DOI:10.2214/AJR.07.3546
AJR 2008; 191:1239-1249
© American Roentgen Ray Society
Comparison of Contrast-Enhanced Sonography with Unenhanced Sonography and Contrast-Enhanced CT in the Diagnosis of Malignancy in Complex Cystic Renal Masses
Emilio Quaia1,
Michele Bertolotto,
Vincenzo Cioffi,
Alexia Rossi,
Elisa Baratella,
Riccardo Pizzolato and
Maria Assunta Cova
1 All authors: Department of Radiology, Cattinara Hospital, University of
Trieste, Strada di Fiume 447, 34149 Trieste, Italy.
Received December 14, 2007;
accepted after revision May 1, 2008.
Address correspondence to E. Quaia
(quaia{at}units.it).
Presented at the 2007 annual meeting of the American Roentgen Ray Society,
Orlando, FL.
Abstract
OBJECTIVE. The objective of our study was to evaluate
contrast-enhanced sonography in the diagnosis of malignancy in complex cystic
renal masses.
MATERIALS AND METHODS. We analyzed a series of 40 cystic renal
masses (diameter, 2–8 cm) with a complex pattern at contrast-enhanced CT
in 40 consecutive subjects (18 men, 22 women; mean age ± SD, 62
± 11 years). Each renal mass was scanned using sonography without
contrast material and after IV injection of sulfur hexafluoride–filled
microbubbles during the arterial (15–40 seconds) and venous
(40–120 seconds from injection) phases. Two radiologists in consensus
assessed onsite the enhancement patterns in the peripheral wall and
intracystic septa and the evidence of solid endocystic components. Three
blinded readers with 2, 6, and 10 years of experience in renal imaging
performed a retrospective off-site interpretation of unenhanced sonography,
contrast-enhanced sonography, and CT images and made a benign or malignant
diagnosis according to refer ence diagnostic criteria for contrast-enhanced
sonography and to the Bosniak classification for CT.
RESULTS. Final diagnoses comprised two multilocular cystic
nephromas, two inflammatory and seven hemorrhagic cysts, and eight
uncomplicated benign cysts and 21 cystic renal cell carcinomas. The overall
diagnostic accuracy of contrast-enhanced sonography was better than unenhanced
sonography and CT (contrast-enhanced sonography vs unenhanced sonography vs
CT: reader 1, 83% vs 30% vs 75%; reader 2, 83% vs 30% vs 63%; reader 3, 80% vs
30% vs 70%; p < 0.05, McNemar test).
CONCLUSION. Contrast-enhanced sonography was found to be better than
unenhanced sonography and CT in the diagnosis of malignancy in complex cystic
renal masses.
Keywords: Bosniak classification • microbubbles • renal cell carcinoma • renal cysts • renal masses • ultrasound contrast media
Introduction
Renal cysts are common incidental findings during the clinical diag nostic
workup of patients [1]. Renal
cysts frequently present an obvious simple cystic pattern at sonography or CT
and such cysts do not deserve any further imaging assessment or surgical
procedure. In some cases, however, renal cysts show a complex pattern and vary
in their malignant potential according to the number and thickness of
intracystic septations and the presence of mural nodules and peripheral
calcifications.
The Bosniak classification
[2,
3] cat ego rizes renal cysts
according to their CT features. Category I cysts are simple benign
fluid-containing cysts with the attenuation of water and thin walls without
septa or calcification. Category II cysts are minimally complicated benign
cysts with hairline-thin septa and fine calcifications in the walls or septa,
or segmental slightly thickened calcifications with or without minimal septal
or mural enhancement. High-attenuation, sharply marginated, completely
intrarenal, nonenhancing cystic masses 
3 cm are also included in this
category. Category IIF, with the "F" referring to follow-up, is
composed of more complex cystic lesions that cannot be classified as category
II or that are complex enough to be characterized as category III because they
may contain an increased number of septa and an increased amount of
calcifications in the walls or septa, which may be thicker and nodular;
high-attenuation, sharply marginated, completely intrarenal, nonenhancing
cystic masses > 3 cm are also included in this category. Category III are
indeterminate cystic masses whose benign or malignant nature cannot be
determined with imaging studies with thickened (> 2 mm) irregular walls or
septa that may appear hyperdense on unenhanced CT and may contain either small
or large amounts of calcification with septal or mural contrast enhancement.
Category IV cysts show either small or large amounts of calcifications within
a thickened, enhancing irregular wall or septum and present enhancing
soft-tissue nodular components adjacent to or extending from the wall or
septum.
The Bosniak classification is considered to be an accurate and efficient
method for treatment planning. Although the Bosniak classification scheme is
very useful for the clinical management of cystic renal masses, inter reader
variation in distinguishing between category II, IIF, and III lesions does
exist [4] and may present
problems in recommending surgical versus conservative management in some
cases. Moreover, CT may not reveal thin intra cystic septations due to volume
averaging, which limits identification of the renal cysts that deserve further
assessment by follow-up. MRI and CT reveal similar findings in most cystic
renal masses, even though MRI may depict additional septa, thickening of the
wall or septa, or enhancement that may lead to an upgraded Bosniak category
and can affect case management
[5].
