DOI: 10.1148/rg.266065057
RadioGraphics 2006;26:1811-1824
© RSNA, 2006
Integrated PET-CT for the Characterization of Adrenal Gland Lesions in Cancer Patients: Diagnostic Efficacy and Interpretation Pitfalls1
Semin Chong, MD,
Kyung Soo Lee, MD,
Ha Young Kim, MD,
Yoon Kyung Kim, MD,
Byung-Tae Kim, MD,
Myung Jin Chung, MD,
Chin A Yi, MD and
Ghee Young Kwon, MD
1 From the Department of Radiology and Center for Imaging Science (S.C., K.S.L., H.Y.K., Y.K.K., M.J.C., C.A.Y.), the Department of Nuclear Medicine (B.T.K.), and the Department of Pathology (G.Y.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, South Korea. Presented as an education exhibit at the 2005 RSNA Annual Meeting. Received April 6, 2006; revision requested May 15 and received May 30; accepted May 31. All authors have no financial relationships to disclose.
Address correspondence to K.S.L. (e-mail: kyungs.lee{at}samsung.com).
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Abstract
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Integrated fluorine-18 fluorodeoxyglucose positron emission tomography (PET)–computed tomography (CT) for adrenal gland imaging in cancer patients allows early detection and accurate localization of adrenal lesions and differentiation of metastatic nodules from benign lesions, thereby facilitating treatment planning.
However, false-positive findings are encountered at integrated PET-CT in approximately 5% of adrenal lesions identified as positive at PET, including adrenal adenomas, adrenal endothelial cysts, and inflammatory and infectious lesions. Moreover, false-negative findings may be seen in adrenal meta-static lesions with hemorrhage or necrosis, small-sized (<10-mm) metastatic nodules, and metastases from pulmonary bronchioloalveolar carcinoma or carcinoid tumors. An awareness of the potential pitfalls of integrated PET-CT enhances the diagnostic efficacy of this modality by allowing differentiation of metastatic adrenal lesions from other abnormalities.
© RSNA, 2006
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Introduction
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The detection of an adrenal lesion in patients with a known malignancy poses a diagnostic problem in terms of whether the lesion is a meta-static growth or a benign "incidentaloma." In addition, the accurate diagnosis of malignant adrenal involvement in cancer patients is required for evaluation of treatment approaches and prognostic assessments. Moreover, noninvasive evaluation of adrenal lesions is desirable to avoid unnecessary complications associated with adrenal biopsy. Dynamic computed tomography (CT) and chemical shift magnetic resonance (MR) imaging have been used to characterize adrenal lesions, with diagnostic accuracies of 81%–100% having been achieved (1–14).
Preliminary results suggest that fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can help characterize metabolically adrenal lesions and differentiate adrenal metastases from benign lesions (15,16). In recent studies, FDG PET showed excellent diagnostic performance in differentiating adrenal lesions detected at CT or MR imaging, with sensitivities of 93%–100%, specificities of 90%–94%, and accuracies of 92%–96% (17–19). Moreover, because FDG PET allows the evaluation of primary lesions as well as metastases, it can be cost effective and may be the modality of choice for the characterization of adrenal lesions, especially in patients with a malignancy.
The integrated PET-CT technique can produce directly functional PET and anatomic CT scans in one session. Moreover, these PET-CT findings are not simply the summation of PET and CT findings; rather, they benefit from a high level of synergism between the two modalities. In addition, PET-CT is superior to PET alone in differentiating benign from malignant adrenal lesions in cancer patients (20–22). In this article, we discuss and illustrate the diagnostic efficacy of integrated PET-CT in differentiating metastatic from benign adrenal lesions. In addition, we compare the efficacy of PET-CT with that of CT and MR imaging in this setting. We also identify the disease conditions that may produce false-positive or false-negative results at integrated PET-CT.
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Incidentalomas and Rates of Metastasis in Patients with an Extraadrenal Malignancy
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Adrenal metastases are observed at approximately 27% of postmortem examinations in patients with a malignant neoplasm of epithelial origin (23,24). The widespread use of state-of-the-art cross-sectional imaging modalities in patients with suspected upper abdominal or lower thoracic disease frequently leads to the detection of an unexpected adrenal nodule or mass (incidentaloma). The prevalence of incidentalomas in these patients has been reported to be 0.35%–5.0% at CT (25,26) and up to 8.7% at autopsy (27). The prevalence of metastatic nodules among nodules detected in the adrenal glands in cancer patients falls in the range of 38%–57% (21,28–30). In a series by Jana et al (20), 30 (38%) of 80 adrenal lesions proved to be metastatic, and according to Sung et al (31), 35 (57%) of 61 adrenal lesions in lung cancer patients proved to be metastatic.
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Image Acquisition and the Interpretation of Adrenal Lesions
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CT and Dynamic CT
The most helpful diagnostic CT features for distinguishing between a metastatic lesion and an adenoma are tumor size and attenuation value. Lesions 1 cm or less in diameter are more likely to be adenomas, whereas lesions 3 cm or larger are usually metastases (Fig 1). A more reliable distinction can be made by measuring the attenuation of a nodule on an unenhanced CT scan: Adrenal adenomas typically have homogeneous low attenuation, whereas metastases have high attenuation. However, approximately 30% of adenomas are lipid poor and have higher attenuation values that overlap with those of other adrenal lesions, including malignant lesions (32). One group of investigators analyzed the CT findings in 272 benign and 223 malignant adrenal tumors from 10 studies. Sensitivities for detecting benign lesions were 47% at a threshold of 2 HU or less and 88% at a threshold of 20 HU or less, and specificities were 100% at a threshold of 2 HU or less and 84% at a threshold of 20 HU or less (33). In adrenal lesions with homogeneous attenuation and smooth margins, unenhanced CT at a threshold of 10 HU or less had a sensitivity of 73% and a specificity of 96% for the diagnosis of adrenal adenoma (34,35). In addition, on the basis of data published prior to 2000, one group of investigators showed that unenhanced CT at a threshold of 10 HU or less was the most cost-effective means of differentiating adrenal adenoma from metastasis in patients with newly diagnosed lung carcinoma (Fig 2) (36). On unenhanced CT scans, noncalcified, nonhemorrhagic adrenal lesions with an attenuation of 43 HU or more prior to contrast enhancement are considered suspicious for malignancy. Moreover, the inconsistent behavior of pheochromocytomas should be kept in mind when assessing an adrenal mass at CT, especially in the appropriate clinical setting (6).
