G Model EURR-6709; No. of Pages 5
ARTICLE IN PRESS European Journal of Radiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors S. Sevcenco a,1 , G. Heinz-Peer b,2 , L. Ponhold b,2 , D. Javor b,2 , F.E. Kuehhas a,1 , H.C. Klingler a,1 , M. Remzi a,3 , P. Weibl a,1 , S.F. Shariat a,1 , P.A. Baltzer b,∗ a b
Medical University of Vienna, Dept. of Urology, Waehringer Gürtel 18-20, 1090 Vienna, Austria Medical University of Vienna, Dept. of Biomedical Imaging and Image-guided Therapy, Waehringer Gürtel 18-20, 1090 Vienna, Austria
a r t i c l e
i n f o
Article history: Received 7 November 2013 Received in revised form 21 February 2014 Accepted 27 February 2014 Keywords: Renal carcinoma Renal mass MRI DWI ADC Papillary
a b s t r a c t Objective: To investigate utility and limitations of 3-Tesla diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiation of benign versus malignant renal lesions and renal cell carcinoma (RCC) subtypes. Materials and methods: Sixty patients with 71 renal lesions underwent 3 Tesla DW-MRI of the kidney before diagnostic tissue confirmation. The images were retrospectively evaluated blinded to histology. Single-shot echo-planar imaging was used as the DW imaging technique. Apparent diffusion coefficient (ADC) values were measured and compared with histopathological characteristics. Results: There were 54 malignant and 17 benign lesions, 46 lesions being small renal masses ≤4 cm. Papillary RCC lesions had lower ADC values (p = 0.029) than other RCC subtypes (clear cell or chromophobe). Diagnostic accuracy of DW-MRI for differentiation of papillary from non-papillary RCC was 70.3% resulting in a sensitivity and specificity of 64.3% (95% CI, 35.1–87.2) and 77.1 (95% CI, 59.9–89.6%). Accuracy increased to 83.7% in small renal masses (≤4 cm diameter) and sensitivity and specificity were 75.0% and 88.5%, respectively. The ADC values did not differ significantly between benign and malignant renal lesions (p = 0.45). Conclusions: DW-MRI seems to distinguish between papillary and other subtypes of RCCs especially in small renal masses but could not differentiate between benign and malignant renal lesions. Therefore, the use of DW-MRI for preoperative differentiation of renal lesions is limited. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Renal cell carcinoma (RCC) survival is improving because of both improved therapeutic strategies and early detection through the increased use of imaging studies [1]. New imaging techniques have
∗ Corresponding author. Tel.: +43 1 40 400 4818; fax: +43 1 40 400 2332. E-mail addresses: [email protected] (S. Sevcenco), [email protected] (G. Heinz-Peer), [email protected] (L. Ponhold), [email protected] (D. Javor), [email protected] (F.E. Kuehhas), [email protected] (H.C. Klingler), [email protected] (M. Remzi), [email protected] (P. Weibl), [email protected] (S.F. Shariat), [email protected] (P.A. Baltzer). 1 Tel.: +43 1 40 400 2616; fax: +43 1 40 400 2601. 2 Tel.: +43 1 40 400 4818; fax: +43 1 40 400 2323. 3 Wiener Ring 3-5, 2100 Korneuburg. Tel.: +43 2262/9004 5740; fax: +43 2262/9004 2850.
also led to an increased detection of incidental renal tumours [2], most of which are 0.05). The ADC differences between papillary and non-papillary RCC was also significant in small renal masses (p = 0.011) revealing
Fig. 2. Example of a 69-year-old male patient showing an irregular mass on the right kidney (white arrows), which was histopathologically diagnosed as clear cell renal carcinoma. (A) b0 s/mm2 image, (B) b1000 s/mm2 image, (C) fat saturated T2-weighted turbo spin echo image, (D) apparent diffusion coefficient (ADC) map (×10−6 mm2 /s). ADC value was measured as 1031 × 10−6 mm2 /s.
Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
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ARTICLE IN PRESS
EURR-6709; No. of Pages 5
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4
Fig. 3. Apparent diffusion coefficient value (×10−6 mm2 /s) distribution demonstrates no significant differences between RCC lesion Fuhrmann grades.
an area under the ROC curve for diagnosis of papillary RCC of 0.837 (p = 0.004); at an ADC cut-off value of ≤0.954 × 10−6 mm2 /s, sensitivity and specificity were 75.0% (95% CI, 34.9–96.8) and 88.5 (95% CI, 69.8–97.6%), respectively. 4. Discussion DW-MRI has been used for differentiating between renal lesions and the RCC subtypes, but our results showed that DW-MRI was not accurate enough to differentiate benign from malignant renal lesions and thus cannot overcome the problem of pre-therapeutic differentiation of renal masses into benign versus malignant. We found a significantly differentiation in ADC values between solid and non-solid lesions but not between benign and malignant renal lesions (p = 0.45, Table 2). In a previous study, Zhang et al. found that ADC values were significantly lower in the solid tissues of renal tumours than in the cystic/necrotic subparts of renal tumours and in benign cysts Table 2 Apparent diffusion coefficients for different lesion subtypes. Lesion type
n
ADC (mean ± SD) (×10−6 mm2 /s)
Malignant Clear cell RCC Papillary RCC Chromophobic RCC Upper tract urothelial carcinoma
54 29 15 6 4
1250 1380 1016 1239 1209
± ± ± ± ±
493 566 377 334 81
1209, 631 1361, 669 920, 607 1249, 533 1221, 151
Benign Oncocytoma Angiomyolipoma Other benign
17 10 3 4
1376 1603 828 1219
± ± ± ±
613 636 227 503
1363, 742 1482, 553 737, n.a. 1036, 880
Renal parenchyma
71
1776 ± 145
RCC, renal cell carcinoma.
ADC (median, IQR) (×10−6 mm2 /s)
1782, 129
[9], suggesting that DW-MRI might allow differentiation between solid and non-solid lesions. In this study, we concentrated on the solid subparts and did not find any ADC differences between benign and malignant renal lesions. In contrast, Taouli et al. [11] investigated 28 RCC and 81 benign lesions, including 49 benign cysts (Bosniak categories I and II). Considering these benign cysts in an approach similar to investigations by Wang et al. and Inci et al., the authors reported the ability to differentiate between benign and malignant lesions [10,11,14]. Non-complicated cysts are straightforward to identify by imaging and do seldom pose a problem for differential diagnosis [17]. Such lesions do obviously present with high ADC values due to their content of free water. Inclusion of simple cysts explains the differences found by the listed publications and the discrepancy with our study which is due to a selection bias. Reported ADC values showed inconsistent absolute numbers across these studies and, furthermore, overlaps between benign and malignant tumours were observed. Our study does not support the previous data suggesting accurate differentiation of benign tumours versus malignant tumours. As outlined above, our patient group might better reflect the real clinical task as obvious benign cysts were not included. Of interest, Taouli et al. support our findings as they did not find significant differences between the solid parts of cystic RCCs and solid RCCs or between the cystic part of RCCs and benign cysts [11]. Inconclusive results regarding RCCs subtype differentiation have been reported [10,11,16]. Higher mean ADC values were found in clear cell RCC versus papillary and chromophobe at b values of 0 and 800 s/mm2 [10]. By contrast, Razek et al. found similar ADC values for papillary and clear cell RCC, but could still differentiate these malignant entities from other malignant tumours [16]. Our results show significantly lower ADC values in papillary RCC compared to non-papillary renal lesions. Papillary RCC has generally a better prognosis than clear cell RCC [18]. This finding may be explained by higher cellularity of the papillary RCC tumour subtype; the cell density restricts the Brownian
Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
G Model EURR-6709; No. of Pages 5
