and in those with von Hippel-Lindau disease. 21 Accurate preoperative assessment of venous tumor involvement is of paramount importance for management. If there is tumor thrombus in the renal vein only, then routine ligation of the vein before nephrectomy is adequate for prevention of tumor embolization. When the inferior vena cava is involved by tumor, but the tumor thrombus does not extend to the hepatic vein level, thrombectomy may be performed through an incision that allows vena caval control above and below the thrombus, a2The tumor thrombus is removed en bloc with the tumor-containing kidney. A thrombus that extends to or above the hepatic veins or into the heart is more safely and completely resected with cardiopulmonary bypass. 12 There is no effective treatment for renal cell carcinoma with distant metastases, and survival is p o o r . 22 However, palliation may sometimes be produced by hormonal therapy using progestins and antiestrogens.22Currently, there is no known effective chemotherapy for renal cell carcinoma. 22Radiation therapy has little place in the

Fig 3. Small renal cell carcinoma. A contrast-enhanced CT scan s h o w s a h o m o g e n e o u s , well-circumscribed 2-cm left renal mass (arrow), The lesion has an attenuation value of 90 HU, as compared w i t h 32 HU on an unenhanced CT scan.

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management of renal cell carcinoma. 22 However, it may be used for the treatment of bone metastases, or occasionally as palliative treatment for a nonresectable tumor associated with severe pain or excessive hematuria. Interferon and other immunologic agents are now being used to treat patients with metastatic disease with some guardedly encouraging preliminary results. 23-25Local resection of painful bone metastases and of solitary pulmonary metastases is sometimes helpful.22

Angioinfarction Percutaneous transcatheter arterial tumor embolization, ie, angioinfarction, was in the past widely used in the management of renal cell carcinoma. Various embolic materials including Gelfoam (Upjohn Co, Kalamazoo, MI), Gianturco coils, autologous blood clot, and 95% alcohol were used for this purpose. 26 Angioinfarction was believed to help in several respects including (1) minimization of blood loss during surgery; (2) creation of perirenal edema, thereby facilitating the development of planes that made resection easier; and (3) stimulation of the immune system, thereby prolonging patient survival. However, several investigators could not document any of these claimed beneficial effects. 26,27Also, serious complications have been described after angioinfarction.27 Accordingly, angioinfarction now has only a limited role in the management of renal cell carcinoma. Currently, the primary indication for angioinfarc-

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tion is to facilitate surgery in patients in whom extremely large renal tumors may cause technical difficulties in securing the renal vasculature before nephrectomy. Angioinfarction may also be used as a palliative procedure for control of pain, hematuria, and metabolic syndromes caused by nonresectabie tumors or for tumors occurring in patients who are unfit for surgery. 26,27 SMALL RENAL CELL CARCINOMAS

Renal cell carcinoma is the most common cause of solitary renal neoplasms < 3 cm in size 5J4,2s (Fig 3). Such lesions are most often detected incidentally during abdominal CT or sonography performed for nonrenal complaints. They are histologically indistinguishable from larger carcinomas encountered in the kidneys and often have histological grades indicating a definite potential for malignant behavior. 5,14,28If followed serially by CT before surgery, they often show gradual enlargement 5,29 (Fig 4). Most such lesions are confined to the kidney and are assigned to stage I. 5'14'28 Although these lesions usually have excellent prognoses if managed surgically, small carcinomas are sometimes associated with metastases 2s,3°,31(Fig 5). Accordingly, these lesions should be classified as carcinomas in an early stage of evolution and should not be classified as adenomas. Most small renal cell carcinomas are sharplymarginated, homogenous lesions on CT. Less commonly they show marginal irregularity, heterogeneity, or central calcification, findings that may suggest pathologically high-grade tumors 31 (Fig 6). Because small peripheral carcinomas are usually low-stage lesions, various investigators have treated these lesions with conservative operations such as partial nephrectomy with good results. 2° However, some surgeons believe that radical nephrectomy is more likely to produce a permanent cure and reserve partial nephrectomy for those patients in whom there is a definite need to preserve renal tissue. 21 Surgery may be avoided in elderly, high-risk patients with small renal cell carcinomas, and such patients can be adequately followed by serial CT. 31 IMAGING DIAGNOSIS AND STAGING

Renal cell carcinoma presents radiologically as a renal mass. Diagnosis is dependent on

Fig 4. Progression of a renal cell carcinoma shown by serial CT in 58-year-old man who had a bladder carcinoma resected 6 years earlier. (A) A contrast-enhanced CT scan shows a 1.8-cm renal mass (arrow). (B) A contrast-enhanced CT scan performed 2 years after (A) shows that the mass (arrows) has enlarged and measures 4 cm.

differentiation from other causes of a renal mass, including simple cysts; pseudoneoplasms such as a prominent column of Bertin, abscess, or hematoma; and neoplasms of other histology, such as lymphoma, renal metastasis, oncocytoma, or angiomyolipoma, all of which require different therapy. If imaging findings raise the likelihood of renal cell carcinoma, the neoplasm should then be staged.