The content of renal cysts typically appears more complex at sonography
than CT owing to the greater accuracy of sonography in depicting thin
intracystic septations and the corpus cular content due to hemorrhage or tumor
debris [1]. Contrast-enhanced
sonography with microbubbles
[6] has been shown to improve
the visualization of renal vessels
[7], to depict tumor
vascularity in solid renal masses
[7–11],
and to improve the sonographic detection of vascularity within the septations
and peri pheral wall of complex cystic renal masses
[7,
11]. Recently, a
classification and diagnostic workup scheme for cystic renal lesions that uses
contrast-enhanced sonography as the reference technique was proposed
[12,
13]. Contrast-enhanced sono
graphy is appropriate in the Bosniak classification of renal cysts and was
found to be superior to CT in detecting additional septa, thickening of the
wall or septa, and solid components
[14–16].
However, no previous study, to our know ledge, has described the diagnostic
impact of contrast-enhanced sonography on the char acterization and diagnostic
workup of com plex cystic renal masses. The aim of this study was to evaluate
contrast-enhanced sonography in the diagnosis of malignancy in complex cystic
renal masses.
Materials and Methods
Patients
This study was approved by the ethics committee, which is equivalent to an
institutional review board, at our institution and patient informed consent
was obtained after the procedure had been fully explained. From a computerized
search of our hospital database of radiologic records between May 2001 and May
2007 performed by one reference radiologist and then cross-referenced to the
histopathologic records, we identified a series of 55 subjects with 55 complex
cystic renal masses ranging from 2 to 8 cm in diameter (mean ± SD, 4.3
± 2.2 cm) that were incidentally detected during abdominal sonography
or CT (n = 35 patients) or during a clinical diagnostic workup
including sonography and CT of the kidneys and urinary tract for micro- or
macroscopic hematuria with or without flank pain (n = 20 patients).
All cystic renal masses revealed a complex pattern at the time of the initial
CT interpretation by the onsite radiologists, consisting of evidence of
thickened or hairlinethin intracystic septa or peripheral wall thickening >
2 mm or evidence of peripheral mural or septal nodules or calcifications.
From 3 to 25 days after detection, each renal mass was scanned using
contrast-enhanced sonography after injection of a suspension of
phospholipid-stabilized microbubbles filled with sulfur hexafluoride (SonoVue,
Bracco). Patients with simple cysts that had a hairline-thin wall and anechoic
content without septa or calcifications or those with complex renal cysts not
scanned by contrast-enhanced sonography were not included in the computerized
search.
We excluded 15 cystic renal masses in 15 pa tients because of suboptimal
quality of the CT study (lack of unenhanced or arterial corticomedullary phase
images in five patients) or of the contrast-enhanced sonography study (failure
in data storage or incomplete lesion visibility due to deep position or bowel
gas interposition in 10 patients). Therefore, 40 renal masses in 40 patients
(18 men, 22 women; mean age ± SD, 62 ± 11 years; median age, 64
years; age range, 29–84 years) were finally included in the study.
CT Examinations
At the time of detection, all cystic renal masses were scanned by
multiphase helical CT performed using either a single-detector scanner
(n = 21; TomoScan Ave1, Philips Healthcare) or an MDCT scanner
(n = 19; Aquilion, Toshiba Medical Systems). A beam collimation of 5
mm and a pitch factor of 1.5 were routinely used with the single-detector
scanner, and dedicated thinner sections of 3 mm with 1-mm slice overlap were
adopted for small masses (< 3 cm in diameter). MDCT data sets were acquired
with the following technical parameters: rotation time, 400 milliseconds; beam
collimation, 64 x 0.5 mm; normalized pitch, 1; reconstruction interval,
3 mm; tube voltage, 120 kVp; and tube current (effective mAs), 180–250
mAs, depending on patient size. Unenhanced images were acquired first.
Afterward, each patient received 120–140 mL (300–350 mg I/mL) of
nonionic iodinated contrast agent (iomeprol [Iomeron, Bracco]) at a rate of
2–3 mL/s followed by 50 mL of saline flush. Scanning delays were 30
seconds for the corticomedullary phase and 90–110 seconds for the
nephrographic phase.
Contrast-Enhanced Sonography Examinations
Two radiologists who have experience in sonography (2 and 8 years,
respectively) and were blinded to the findings of the reference procedures
were involved in the scanning. Patients were scanned with state-of-the-art
sonography digital equipment (Sequoia, Acuson–Siemens [n = 32
patients or EsaTune, Esaote [n = 8 patients]) using a 2–5-MHz
wideband convex-array transducer. Each lesion was scanned first using
unenhanced gray-scale sonography with noise- and speckle-reducing modes, such
as tissue harmonic and compound imaging, and then using color or power Doppler
sonography with spectral analysis of peripheral and intralesional tumoral
vessels. Doppler parameters were optimized to detect slow flow velocities: a
pulse repetition frequency of 700 Hz, medium wall filter, and
low-velocity-flow optimization. Color gain was raised until color noise became
evident and was then lowered slightly to clean the image.
Each renal mass was scanned after the injection of an IV bolus of
microbubbles (2.4 mL) followed by a 10-mL normal saline flush using a 20- or
22-gauge peripheral cannula. The technical parameters were as follows: Cadence
Contrast Pulse Sequencing (Acuson–Siemens Medical Solutions) (n
= 32 patients) or Contrast Tuned Imaging (Esaote) (n = 8) as
contrast-specific modes with sensitivity similar to microbubble harmonic
signal, low transmit power insonation (mechanical index, 0.09–0.14),
dynamic range of 65 dB, temporal resolution between frames of 75–100
milliseconds (10–13 frames per second), echo-signal gain below noise
visibility to allow the best visualization of the renal mass and adjacent
renal parenchyma, lowest possible frame rate (7–9 Hz), signal
persistence turned off, and one focus set immediately below the renal mass.