ARTICLE IN PRESS S. Sevcenco et al. / European Journal of Radiology xxx (2014) xxx–xxx
motion of the water molecules within the tumour. However, previous work did not find strong or significant correlations here [13]. Furthermore, perfusion effects may increase ADC values: lower perfusion in papillary RCC has been suggested as a possible cause of low ADC values in papillary RCC [11]. Of note, although data is in parts inconsistent, contrast enhanced MRI has been described as diagnostic for diagnosis RCC subtypes [19–21]. In small renal masses, such differentiation was even better, possibly due to confounding structural changes (i.e. regressive changes) in advanced renal malignancies. Similar results were reported by Agnello et al. [22]. Although DW-MRI has been considered as alternative to contrast-enhanced MRI and contrast-enhanced computed tomography in patients with renal dysfunction in order to avoid contrast agent-induced nephropathy [23], our findings question the clinical value of this method due to the absence of rule-in or rule-out criteria for lesion diagnosis. In this study, ADC values were not significantly associated with RCC nuclear grades, in contrast to the findings of Rosenkranz et al. [24], who concluded that higher ADC values increased the accuracy of distinguishing between low- and high-grade RCCs, compared with conventional MRI. The lack of correlation in the present study may be related to ADC value determination, based on the measurement of the movement of freely mobile water molecules and influenced by factors including cell membrane integrity, cellularity, viscosity, and the nuclear-to-cytoplasmic ratio. Fuhrmann grading, however, is based on nuclear features, including nuclear size and shape and the prominence of nucleoli [25]. This distinction was also acknowledged by Rosenkranz et al. [24]. Therefore, ADC is not a biomarker for prediction of biological aggressiveness. In our study, we were unable to differentiate between RCC and UTUC. This needs to be considered when interpreting DW-MRIs. Contrasting results have been reported by Paudyal et al. [15]. The authors have shown that the ADC value was significantly higher for RCC than for upper tract urothelial carcinoma (UTUC). However, because of the limited number of included UTUCs, conclusions cannot be drawn regarding the value of DW-MRI for distinguishing between RCC and UTUC. The small number of lesions in our study limits our ability to detect subtle differences between renal lesion subtypes. However, subtle differences are of minor interest if accurate diagnosis of renal lesions is warranted. In addition, the low number of benign lesions may be considered a limitation of the current study. However, simple benign cysts were not investigated, as they do not pose a diagnostic challenge in clinical practice. As a result, we deem our results to better reflect the clinical task of differentiation between benign and malignant lesions. As prior work has shown such measurements to be reproducible [26], we did not investigate the reproducibility of ADC measurements. The small ROI for sampling of solid lesion parts does not account for tumour heterogeneity. Although ADC values in solid tumour subparts did not show diagnostically relevant differences between most renal lesion subgroups, a more complex approach addressing tissue heterogeneity may possibly yield diagnostic results. A final limitation is the high number of cases which had to be excluded due to insufficient image quality related to breathing motion. In incooperative patients, the respiratory triggering may fail, limiting the applicability of DWI in severely ill and noncompliant patients. 5. Conclusions Our results do not support DW-MRI as an accurate diagnostic test for renal lesion differentiation. Although ADC differences between papillary and non-papillary RCC subtypes were identified,
5
