1 CLINICAL STUDY
2 Computed tomography criteria for discrimination of adrenal adenomas and adrenocortical
3 carcinomas - analysis of the German ACC registry
4
Stephan Petersenn1 and Paul-Ajoy Richter2, Thomas Broemel3, Christian O. Ritter4, Timo
5 Deutschbein5, Frank-Ulrich Beil2, Bruno Allolio5, Martin Fassnacht5,6 for the German ACC Study 6 Group
7 1 ENDOC Center for Endocrine Tumors, Hamburg, Germany
8 2 Department of Internal Medicine, University of Hamburg, Hamburg, Germany
9 3 Praenobis Hamburg, Hamburg, Germany
10 4 Department of Radiology, University Hospital, University of Würzburg, Würzburg, Germany
11 5 Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital, University of
12 Würzburg, Würzburg, Germany
13 6 Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany
14 SP and PAR should be considered shared first author.
15 16 Corresponding Author: 17 Prof. Dr med. Stephan Petersenn,
18 ENDOC Center for Endocrine Tumors,
19 Altonaer Str. 59, 20357 Hamburg, Germany;
20 phone: +49 40 401 87985; fax: +49 40 401 87986;
21 e-mail: stephan.petersenn@endoc-med.de
22 Short Title: adrenocortical carcinoma in unenhanced CT
23 Key terms: adrenal cancer; adrenal tumors; adrenocortical adenoma; adrenal incidentaloma;
24 unenhanced CT
25 Word Count: 3773
1 Abstract
2 Objective: Thresholds of 2-20 Hounsfield units (HU) in unenhanced computed tomography (CT) are
3 suggested to discriminate benign adrenal tumors (BAT) from malignant adrenal tumors. However,
4 these studies included only low numbers of adrenocortical carcinomas (ACC). This study defines a 5 HU threshold by inclusion of a large cohort of ACC.
6 Design: Retrospective blinded, comparative analysis of CT scans from 51 patients with ACC (30 7 females, median age 49 years) and 25 with BAT (12 females, 64 years) diagnosed 2005-2010.
8 Methods: Evaluation of tumor density in unenhanced CT by 2 blinded investigators.
10
9 Results: Median tumor size was 9 cm (range 2.0-20) for ACC vs. 4 cm (2.0-7.5) for BAT (p<0.0001). In ACC, median unenhanced HU value was 34 (range 14-74) in comparison to 5 (-13-40) in BAT
11 (p<0.0001). ROC analysis revealed HU of 21 as threshold with best diagnostic accuracy (sensitivity 12 96%, specificity 80%, AUC 0.89). However, two ACC with 5 and 6 cm would have been missed. 13 Setting the threshold to 13.9 allowed for 100% sensitivity, but lower specificity of 68%.
14 Conclusions: This first large study on ACC confirmed that the vast majority of ACC have unenhanced HU > 21. However, to avoid misdiagnosing an ACC as benign a threshold of 13 should be
15 16 used.
1 Introduction
2
An incidentally detected adrenal lesion (incidentaloma) is a common finding during abdominal computed tomography (CT). Lesions of 1 cm or larger are reported to occur in up to 5% of patients.
3
4 5
6
Most of these lesions in patients with no known malignancy will prove to be benign. Usually, conventional imaging tries to discriminate benign adrenal tumors (BAT) - mainly adrenocortical adenomas - from non-adenomas. This group mainly consists of adrenocortical carcinomas (ACC), adrenal metastases from other malignancies, but also pheochromocytomas. A pooled analysis of multiple published studies by Boland et al. 1 suggested an attenuation threshold of 10 HU for regular unenhanced CT to detect malignant lesions with a sensitivity of 98% and a specificity of 71%.
7
8 9 10 However, all of the larger studies on this topic primarily focused on adrenal metastases and did include very few ACC 1-9.
11 12
13
ACC has an annual incidence of only 1-2 cases per million people but is one of the most aggressive endocrine malignancies. ACC is more frequent in women than in men (1.5:1) and appears at any age, but the highest prevalence is in the fourth and fifth decade. Patients with functional tumors often present with hormonal symptoms (40-60%), in the majority with Cushing’s syndrome, while patients with non-functional tumors either suffer from symptoms of the mass effect or the tumor is - in about 15% of case - detected incidentally 10, 11. During CT scans, ACC are typically heterogeneous tumors with ill-defined margins, calcifications and evidence of necrosis or hemorrhage. Most lesions are larger than 6 cm when detected 12, 13. There are only a small number of studies evaluating the radiological characteristics of ACC. However, early detection of these rapidly growing tumors might be the only chance for cure in these patients and, therefore, reliable imaging criteria are needed to
14 15 16 17 18 19 20 21
22 avoid missing the diagnosis of an ACC. Thus, the purpose of this study was to evaluate differences in radiological behaviour of ACC and BAT, re-evaluating the performance of unenhanced CT scans in a large cohort by independent investigators.