Excretory Urography Excretory urography usually cannot determine the nature of a renal mass. However, there are several urographic signs that suggest renal

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Fig 5. Small renal cell carcinoma with sacral metastasis. The patient was a 42-year-old man who complained of low back pain. (A) A lytic metastasis (arrowhead) is present in the right sacral ala. (B) CT performed to search for a primary neoplasm shows a small left renal mass (arrowhead) with thick peripheral calcification. Histological examination showed a high-grade renal cell carcinoma with sarcomatoid changes.

carcinoma. One is calcification, which occurs in about 13% of renal cell carcinomas, as shown by urography, and which is usually amorphous and located centrally in the mass. 32 However, a carcinoma may show peripheral or central curvilinear or annular calcification, which may cause it to be mistaken for a calcified simple renal cyst33 (Fig 7). Renal cell carcinoma sometimes invades a calyx or the renal pelvis causing a smooth or irregular filling defect. It may also obstruct the collecting system causing localized hydrocalyces or hydronephrosis. Pelvic and ureteral notching may occur from peripelvic and periureteric collateral veins formed because of tumor invasion and occlusion of the renal vein. The absence of contrast excretion by a kidney

containing a carcinoma usually indicates renal vein occlusion by tumor extension.

Computed Tomography CT technique. Because unopacified bowel loops may simulate perinephric masses and retroperitoneal adenopathy, patients undergoing renal CT should receive oral contrast medium. Unenhanced scans of the liver and kidneys should always be performed first. Liver metastases from renal cell carcinoma are often hypervascular and may therefore be easier to detect on unenhanced scans. Unenhanced scans also permit contrast enhancement of a renal lesion to be measured and ensure that renal parenchymal calcifications, renal calculi, renal

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Fig 6. Renal cell carcinoma. (A) A small (2.9 cm) renal mass (arrow} has a higher density than normal renal paranchyma on an unenhanced CT scan. (B} A pracontrast scan through the upper part of the lesion shows a small focus of amorphous calcification (arrow}, (C) A contrast-enhanced CT scan shows that the mass (arrow} enhances less than normal renal parenchyma and shows low-density areas caused by tumor necrosis. The mass has an indistinct interface with adjacent renal parenchyma.

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and perinephric hemorrhage, and fat and calcification in a renal mass will not be obscured by contrast medium. 34 Usually, contiguous 10-ram-thick CT sections are obtained unless there is a known small renal lesion, when 5-ram-thick scans should be performed. Administration of intravenous (IV) contrast medium is a fundamental requirement for CT evaluation of renal masses provided renal function is normal. Enhancement of a mass indicates that the lesion is vascular, and is therefore likely a neoplasm. Contrast medium should be administered rapidly with a mechanical injector via an antecubital vein as a 150-mL bolus containing 40 to 45 g of iodine at a rate of 1.5 to 2 mL/sec. Scans of the liver and kidneys are performed using dynamic incremental or helical (spiral) CT scanning. 35,36 Helical CT is particularly helpful for evaluating small renal lesions because of lack of registration artifacts. It also minimizes partial volume averaging because overlapping sections can be reconstructed at small intervals from the volumetric data acquisition. 37 Scans obtained with dynamic or helical technique often show a cortical nephrogram. Because of the relative lack of medullary enhancement, small masses can be overlooked. Accordingly, the kidneys should be re-examined by conventional axial scanning after completion of a dynamic or helical scan. The nephrogram is then usually homogeneous and a pyelogram is apparent. CT diagnosis. The CT appearance of renal cell carcinoma varies depending on its size, vascularity, and the extent of necrosis or cystic change. Neoplasms may be hypodense, isodense, or hyperdense as compared with normal renal parenchyma on unenhanced CT scans 38 (Fig 6). Tumor calcification occurs in as many as 31% of cases and may take the form of amorphous internal calcification or curvilinear calcification, which may be peripheral or centraP 8 (Figs 5 to 7). Renal cell carcinomas rarely contain small amounts of fat because of osseous metaplasia of the nonepithelial stromal part of the tumor with the formation of fatty marrow elements and trabeculae) 9,4°The combination of fat and Calcification should suggest the correct diagnosis because fat-containing renal angiomyolipomas usually do not calcify. After IV contrast medium administration, most renal cell carcinomas enhance, but usually

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Fig 7. Curvilinear calcification in a renal cell carcinoma. (A) An early film from an excretory urogram shows a right renal mass (arrows) with a central area of curvilinear calcification. (B) A contrast-enhanced CT scan shows a low-density soft tissue mass (arrow) extending beyond the curvilinear calcification. There is an enlarged retrocaval lymph node (arrowhead) containing a lowdensity metastasis (Courtesy of G. David Dixon, MD).

to a lesser extent than normal renal parenchyma (Fig 6), although transient hyperdensity may be seen during the early arterial phase of a helical CT study. Only large increases in attenuation value (at least 10 Hounsfield units) indicate true enhancement, because small increases may result from partial volume averaging even on thin

CT sections. 31 Enhancement is often heterogeneous because of tumor hemorrhage and necrosis. The mass sometimes shows an indistinct interface with the surrounding parenchyma and frequently has a lobulated or irregular outer margin. With the use of these CT criteria, a diagnostic accuracy of > 95% can be achieved.

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Fig 8. Multilocular cystic renal cell carcinoma. A contrastenhanced CT scan shows a welldefined, mainly fluid-attenuation mass in the right kidney. There are multiple, enhancing septa throughout the lesion, which also shows a thickened wall. A right radical nephrectomy was performed,

However, small renal carcinomas often have distinct, smooth margins and appear homogeneous and therefore may be be indistinguishable from benign renal neoplasms, such as oncocytomas, on CT 5 (Fig 3). Cystic renal cell carcinomas often pose significant diagnostic problems because they may be difficult to differentiate from hemorrhagic renal cysts.34 Findings that suggest cystic renal cell carcinoma include thick, irregular mural or septal calcification, numerous or thick (> 1 mm), irregular septa, and uniform or slightly nodular wall thickening (Fig 8), although complicated cysts and benign renal neoplasms may show some of these features. 34 Such lesions require surgical exploration unless contraindicated because of the patient's advanced age or poor general medical condition. 34 Cystic lesions