The arterial phase was timed from 10 to 40 seconds after microbubble
injection, after which the venous phase encompassed the time interval from 45
seconds after microbubble injection until the microbubbles disappeared.
Distinct digital cine clips for the unenhanced sonography and for the
arterial and venous phases of contrast-enhanced sonography were stored on a PC
(Pentium 4, Intel) connected to the sonography equipment by a high-performance
hardware-based real-time Moving Picture Experts Group-2 (MPEG-2) encoder
(MVR1000 card, Mediacruise software, Canopus) and frame-grabber software
(Mediacruise, Canopus). Cine clips were subsequently stored on DVDs after the
end of scanning.
Onsite Visual Analysis by Consensus
The digital cine clips of unenhanced sonography and contrast-enhanced
sonography were preliminarily reviewed onsite by the two radiologists involved
in scanning immediately after the end of the examination. The analysis was
performed on screen (Intel, Pentium 4 with 19-inch [48-cm] thin-film
transistor [TFT] display). The following features of each cystic renal mass
were recorded: size of the mass; the number of locules in the cyst; diffuse
wall or septal thickness 2 mm or > 2 mm; presence of septa (few or
multiple septa); presence of focal wall or septal thickening; presence and
size of solid endocystic components, including mural and septal nodules;
presence and size of calcifications; echogenicity of the cyst; and presence of
contrast enhancement of the peripheral wall or intracystic septa or evidence
of solid endocystic components after microbubble injection. A nodule, septum,
or wall was considered enhancing on visual analysis if there was evidence of
microbubbles traveling inside it. Discrepant interpretations were resolved by
consensus after involvement of an additional reader with similar experience in
contrast-enhanced sonography.
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Fig. 1A —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Evidence of contrast enhancement in hairline-thin
septa (< 2 mm).
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Fig. 1B —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Continuous or discontinuous enhancement of
peripheral wall.
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Fig. 1C —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Enhancement involving both peripheral wall and
hairline-thin intracystic septa.
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Fig. 1D —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Peripheral enhancing mural nodules.
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Fig. 1E —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Peripheral enhancing wall combined with thickened
enhancing septa (> 2 mm).
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Fig. 1F —Drawings show different vascularity profiles that may be
observed in complex cystic renal masses after microbubble contrast agent
injection. Profiles shown in A–C were considered diagnostic for
benignancy, whereas profiles shown in D–F were considered
diagnostic for malignancy. Peripheral thickened enhancing wall with thickened
enhancing septa and enhancing mural and septal nodules.
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Retrospective Off-Site Interpretation
The off-site independent review of unenhanced sonography, contrast-enhanced
sonography, and CT scans was performed by three independent readers who were
radiologists with 2, 6, and 10 years' experience in renal imaging and
affiliated with the center where the study was performed. The readers had not
been involved in the scanning and were blinded to patient identity, clinical
histor ies, histology results, and other imaging findings.
All readings of unenhanced sonography and contrast-enhanced sonography
digital cine clips were performed separately by each reader with a 1-day
interval on the same computer (Intel, Pentium 4 with 19-inch [48-cm] TFT
display and resolution of 2,560 x 1,600 pixels) at a central location
using PowerDVD software (CyberLink). During each session, a sequence of the
unenhanced sonography and contrast-enhanced sonography cine clips of the
different cystic renal masses was randomly assigned to each reader and any
patient-identifying information was masked. Readers were asked to express a
diagnosis of benignancy or malignancy for each complex cystic renal mass after
reviewing the unenhanced sonography and contrast-enhanced sonography cine
clips.
The malignancy criteria for unenhanced sonography included evidence of
thickened (> 2 mm) irregular wall or septa with or without gross
calcifications or mural or septal nodules with vascular signals on color or
power Doppler analysis. According to these criteria, the three readers rated
their diagnostic confidence on a 5-grade scale: 1, definitely benign, evidence
of hairline-thin intracystic septa; 2, probably benign, evidence of
hairline-thin intracystic septa with addition of fine calcifications in the
walls or septa; 3, indeterminate, increased number of septa or increased
amount of calcifications or corpusc ular echoic content; 4, probably
malignant, thick, irregular walls or septa; and 5, definitely malignant,
peripheral mural nodules with vascular signals at color Doppler analysis.
The malignancy criteria for contrast-enhanced sonography were developed
from previous studies [9,
12,
13,
15]. Figure
1A,
1B,
1C,
1D,
1E,
1F shows the different
vascularity profiles that may be observed in a complex cystic renal mass after
microbubble contrast agent injection. According to these criter ia, the three
readers rated their diagnostic confidence on a 5-grade scale: 1, definitely
benign, evidence of contrast enhancement in the hairline-thin septa or
continuous or discontinuous enhancement of the peripheral wall; 2, probably
benign, en hancement involving both the peripheral wall and the hair line-thin
intracystic septa; 3, indeter minate, limited or absent visibility of intra
cystic septa or mural nodules due to peripheral wall calcifications; 4,
probably malignant, peri pheral enhancing wall combined with thickened
enhancing septa; and 5, definitely malignant, evidence of peripheral enhancing
mural nodules or peripheral thickened enhancing wall with thickened enhancing
septa and enhancing mural and septal nodules.
