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DOI:10.2214/AJR.04.1751
AJR 2006; 187:W21-W24
© American Roentgen Ray Society


Clinical Observations

Adrenocortical Carcinoma: Contrast Washout Characteristics on CT

James M. A. Slattery1, Michael A. Blake1, Mannudeep K. Kalra2, Joseph Misdraji3, Ann T. Sweeney4, Paul M. Copeland5, Peter R. Mueller1 and Giles W. Boland1

1 Department of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital, 55 Fruit St., White 270C, Boston, MA 02114.
2 Department of Radiology, Emory University Hospital, Alanta, GA.
3 Department of Pathology, Massachusetts General Hospital, Boston, MA.
4 St. Elizabeth's Medical Center, Boston, MA 02135.
5 Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.

Received November 11, 2004; accepted after revision May 9, 2005.

 
J. M. A. Slattery and M. A. Blake contributed equally to the study and to this article.

Address correspondence to G. W. Boland (gboland{at}partners.org).

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Abstract
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
OBJECTIVE. The purpose of this study was to characterize pathologically proven adrenocortical carcinoma by examination of washout attenuation characteristics on contrast-enhanced CT images.

CONCLUSION. Adrenocortical carcinoma has relative contrast retention on delayed contrast-enhanced CT. All tumors in this series had a relative percentage washout less than 40%, a finding consistent with malignant disease.

Keywords: adrenal gland • adrenocortical carcinoma • cancer • CT • contrast washout


Introduction
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
The CT characteristics of adrenocortical carcinoma (ACC) have been described [1-3]. ACC is typically a large heterogeneous mass with irregular margins and inhomogeneous enhancement of solid components after IV administration of contrast medium. Data suggest that the size of an adrenocortical tumor measured with CT is a good predictor of malignancy [4-7]. A review of six published series [8] showed that 92% of ACCs (105/114 carcinomas) were larger than 6 cm in diameter. In contrast, most adrenocortical adenomas are small and homogeneous, although occasionally they can be larger than 5 cm and have hemorrhage, necrosis, and calcifications mimicking carcinoma [9]. As the use of CT continues to grow, it is likely that smaller ACCs will be detected, making it more difficult to differentiate these tumors from adenomas. In the absence of metastatic disease, the differential diagnosis of small to intermediate-sized tumors is ACC versus large adrenocortical adenoma or pheochromocytoma [9]. Several reports have described the characteristics of adrenal masses on unenhanced, contrast-enhanced, and delayed contrast-enhanced CT scans for noninvasive differentiation of benign from malignant lesions [10-17]. The washout characteristics of adrenal masses after IV contrast enhancement have improved the sensitivity and specificity of characterization of adrenal masses. However, little specific information is available on the washout characteristics of ACC. The purpose of this study was to assess the washout characteristics of ACC on delayed contrast-enhanced CT scans and to determine whether these characteristics aid in differentiating ACC from adrenal adenoma.


Materials and Methods
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Abstract
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Materials and Methods
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Patients
Our institutional review board approved this retrospective study, and the requirement for patient consent was waived. A search of electronic medical records identified the cases of seven patients with ACC who had undergone unenhanced CT, CT with IV administration of contrast material, and delayed contrast-enhanced CT between 1997 and 2003. The age range of the five women and two men was 30-84 years (mean, 64 years). All patients had symptomatic presentations. Four had Cushing's syndrome (including one with virilization), and three had localized pain. Four tumors were situated in the right adrenal gland and three in the left adrenal gland. The average size of the tumors was 9.8 cm in maximum diameter (range, 5.3-14 cm). According to the staging criteria proposed by MacFarlane [18] and modified by Sullivan et al. [19], two patients had stage II disease, four had stage III disease, and one had stage IV disease.

Five patients underwent radical adrenalectomy or nephrectomy with adrenalectomy. In one of these five cases, the initial biopsy findings were interpreted as probable ACC on the basis of tumor size, but a benign adrenocortical tumor could not be morphologically excluded, and the patient underwent adrenalectomy. In another case, the diagnosis of metastatic ACC was established on the basis of liver biopsy findings, but the patient underwent adrenalectomy 1 month later for control of bleeding from duodenal ulcers believed to be caused by steroid excess. In the other two of the seven cases, the diagnosis of ACC was established by fine-needle aspiration biopsy with cell block of the adrenal gland or by fine-needle aspiration biopsy and core biopsy of a paracaval lymph node.