23 24 25
26 Subjects and methods
27 Patient recruitment
1 2
3 4 5
6
7 8
The German Adrenocortical Carcinoma Registry includes a large number of patients with defined ACC and was therefore utilized to study the radiological behavior of adrenocortical cancer in comparison to BAT. The ACC registry is approved by the ethics committee of the University of Wurzburg. All patients provided written informed consent. This database was searched to identify patients with localized ACC diagnosed between 2005 and 2010 with digitally available CT scans. ACC had been histopathologically proven and patients had undergone unenhanced abdominal CT imaging before any other treatment. Initial screening identified 167 patients with localized tumors, but in 62 patients no digital data of the CT were available and in 54 patients only enhanced CT was performed. Thus, finally 51 patients (21 males and 30 females) with a median age of 49 (range 17-79 years) were analyzed. The control group included 25 patients with BAT, with histologic exclusion of malignancy or a follow-up of the last 6 months without any relevant tumor growth (12 males and 13 females with a median age of 64 (range 25-85 years)). This was an unbiased selection of patients with
19 20 21
9 10 11 12 13 adrenal tumors recruited from the centers in Würzburg and Hamburg. The number of patients was 14 limited by the strict entry criteria and the focus on CT, excluding patients with MRI. 15 16 17 Image analysis 18 The CT images of all patients were independently analyzed by two investigators blinded concerning the pathological diagnosis and using MERLIN PACS Software (Phoenix-PACS) for morphological characteristics. Mismatches were solved by consensus. The following morphological characteristics were documented: localization (left versus right adrenal gland versus bilateral disease), size 22 (maximum axial diameter), shape (sustained (maintained) versus not sustained), margin definition 23 (well defined versus ill defined), tumor homogeneity (homogeneous versus inhomogeneous), 24 unenhanced HU (Figure 1A and B). The region of interest (ROI) was carefully hand drawn over one- half to two third of the mass, avoiding necrotic or hemorrhagic areas 14. 25 26
27 Statistical analysis
1 Results are expressed as median (range) unless otherwise mentioned. Data analysis was performed 2 with GraphPad Prism 6.0 for Windows. p<0.05 was considered statistically significant. The Mann-
3 Whitney-Test and the Fisher’s exact test were used, as appropriate. The thresholds for tumors size and
4
HU values were calculated by ROC analysis, aiming for a sensitivity of at least 95% for ACC. Inter-
5 rater-reliability was calculated by concordance correlation coefficient. Furthermore, confidence
6 interval for inter-rater-reliability was calculated.
7
8 9 10
Results
Baseline characteristics and an overview of the main radiological findings are provided in Table 1.
11 Tumor size
12 The median diameter of ACC was 9 cm (range 2.0-20 cm). Forty-six ACC (90%) had maximal 13 14 diameters of more than 5 cm while four (8%) had maximal diameters between 3 and 5 cm and one (2%) had a maximal diameter smaller than 3 cm. The median diameter of BAT was 4 cm (range 2.0- 15 7.5 cm, Figure 2A). ROC analysis aiming for at least 95% sensitivity to detect ACC revealed a 16 threshold of 3.9 cm (sensitivity 98%, specificity 40%, AUC 0.93, 95% CI 0.88 - 0.99, p<0.0001; 17 Figure 2B). One ACC would have been missed by this suggested threshold: It was a left sided tumor
18 19 20
with well-defined margin, inhomogeneous appearance and unenhanced HU of 34. Using a threshold of 5 or 6 cm resulted in even lower sensitivity of 90% and 80%. Limiting the analysis to those tumors smaller or equal to 6 cm (10 ACC, 23 BAT) or 8 cm (18 ACC, 25 BAT), the threshold of 3.9 cm demonstrated a sensitivity of 90% and 94%, respectively, and a specificity of 44% and 40%.
