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MAGING TEACHING CASE

Extensive Infiltrating Renal Cell Carcinoma With Minimal Distortion ofthe Renal Anatomy Mimicking Benign Renal Vein Thrombosis

Elizabeth M. Hecht, MD,1 Nicole Hindman, MD,1 William C. Huang, MD,2

Andrew B. Rosenkrantz, MD,1 and Jonathan Melamed, MD3

INDEX WORDS: Renal cell carcinoma; renal vein thrombosis; computed tomography; magneticresonance imaging.

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INTRODUCTION

Malignancies of the kidney can present withn infiltrative appearance and may include lym-homa; metastatic disease; epithelial tumors, suchs invasive transitional cell carcinoma; medul-ary carcinoma; renal sarcoma; and occasionally,ggressive renal cell carcinoma (RCC).1,2 Al-hough an infiltrative appearance is not commonor RCC, it can occur in up to 6% of cases.2

hese tumors do not present as discrete expan-ile masses, but instead show an infiltrative pat-ern of growth preserving the overall size andontour of the kidney. The normal internal archi-ecture of the kidney is replaced and obliteratedy tumor. This infiltrative appearance can evenimic benign infectious and inflammatory pro-

esses, such as bacterial and xanthogranuloma-ous pyelonephritis2 or benign renal vein throm-osis.In this case study, we discuss and compare the

maging features of infiltrative renal tumors andenal vein obstruction and discuss the potentialitfalls of diagnosis.

CASE REPORT

linical History and Initial LaboratoryData

A 45-year-old man with no significant medical or surgicalistory presented to the emergency department with flankain for 2 weeks and fever. Initial laboratory data, includingbasic metabolic panel, complete blood cell count, liver

nzymes, and lipase, were normal, including serum ureaitrogen level of 18 mg/dL (6.4 mmol/L) and serum creati-ine level of 1.3 mg/dL (114.9 �mol/L; estimated glomeru-ar filtration rate, 63 mL/min/1.73 m2 [1.1 mL/s/1.73 m2]).rothrombin time was mildly increased to 13.1 secondsreference range, 9.7-12.8 seconds), but international normal-zed ratio and partial thromboplastin time were normal.here was an increased erythrocyte sedimentation rate of 61m/h (reference range, 0-10 mm/h) and C-reactive protein

evel of 109 mg/L (reference, �10 mg/L). Urinalysis wasemarkable for high specific gravity �1.030 g/mL (refer-nce, �1.030 g/mL), and there were trace proteins in urine.

hysical examination findings were unremarkable, except

merican Journal of Kidney Diseases, Vol 55, No 5 (May), 2010: p

or temperature to 99.8°F. Urinalysis results were unremark-ble. On the basis of the computed tomographic (CT)ndings described next, a hematologic workup was per-ormed to determine whether the patient had an underlyingoagulopathy. Coagulation profile showed factor VIII levelf 170 IU/dL (normal, 65-150 IU/dL), but factor V, prothrom-in, protein C and S, antithrombin III, anticardiolipin antibod-es, dilute Russel viper venom screen, and activated protein

resistance assay results were normal. Based on CT find-ngs and laboratory data, the diagnosis of a benign renal veinhrombosis was believed to be most likely. The patient wasreated with anticoagulation therapy and discharged to homedays later. Two weeks later, the patient experienced wors-

ning abdominal pain and was readmitted.

magingStudies

Initial contrast-enhanced CT scan showed a thrombus inhe right renal vein that protruded slightly into the inferiorena cava (IVC). The right kidney was enlarged, with aelayed nephrogram and perinephric fat stranding withoutvidence of discrete renal mass and relatively normal corti-omedullary differentiation characteristic of acute renal veinbstruction (Fig 1A and B). CT scan repeated 2 weeks laterhowed no change in appearance of the kidney and renalein despite anticoagulation. Magnetic resonance imagingMRI) was performed 1 day later to exclude underlyingalignancy. On MRI, no internal enhancement was detected

n the thrombus, favoring a nontumoral thrombus, althoughhere was minimal disruption of the corticomedullary nephro-ram anteriorly (Fig 1C and D). The CT and MRI findings ofreserved corticomedullary differentiation with an extensiveonenhancing thrombus supported a diagnosis of a benignenal vein thrombosis. However, in the absence of a defini-ive underlying cause and because there was no evidence of

From the Departments of 1Radiology, 2Urology, andPathology, New York University Langone Medical Center,ew York, NY.Received May 15, 2009. Accepted in revised form Septem-

er 3, 2009. Originally published online as doi:10.1053/j.jkd.2009.09.030 on December 7, 2009.Address correspondence to Elizabeth M. Hecht, MD,

epartment of Radiology, University of Pennsylvania Healthystem, 3400 Spruce St, Philadelphia, PA 19104. E-mail:lizabeth.hecht@uphs.upenn.edu