Scanning Technique
In six of seven patients, imaging was performed with a 4-MDCT scanner (LightSpeed QX/I, GE Healthcare). The other patient underwent imaging with a nonhelical unit (HiSpeed Advantage, GE Healthcare). Scanning parameters were as follows: 120-140 kVp, 200-300 mA, 1.0-second gantry rotation time, 7.5- to 15-mm table feed per gantry rotation, 1.5:1 pitch, and 2.5- to 5.0-mm slice profile.

Unenhanced images were obtained before IV administration of contrast material. A power injector was used to administer 100-120 mL of 300 mg I/mL iodinated contrast material (Oxilan 300 [ioxilan], Cook Imaging) through an antecubital vein at a rate of 2.5 mL/s. Dynamic contrast-enhanced images were obtained after a scan delay of approximately 75 seconds. Delayed images were obtained after a mean delay of 9.1 minutes (range, 7-17 minutes) after contrast injection. Six of seven delayed scans were obtained 10 minutes or less after contrast injection (three at 7 minutes, one at 9 minutes, and one at 10 minutes). The other scan was obtained 17 minutes after injection. Scan delay times were calculated from the electronic alphanumeric information on the image.

Image Analysis
Images were reviewed on a digital picture-archiving diagnostic workstation (Impax RS 3000 1K review station, AGFA Technical Imaging Systems). All images were reviewed by two radiologists. The diameter of each adrenal mass was measured on the slice with the largest surface area. The largest dimension was used to represent the diameter of the lesion. The region of interest selected for attenuation measurement was an ovoid or circular area that covered one half to two thirds of the largest uniformly enhancing area within the adrenal tumor without including adjacent retroperitoneal fat or inhomogeneous necrotic regions. The region of interest covered a mean area of 2.8 cm2 (range, 1.9-4.3 cm2). Average attenuation measurements (mean of two) were obtained on the unenhanced, enhanced, and delayed images. The data recorded were entered into a Microsoft Excel worksheet. Mean values for the unenhanced, enhanced, and delayed CT attenuation of uniformly enhancing foci were calculated. Relative percentage washout (RPW) was calculated as follows:

Formula

Relative percentage washout less than 40% on images with a scan delay of 17 minutes, and less than 50% on images with a scan delay of 7-10 minutes was considered a sign of malignancy. These values are consistent with previously published data [16, 17].


Results
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Materials and Methods
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The results are shown in Table 1.


View this table:
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TABLE 1: CT Characteristics of Adrenocortical Carcinoma

 

Unenhanced CT
The unenhanced attenuation values of the tumors ranged from 32 to 45 H (mean, 39 H). No lesion contained areas of fat attenuation. All lesions contained areas of necrosis.

Portal Venous Enhanced CT
Portal venous scanning was performed after a delay of 75 seconds for all lesions. All tumors had uniformly enhancing foci suitable for contrast washout analysis (Figs. 1A and 1B). Attenuation values on enhanced portal venous phase CT scans ranged from 64 to 95 H (mean, 79 H).


Figure 1
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Fig. 1A Left adrenocortical carcinoma in 54-year-old woman. Axial contrast-enhanced CT images show attenuation value measured with region of interest (oval) over uniformly enhanced solid component of lesion to avoid lateral necrotic low-attenuation component. Dev = deviation. Portal venous phase.

 

Figure 2
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Fig. 1B Left adrenocortical carcinoma in 54-year-old woman. Axial contrast-enhanced CT images show attenuation value measured with region of interest (oval) over uniformly enhanced solid component of lesion to avoid lateral necrotic low-attenuation component. Dev = deviation. Axial delayed contrast-enhanced CT image at same level as A. Uniformly enhancing solid component shows minimal washout consistent with malignancy.

 
Delayed Contrast-Enhanced CT
Delayed attenuation values ranged from 55 to 70 H (mean, 63 H). All six lesions depicted with a delay time of 7-10 minutes had a relative percentage washout less than 40% (range, 14.4-32.1%; mean, 21.6%), a finding consistent with malignancy. The seventh lesion, which was depicted with a delay of 17 minutes, had a relative percentage washout of 14.8%, also consistent with malignancy. No lesion exhibited a wash-in phenomenon.


Discussion
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Materials and Methods
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Discussion
References
 
Although recognizing that 75% of the lesions are benign, the National Institutes of Health State-of-the-Science adrenal incidentaloma panel [20] has suggested that adrenal lesions larger than 6 cm in diameter be excised. Therefore, although size remains an important criterion for differentiating benign and malignant adrenocortical neoplasms, size alone is insufficient for differentiating relatively large ACCs from small ACCs. The medical literature contains scant information regarding the CT characteristics of ACC [21].