Visual analysis of CT images was retrospectively performed by the same
readers 4 weeks after they had reviewed the digital cine clips recorded during
the sonography examination. All readings were performed separately by each
reader with a 1-day interval on a PACS-integrated workstation (19-inch [48-cm]
TFT display; resolu tion, 2,560 x 1,600 pixels; EbitAET, Esaote) at a
central location using a pro prietary soft ware pack age (EbitAET, Esaote).
The diagnostic criteria included evaluation of both unenhanced and
contrast-enhanced CT scans and corresponded to the Bosniak classification
system. Enhancement of the solid endocystic components was assessed by
measuring the region of interest on CT images, and enhancement was considered
present when attenuation increased by more than 15 HU. According to these
criteria, both readers rated their diagnostic confidence on a 5-grade scale:
definitely (grade 1) or probably (grade 2) benign for cystic renal masses
exhibiting a Bosniak I, II, or IIF pattern; indeterminate (grade 3) for those
with a Bosniak III pattern; probably (grade 4) or definitely (grade 5)
malignant for those exhibiting a Bosniak IV pattern.
Reference Standards for Diagnosis
The diagnosis and clinical management of the complex renal cysts were
determined by the findings at the time of the initial interpretation of the CT
scan. The cystic renal masses that were classified as Bosniak category III or
IV (n = 28) were surgically resected, whereas those classified as
Bosniak category IIF (n = 5) or II (n = 7) underwent imaging
follow-up consisting of CT alone or conventional sonography and CT for a
minimum of 12 months and a maximum of 24 months (mean follow-up time, 18
months). All follow-up examinations were interpreted by on-site radiologists
with at least 5 years' experience. The criteria used to assess the stability
of a mass were the absence of an increase in size, as measured on transverse
CT images, and the absence of morphologic and contrast-enhancement changes.
Cystic renal masses that showed morphologic changes at follow-up, including
the appearance of septal thickening or of mural and septal nodules (n
= 4), were surgically resected.
Statistical Analysis
A biostatistician participated in the statistical analysis performed by a
computer software package (Analyze-It, version 1.63, Analyze-It Software).
Sample size was determined with the assumption of an estimated diagnostic
accuracy of 85% and a 95% CI of 10%
[17]. Retrospective benign or
malignant diagnosis was considered true-positive (lesion correctly assessed as
malignant with confidence level of 4 or 5), false-negative (malignant lesion
incorrectly assessed as benign with confidence level of 1 or 2 or assessed as
indeterminate with confidence level of 3), true-negative (lesion correctly
assessed as benign with confidence level of 1 or 2), or false-positive (benign
lesion incorrectly assessed as malignant with confidence level of 4 or 5 or
assessed as indeterminate with confidence level of 3).
The weighted kappa statistic was calculated to assess interreader agreement
in diagnostic confidence for unenhanced sonography, contrast-enhanced
sonography, and CT. Agreement was graded as poor (
< 0.20), fair
(
0.20 and < 0.40), moderate ( 0.40 and < 0.60), good ( 0.60
and < 0.80), or very good ( 0.8–1). The McNemar test was used to
compare the sensitivity and specificity of unenhanced sonography,
contrast-enhanced sonography, and CT, whereas improvement in diagnostic
confidence was assessed using receiver operating characteristic (ROC) curve
analysis by plotting the sensitivity (true-positive fraction) against 1
– specificity (false-positive fraction). The area under each ROC curve
was calculated using a nonparametric method
[18], and the method proposed
by Hanley and McNeil [19] was
used to compare areas under each ROC curve. A p value < 0.05 was
considered to indicate a statistically significant difference.
Results
Onsite Visual Analysis by Consensus
Table 1 shows the final
diagnoses obtained by reference standard procedures. After microbubble
injection, benign lesions revealed peripheral wall enhancement involving
(n = 8) or not involving (n = 11) the intracystic septa
(Fig. 2A,
2B,
2C). Inflammatory and
hemorrhagic cysts revealed peripheral wall enhancement without any intracystic
septa (Fig. 3A,
3B,
3C). In multilocular cystic
nephromas, hairline-thin and thickened enhancing septa were observed together
with a thickened peripheral enhancing wall (Fig.
4A,
4B,
4C,
4D). After microbubble
injection, cystic renal cell carcinomas revealed peripheral enhancing mural
nodules with or without thickened enhancing septa (n = 3; Fig.
5A,
5B,
5C), thickened peripheral
enhancing wall combined with thickened enhancing intratumoral septa
(n = 9), or peripheral thickened enhancing wall with enhancing mural
and septal nodules (n = 9; Fig.
6A,
6B,
6C).
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Fig. 2A —Complex benign cystic renal mass (stable at 24-month
follow-up) on right kidney in 47-year-old woman. Longitudinal baseline
sonography image of right kidney shows 4-cm multiloculated cystic mass
(arrow) with several thin septa.
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Fig. 2B —Complex benign cystic renal mass (stable at 24-month
follow-up) on right kidney in 47-year-old woman. Longitudinal
contrast-enhanced sonography images obtained by contrast-specific mode Cadence
Contrast Pulse Sequencing (Acuson–Siemens Medical Solutions). Software
suppresses tissue background, with almost complete cancellation of intracystic
septa with evidence of only slight enhancement in thin intracystic septa
(arrow, B) during arterial phase (B). Cystic lesion
(arrow, C) was classified as benign after review of
contrast-enhanced sonography scan (C). Transverse contrast-enhanced CT
image of right kidney obtained during nephrographic phase shows evident septa
and intracystic septal calcification. Lesion was classified as Bosniak IIF
lesion. Cystic lesion underwent imaging follow-up on CT, which revealed no
increase in diameter and no change in morphology or contrast enhancement.