21 22 23 Shape, margin and homogeneity of the tumors
24 None of the analyzed tumors (ACC and BAT) were sustained in shape. 28 ACC (55%) had well- 25 26 defined margins, whereas this was the case in 21 BAT (84%, p<0.05) leading to an odds ratio of 4.3 for ACC with an ill-defined margin (sensitivity 45%, specificity 84%). All ACC had an inhomogeneous appearance, while 14 of the BAT (56%) were homogeneous (p<0.0001). Thus, an
27
1 inhomogeneous tumor structure (with a sensitivity of 100%) resulted in an odds ratio of 130 for ACC,
2 but the specificity was rather low with 56%.
3
4 CT Densitometry
5 First, inter-rater-reliability was analyzed comparing results for all tumors, with a very high agreement
6 (inter-rater-reliability p=0.96, 95% CI 0.93-0.97). To understand the relevance of observer variation in
7 more detail, we analyzed the mean differences in HU for unenhanced CT values between the two
8 radiologists. As we found some association with absolute HU values, with a few outliers for high
readings, we limited the analysis to the critical range of HU values between -30 and 30, resulting in a
9 10 mean difference of 2.5 HU.
11 The median unenhanced HU value in the region of interest was 34 (range 14-74 HU) in ACC while the 12 median HU value in BAT was 5 (range -13-40 HU, Figure 3A; p<0.0001). ROC analysis aiming for at
13 least 95% sensitivity to detect ACC revealed a threshold of 21 for unenhanced HU (sensitivity 96%, specificity 80%, AUC 0.89, 95% CI 0.79 - 0.98, p<0.0001; Figure 3B). However, by using this threshold two ACC patients would have been misclassified. These tumors were 5 and 6 cm in size,
18 19 20
14 15 16 inhomogeneous, but with a well-defined margin and HU of 14 and 20. Setting the threshold for HU to 17 13.9 HU allowed for 100% sensitivity, but lower specificity of 68%. Of note, applying the currently used threshold of 10 HU resulted in even lower specificity of 58% (Table 2). Thereby, in ten out of twenty-five BAT additional imaging would have been required to discriminate them from malignant tumors. On the other hand, unenhanced HU higher than 39.5 were highly suggestive of ACC
21 (sensitivity 31%, specificity 96%).
22 Again, we performed separate analyses for tumors smaller or equal to 8 cm and 6 cm, respectively, in
which the specificity for the threshold of 13.9 fell as expected, but was still 68% and 65% respectively (Figure 3C and D, Table 2). As revealed by AUC values and 95% confidence intervals, both CT
23 24 25 densitometry and tumor size demonstrated high accuracy for the correct diagnosis, without significant
26
difference between the two. However, with the emphasis on high sensitivity of at least 95%, CT
27 densitometry clearly revealed the best accuracy.
28
1 Combination of various radiological parameters
2
The combination of CT densitometry (as the single best parameter) with morphological parameters
3 like shape, margin, and/or homogeneity resulted in a loss of accuracy. Even when combining CT
densitometry with the second best parameter tumor size, accuracy dropped due to a loss of either 4 5 sensitivity or specificity. In the best scenario, applying optimal thresholds of 21 HU and 5.8 cm 6 instead of those with sensitivity of at least 95% and requesting either to be positive for the diagnosis of ACC, sensitivity increased slightly to 98%, but specificity dropped to 68%.
7 8 9 10
Discussion:
11 12 13 14 15 16
CT densitometry has frequently been reported as an effective imaging technique to differentiate BAT from malignant lesions of the adrenal glands and a cut-off of < 10 HU in unenhanced CT was proposed to exclude malignant tumors 1. However, this threshold was never investigated including a sufficiently large cohort of ACC. Now in our study, we demonstrate that by using a threshold of 13 HU no ACC would have been missed.
Whereas many recommendations on the management of adrenal incidentaloma still rely on the size of the adrenal mass 15-17, a recent guideline from the Italian Association of Clinical Endocrinologists 17 emphasizes the importance of specific imaging criteria like unenhanced HU 18. However, size has 18 19 20 21 certainly some predictive value, because most adenomas are smaller than 4 cm, whereas ACC have a median size of 11 cm 19. Although the 3.9 cm cut-off of the present study yields a higher sensitivity (98% for ACC in comparison to the 5 cm cut-off), it involves a lower specificity (40%). Nevertheless, just one ACC patient would have been missed using a threshold of 4 cm, while 5 patients and 10
23 24 25 26
22 patients would have been misdiagnosed when applying the 5 cm and the 6 cm cut-offs, respectively. Although in most series the number of patients with ENSAT stage I tumors (i.e., tumor size ≤ 5 cm) is only between 3-6 % 20-22, it should be kept in mind that the size of a tumor may depend on the time point of diagnosis during development of the disease. With more frequent use of radiologic procedures, ACC may be diagnosed at an earlier stage and with smaller size, making size a less reliable parameter to differentiate BAT and ACC.