Fig 9. Cystic renal cell carcinoma. A contrast-enhanced CT scan shows a low-density (23 HU) right renal mass, The mass shows a thickened wall and enhancing solid elements (arrows) posteriorly. Simple cysts are present in the left kidney.

with marked marginal irregularity or solid vascular elements (Fig 9) all require surgery because they have a high likelihood of being malignant. 34 Abdominal CT staging. CT has an overall accuracy of about 90% in the abdominal staging of renal cell carcinoma. 35,41The accuracy of CT staging is enhanced by the use of dynamic or helical scanning after a rapid IV bolus injection of contrast medium. 35,41 When a renal cell carcinoma is confined by the renal capsule the adjacent perinephric fat and renal fascia appear normal on CT (Figs 3 and 6). Perinephric invasion is suggested by a perinephric softtissue mass at least 1 cm in diameter (Fig 10), but lesser degrees of perinephric involvement are difficult to diagnose by CT. 35'41"43 Perinephric soft-tissue stranding is an unreliable indicator of tumor extension because it may also result

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Regional lymph node metastases may be suspected if the affected nodes measure at least 1 cm in the long axis (Figs 7, 10, and 11). However, lymph nodes 1 to 2 cm in diameter may be caused by reactive hyperplasia as well as to metastases. 41 Lymph nodes larger than 2 cm in size are almost always caused by metastases. 41,42 Enlarged nodes resulting from reactive hyperplasia and normal-sized nodes containing microscopic neoplastic loci are common causes of false-positive and false-negative interpretaFig 10. A contrast-enhanced CT scan shows a left renal cell carcinoma extending through the renal capsule and causing a mass (white arrow) in the perinephric space, The left renal fascia (arrowheads) is thickened (compare with the normal right side). Note the metastatic involvement of an enlarged left para-aortic lymph node (black arrow),

from a resolving perinephric hematoma, fat necrosis, dilated collateral blood vessels, or edema of connective tissue septa. Inability to determine accurately the presence or absence of small amounts of extracapsular, perinephric tumor extension accounts for over half of CT staging errors. 41 Venous tumor invasion can only be definitely diagnosed on CT if there is identifiable thrombus in the renal vein or inferior vena cava with or without venous enlargement 35 (Figs 11 and 12). Ipsilateral renal vein enlargement on CT without identifiable tumor thrombus is not a reliable sign of venous tumor extension. Although it may reflect the presence of tumor thrombus, it more frequently results from increased blood flow caused by a hypervascular tumor 35 (Fig 13). Errors in diagnosis of venous tumor extension on CT often occur when large right-sided tumors cause marked distortion of the ipsilateral renal vein and inferior vena cava. 35,41CT has difficulty showing the cephalad extent of thrombus in the retrohepatic vena cava and right atrium. Streaming of contrast medium, laminar flow layering, or rapid opacification of the renal veins while the lower extremity venous return remains unopacified may all produce false-positive results of vena caval tumor extension. 19 Accordingly, if CT suggests vena caval tumor extension, but the cephalad extent of tumor cannot be determined, magnetic resonance (MR) imaging or ultrasound should be performed 19 (Fig 12). These techniques usually accurately evaluate the cephalad extent of caval thrombus relative to the diaphragm, hepatic veins, and right atrium. 19,44

Fig 11. Renal cell carcinoma with venous extension and regional lymph node metastases, (A) A contrast-enhanced CT scan shows a right renal mass (black arrow), The right renal vein (white arrow) is enlarged and occupied by tumor that has also extended into the inferior vena cava. A metastasis (arrowhead) is present in the right lobe of the liver. (B) A Tl-weighted MR scan (SE 500/16) shows that the renal neoplasm (arrow) has a higher signal intensity than the normal renal parenchyma. The renal vein (arrowhead) is enlarged, and the normal signal void is replaced by tissue of signal intensity similar to that of the renal mass, Tumor is also present in the vena cava (curved arrow), Enlarged central retroperitoneal lymph nodes (open arrows) containing metastases are present,

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Fig 12. Vena caval extension of renal cell carcinoma, (A) A renal cell carcinoma (not shown) has extended into retrohepatic inferior vena cava (arrowhead), which is enlarged by a heterogeneous neoplastic thrombus. (B) A sagittal ultrasound scan shows enlargement of the inferior vena cava (arrowheads) caused by heterogeneous thrombus. The tumor (arrow) extends into the right atrium (A),

tion, respectively. The sensitivity of CT lymph node staging is reported as 83% to 89%. 41 CT may show direct tumor invasion of adjacent muscles (Fig 14), including the diaphragm, psoas, quadratus lumborum, or erector spinae, as well as invasion of adjacent viscera, such as the liver, colon, pancreas, or spleen. Loss of fat planes between the tumor and adjacent structures such as the liver or psoas muscle is not necessarily a sign of tumor invasion. 41 Such invasion should be suggested only when there is enlargement or density change in the adjacent structure (Fig 14). Ultrasound and MRI are often helpful in determining whether the tumor is merely adjacent to or has invaded a structure