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Fig. 2C —Complex benign cystic renal mass (stable at 24-month
follow-up) on right kidney in 47-year-old woman. Longitudinal
contrast-enhanced sonography images obtained by contrast-specific mode Cadence
Contrast Pulse Sequencing (Acuson–Siemens Medical Solutions). Software
suppresses tissue background, with almost complete cancellation of intracystic
septa with evidence of only slight enhancement in thin intracystic septa
(arrow, B) during arterial phase (B). Cystic lesion
(arrow, C) was classified as benign after review of
contrast-enhanced sonography scan (C). Transverse contrast-enhanced CT
image of right kidney obtained during nephrographic phase shows evident septa
and intracystic septal calcification. Lesion was classified as Bosniak IIF
lesion. Cystic lesion underwent imaging follow-up on CT, which revealed no
increase in diameter and no change in morphology or contrast enhancement.
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Fig. 3B —Complex renal mass on right kidney in 55-year-old man.
Transverse contrast-enhanced sonography image obtained by contrast-specific
mode Cadence Contrast Pulse Sequencing (Acuson–Siemens Medical
Solutions) shows discontinuous enhancement in peripheral thickened wall
(arrow) sparing cystic portion of lesions. Lesion was classified as
benign according to contrast-enhanced sonography vascularity pattern.
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Fig. 3C —Complex renal mass on right kidney in 55-year-old man.
Coronal reformation from contrast-enhanced CT image of right kidney obtained
during nephrographic phase shows evident cystic pattern with peripheral wall
thickening (> 2 mm) (arrow). Lesion was classified as Bosniak III
lesion and was considered indeterminate at retrospective CT analysis.
Histologic analysis of surgical specimen revealed complicated hemorrhagic
cyst.
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Fig. 4B —Complex renal mass on right kidney in 32-year-old woman.
Transverse contrast-enhanced sonography images obtained by contrast-specific
mode Contrast Tuned Imaging (Esaote) show contrast enhancement in both
peripheral wall (arrows, B; large arrow, C)
and hairline-thin intracystic septa (small arrow, C) during
arterial phase. Lesion was classified as benign according to contrast-enhanced
sonography vascularity pattern.
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Fig. 4C —Complex renal mass on right kidney in 32-year-old woman.
Transverse contrast-enhanced sonography images obtained by contrast-specific
mode Contrast Tuned Imaging (Esaote) show contrast enhancement in both
peripheral wall (arrows, B; large arrow, C)
and hairline-thin intracystic septa (small arrow, C) during
arterial phase. Lesion was classified as benign according to contrast-enhanced
sonography vascularity pattern.
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Fig. 4D —Complex renal mass on right kidney in 32-year-old woman.
Transverse contrast-enhanced CT image of right kidney obtained during
nephrographic phase shows thickened enhancing wall (arrow). Lesion
was classified as Bosniak category III lesion and was considered indeterminate
at retrospective CT analysis. Histologic analysis of surgical specimen
revealed multilocular cystic nephroma. (Reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25])
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Fig. 5A —Complicated malignant cystic renal mass on right kidney in
58-year-old man. (B and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Longitudinal baseline
sonography image shows solidlike mass (arrow) in lower pole of right
kidney.
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Fig. 5B —Complicated malignant cystic renal mass on right kidney in
58-year-old man. (B and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Contrast-enhanced
sonography image of right kidney obtained by contrast-specific mode Contrast
Tuned Imaging (Esaote)shows 6-cm uniloculate cystic mass with several
enhancing mural nodules (arrows). Lesion was classified as malignant
according to contrast-enhanced sonography vascularity pattern.
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Fig. 5C —Complicated malignant cystic renal mass on right kidney in
58-year-old man. (B and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Transverse
contrast-enhanced CT image of right kidney obtained during nephrographic phase
shows complex renal mass with peripheral enhancing mural nodules
(arrow). Lesion was classified as malignant according to Bosniak
classification. Histologic analysis of surgical specimen revealed cystic clear
cell renal cell carcinoma.
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Fig. 6A —Complicated malignant cystic renal mass on left kidney in
78-year-old man. (A and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Oblique
contrast-enhanced sonography images of left kidney obtained by
contrast-specific mode Contrast Tuned Imaging (Esaote) show 8-cm
multiloculated cystic mass with several enhancing thickened septa, mural
nodules (arrows, A), and septal nodules. Lesion was classified
as malignant according to contrast-enhanced sonography vascularity
pattern.
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Fig. 6B —Complicated malignant cystic renal mass on left kidney in
78-year-old man. (A and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Oblique
contrast-enhanced sonography images of left kidney obtained by
contrast-specific mode Contrast Tuned Imaging (Esaote) show 8-cm
multiloculated cystic mass with several enhancing thickened septa, mural
nodules (arrows, A), and septal nodules. Lesion was classified
as malignant according to contrast-enhanced sonography vascularity
pattern.
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Fig. 6C —Complicated malignant cystic renal mass on left kidney in
78-year-old man. (A and C reprinted with permission from Quaia
E, ed. Contrast media in ultrasonography: basic principles and clinical
applications. Heidelberg, Germany: Springer-Verlag, 2005
[25]) Transverse
contrast-enhanced CT image of left kidney obtained during nephrographic phase
shows complex renal mass (arrow) with thickened enhancing septa.
