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CENTURY OF
1906 2006
AJR IMAGING
MEDICAL
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 Giles W. Boland1
Keywords: adrenal gland, adrenocortical carcinoma, cancer, CT, contrast washout
DOI:10.2214/AJR.04.1751
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.
1Department of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital, 55 Fruit St., White 270C, Boston, MA 02114. Address correspondence to G. W. Boland (gboland@partners.org).
2Department of Radiology, Emory University Hospital, Alanta, GA.
3Department of Pathology, Massachusetts General Hospital, Boston, MA.
4St. Elizabeth’s Medical Center, Boston, MA 02135.
5Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.
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OBJECTIVE. The purpose of this study was to characterize pathologically proven adreno- cortical 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.
T he CT characteristics of adreno- cortical carcinoma (ACC) have been described [1-3]. ACC is typ- ically a large heterogeneous mass with irregular margins and inhomogeneous enhancement of solid components after IV administration of contrast medium. Data sug- gest that the size of an adrenocortical tumor measured with CT is a good predictor of ma- lignancy [4-7]. A review of six published se- ries [8] showed that 92% of ACCs (105/114 carcinomas) were larger than 6 cm in diame- ter. In contrast, most adrenocortical ade- nomas 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 diffi- cult to differentiate these tumors from ade- nomas. In the absence of metastatic disease, the differential diagnosis of small to interme- diate-sized tumors is ACC versus large adrenocortical adenoma or pheochromocy- toma [9]. Several reports have described the characteristics of adrenal masses on unen- hanced, contrast-enhanced, and delayed con- trast-enhanced CT scans for noninvasive dif- ferentiation of benign from malignant lesions [10-17]. The washout characteristics of adre- nal masses after IV contrast enhancement have improved the sensitivity and specificity of characterization of adrenal masses. How- ever, little specific information is available on the washout characteristics of ACC. The pur- pose 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 Patients
Our institutional review board approved this ret- rospective 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 adre- nal gland. The average size of the tumors was 9.8 cm in maximum diameter (range, 5.3-14 cm). Ac- cording to the staging criteria proposed by MacFar- lane [18] and modified by Sullivan et al. [19], two patients had stage II disease, four had stage III dis- ease, 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 in- terpreted as probable ACC on the basis of tumor size, but a benign adrenocortical tumor could not be morphologically excluded, and the patient under- went 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 ste- roid 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 ro- tation time, 7.5- to 15-mm table feed per gantry ro- tation, 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 injec- tor was used to administer 100-120 mL of 300 mg I/mL iodinated contrast material (Oxilan 300 [iox- ilan], Cook Imaging) through an antecubital vein at a rate of 2.5 mL/s. Dynamic contrast-enhanced im- ages were obtained after a scan delay of approxi- mately 75 seconds. Delayed images were obtained after a mean delay of 9.1 minutes (range, 7-17 min- utes) after contrast injection. Six of seven delayed scans were obtained 10 minutes or less after con- trast injection (three at 7 minutes, one at 9 minutes, and one at 10 minutes). The other scan was ob- tained 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-ar- chiving diagnostic workstation (Impax RS 3000 1K review station, AGFA Technical Imaging Sys- tems). All images were reviewed by two radiolo- gists. 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 adja- cent retroperitoneal fat or inhomogeneous ne- crotic regions. The region of interest covered a mean area of 2.8 cm2 (range, 1.9-4.3 cm2). Aver- age 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 at- tenuation of uniformly enhancing foci were cal- culated. Relative percentage washout (RPW) was calculated as follows:
RPW = 100 x enhanced H
(enhanced H-delayed H)
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 min- utes was considered a sign of malignancy. These values are consistent with previously published data [16, 17].
Results
The results are shown in Table 1.