classification accuracy between these subtypes was not precise enough to rely on DW-MRI as a single diagnostic tool. Conflict of interest The authors declare that they have no conflict of interest to declare. References [1] Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001;166(5):1611–23. [2] Jayson M, Sanders H. Increased incidence of serendipitously discovered renal cell carcinoma. Urology 1998;51(2):203–5. [3] Van Poppel H, Becker F, Cadeddu JA, et al. Treatment of localised renal cell carcinoma. Eur Urol 2011;60(4):662–72. [4] Remzi M, Ozsoy M, Klingler H-C, et al. Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter. J Urol 2006;176(3):896–9. [5] Baltzer PAT, Renz DM, Herrmann K-H, et al. Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques. Eur Radiol 2009;19(7):1612–20. [6] Tsougos I, Svolos P, Kousi E, et al. Differentiation of glioblastoma multiforme from metastatic brain tumor using proton magnetic resonance spectroscopy, diffusion and perfusion metrics at 3 T. Cancer Imag 2012;12:423–36. [7] Kido A, Fujimoto K, Okada T, Togashi K. Advanced MRI in malignant neoplasms of the uterus. J Magn Reson Imaging 2013;37(2):249–64. [8] Lecouvet FE, Lhommel R, Pasoglou V, et al. Novel imaging techniques reshape the landscape in high-risk prostate cancers. Curr Opin Urol 2013. [9] Zhang J, Tehrani YM, Wang L, et al. Renal masses: characterization with diffusion-weighted MR imaging—a preliminary experience. Radiology 2008;247(2):458–64. [10] Wang H, Cheng L, Zhang X, et al. Renal cell carcinoma: diffusion-weighted MR imaging for subtype differentiation at 3.0 T. Radiology 2010;257(1):135–43. [11] Taouli B, Thakur RK, Mannelli L, et al. Renal lesions: characterization with diffusion-weighted imaging versus contrast-enhanced MR imaging. Radiology 2009;251(2):398–407. [12] Sandrasegaran K, Sundaram CP, Ramaswamy R, et al. Usefulness of diffusionweighted imaging in the evaluation of renal masses. AJR Am J Roentgenol 2010;194(2):438–45. [13] Goyal A, Sharma R, Bhalla AS, et al. Diffusion-weighted MRI in renal cell carcinoma: a surrogate marker for predicting nuclear grade and histological subtype. Acta Radiol 2012;53(3):349–58. [14] Inci E, Hocaoglu E, Aydin S, Cimilli T. Diffusion-weighted magnetic resonance imaging in evaluation of primary solid and cystic renal masses using the Bosniak classification. Eur J Radiol 2012;81(5):815–20. [15] Paudyal B, Paudyal P, Tsushima Y, et al. The role of the ADC value in the characterisation of renal carcinoma by diffusion-weighted MRI. Br J Radiol 2010;83(988):336–43. [16] Razek AAKA, Farouk A, Mousa A, Nabil N. Role of diffusion-weighted magnetic resonance imaging in characterization of renal tumors. J Comput Assist Tomogr 2011;35(3):332–6. [17] Israel GM, Hindman N, Bosniak MA. Evaluation of cystic renal masses: comparison of CT and MR imaging by using the Bosniak classification system. Radiology 2004;231(2):365–71. [18] Delahunt B, Eble JN, McCredie MR, et al. Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases. Hum Pathol 2001;32(6):590–5. [19] Sun MRM, Ngo L, Genega EM, et al. Renal cell carcinoma: dynamic contrastenhanced MR imaging for differentiation of tumor subtypes–correlation with pathologic findings. Radiology 2009;250(3):793–802. [20] Kim JH, Bae JH, Lee KW, et al. Predicting the histology of small renal masses using preoperative dynamic contrast-enhanced magnetic resonance imaging. Urology 2012;80(4):872–6. [21] Vargas HA, Chaim J, Lefkowitz RA, et al. Renal cortical tumors: use of multiphasic contrast-enhanced MR imaging to differentiate benign and malignant histologic subtypes. Radiology 2012;264(3):779–88. [22] Agnello F, Roy C, Bazille G, et al. Small solid renal masses: characterization by diffusion-weighted MRI at 3 T. Clin Radiol 2013. [23] Giannarini G, Petralia G, Thoeny HC. Potential and limitations of diffusionweighted magnetic resonance imaging in kidney, prostate, and bladder cancer including pelvic lymph node staging: a critical analysis of the literature. Eur Urol 2012;61(2):326–40. [24] Rosenkrantz AB, Niver BE, Fitzgerald EF, et al. Utility of the apparent diffusion coefficient for distinguishing clear cell renal cell carcinoma of low and high nuclear grade. AJR Am J Roentgenol 2010;195(5):W344–51. [25] Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6(7):655–63. [26] Bilgili MYK. Reproductibility of apparent diffusion coefficients measurements in diffusion-weighted MRI of the abdomen with different b values. Eur J Radiol 2012;81(9):2066–8.
Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
ARTICLE IN PRESS European Journal of Radiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors S. Sevcenco a,1 , G. Heinz-Peer b,2 , L. Ponhold b,2 , D. Javor b,2 , F.E. Kuehhas a,1 , H.C. Klingler a,1 , M. Remzi a,3 , P. Weibl a,1 , S.F. Shariat a,1 , P.A. Baltzer b,∗ a b
Medical University of Vienna, Dept. of Urology, Waehringer Gürtel 18-20, 1090 Vienna, Austria Medical University of Vienna, Dept. of Biomedical Imaging and Image-guided Therapy, Waehringer Gürtel 18-20, 1090 Vienna, Austria
a r t i c l e
i n f o
Article history: Received 7 November 2013 Received in revised form 21 February 2014 Accepted 27 February 2014 Keywords: Renal carcinoma Renal mass MRI DWI ADC Papillary
a b s t r a c t Objective: To investigate utility and limitations of 3-Tesla diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiation of benign versus malignant renal lesions and renal cell carcinoma (RCC) subtypes. Materials and methods: Sixty patients with 71 renal lesions underwent 3 Tesla DW-MRI of the kidney before diagnostic tissue confirmation. The images were retrospectively evaluated blinded to histology. Single-shot echo-planar imaging was used as the DW imaging technique. Apparent diffusion coefficient (ADC) values were measured and compared with histopathological characteristics. Results: There were 54 malignant and 17 benign lesions, 46 lesions being small renal masses ≤4 cm. Papillary RCC lesions had lower ADC values (p = 0.029) than other RCC subtypes (clear cell or chromophobe). Diagnostic accuracy of DW-MRI for differentiation of papillary from non-papillary RCC was 70.3% resulting in a sensitivity and specificity of 64.3% (95% CI, 35.1–87.2) and 77.1 (95% CI, 59.9–89.6%). Accuracy increased to 83.7% in small renal masses (≤4 cm diameter) and sensitivity and specificity were 75.0% and 88.5%, respectively. The ADC values did not differ significantly between benign and malignant renal lesions (p = 0.45). Conclusions: DW-MRI seems to distinguish between papillary and other subtypes of RCCs especially in small renal masses but could not differentiate between benign and malignant renal lesions. Therefore, the use of DW-MRI for preoperative differentiation of renal lesions is limited. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Renal cell carcinoma (RCC) survival is improving because of both improved therapeutic strategies and early detection through the increased use of imaging studies [1]. New imaging techniques have
∗ Corresponding author. Tel.: +43 1 40 400 4818; fax: +43 1 40 400 2332. E-mail addresses: [email protected] (S. Sevcenco), [email protected] (G. Heinz-Peer), [email protected] (L. Ponhold), [email protected] (D. Javor), [email protected] (F.E. Kuehhas), [email protected] (H.C. Klingler), [email protected] (M. Remzi), [email protected] (P. Weibl), [email protected] (S.F. Shariat), [email protected] (P.A. Baltzer). 1 Tel.: +43 1 40 400 2616; fax: +43 1 40 400 2601. 2 Tel.: +43 1 40 400 4818; fax: +43 1 40 400 2323. 3 Wiener Ring 3-5, 2100 Korneuburg. Tel.: +43 2262/9004 5740; fax: +43 2262/9004 2850.
also led to an increased detection of incidental renal tumours [2], most of which are 0.05). The ADC differences between papillary and non-papillary RCC was also significant in small renal masses (p = 0.011) revealing
Fig. 2. Example of a 69-year-old male patient showing an irregular mass on the right kidney (white arrows), which was histopathologically diagnosed as clear cell renal carcinoma. (A) b0 s/mm2 image, (B) b1000 s/mm2 image, (C) fat saturated T2-weighted turbo spin echo image, (D) apparent diffusion coefficient (ADC) map (×10−6 mm2 /s). ADC value was measured as 1031 × 10−6 mm2 /s.
Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
G Model
ARTICLE IN PRESS
EURR-6709; No. of Pages 5
S. Sevcenco et al. / European Journal of Radiology xxx (2014) xxx–xxx
4
Fig. 3. Apparent diffusion coefficient value (×10−6 mm2 /s) distribution demonstrates no significant differences between RCC lesion Fuhrmann grades.
an area under the ROC curve for diagnosis of papillary RCC of 0.837 (p = 0.004); at an ADC cut-off value of ≤0.954 × 10−6 mm2 /s, sensitivity and specificity were 75.0% (95% CI, 34.9–96.8) and 88.5 (95% CI, 69.8–97.6%), respectively. 4. Discussion DW-MRI has been used for differentiating between renal lesions and the RCC subtypes, but our results showed that DW-MRI was not accurate enough to differentiate benign from malignant renal lesions and thus cannot overcome the problem of pre-therapeutic differentiation of renal masses into benign versus malignant. We found a significantly differentiation in ADC values between solid and non-solid lesions but not between benign and malignant renal lesions (p = 0.45, Table 2). In a previous study, Zhang et al. found that ADC values were significantly lower in the solid tissues of renal tumours than in the cystic/necrotic subparts of renal tumours and in benign cysts Table 2 Apparent diffusion coefficients for different lesion subtypes. Lesion type
n
ADC (mean ± SD) (×10−6 mm2 /s)
Malignant Clear cell RCC Papillary RCC Chromophobic RCC Upper tract urothelial carcinoma
54 29 15 6 4
1250 1380 1016 1239 1209
± ± ± ± ±
493 566 377 334 81
1209, 631 1361, 669 920, 607 1249, 533 1221, 151
Benign Oncocytoma Angiomyolipoma Other benign
17 10 3 4
1376 1603 828 1219
± ± ± ±
613 636 227 503
1363, 742 1482, 553 737, n.a. 1036, 880
Renal parenchyma
71
1776 ± 145
RCC, renal cell carcinoma.
ADC (median, IQR) (×10−6 mm2 /s)
1782, 129
[9], suggesting that DW-MRI might allow differentiation between solid and non-solid lesions. In this study, we concentrated on the solid subparts and did not find any ADC differences between benign and malignant renal lesions. In contrast, Taouli et al. [11] investigated 28 RCC and 81 benign lesions, including 49 benign cysts (Bosniak categories I and II). Considering these benign cysts in an approach similar to investigations by Wang et al. and Inci et al., the authors reported the ability to differentiate between benign and malignant lesions [10,11,14]. Non-complicated cysts are straightforward to identify by imaging and do seldom pose a problem for differential diagnosis [17]. Such lesions do obviously present with high ADC values due to their content of free water. Inclusion of simple cysts explains the differences found by the listed publications and the discrepancy with our study which is due to a selection bias. Reported ADC values showed inconsistent absolute numbers across these studies and, furthermore, overlaps between benign and malignant tumours were observed. Our study does not support the previous data suggesting accurate differentiation of benign tumours versus malignant tumours. As outlined above, our patient group might better reflect the real clinical task as obvious benign cysts were not included. Of interest, Taouli et al. support our findings as they did not find significant differences between the solid parts of cystic RCCs and solid RCCs or between the cystic part of RCCs and benign cysts [11]. Inconclusive results regarding RCCs subtype differentiation have been reported [10,11,16]. Higher mean ADC values were found in clear cell RCC versus papillary and chromophobe at b values of 0 and 800 s/mm2 [10]. By contrast, Razek et al. found similar ADC values for papillary and clear cell RCC, but could still differentiate these malignant entities from other malignant tumours [16]. Our results show significantly lower ADC values in papillary RCC compared to non-papillary renal lesions. Papillary RCC has generally a better prognosis than clear cell RCC [18]. This finding may be explained by higher cellularity of the papillary RCC tumour subtype; the cell density restricts the Brownian
Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