Studies of the washout profiles of adrenal masses have shown that such profiles can aid in successful differentiation of adenoma from malignant lesions [13, 14, 17, 22]. Pena et al. [17] compared the decrease in attenuation values on dynamic CT scans with the values on scans obtained with a 10-minute delay (range, 5-15 minutes) and found that adenomas have a relative percentage washout greater than 50%, regardless of the fat content of the mass. Malignant tumors have a relative percentage washout less than 50%. Using this technique, Pena et al. calculated a sensitivity of 98% and a specificity of 100% in the diagnosis of adrenal adenoma. In a similar study Caoili and coworkers [16] compared enhancement washout values at 15 minutes with portal venous enhanced attenuation values.

ACC has been included in the nonadenoma population in some studies of washout characteristics of adrenal lesions. Two studies by Szolar and Kammerhuber [12, 23] described three and six ACCs. Although specific details regarding the washout characteristics of those tumors were not reported, one can infer that the washout characteristics of the lesions were similar to those of other nonadenoma lesions. In two studies by Caoili et al. [16, 22], one ACC was included in the nonadenoma population, but specific washout analysis for ACC was reported in only the more recent publication [22]. The lesion was a 3-cm highly differentiated ACC with a relative percentage washout of 53% on scans obtained with a 15-minute delay. Although these enhancement washout figures are similar to those of an adenoma, the authors conceded that this tumor may have been an atypical example of ACC.

Although to our knowledge no specific results on the washout characteristics of large adrenal adenomas have been reported, studies addressing the relative percentage washout of adrenal adenomas have shown lipid-rich adenomas measuring 6.0 cm and lipid-poor adenomas measuring 4.2 cm that have relative percentage washout characteristics similar to those of smaller adenomas [16]. A critical factor in such lesions, however, is that applying the size criterion alone may result in a presumptive diagnosis of malignancy.

The results of our study showed that ACC has relative contrast washout characteristics similar to those previously determined for adrenal metastatic lesions and that ACC can be differentiated from adrenal adenoma on this basis. In our series, the mean relative percentage washout was 21% (range, 14.4-32.1%). This result compares favorably with the 2-43% range of relative percentage washout of nonadenomas previously reported by Pena et al. [17].

Our study had several limitations. First, it was an observational review and comprised a small number of cases. ACC is a rare tumor, however, and single-institution numbers of lesions visualized with delayed CT are limited. Second, the tumors in our series were, for the most part, large and presented with symptoms. Large tumors are already viewed clinically as suspicious and are more likely to contain areas of cystic degeneration, necrosis, and hemorrhage, all of which can complicate diagnosis with CT and the calculation of enhancement washout values. Third, the scanning techniques used to examine the lesions were not uniform. This limitation was largely the result of the retrospective nature of the study and the rarity of ACC. Studies have been conducted with nonuniform scanning, particularly varied slice thickness, in addressing contrast washout of adrenal lesions [16]. In our study the delays after injection of contrast material were not uniform. In five cases scans were obtained fewer than 10 minutes after injection. On this basis it can be argued that relative percentage washout was falsely low in these patients. Previous studies, however, have shown that a delay range of 5-15 minutes can be used with high sensitivity and specificity for differentiation of benign from malignant disease [16, 17]. Furthermore, as Korobkin et al. [14] have suggested, even at 45 minutes, metastatic lesions wash out by only approximately 30% on average in comparisons of delayed and dynamic attenuation profiles. This finding suggests that early delayed scanning (< 10 minutes) does not produce falsely low relative percentage washout. It is likely that the low relative percentage washout calculated in these patients would have remained less than 50% even at 15 minutes and perhaps even at 45 minutes. The longest delay in our series was 17 minutes, and the corresponding relative percentage washout was still less than 40%. Finally, given the range of delay times (7-17 minutes) after injection in our study, the absolute percentage washout was not calculated, because, to our knowledge, no previous comparative studies have been conducted with a delay of less than 15 minutes for assessment of absolute percentage washout of adrenal lesions. Furthermore, absolute percentage washout can be calculated only if investigators know the unenhanced CT attenuation value, which often is unavailable in clinical practice.

In conclusion, prospective studies of smaller tumors are necessary to determine whether washout values are helpful in differentiating adenomas from small carcinomas. Although size remains a critical factor in the evaluation of adrenocortical neoplasms, analysis of contrast washout characteristics may be a useful diagnostic adjunct for characterizing these lesions, particularly when size is indeterminate.


References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 

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