© 2010 by the National Kidney Foundation, Inc.0272-6386/10/5505-0022$36.00/0

doi:10.1053/j.ajkd.2009.09.030

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esponse to anticoagulation therapy, additional workup, in-luding ureteroscopy and percutaneous biopsy, was recom-ended to exclude occult neoplasm. The patient refused,

nd instead, short-interval follow-up was recommended.he patient returned for MRI 2 months later. The follow-upRI showed enhancement within the renal vein thrombus

nd extension of the thrombus superiorly into the IVCithout involvement of the intrahepatic IVC. There also was

ncreasing disruption of the corticomedullary architecturend replacement of normal parenchyma with an abnormal-nhancing soft-tissue mass (Fig 2A-C). A retrograde uro-ram was obtained to exclude urothelial cancer, and nonderlying calyceal abnormality was found to suggest theresence of a transitional cell carcinoma.

iagnosis

The patient underwent radical right nephrectomy and IVChrombectomy. Pathologic examination showed a papillarytype 2) RCC infiltrating the renal parenchyma with involve-ent of the renal medulla, main renal vein, and IVC (Fig 2C

nd D).

linical Follow-up

The patient required a postoperative blood transfusionith 2 units of packed red blood cells, but otherwise experi-

nced no immediate complication and was discharged toome after 1 week on aspirin therapy. However, the patientas readmitted 1 week later with shortness of breath and

atigue. A left pleural effusion was found on a chest radio-raph, and the patient underwent thoracentesis, but no malig-ant cells were detected. A CT angiogram of the chesthowed a pulmonary embolism, and the patient was startedn anticoagulation therapy and discharged to home 6 daysater.

DISCUSSION

This case shows that an RCC occasionally canresent as an infiltrating mass with minimal to noisruption of the normal morphologic state of theidney, potentially simulating a benign process,uch as benign renal vein thrombosis. In thisase, the tumor was a type 2 papillary RCC,hich, in contradistinction to a type 1 papillaryeoplasm, presents more often as an aggressivenfiltrating soft-tissue mass.3 Papillary RCC ishe second most common RCC of the proximalenal tubules, accounting for 10%-15% of pri-ary renal neoplasms.4 Papillary RCCs are clas-

ified further into subtypes based on their nucleareatures and cytoplasmic content. Histologic dis-inction is important because compared with type, type 2 papillary RCCs present at a later stagend are associated with worse outcome.5 In gen-ral, at imaging, papillary RCC presents as a

Figure 1. Contrast-enhanced computed tomographiccan shows a thrombus in the right renal vein (solid arrow),nlargement of the right kidney, delayed nephrogram (pro-

onged corticomedullary phase), and perinephric strandingithout focal mass on (A) axial and (B) coronal reconstruc-

ions. Subsequent magnetic resonance imaging showsimilar findings with delayed enhancement of the rightidney on (C) nephrographic and urographic phases witho enhancement of the renal thrombus (solid arrow) con-rmed by subtraction (postcontrast data set � precontrastata set), (D) but some asymmetry in the corticomedullary

mall well-circumscribed mass showing low sig-

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al on T2-weighted MRI compared with renalarenchyma6 and enhances homogeneously onT scan and MRI, but to a lesser degree than theore common clear cell type RCC.7,8 However,

lear cell RCC shows high signal intensity com-ared with renal cortex on T2-weighted MRI andften is inhomogeneous and hypervascular com-ared with normal cortex on contrast-enhancedT scanning and/or MRI.6-8 Although cross-

ectional imaging characteristics are very helpfulor the detection of renal tumors and may evenuggest tumor type, histologic sampling is theold standard. As recommended in this case,ercutaneous biopsy of solid renal masses maye warranted in some cases to exclude benignesions, such as lipid poor angiomyolipomas, ornfection, to spare patients more aggressive treat-

Figure 2. Follow-up magnetic resonance imaging showoronal reconstruction of the postcontrast 3-dimensionalmages with replacement of normal parenchyma by tumor (onfirmed on a coronal subtraction image. (C) The subrientation to show the extension of thrombus into the supumor at imaging correlates well with the gross pathology.