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such as the liver or psoas muscle 45 (Fig 14). Abdominal CT is also useful for showing hematogenous metastases to the liver, contralateral adrenal gland or kidney, and lumbar vertebrae (Fig 1 1). Bilateral synchronous renal cell carcinoma is also readily detected by CT. Postnephrectomy evaluation. Renal bed recurrence of neoplasm occurs in about 5% of patients after radical nephrectomy, as detected by follow-up CT. 46 Patients with large, invasive stage III and IV tumors have a higher risk of local recurrence than those with small low-stage tumors. 47 Renal bed recurrence is most likely to occur within 2 years of nephrectomy. 46If asymptomatic neoplasm recurrence is detected at an early stage, it may be amenable to local surgery, resulting in improved survival. 4s CT may detect neoplasm recurrence in the renal fossa by showing a soft-tissue mass. 49 However, normal structures migrate into the renal fossa after nephrectomy and may simulate recurrent tumor. The liver, ascending colon, second part of duodenum, pancreatic head, and small bowel migrate into the right renal fossa. The pancreatic tail, spleen, and large and small bowel migrate into the left renal fossa. 46 Interpretational errors can be avoided by ensuring adequate bowel opacification with oral contrast medium. Postoperative scarring in the renal fossa is distinguished from neoplasm recurrence if the area shows no change on serial CT examinations. 47 Local neoplasm recurrence may also be suggested by enlargement or irregularity of the psoas muscle on the side of the nephrectomy, although this appearance may be caused by postoperative scarring 49 (Fig 15). CT may also detect tumor recurrence in the retroperitoneal lymph nodes, in the inferior vena cava, and around the aorta and inferior vena cava. Liver metastases, adrenal metastases, and metastases in the opposite kidney are also easily identified by CT. 47,49 Ideally, all patients managed by radical nephrectomy or partial nephrectomy for renal cell carcinoma should have a baseline postoperative CT scan and later scans at regular intervals. This is particularly important in patients with large invasive tumors. 47

Magnetic Resonance Imaging Magnetic resonance imaging technique. Conventional spin-echo (SE) sequences are usually used for evaluating renal masses. Usually both

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Fig 13. Left renal cell carcinoma with renal vein enlargement (arrow) on a contrast-enhanced CT scan (A), The right kidney is atrophic, On protondensity-weighted MRI (B) (SE 2100/30), the left renal vein (arrow) is enlarged but shows a normal signal void, indicating that venous enlargement is caused by increased blood flow rather than tumor extension, The inferior vena cava (open arrow) is normal,

T1- and T2-weighted images are acquired in the axial plane, although both the coronal and sagittal planes are sometimes helpful, s° Fatsuppressed Tl-weighted spin-echo images before and after IV gadolinium enhancement are also useful in evaluating renal masses sl,s2 (Fig 16). They are characterized by high-contrast resolution and minimal phase or chemical shift

artifact 51,52 (Fig 16). Gradient-echo fast lowangle shot [FLASH] images are also helpful for evaluating renal masses. The images are acquired in the axial, sagittal, or coronal planes during breath holding so that respiratory motion artifacts are significantly reduced, sl,s2 Precontrast images of the kidneys are first obtained. Gadopentetate dimeglumine is then

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Fig 14. Left renal cell carcinoma with extension beyond the renal fascia. (A} The tumor invades the posterior abdominal wall via the left quadratus lumborum muscle (black arrow). Tumor has grown along a needle-biopsy track in the subcutaneous tissues (curved arrow). There is tumor invasion of the descending colon (open arrow), which w a s confirmed at surgery, Although the neoplasm abuts the left psoas muscle, there was no actual muscle invasion, c, colon; p, psoas muscle. (B) A contrastenhanced Tl-weighted MR scan (SE 500/15) shows that the neoplasm does not invade the psoas muscle, However, there is abdominal wall invasion (long arrow) and colon invasion (short arrow). C, colon; P, psoas muscle.

injected IV by hand in a dose of 0.1 mmol/kg over 5 seconds with the patient positioned in the bore of the magnet. Imaging is started during breath-holding at 20 to 30 seconds after a rapid saline flush of the IV catheter has been performed. These images show striking corticomedullary differentiation and also marked enhancement of the renal vein blood (Fig 17). FLASH images obtained after a slight delay show a homogeneous tubular ncphrogram. MR diagnosis and tumor staging. The appearance of renal cell carcinoma on unenhanced MR SE images varies depending on whether the neoplasm is homogeneous or contains areas of hemorrhage or necrosis53 (Fig 17). In the absence of hemorrhage and necrosis, the signal

intensity of renal cell carcinoma is similar to that of normal renal parenchyma on both T1and T2-weighted images. Tumors smaller than 3 cm in diameter are therefore detected in only 63% of unenhanced sequences. 53 Tumors containing areas of hemorrhage and necrosis often appear heterogeneous on unenhanced SE images 53 (Fig 18). Tumor calcification is difficult to appreciate on almost all MR pulse sequences, and this limits the usefulness of MRI in evaluating renal masses. Recent studies using fat-saturation SE and fast scanning techniques combined with gadolinium-diethylenetriamine pentaacetic acid enhancement and breath-holding have made MRI comparable to CT in the detection and charac-

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Fig 15, Local recurrence of renal cell carcinoma 7 years after nephrectomy for right renal cell carcinoma, Patient presented with upper gastrointestinal bleeding. (A) An enhancing mass (curved arrow) causes enlargement of the right psoas muscle, The third part of the duodenum (straight arrow) and the inferior vena cava (arrowhead) are adherent to the mass. (B) MRI (SE 500/15) performed after IV injection of gadolinium-diethylenetriamine pentaacetic acid shows an enhancing mass (curved arrow) involving the right psoas muscle, Endoscopy with biopsy showed clear cell carcinoma invading the third part of the duodenum (straight arrow).