27
2
1 One of the first publications on unenhanced CT was the study by Lee et al. 6 characterizing 66 adrenal masses by three independent radiologists and classified 22 to be malignant, but did not differentiate the kind of malignancy or mentioned the HU for the different tumor entities. Boland et al. 1 summarized later data from 10 publications detailing on only 22 ACC of a total of 223 malignant tumors and 272 benign lesions. Subsequent studies mostly re-evaluated the suggested threshold of 10 HU in series focusing on BAT in comparison to adrenal metastases. In addition, Hamrahian et al. 4
3
4 5
6
8
9
10
11
7 provided data for thresholds of 10 and 20 HU in 290 patients with adrenal masses including 15 ACC, but focused on the comparison of adenomas/hyperplasia (156 patients) versus non-adenomas. The same applies to Ctvrtlik et al. 2, analyzing a cut-off of 23 HE. Zhang et al. 23 studied 41 ACC, but did not determine an attenuation threshold. Table 3 provides a summary of all studies analyzing unenhanced CT that included more than 3 ACC. All but one of these 64 ACC had a HU > 20, but even the largest study 3 included only 17 ACCs. One of these 64 ACC was reported as having an unenhanced HU of only 0.7, but was postoperatively carefully reviewed and described as spongiocyte hyperplasia with a Weiss score of 5 3.
12
13
14
15 Here, we utilized the German ACC Registry including its large series of histopathologically proven 16 ACC. The analysis showed that the median attenuation of ACC is significantly higher than of BAT. 17 The vast majority of ACC had unenhanced HU of more than 21 HU, a threshold with high sensitivity (96%) and reasonable specificity (80%) for ACC. However, two ACC with 5 and 6 cm in diameter were missed by that threshold. Setting the threshold to 13.9 HU allowed for 100% sensitivity, but lower specificity of 68%. The frequently used 10-HU threshold diagnosed ten out of twenty-five BAT (40%) as non-adenoma and would therefore lead to additional investigations. Due to the higher
18 19 20 21 22 incidence of adrenal adenomas compared to carcinomas, this also means, that adrenal tumors with
25 26
23 unenhanced CT values of more than 10 HU are frequently adenomas. Patients with HU values in 24 between 13.9 and 21 HU should be examined very carefully. Limiting our analysis to tumors of less than 6 or 8 cm (the group of tumors most difficult to determine the diagnosis prior surgery), a threshold of 13.9 provided the highest sensitivity, whereas thresholds around 21 HU offered a good compromise between sensitivity and specificity, again suggesting to carefully discuss patients in-
27
28 between and considering other criteria in addition. The mean difference between observers of 2.5 HU
1 may be relevant for readings near to the thresholds. We therefore suggest readings by two independent
2 observers for HU values in the critical range, as well careful interpretation in the context of observer
3 variation.
4 5
6
7
As already described by others, there are more criteria to differentiate incidentalomas like margin definition and tumor homogeneity. According to Boland et al. 13 cortical adenoma have no specific morphologic features, most are small, smooth, heterogeneous with a well-defined margin when detected. On the other hand, the presence of ill-defined margins is often a sign of a more aggressive nature. ACC are typically ill-defined, heterogeneous and irregular lesions with calcifications in up to 30% of cases 5, 24, 25. In the present study 21 of 25 BAT (84%) had a well-defined margin while 28 of 51 ACC (55%) were also well-defined. Zhang et al. 23 reported similar results, with 29 of 41 ACC (71%) being described as well-defined. Furthermore, 11 of 25 patients with BAT (44%) had an inhomogeneous tumor structure while patients with ACC were inhomogeneous in all cases. Nevertheless, the analysis of tumor margin and tumor homogeneity yielded statistically significant criteria to differentiate adrenal tumors in our series, and may therefore add to the interpretation of the