ent.9 However, percutaneous biopsy is contra- fi

ndicated for lesions that could be urothelialarcinoma because of the higher incidence ofeeding of the biopsy tract.10 Urothelial carcino-as of the upper tract normally are diagnosed

sing urography and/or ureteroscopy.In this case example, the lack of a discrete

enal mass and lack of enhancement of the renalein thrombus made the correct imaging diagno-is difficult and led to an initial diagnosis ofenign renal vein thrombosis. Acute renal veinhrombosis may occur secondary to many causes,uch as a hypercoagulable state, for example,ephrotic syndrome related to membranous glo-erulonephritis, dehydration (in infants), trauma,

eoplasm, and infection.11 Imaging features in-lude a distended renal vein with an intraluminallling defect manifested by lack of contrast opaci-

ation of the right kidney (dotted arrow) on (A) axial and (B)ighted frequency selective fat suppressed gradient echoarrows) and new enhancing tumor thrombus (solid arrows)

image is presented in a slightly more oblique coronall inferior vena cava. (D) The infiltrative appearance of the

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cation and renal vein wall thickening.11 The

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bstructed venous outflow can lead to intrarenalnd perinephric edema, enlargement of the kid-ey, and abnormal enhancement manifested by atriated or delayed nephrogram (Fig 3).11 Nontu-oral or bland thrombus will not show internal

nhancement.When enhancement of the tumor thrombus in

he renal vein and extension of the thrombus intohe vena cava became evident on follow-up imag-ng, the diagnosis of malignancy was estab-ished. In this case, diagnostic considerationsther than RCC included lymphoma and transi-ional cell carcinoma. The latter essentially wasuled out by the retrograde pyelogram and onlyarely is associated with renal vein thrombosis.12

ymphoma characteristically encases vasculartructures without invasion, thereby distinguish-ng it from RCC.

The infiltrative soft-tissue mass itself was dif-cult to appreciate on initial scans. The cortico-edullary pattern of enhancement was preserved

nd simulated a delayed nephrogram comparedith the contralateral kidney, and this can be

een with renal obstruction. The relatively mildnhancement of the tumor compared with renalortex mimicked that of normal renal medulla. Ineneral, when imaging renal masses, particularlyelatively hypovascular renal masses, such asypovascular RCC and lymphoma, an optimizedmaging technique is critical. Postcontrast CTcanning or MRI in the nephrographic (venous)

Figure 3. Axial image from a contrast-enhanced com-uted tomographic scan shows similar imaging findings indifferent patient with acute benign (not associated with

umor) left renal vein thrombosis (arrowheads) caused bynderlying hematologic coagulopathy, which resolved withnticoagulation. Note that the right renal vein is patentdotted arrow). An incidental nonobstructing renal calculuss present in the left kidney (solid arrow).

hase of enhancement is essential for the detec- v

ion of small masses, especially those located inhe medullary portion of the kidney, because asn this case, they can be overlooked easily oristaken for unenhanced medulla in the cortico-edullary phase.13

Other renal tumors that also can present asnfiltrating masses that should be mentionedbut are less common and not primarily consid-red in this case) are renal sarcomas, carcino-arcoma, medullary tumors, and metastatic dis-ase. Primary renal sarcoma is an extremelyare tumor with a poor prognosis, and althoughbout half these tumors are leiomyosarcomasnd generally present as well-circumscribedesions, certain subtypes, such as rhabdomyo-arcoma, are infiltrative in their growth pat-ern.2 Carcinosarcoma is another extremelyare highly aggressive infiltrating neoplasmhat can arise from the renal pelvis, but moreommonly from the bladder. Medullary neo-lasms, such as collecting duct carcinoma, areggressive tumors characteristically centeredn the renal medulla and invading the renalinus, thus, mimicking invasive urothelial neo-lasms.2 Although the incidence of urothelialeoplasm is far more common, histologic dis-inction between a primary renal neoplasm asound in this case and urothelial cancer isssential because management differs, with theatter requiring nephroureterectomy and sur-eillance for synchronous tumors.2 Finally,etastatic disease only rarely presents as an

nfiltrating mass and in patients with knownrimary tumors, such as lung, breast, or gastro-ntestinal neoplasms.

In summary, this case illustrates that an infil-rating renal neoplasm may be difficult to detectt imaging because it may preserve the normalrchitecture of the kidney. In this clinical ex-mple, progression of the renal vein thrombusespite ongoing anticoagulation prompted con-ern for underlying tumor, even in the absence ofdiscernable mass, and biopsy was appropri-

tely recommended. When enhancement of thehrombus became evident and the thrombus ex-ended into the IVC, the diagnosis of malignancyas established. Thus, this case shows that an

nfiltrating neoplasm can simulate benign renal

ein thrombosis.

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ACKNOWLEDGEMENTSThe authors acknowledge Dr Morton A. Bosniak of New

ork University Langone Medical Center for his contribu-ion to the writing of this article.

Support: None.Financial Disclosure: None.

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