Fig 16, Renal cell carcinoma with early perinephric extension, Unenhanced fat-suppressed Tl-weighted MR image (600/ 15) shows a large neoplasm (arrows) in the lower pole of the right kidney. There is early extension into the perinephric fat (open arrow) and associated renal fascial thickening (curved arrows).

Fig 17. Renal cell carcinoma. A gradient-echo (168/6; flip angle = 75 °) MR image obtained during breath-holding after IV gadolinium injection shows a 3.6-cm left renal tumor (arrows) with a low-density area (arrowhead) representing tumor necrosis.

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Fig 18, Left renal cell carcinoma. (A) Tl-weighted MRI (SE 500/17) shows a heterogeneous tumor (arrows) with slightly higher intensity than the normal renal parenchyma. (B} Proton-density-weighted MRI (SE 2100/30) slightly caudal to (A) accentuates the heterogeneity of the lesion (arrows). Note the signal void in the normal left renal vein (curved arrow),

terization of renal masses51,52 (Figs 16 and 17). On gadolinium-enhanced gradient-echo images there is a marked increase in contrast between tumor and normal renal parenchyma, and renal cell carcinomas usually show heterogeneous enhancement less than that of normal renal parenchyma (Fig 17). Gadolinium-enhanced MRI provides a safe alternative to CT in patients with renal insufficiency or previous reactions to IV iodinated contrast medium. 54MRI is

particularly useful in detecting venous tumor involvement when CT findings are indeterminate. 19,44Tumor thrombus in the renal vein and inferior vena cava may be suspected on T1weighted SE pulse sequences if the signal void of flowing blood is replaced by relatively high signal because of tumor thrombus (Figs 11 and 19). Tumor thrombi emit signal with an intensity similar to that of the primary neoplasm on different pulse sequences. Unenhanced gradient-

Fig 19. Vena caval extension of right renal cell carcinoma. (A) An unenhanced Tl-weighted MR scan (SE 500/17) shows a large right renal tumor with intracaval tumor (arrow) at the level where the three hepatic veins (arrowheads) join the cava. (B) A sagittal Tl-weighted MR scan shows intracaval tumor (black arrows). The supradiaphragmatic part of the cava (white arrow) is unaffected.

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echo images are also useful for detecting venous tumor extension. With this technique, flowing blood has a markedly increased signal intensity and appears white, whereas tumor thrombus has a medium signal intensity and appears as an IV filling defect 44 (Fig 20). MRI using the sagittal and coronal planes is particularly helpful in evaluating the superior extent of caval tumor thrombus relative to the diaphragm, hepatic veins, and right atrium 19,44(Fig 19).

Sonography Renal cell carcinoma presents on sonography as a solid, cystic, or complex mass. 55 Solid lesions transmit sound poorly so that acoustic transmission is either unchanged or decreased when compared with that of normal renal parenchyma. Tumor echogenicity is related to tumor size. 55 In one study, of 53 solid renal cell carcinomas larger than 3 cm in size, 19% were hypoechoic compared with renal parenchyma, 45% were isoechoic, and 36% were hyperechoic, with most of the latter being slightly hyperechoic compared with renal parenchymaY Among 28 solid carcinomas < 3 cm in size, 4% were hypoechoic compared with renal parenchyma, 11% were isoechoic, 50% were slightly hyperechoic, and 35% were markedly hyperechoic compared with renal parenchyma 55 (Fig 21). Accordingly, small hyperechoic renal cell carcinomas and small hyperechoic angiomyoli-

Fig 20. Vena caval extension of left renal cell carcinoma. Gradient-echo MRI (60/12; flip angle = 60 °) shows tumor extension along the left renal vein (arrow) and into the inferior vena cava. Flowing blood in the cava appears white, and the tumor is shown as a filling defect (arrowhead) (Courtesy of Richard L. Ehman, MD),

Fig 21. Renal cell carcinoma in a 10-year-old boy. A longitudinal sonogram of the right kidney shows a hyperechoic, homogeneous, well-circumscribed, 3-cm mass (arrow) in the lower pole.

pomas often are not distinguishable by ultrasound. However, small renal cell carcinomas may show anechoic rims caused by tumor pseudocapsules and may contain small anechoic areas because of tumor necrosis 56 (Fig 22), features not usually found in angiomyolipomas. 56 Nevertheless, small hyperechoic renal masses should not be assumed to be angiomyolipomas and should always be further evaluated by CT to confirm or exclude the presence of fat within an angiomyolipomaY Small angiomyolipomas do not require surgery, whereas small renal cell carcinomas are often resected. Sonography is less accurate than CT or MRI in tumor staging. Failure to visualize adequately the central retroperitoneal region, renal vessels, and infrahepatic vena cava may occur in more than 50% of patients, usually because of overlying intestinal gas. 45,57 Metastases in regional lymph nodes are therefore difficult to detect by ultrasound. Moreover, the perinephric and pararenal spaces are difficult to distinguish by ultrasound because sonography usually does not show the renal fascia as a distinct layer. Tumor extension into the perinephric space is therefore difficult to detect by ultrasound. Ultrasound also cannot detect muscle invasion, so that stage IVA tumors may be incorrectly staged. 45 Sonography may be useful in detecting venous extension of renal cell carcinoma 58 and particularly for showing proximal caval and right atrial tumor extension (Fig 12). Tumor

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Fig 22. Left renal cell carcinoma. (A) A coronal sonogram shows a poorly-defined 2.7-cm mass (arrows) in the midregion of the left kidney. The mass is mainly isoechoic with normal renal parenchyma, but shows a small central anechoic area caused by tumor necrosis. (B) A left selective renal arteriogram performed for surgical planning shows abnormal tumor vessels in the mass (arrows).