8 9 10
11
12 13 14
15 CT in individual cases.
16 17 18 19 20 21 Obviously, there are alternative imaging tools to characterize adrenal lesions like chemical shift magnetic resonance imaging (CS-MRI) or 2-[18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). There exists some controversy about which test (CT or CS-MRI) might offer superior sensitivity and specificity for detecting lipid-rich lesions. CS-MRI might be superior when evaluating lipid-poor adenomas 26. In general, MRI is less standardized and more expensive than CT imaging, although it has the advantage of lacking radiation 14,27-29. The most important disadvantage of CS-MRI 22 is that - to the authors knowledge - there are no studies of CS-MRI criteria with a relevant number of 23 ACC 30. 18F-FDG-PET may offer additional information. Metabolically active malignant lesions trap 24 25
18F-FDG intracellularly, whereas most benign lesions fail to accumulate this radioisotope 3, 31-33. Thus, FDG-PET might be helpful in patients with undetermined adrenal mass by conventional imaging.
26 Our study has certain limitations. First, the number of analyzed BAT and ACC is still relatively low.
27 However, it included almost as many ACCs as the 7 largest studies on adrenal imaging (describing at
28 least 3 ACC) together (Table 3). Second, the selection of patients for this study was not prospectively
1 or consecutively, but based on availability of digitally CT scans. We believe that this procedure 2 unlikely harbors a relevant bias. Third, only in a subset of 12 patients with BAT the diagnosis was 3 4 5 proved by histology. However, all BAT patients without surgery had a least one imaging in a time interval of at least 6 months. Since virtually all ACC grow very rapidly the likelihood that we missed an ACC seems to be rather low. Forth, we did not analyze the value of delayed wash-out CT. 6 However, this presumably very accurate method was performed in less than 10% of the patients 7 preventing any reliable analysis. Finally, our study did not include other “non-adenomas” like 8 metastases from extra-adrenal malignancies or pheochromocytomas. However, the later are usually 9 easy to diagnose with the measurement of plasma or urinary metanephrines and the results of imaging studies on metastases are already very strong not requiring additional data. In addition to the large number of ACC, another strength of this study should be mentioned, namely the fact that all images
10
11 12 were reviewed by two independent and blinded readers.
13 In conclusion, our study including the by far largest number of ACC of any adrenal imaging study 14 confirms that adrenal masses with a mean HU value below 21 are most likely of benign nature. 15 However, to avoid misdiagnosing an ACC as a benign adenoma, a lower threshold of 13 should be used. For tumors with HU levels between 13 and 40 additional measures like delayed wash-out CT, MR with chemical shift and wash-out or FDG-PET may be warranted to further exclude or suggest the malignancy of the lesion.
16 17 18 19 20 Declaration of interest
21 The authors declare that there is no conflict of interest that could be perceived as prejudicing the
22 impartiality of the research reported.
23
24 Funding
25
This research did not receive any specific grant from any funding agency in the public, commercial, or
26 not-for-profit sector.
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1 Legends:
2
Figure 1A: Axial unenhanced CT scan demonstrates 4.1 cm (L) inhomogeneous and ill defined ACC
3 in the right adrenal gland in a 66-year-old man (min, max and mean depict the respective values for
4 lowest, highest and mean HU, as derived from the software for the region of interest marked by the 5 investigator)
6 Figure 1B: Axial unenhanced CT scan demonstrates 4.4 cm (L) homogeneous and well defined BAT in the left adrenal gland in 50-year-old woman man (min, max and mean depict the respective values
7
8 for lowest, highest and mean HU, as derived from the software for the region of interest marked by the investigator).
9
10 Figure 2: Tumor sizes of 25 BATs and 51 ACC (A) with the corresponding ROC curve (B). The 11 horizontal line in A indicates the median value; the angle bisector in B represents AUC = 50%.