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 af- ter a delay of 75 seconds for all lesions. All tu- mors had uniformly enhancing foci suitable for contrast washout analysis (Fig. 1). Atten- uation values on enhanced portal venous phase CT scans ranged from 64 to 95 H (mean, 79 H).
| Patient Data | CT Characteristics of Lesion | ||||||
|---|---|---|---|---|---|---|---|
| Age (y) | Sex | Size (cm) | Unenhanced CT (H) | Portal Venous Enhanced CT (H) | Delay (min) | Delayed CT (H) | Relative Percentage of Washout |
| 66 | F | 11.7 | 41.9 | 84.7 | 7 | 69.6 | 17.8 |
| 74 | M | 14.0 | 43.0 | 74.9 | 7 | 61.6 | 17.8 |
| 51 | F | 6.8 | 45.0 | 79.2 | 7 | 64.3 | 18.8 |
| 84 | F | 13.3 | 35.1 | 94.7 | 7 | 64.3 | 32.1 |
| 30 | F | 10.2 | 40.7 | 86.1 | 9 | 61.5 | 28.6 |
| 78 | F | 5.3 | 36.0 | 74.9 | 10 | 64.1 | 14.4 |
| 66 | M | 7.1 | 31.8 | 64.2 | 17 | 54.7 | 14.8 |
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 rela- tive percentage washout less than 40% (range, 14.4-32.1%; mean, 21.6%), a finding consis- tent with malignancy. The seventh lesion, which was depicted with a delay of 17 min- utes, had a relative percentage washout of 14.8%, also consistent with malignancy. No lesion exhibited a wash-in phenomenon.
Discussion
Although recognizing that 75% of the le- sions are benign, the National Institutes of Health State-of-the-Science adrenal inciden- taloma panel [20] has suggested that adrenal lesions larger than 6 cm in diameter be ex- cised. Therefore, although size remains an important criterion for differentiating benign and malignant adrenocortical neoplasms, size alone is insufficient for differentiating rela- tively 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 ade- nomas 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 diag- nosis of adrenal adenoma. In a similar study Caoili and coworkers [16] compared en- hancement washout values at 15 minutes with portal venous enhanced attenuation values.
ACC has been included in the nonadenoma population in some studies of washout char- acteristics 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 le- sions. 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 per-
CT of Adrenocortical Carcinoma
centage washout of 53% on scans obtained with a 15-minute delay. Although these en- hancement washout figures are similar to those of an adenoma, the authors conceded that this tumor may have been an atypical ex- ample of ACC.
Although to our knowledge no specific re- sults on the washout characteristics of large adrenal adenomas have been reported, studies addressing the relative percentage washout of adrenal adenomas have shown lipid-rich ade- nomas measuring 6.0 cm and lipid-poor ade- nomas 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 apply- ing the size criterion alone may result in a pre- sumptive diagnosis of malignancy.
The results of our study showed that ACC has relative contrast washout characteristics similar to those previously determined for adre- nal metastatic lesions and that ACC can be dif- ferentiated 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 nonad- enomas 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 le- sions visualized with delayed CT are limited. Second, the tumors in our series were, for the most part, large and presented with symp- toms. Large tumors are already viewed clini- cally as suspicious and are more likely to con- tain areas of cystic degeneration, necrosis, and hemorrhage, all of which can complicate diagnosis with CT and the calculation of en- hancement washout values. Third, the scan- ning 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 address- ing contrast washout of adrenal lesions [16]. In our study the delays after injection of con- trast 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, how- ever, 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 com- parisons of delayed and dynamic attenuation
profiles. This finding suggests that early de- layed scanning (< 10 minutes) does not pro- duce 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 min- utes 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 per- centage 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 abso- lute 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 differ- entiating adenomas from small carcinomas. Although size remains a critical factor in the evaluation of adrenocortical neoplasms, anal- ysis of contrast washout characteristics may be a useful diagnostic adjunct for characteriz- ing these lesions, particularly when size is in- determinate.
Area 2.45 cm
2
Avg 68.71 HU
Area 2.78 cm Avg 65.49 HU
2
Dev 23.30
Dev 23.24
A
B
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Slattery et al.
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