thrombus in the renal vein or the inferior vena cava can be identified as an area of diffuse echoes within the lumen of the vessel that may or may not be dilated (Fig 12). Doppler ultrasound can help in identifying renal vein occlusion caused by tumor thrombus. Sonography is superior to CT for showing the relationship of right upper pole tumors to the liver. 45

Angiography Arteriography. Arteriography was in the past almost routinely used in the preoperative investigation of a suspected renal cell carcinoma. However, it has now been almost entirely replaced by less invasive methods such as CT, MRI, and ultrasound. However, arteriography is sometimes needed for vascular mapping in patients undergoing partial nephrectomy for small neoplasms or multiple tumors occurring in a solitary kidney, patients with bilateral primary neoplasms, and patients with a neoplasm in a horseshoe kidney.59 Other indications for arteriography include a questionable

small contralateral renal tumor, differentiation of invasive urothelial carcinoma from renal cell carcinoma, cases in which the organ of origin of the neoplasm is obscure (eg, renal versus adrenal), instances where there is suspected vascular disease in the opposite kidney, and tumor angioinfarction. Arterial digital subtraction angiography is as accurate as conventional angiography for these purposes. 19 Many renal cell carcinomas show increased vascularity and are therefore readily diagnosed by selective renal arteriography. However, hypovascular carcinomas may be difficult or impossible to diagnose angiographically. The most characteristic arteriographic finding is the presence of "tumor" vessels (Figs 22 and 23). These are irregular in outline, tortuous with an absence of normal tapering, randomly distributed, variable in size, and unpredictable in branching (Figs 22 and 23). In hypervascular neoplasms, the tumor vessels are often dilated and the main renal artery enlarged. Arteriovenous communi-

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ating renal cell carcinoma because venous extension can usually be accurately assessed by such noninvasive techniques as sonography, CT, or MRI.

Percutaneous Biopsy Pcrcutaneous biopsy of a solid renal mass is not usually indicated because the technique may sample benign-appearing parts of a carcinoma, 63and because it may result in pneumothorax, perinephric hemorrhage, 64or tumor growth along the needle track 65 (Fig 14). However, the technique is sometimes indicated in patients with lymphoma or other known neoplasms when there is a renal mass. Distinction of renal lymphoma and metastases from renal cell carcinoma has obvious therapeutic considerations.

Chest Radiography and CT

Fig 23. Right selective renal arteriogram shows a hypervascular tumor in the lower pole of the right kidney. There is arteriovenous shunting with opacification of two renal veins (curved arrows) and the inferior vena cava (arrows). Tumor thrombus is present in the larger, more cephalic renal vein.

cations often cause early opacification of the renal vein (Fig 23). Arteriography may also help in tumor staging. Renal vein tumor extension may be suspected if the vein shows a filling defect (Fig 23), 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 shown. 6° Arteriography is of limited value in detecting extrarenal tumor spread. 33,61,62 A carcinoma may extend into the perinephric tissues without angiographic evidence of such extension. Furthermore, noninvasive intracapsular tumors may have an extensive blood supply from capsular, lumbar, adrenal, phrenic, hepatic, and even mcsenteric arteries. 62 However, arteriography can accurately identify a small metastasis in the adrenal glands, liver, or opposite kidney.

Inferior vena cavography and renal phlebography. Inferior vena cavography and renal phlebography are rarely required nowadays for evalu-

The lungs are the most common site for metastases from renal cell carcinoma. Mediastinal lymph node involvement may occur and often coexists with pulmonary involvement.9,66 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 performed at the time of the abdominal CT examination. Accurate evaluation of lung involvement is important because complete surgical resection of a solitary pulmonary metastasis may increase the 5-year survival rate of affected patients.

Skeletal Scintigraphy About 85% of patients with bone metastases from renal cell carcinoma have bone pain. 67,68 Accordingly, the frequency of asymptomatic bone metastases in patients with renal cell carcinoma is low. Therefore, there is reason to question the use of skeletal scintigraphy in many institutions as a routine staging procedure for renal cell carcinoma. 67,68 However, if a patient with suspected renal cell carcinoma complains of bone pain, a skeletal scintigram should be performed and supplemented, if necessary, by plain films or CT of the affected area (Fig 5).

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EVALUATION OF SUSPECTED RENAL CELL CARCINOMA

The diagnostic pathway is determined to some extent by how the tumor is discovered. If discovered incidentally by CT, no further investigation may be necessary. However, in patients suspected of having a renal neoplasm because of symptoms such as hematuria, excretory urography should be performed first, because 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 imaging study because excretory urography is unreliable in differentiating between benign and malignant renal masses. Because sonography is less accurate than CT in tumor staging, CT is usually the preferred next procedure in patients with urographic findings suggesting renal cell carcinoma. MRI assumes a primary role in tumor diagnosis and staging in those patients in whom contrast-

enhanced CT scanning is contraindicated because of previous major reactions to contrast material or the presence of renal functional impairment. If CT shows a solid renal mass and clearly reveals local tumor extension, imaging evaluation of the primary neoplasm may stop at this point. However, CT sometimes fails to determine whether there is vena caval tumor extension particularly when the cava is distorted by large right-sided tumors. In such circumstances, the cava and right atrium may be evaluated further by sonography or MRI. Inferior vena cavography is rarely required. Preoperative renal arteriography is rarely needed in patients with renal cell carcinoma. However, it is sometimes needed to obtain a preoperative vascular map in patients undergoing partial nephrectomy or for tumor angioinfarction. If chest radiographs show pulmonary, pleural, or mediastinal metastases, no further diagnostic procedure is indicated. However, if the chest radiograph is normal, thoracic CT may be needed. Skeletal scintigraphy supplemented by plain films or CT is required in patients who complain of bone pain.