12 Figure 3: Mean HU of 25 BATs and 51 ACC (A) with the corresponding ROC curves for the entire 13 cohort (B), tumors ≤ 8 cm (C) and ≤6 cm (D). The horizontal line in A indicates the median value; the 14 angle bisector in B,C,D represents AUC = 50
| Benign Adrenal Tumors (BAT) | Adrenocortical Carcinomas (ACC) | |||||
|---|---|---|---|---|---|---|
| Variable | Maximum diameter (cm) | Maximum diameter (cm) | ||||
| ≤ 6 | > 6 | Total | ≤ 6 | > 6 | Total | |
| Number of Tumors | 23 | 2 | 25 | 10 | 41 | 51 |
| Sex | ||||||
| Female | 11 | 2 | 13 | 6 | 24 | 30 |
| Male | 12 | 0 | 12 | 4 | 17 | 21 |
| Localization | ||||||
| Right | 16 | 2 | 18 | 3 | 11 | 14 |
| Left | 7 | 0 | 7 | 7 | 30 | 37 |
| Tumor Margin | ||||||
| Well-defined | 19 | 2 | 21 | 7 | 20 | 27 |
| Ill-defined | 4 | 0 | 4 | 3 | 21 | 24 |
| Tumor Structure | ||||||
| Homogeneous | 13 | 1 | 14 | 0 | 0 | 0 |
| Non-homogeneous | 10 | 1 | 11 | 10 | 41 | 51 |
| Unenhanced CT (mean HU) | ||||||
| ≤ 0 | 9 | 2 | 11 | 0 | 0 | 0 |
| 0<x≤10 | 4 | 0 | 4 | 0 | 0 | 0 |
| 10<x≤20 | 5 | 0 | 5 | 2 | 0 | 2 |
| 20 < x ≤ 40 | 5 | 0 | 5 | 5 | 32 | 37 |
| > 40 | 0 | 0 | 0 | 3 | 9 | 12 |
| Tumors (cm) | n | Threshold (HU) | Sensitivity (%) | Specificity (%) | AUC | Significance level |
|---|---|---|---|---|---|---|
| all | 76 | 21.0 | 96.1 | 80.0 | 0.89 | p<0.0001 |
| 13.9 | 100 | 68.0 | ||||
| 10.0 | 100 | 58.0 | ||||
| ≤ 8 | 43 | 21.5 | 88.8 | 80.0 | <0.001 | |
| 17.0 | 94.4 | 76.0 | ||||
| 13.9 | 100 | 68.0 | ||||
| ≤ 6 | 33 | 22.5 | 80.0 | 78.3 | <0.05 | |
| 17.0 | 90.0 | 73.9 | ||||
| 13.9 | 100 | 65.2 |
| Author | Benign Adrenal Tumors (BAT) | Adrenocortical Carcinomas (ACC) | |||||
|---|---|---|---|---|---|---|---|
| Year | N | Mean HU (±SD) | Range | N | Mean HU (±SD) | Range | |
| Ctvrtlik et al. 11 2 | 2009 | 37 | 6± 13 | -10-42 | 4 | 36±7 | 28-43 |
| Groussin et al. 3 | 2009 | 41 | 17 | -27-40 | 17 | 34 | 0.7-55 |
| Remer et al. (O1) | 2006 | 105 | 18± 14 | -27-51 | 8 | 39±7 | 37-49 |
| Slattery et al. 34 | 2006 | - | - | - | 7 | 42* | 31.8-45 |
| Hamrahian et al. +24 | 2005 | 79 | 19* | -19-43 | 7 | 36* | 31-43 |
| Szolar et al. 9 | 2005 | 24 | 8± 18 | 21-27 | 11 | 39± 14 | 23-52 |
| Rockall et al. 8 | 2004 | 20 | 11 | -16-41 | 10 | 28 | 20-31 |
Note. * Median HU; 11 threshold: 23 HU (Sens 89%. Spec 100%); 12 threshold: 20 HU (sensitivity 58%. specificity 97%); O1 Observer 1.
PubMed was searched for the following keywords: Incidentaloma (Adrenal Mass or Adrenal Tumor or Adrenal Cancer or Adrenocortical Carcinoma) AND computed tomography (CT) AND Hounsfield units (HU).
D
L=41.47mm
mean=40.75 max=104.00 min =- 26.00 area=197.96mm2 d=15.88mm
L=44.43mm
mean =- 5.99 max=28.00 min =- 35.00 area=400.55mm2 d=22.58mm
Tumor size (cm)
25
20
15
10
5
0
BAT
ACC
Sensitivity (%)
100
80
60
40
20
0
0 20 40 60 80 100
100 % - Specificity (%)
Pag80gof 24
HU
60
40
20
0
-20
BAT
ACC
Sensitivity (%)
100
80
60
40
20
0
T
0
20
40
60
80
100
100 % - Specificity (%)
Sensitivity (%)
100
80
60
40
20
0
0
20
40
60
80
100
100 % - Specificity (%)
Sensitivity (%)
100
80
60
40
20
0
0
20
40
60
80
100
100 % - Specificity (%)