G Model EURR-6709; No. of Pages 5
ARTICLE IN PRESS S. Sevcenco et al. / European Journal of Radiology xxx (2014) xxx–xxx
motion of the water molecules within the tumour. However, previous work did not find strong or significant correlations here [13]. Furthermore, perfusion effects may increase ADC values: lower perfusion in papillary RCC has been suggested as a possible cause of low ADC values in papillary RCC [11]. Of note, although data is in parts inconsistent, contrast enhanced MRI has been described as diagnostic for diagnosis RCC subtypes [19–21]. In small renal masses, such differentiation was even better, possibly due to confounding structural changes (i.e. regressive changes) in advanced renal malignancies. Similar results were reported by Agnello et al. [22]. Although DW-MRI has been considered as alternative to contrast-enhanced MRI and contrast-enhanced computed tomography in patients with renal dysfunction in order to avoid contrast agent-induced nephropathy [23], our findings question the clinical value of this method due to the absence of rule-in or rule-out criteria for lesion diagnosis. In this study, ADC values were not significantly associated with RCC nuclear grades, in contrast to the findings of Rosenkranz et al. [24], who concluded that higher ADC values increased the accuracy of distinguishing between low- and high-grade RCCs, compared with conventional MRI. The lack of correlation in the present study may be related to ADC value determination, based on the measurement of the movement of freely mobile water molecules and influenced by factors including cell membrane integrity, cellularity, viscosity, and the nuclear-to-cytoplasmic ratio. Fuhrmann grading, however, is based on nuclear features, including nuclear size and shape and the prominence of nucleoli [25]. This distinction was also acknowledged by Rosenkranz et al. [24]. Therefore, ADC is not a biomarker for prediction of biological aggressiveness. In our study, we were unable to differentiate between RCC and UTUC. This needs to be considered when interpreting DW-MRIs. Contrasting results have been reported by Paudyal et al. [15]. The authors have shown that the ADC value was significantly higher for RCC than for upper tract urothelial carcinoma (UTUC). However, because of the limited number of included UTUCs, conclusions cannot be drawn regarding the value of DW-MRI for distinguishing between RCC and UTUC. The small number of lesions in our study limits our ability to detect subtle differences between renal lesion subtypes. However, subtle differences are of minor interest if accurate diagnosis of renal lesions is warranted. In addition, the low number of benign lesions may be considered a limitation of the current study. However, simple benign cysts were not investigated, as they do not pose a diagnostic challenge in clinical practice. As a result, we deem our results to better reflect the clinical task of differentiation between benign and malignant lesions. As prior work has shown such measurements to be reproducible [26], we did not investigate the reproducibility of ADC measurements. The small ROI for sampling of solid lesion parts does not account for tumour heterogeneity. Although ADC values in solid tumour subparts did not show diagnostically relevant differences between most renal lesion subgroups, a more complex approach addressing tissue heterogeneity may possibly yield diagnostic results. A final limitation is the high number of cases which had to be excluded due to insufficient image quality related to breathing motion. In incooperative patients, the respiratory triggering may fail, limiting the applicability of DWI in severely ill and noncompliant patients. 5. Conclusions Our results do not support DW-MRI as an accurate diagnostic test for renal lesion differentiation. Although ADC differences between papillary and non-papillary RCC subtypes were identified,
5
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Please cite this article in press as: Sevcenco S, et al. Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.02.026