REFERENCES 1. Petersen RO: Urologic Pathology. Philadelphia, PA, Lippincott, 1992 2. Bennington JL, Beckwith JB: Tumors of the kidney, renal pelvis and ureter (Fascicle 12), in Atlas of Tumor Pathology, 2nd series. Washington DC, Armed Forces Institute of Pathology, 1975 3. Levine E, Collins DL, Horton WA, et al: CT screening of the abdomen in yon Hippel-Lindau disease. AIR 139:505510, 1982 4. Levine E, Slusher SL, Grantham JJ, et al: Natural history of acquired renal cystic disease in dialysis patients: A prospective longitudinal CT study. AJR 156:501-506, 1991 5. Levine E, Huntrakoon M, Wetzel LH: Small renal neoplasms: Clinical, pathologic, and imaging features. A I R 153:69-73, 1989 6. Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. J Uro1101:297301, 1969 7. Holland JM: Cancer of the kidney--Natural history and staging. Cancer 32:1030-1042, 1973 8. Arkless R: Renal carcinoma: How it metastasizes. Radiology 84:496-501, 1965 9. Lang EK: Renal cell carcinoma presenting with metastases to pulmonary hilar nodes. J Urol 118:543-546, 1977 10. Goncharenko V, Gerlock AJ, Kadir S, et al: Incidence and distribution of venous extension in 70 hypernephromas. AJ R 133:263-265, 1979 11. Madayag MA, Ambos MA, Lefleur RS, et al: Involve-

ment of the inferior vena cava in patients with renal cell carcinoma. Radiology 133:321-326, 1979 12. Clayman RV, Gonzalez R, Fraley EE: Renal cell cancer invading the inferior vena cava: Clinical review and anatomical approach. J Urol 123:157-163, 1980 13. Cherrie R J, Goldman DG, Linder A, et al: Prognostic implications ofvena caval extension of renal cell carcinoma. J Urol 128:910-912, 1982 14. Smith SJ, Bosniak MA, Megibow AJ, et al: Renal cell carcinoma: Earlier discovery and increased detection. Radiology 170:699-703, 1989 . 15. MeNichols DW, Segura JW, de Weerd JH: Renal cell carcinoma: Long-term survival and late recurrence. J Urol 126:17-23, 1981 16. Waters WB, Richie JP: Aggressive surgical approach to renal cell carcinoma: Review of 130 cases. J Urol 122:306-308, 1979 17. Virdi JS, Kelly DG: Prognostic value of renal venous involvement in renal carcinoma. Br J Uro169:481-485, 1992 18. Beahrs OH, Myers MH: Manual for Staging of Cancer. Philadelphia, PA, Lippincott, 1983 19. Parks CM, Kellett MJ: Staging renal cell carcinoma. Clin Radio149:223-230, 1994 20. Provet J, Tessler A, Brown J, et al: Partial nephrectomy for renal cell carcinoma: Indications, results and implications. J Urol 145:472-476, 1991 21. Noviek AC, Streem S, Montie JE, et al: Conservative

RENAL CELL CARCINOMA

surgery for renal cell carcinoma: A single-center experience with 100 patients. J Urol 141:835-839, 1989 22. Bracken RB: Renal carcinoma: Clinical aspects and therapy. Semin Roentgeno122:241-247, 1987 23. Krown SE: Therapeutic options in renal cell carcinoma. Semin Oncol 12:13-17, 1985 (suppl 5) 24. Ramsey J: Immunotherapy and chemotherapy for carcinoma of the kidney. Br J Urol 70:465-468, 1992 25. Rosenberg SA, Lotze MT, Yang JC, et al: Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 7:1863-1874, 1989 26. Lanigan D, Jurriaans E, Hammonds JC, et al: The current status of embolization in renal cell carcinoma--A survey of local and national practice. Clin Radiol 46:176178, 1992 27. Mebust WK, Weigel JW, Lee KR, et al: Renal cell carcinoma--angioinfarction. J Urol 131:231-235, 1984 28. Amendola MA, Bree RL, Pollack HM, et al: Small renal cell carcinomas: Resolving a diagnostic dilemma. Radiology 166:637-641, 1988 29. Birnbaum BA, Bosniak MA, Megibow AJ, et al: Observations on the growth of renal neoplasms. Radiology 176:695-701, 1990 30. Curry NS, Schabel SI, Betsill WL: Small renal neoplasms: Diagnostic imaging, pathologic features, and clinical course. Radiology 158:113-117, 1986 31. Bosniak MA: The small ( < 3 cm) renal parenchymal tumor: Detection, diagnosis and controversies. Radiology 179:307-317, 1991 32. Daniel WW, Hartman GW, Witten DM, et al: Calcified renal masses: A review of ten years' experience at the Mayo Clinic. Radiology 103:503-508, 1972 33. Weyman PJ, McClennan BL, Lee JKT, et al: CT of calcified renal masses. A JR 138:1095-1099, 1982 34. Bosniak MA: The current radiological approach to renal cysts. Radiology 158:1-10, 1986 35. Zeman RK, Cronan JJ, Rosenfield AT, et al: Renal cell carcinoma: Dynamic thin-section CT assessment of vascular invasion and tumor vascularity. Radiology 167:393396, 1988 36. Zeman RK, Fox SH, Silverman PM, et al: Helical (spiral) CT of the abdomen. AJR 160:719-725, 1993. 37. Silverman SG, Lee BY, Seltzer SE, et al: Small (_< 3 cm) renal masses: Correlation of spiral CT features and pathologic findings. AJR 163:597-605, 1994 38. Zagoria RJ, Wolfman NT, Karstaedt N, et al: CT features of renal cell carcinoma with emphasis on relation to tumor size. Invest Radiol 25:261-266, 1990 39. Strotzer M, Lehner KB, Becker K: Detection of fat in a renal cell carcinoma mimicking angiomyolipoma. Radiology 188:427-428, 1993 40. Helenon O, Chretien Y, Paraf F, et al: Renal cell carcinoma containing fat: Demonstration with CT. Radiology 188:429-430, 1993 41. Johnson CD, Dunnick NR, Cohan RH, et al: Renal adenocarcinoma: CT staging of 100 tumors. AJR 148:59-63, 1987 42. Levine E, Lee KR, Weigel J: Preoperative determination of abdominal extent of renal cell carcinoma by computed tomography. Radiology 132:395-398, 1979