Lesion was classified as malignant according to Bosniak classification.
Histologic analysis of surgical specimen revealed cystic clear cell renal cell
carcinoma.
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Retrospective Off-Site Interpretation
Table 2 shows the results of
the retrospective image interpretation of unenhanced sonog raphy,
contrast-enhanced sonography, and CT. Two (according to reader 1), 10 (reader
2), and four (reader 3) cystic renal masses, respect ively, were correctly
classified as benign after review of the contrast-enhanced sonog raphy scans,
whereas the same renal masses were classified as indeterminate after review of
the CT images. On the other hand, one (according to reader 3) or two (readers
1 and 2) cystic renal masses were correctly characterized as malignant after
review of the contrast-enhanced sonog raphy scans, which showed a solid
enhancing mural nodule missed at CT. After review of the contrast-enhanced
sonog raphy scans, all readers misclassified two benign cystic renal
masses—corresponding to multilocular cystic nephromas—with
evidence of en hancing peripheral wall and thickened intracystic septations
and one (according to reader 3) or three (readers 1 and 2) malignant renal
masses with diffuse mural calcifications, which limited visibility of the
enhancing peripheral wall, mural nodules, and intracystic septa. The same
cystic renal masses were classified as Bosniak category IIF or III after
review of the CT scans.
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TABLE 2: Off-Site Retrospective Analysis: Diagnostic Performance and Confidence
for Contrast-Enhanced Sonography and CT for the Three Different
Readers
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Contrast-enhanced sonography was bet ter than unenhanced sonography in both
diagnostic performance and confidence (p < 0.05) for all readers.
Contrast-enhanced sonography had a higher diagnostic per
formance—sensitivity, specificity, positive and negative predictive
values, and overall accuracy—than CT (p < 0.05) for all
readers except for reader 3 who showed the same value of sensitivity for
contrast-enhanced sonography and CT. Contrast-enhanced sono g raphy and CT
yielded similar diagnos tic confidence (p > 0.05) for all readers
with a high value of the area under the ROC curve (Fig.
7A,
7B,
7C).
Table 3 shows interreader agree
ment in the characterization of cystic renal tumors on unenhanced sonography,
contrast-enhanc ed sonography, and CT.
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Fig. 7A —Graphs show receiver operating characteristic (ROC) curve
analyses for individual readers for CT (dotted line),
contrast-enhanced sonography (solid line), and baseline sonography
(dashed line). Diagonal gray line represents hypothetical technique
that is unable to distinguish malignant from benign cystic renal masses.
Graphs show ROC curves for readers 1 (A), 2 (B), and 3
(C). Area under each ROC curve expresses each reader's diagnostic
confidence in diagnosis of malignancy. Difference in diagnostic confidence
between contrast-enhanced sonography and CT was not statistically
significant.
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Fig. 7B —Graphs show receiver operating characteristic (ROC) curve
analyses for individual readers for CT (dotted line),
contrast-enhanced sonography (solid line), and baseline sonography
(dashed line). Diagonal gray line represents hypothetical technique
that is unable to distinguish malignant from benign cystic renal masses.
Graphs show ROC curves for readers 1 (A), 2 (B), and 3
(C). Area under each ROC curve expresses each reader's diagnostic
confidence in diagnosis of malignancy. Difference in diagnostic confidence
between contrast-enhanced sonography and CT was not statistically
significant.
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Fig. 7C —Graphs show receiver operating characteristic (ROC) curve
analyses for individual readers for CT (dotted line),
contrast-enhanced sonography (solid line), and baseline sonography
(dashed line). Diagonal gray line represents hypothetical technique
that is unable to distinguish malignant from benign cystic renal masses.
Graphs show ROC curves for readers 1 (A), 2 (B), and 3
(C). Area under each ROC curve expresses each reader's diagnostic
confidence in diagnosis of malignancy. Difference in diagnostic confidence
between contrast-enhanced sonography and CT was not statistically
significant.
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TABLE 3: Interreader Agreement in the Characterization of Cystic Renal Tumors on
Unenhanced Sonography, Contrast-Enhanced Sonography, and CT
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Discussion
Sonography is very effective in revealing the cystic component of a renal
mass, even though it is limited in the characterization of complex renal cysts
[1]. Contrast-enhanced
sonography with microbubbles was recently proposed for the characterization of
complex renal cysts
[7–10,
12,
13]. Microbubble contrast
agents are true intravascular agents and have a short lifetime (< 10
minutes) and, not being nephrotoxic, can be administered to patients with
renal insufficiency. Microbubble contrast agents have been widely used in the
heart and liver, whereas their use in the kidney has been less exhaustively
studied because of the multiple competing imaging techniques that allow
complete assessment of renal pathology. A classification and workup scheme
based on contrast-enhanced sonography as the reference technique has recently
been proposed for renal cystic lesions
[12,
13], in which the absence of
enhancement after microbubble injection implies no further workup, whereas
evidence of thickened septations or mural nodules with contrast enhancement
after microbubble injection is considered a reliable criterion for
malignancy.
The results of our study confirm that benign and malignant complex renal
cysts present typical enhancement patterns at contrast-enhanced sonography
[14–16].