147

43. Winfield AC, Gerlock AJ, Shaft MI: Perirenal cobwebs: A C T sign of renal vein thrombosis. J Comput Assist Tomogr 5:705-708, 1981 44. Roubidoux MA, Dunnick NR, Sostman HD, et al: Renal carcinoma: Detection of venous extension with gradient-echo MR imaging. Radiology 182:269-272, 1992 45. Levine E, Maklad NF, Rosentbal SJ, et al: Comparison of computed tomography and ultrasound in abdominal staging of renal cancer. Urology 16:317-322, 1980 46. Ramchandani P, Coleman BG, Pollack HM, et al: CT evaluation after radical nephrectomy for renal cell carcinoma. Radiology 181(P):125, 1991 (abstr) 47. Alter AJ, Uehiing DT, Zwiebel WJ: Computed tomography of the retroperitoneum following nephrectomy. Radiology 133:663-668, 1979 48. Murphy GP, Moore RH, Kenny GM: Current results from primary and secondary treatment of renal cell carcinoma. J Urol 104:523-527, 1970 49. Bernardino ME, deSantos LA, Johnson DE, et al: Computed tomography in the evaluation of post-nephrectomy patients. Radiology 130:183-187, 1979 50. Hricak H, Crooks L, Sheldon P, et al: Nuclear magnetic resonance imaging of the kidney. Radiology 146: 425-432, 1983 51. Semelka RC, Hricak H, Stevens SK, et al: Combined gadolinium-enhanced and fat-saturation MR imaging of renal masses. Radiology 178:803-809, 1991 52. Semelka RC, Shoenut JP, Kroeker MA, et al: Renal lesions: Controlled comparison between CT and 1.5-T MR imaging with nonenhanced and gadolinium-enhanced fatsuppressed spin-echo and breath-hold FLASH techniques. Radiology 182:425-430, 1992 53. Hricak H, Thoeni RF, Carroll PR, et al: Detection and staging of renal neoplasms: A reassessment of MR imaging. Radiology 166:643-649, 1988 54. Rofsky NM, Weinreb JC, Bosniak MA, et al: Renal lesion characterization with gadolinium-enhanced MR imaging: Efficacy and safety in patients with renal insufficiency. Radiology 180:85-89, 1991 55. Forman HP, Middleton WD, Melson GL, et al: Hyperechoic renal cell carcinomas: Increase in detection at ultrasound. Radiology 188:431-434, 1993 56. Yamashita Y, Ueno S, Makita O, et al: Hyperechoic renal tumors: Anechoic rim and intratumoral cysts in US differentiation of renal Cell carcinoma from angiomyolipoma. Radiology 188:179-182, 1993 57. Webb JAW, Murray A, Bary PR, et al: The accuracy and limitation of ultrasound in the assessment of venous extension in renal carcinoma. Br J Urol 60:14-17, 1987 58. Ghiatas AA, Bazan C, Brehm C, et al: Sonography versus MR imaging in the evaluation of the renal veins and inferior vena cava in renal malignancies. Radiology 189(P): 110, 1993 (abstr) 59. Mauro MA, Wadsworth DE, Stanley RJ, et al: Renal cell carcinoma: Angiography in the CT era. AJR 139:11351138, 1982 60. Simpson A, Baron MG, Mitty HA: Angiographic patterns of venous extension of hypernephroma. J Urol 111:441-444, 1974 61. Bracken B, Jonsson K: How accurate is angiographic staging of renal cell carcinoma? A JR 120:653-659, 1974

148

62. Buist TAS: Parasitic arterial supply to intracapsular renal cell carcinoma. AJR 120:653-659, 1974 63. Sherwood T, Trott PA: Needling renal cysts and tumors: Cytology and radiology. Br Med J 3:755-758, 1975 64. Helm CW, Burwood RJ, Harrison NW, et al: Aspiration cytology of solid renal tumors. Br J Urol 55:249-253, 1983 65. Bush WH, Burnett LL, Gibbons RP: Needle tract seeding of renal cell carcinoma. AJR 129:725-727, 1977

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66. Latour A, Shulman HS: Thoracic manifestations of renal cell carcinoma. Radiology 121:43-48, 1976 67. Rosen PR, Murphy KG: Bone scintigraphy in the initial staging of patients with renal cell carcinoma: Concise communication. J Nucl Med 25:289-291, 1984 68. Lindner A, Goldman DG, deKernion JB: Costeffective analysis of prenephrectomy radioisotope scans in renal cell carcinoma. Urology 22:127-129, 1983