In cases of malignancy, the peripheral wall or intratumoral septa and the
mural or septal nodules mainly revealed intense contrast enhancement after
microbubble injection. Some minimal septal enhancement may also occur in
benign cystic renal lesions, although a few microbubbles traveling in the
septa are unlikely to represent a malignancy. In our series, evidence of
microbubbles in the peripheral wall or septa led to the misdiagnosis of two
benign renal cysts. Also multilocular cystic nephromas revealed hairline-thin
and thick enhancing septa with peripheral wall enhancement and were
misclassified as malignant after review of contrast-enhanced sonography scans.
Inflammatory or hemorrhagic cysts showed exclusively a peripheral enhancing
regular wall and were not misdiagnosed because they did not reveal intracystic
septations. Cystic renal masses with diffuse mural calcification were
misdiagnosed because of the impossibility of assessing the cystic content and
intracystic components at sonography. Malignant cystic renal masses revealed
peripheral wall enhancement, even though this finding was always associated
with thickened enhancing intratumoral septa or with enhancing mural and septal
nodules.
The Bosniak classification of the appearance of renal cysts at CT is
accurate for predicting malignancy at contrast-enhanced CT
[2,
3], and the presence of either
nodular or septal enhancement has shown the highest diagnostic accuracy
[20]. However, there is a
problem in confidently diagnosing cystic renal masses that were classified as
Bosniak category III at CT
[20,
21]. Several invasive methods
have been proposed to address this problem, including laparoscopic evaluation
with biopsy of the mass [22]
and CT-guided biopsy [23]. All
of these diagnostic methods are invasive, and use of a noninvasive imaging
technique that could increase the diagnostic confidence of CT is
advocated.
In our study, contrast-enhanced sonography had superior diagnostic accuracy
in comparison with CT and improved the characterization of complex renal cysts
that had been classified as indeterminate at CT. This finding was due to the
discrepancy between CT and contrast-enhanced sonography in depicting septal
vascularity and may be explained by the high sensitivity of contrast-enhanced
sonography both in detecting microbubble signals in the peripheral wall or in
the intracystic septa and in revealing the solid enhancing component in the
renal cysts that was not shown by CT. The high sensitivity of
contrast-enhanced sonography is determined by the contrast-specific techniques
that suppress the signals from the stationary tissues and enhance the harmonic
signals produced by the microbubbles. However, the same high sensitivity of
the microbubble signal from contrast-enhanced sonography led to the
misclassification of a minority of benign cystic renal masses with enhancing
peripheral wall and thickened intracystic septa.
Differently from the previous studies
[14,
16] in which investigators
described the capabilities of contrast-enhanced sonography compared with CT in
the classification of complex cystic renal masses with the Bosniak system
[2,
3], in our study we used an
independent diagnostic classification system for contrast-enhanced sonography
that was based on the enhancement patterns involving or not involving the
peripheral wall, the intracystic septa, and the mural or septal nodules. We
consider this independent classification system necessary because of the
higher sensitivity to contrast provided by contrast-enhanced sonography
compared with CT, which results from the different physical principles and
pharmacokinetic properties of microbubbles versus iodinated contrast agents
(resonance phenomenon vs x-ray attenuation; blood-pool distribution vs leakage
in the interstitial space).
Interreader agreement was progressively lower in contrast-enhanced
sonography according to the increasing difference in reader experience, which
indicates that a learning curve in image interpretation must be considered in
contrast-enhanced sonography. On the other hand, the interreader agreement was
moderate also in the analysis of the CT images in which the Bosniak
classification system was used. This was determined by the 19 cases that were
classified as Bosniak category IIF or III in which the interreader variation
is known to be quite high [4,
24]. Moreover, on
contrast-enhanced sonography the diffuse mural calcifications in some cystic
renal masses prevented the thickness of the wall or septa (or both) from being
evaluated because of back-shadowing. Therefore, meticulous evaluation is
necessary for lesions showing diffusely calcified septa or wall on
contrast-enhanced sonography images.
According to the results of this study, contrast-enhanced sonography should
be used to evaluate every renal mass with a complex cystic appearance at
unenhanced sonography provided that the lesion can be explored adequately. CT
should be used for staging complex cystic renal masses that reveal a malignant
enhancement pattern at contrast-enhanced sonography. A cystic renal mass
exhibiting an enhancing peripheral wall and thickened intracystic septa or
mural nodules (or both) after microbubble injection should be considered
malignant. Contrast-enhanced sonography should be considered an alternative to
CT [23] in the follow-up of
complex renal cysts whenever these cysts can be adequately evaluated with
contrast-enhanced sonography. Contrast-enhanced sonography can be used in the
char acterization of complex cystic renal masses in patients with renal
insufficiency and with contraindications to contrast-enhanced CT or MRI.
However, contrast-enhanced sonography presents some clear limitations due to
deep lesion location and bowel gas interposition that limit the visibility of
the enhancement pattern after microbubble injection.
The present study has some limitations. First, its retrospective nature
limits extrapolation of the results to a clinical setting. Second, the
analysis of contrast en hancement was merely visual and quantitative analysis
of the solid portion of each cystic renal mass was not performed. Quantitative
analysis could allow a more reproducible study of peripheral or septal
enhancement. Third, the number of lesions included was relatively small, but
this is because complex renal masses are infrequently identified. Fourth, not
all diagnoses were confirmed pathologically.
In conclusion, contrast-enhanced sonography allows reliable
characterization of indeterminate cystic renal masses, and in this study it
was found to perform better than unenhanced sonography and CT in the diagnosis
of malignancy in complex cystic renal masses.
References
- Hélénon O, Correas JM, Balleyguier C, Ghoudani M,
Cornud F. Ultrasound of renal tumors. Eur Radiol2001; 11:1890
–1901[CrossRef][Medline]
- Bosniak MA. The current radiological approach to renal cysts.
Radiology 1986;158
: 1–10[Abstract/Free Full Text]
- Bosniak MA. Difficulties in classifying cystic lesions of the
kidney. Urol Radiol 1991;13
: 91–93[Medline]
- Siegel CL, McFarland EG, Brink JA, Fisher AJ, Humphrey P, Heiken
JP. CT of cystic renal masses: analysis of diagnostic performance and
interobserver variation. AJR 1997;169
: 813–818[Abstract/Free Full Text]
- Israel G, Hindman N, Bosniak MA. Evaluation of cystic renal masses:
comparison of CT and MR imaging by using the Bosniak classification system.
Radiology 2004;231
: 365–371[Abstract/Free Full Text]
- Correas JM, Claudon M, Tranquart F, Hélénon O.
Contrast-enhanced ultrasonography: renal applications [in French].
J Radiol 2003;84
(12 Pt 2):2041
–2054[Medline]
- Correas JM, Claudon M, Tranquart F, Hélénon AO. The
kidney: imaging with microbubble contrast agents. Ultrasound
Q 2006; 22:53
–66[Medline]
- Ascenti G, Gaeta M, Magno C, et al. Contrast-enhanced
second-harmonic sonography in the detection of pseudocapsule in renal cell
carcinoma. AJR 2004;182
:1525
–1530[Abstract/Free Full Text]
- Quaia E, Siracusano S, Bertolotto M, Monduzzi M, Mucelli RP.
Characterization of renal tumours with pulse inversion harmonic imaging by
intermittent high mechanical index technique: initial results. Eur
Radiol 2003; 13:1402
–1412[Medline]
- Tamai H, Takiguchi Y, Oka M, et al. Contrast-enhanced
ultrasonography in the diagnosis of solid renal tumors. J
Ultrasound Med 2005; 24:1635
–1640[Abstract/Free Full Text]
- Kim AY, Kim SH, Kim YJ, Lee IH. Contrast-enhanced power Doppler
sonography for the differentiation of cystic renal lesions: preliminary study.
J Ultrasound Med 1999;18
: 581–588[Abstract]
- Robbin ML. Ultrasound contrast agents: a promising future.
Radiol Clin North Am 2001;39
: 399–414[CrossRef][Medline]
- Robbin ML, Lockhart ME, Barr RG. Renal imaging with ultrasound
contrast: current status. Radiol Clin North Am2003; 41:963
–978[CrossRef][Medline]
- Bertolotto M, Barozzi L, Valentino M, et al. Evaluation of cystic
renal masses with contrast-enhanced US comparison with CT. In:
Radiological Society of North America scientific assembly and
annual meeting program. Oak Brook, IL: Radiological Society of
North America, 2006:404
–405
- Park BK, Kim B, Kim SH, Ko K, Lee HM, Choi HY. Assessment of cystic
renal masses based on Bosniak classification: comparison of CT and
contrast-enhanced US. Eur J Radiol 2007;61
: 310–314[CrossRef][Medline]
- Ascenti G, Mazziotti S, Zimbaro G, et al. Complex cystic renal
masses: characterization with contrast-enhanced US.
Radiology 2007;24
: 158–165
- Eng J. Sample size estimation: how many individuals should be
studied? Radiology 2003;227
: 309–313[Abstract/Free Full Text]
- Beck JR, Shultz EK. The use of relative operating characteristic
(ROC) curves in test performance evaluation. Arch Pathol Lab
Med 1986; 110:13
–20[Medline]
- Hanley JA, McNeil BJ. A method of comparing the areas under
receiver operating characteristic curves derived from the same cases.
Radiology 1983;148
: 839–843[Abstract/Free Full Text]
- Benjaminov O, Atri M, O'Malley M, Lobo K, Tomlinson G. Enhancing
component on CT to predict malignancy in cystic renal masses and interobserver
agreement of different CT features. AJR2006; 186:665
–672[Abstract/Free Full Text]
- Harisinghani MG, Maher MM, Gervais DA, et al. Incidence of
malignancy in complex cystic renal masses (Bosniak category III): should
imaging-guided biopsy precede surgery? AJR2003; 180:755
–758[Abstract/Free Full Text]
- Limb J, Santiago L, Kaswick J, Bellman GC. Laparoscopic evaluation
of indeterminate renal cysts: long term follow-up. J
Endourol 2002; 16:79
–82[CrossRef][Medline]
- Lang EK, Macchia RJ, Gayle B, et al. CT-guided biopsy of
indeterminate renal cystic masses (Bosniak 3 and 2F): accuracy and impact on
clinical management. Eur Radiol 2002;12
:2518
–2524[Medline]
- Israel GM, Bosniak MA. Follow-up CT of moderately complex cystic
lesions of the kidney (Bosniak category IIF). AJR2003; 181:627
–633[Abstract/Free Full Text]
- Quaia E, ed. Contrast media in ultrasonography: basic
principles and clinical applications. Heidelberg, Germany:
Springer-Verlag, 2005
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S. Romano
Radiology in Italy: What Is Happening?
Am. J. Roentgenol.,
October 1, 2009;
193(4):
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Abstract
Introduction