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Figure 1a. Metastatic adrenal mass from lung adenocarcinoma in a 52-year-old man. (a) Transverse contrast material–enhanced abdominal CT scan shows a 10-cm mass with central low attenuation (arrows) in the left adrenal gland. (b) Integrated PET-CT scan shows increased FDG uptake (maximum standardized uptake value [SUV], 12.8) in the left adrenal gland (arrows). (c) Photograph of the adrenonephrectomy specimen shows a large, well-defined, yellowish adrenal mass (arrows) superior to the left kidney (K).
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Figure 1b. Metastatic adrenal mass from lung adenocarcinoma in a 52-year-old man. (a) Transverse contrast material–enhanced abdominal CT scan shows a 10-cm mass with central low attenuation (arrows) in the left adrenal gland. (b) Integrated PET-CT scan shows increased FDG uptake (maximum standardized uptake value [SUV], 12.8) in the left adrenal gland (arrows). (c) Photograph of the adrenonephrectomy specimen shows a large, well-defined, yellowish adrenal mass (arrows) superior to the left kidney (K).
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Figure 1c. Metastatic adrenal mass from lung adenocarcinoma in a 52-year-old man. (a) Transverse contrast material–enhanced abdominal CT scan shows a 10-cm mass with central low attenuation (arrows) in the left adrenal gland. (b) Integrated PET-CT scan shows increased FDG uptake (maximum standardized uptake value [SUV], 12.8) in the left adrenal gland (arrows). (c) Photograph of the adrenonephrectomy specimen shows a large, well-defined, yellowish adrenal mass (arrows) superior to the left kidney (K).
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Figure 2a. Adrenal adenoma in a 50-year-old man with lung adenocarcinoma. (a) Transverse unenhanced CT scan shows a 29-mm lesion with homogeneous low attenuation of –8 HU (arrow) in the left adrenal gland, findings that suggest a fat-containing adenoma. (b) Integrated PET-CT scan shows little FDG uptake in the lesion (arrow), a finding that is consistent with a benign lesion. The lesion did indeed prove to be benign, showing no interval growth over a period of more than 12 months.
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Figure 2b. Adrenal adenoma in a 50-year-old man with lung adenocarcinoma. (a) Transverse unenhanced CT scan shows a 29-mm lesion with homogeneous low attenuation of –8 HU (arrow) in the left adrenal gland, findings that suggest a fat-containing adenoma. (b) Integrated PET-CT scan shows little FDG uptake in the lesion (arrow), a finding that is consistent with a benign lesion. The lesion did indeed prove to be benign, showing no interval growth over a period of more than 12 months.
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Multi–detector row CT scanners are commonly used for dynamic adrenal gland studies. Scanning is usually performed with the following parameters: 120–140 kVp, 200–300 mAs, 0.5–1.0-second gantry rotation time, 5–10-mm beam width, 1.2–1.5 pitch, and a 2.5-mm reconstruction thickness with a standard reconstruction algorithm. Initially, unenhanced images are obtained, after which 100–120 mL of contrast medium (300 mg of iodine per milliliter) is intravenously administered with a power injector at a rate of 2.5 mL/sec. Dynamic contrast-enhanced portal venous phase CT scans are normally obtained 75 seconds after starting the contrast medium injection. Delayed images may also be obtained 10 minutes after starting injection. On dynamic adrenal CT scans, relative and absolute percentage enhancement washout values can be calculated, and lesions with a relative percentage washout of 37%–50% (or more) or an absolute percentage washout of more than 60% may be regarded as benign adenomas (Figs 3, 4). Relative percentage washout is calculated with the following formula: washout percentage = 100 x ([EA – DA]/EA), where EA is attenuation (in Hounsfield units) on contrast-enhanced scans and DA is attenuation on delayed contrast-enhanced scans (usually at 10 minutes after starting injection). Absolute percentage washout is calculated as 100 x ([EA – DA]/[EA – attenuation value at unenhanced CT]).
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Figure 3a. Adrenal adenoma in a 60-year-old man with non–small cell lung cancer. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 34-mm ovoid mass (arrow) in the left adrenal gland. The calculated percentage washout was 68%, a finding that suggested adrenal adenoma. (c) Integrated PET-CT scan shows little FDG uptake in the mass (arrow) (maximum SUV, 2.1), a finding that helped confirm a benign adrenal lesion. The lesion showed no interval growth over a period of more than 12 months (cf Fig 2).
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Figure 3b. Adrenal adenoma in a 60-year-old man with non–small cell lung cancer. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 34-mm ovoid mass (arrow) in the left adrenal gland. The calculated percentage washout was 68%, a finding that suggested adrenal adenoma. (c) Integrated PET-CT scan shows little FDG uptake in the mass (arrow) (maximum SUV, 2.1), a finding that helped confirm a benign adrenal lesion. The lesion showed no interval growth over a period of more than 12 months (cf Fig 2).
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Figure 3c. Adrenal adenoma in a 60-year-old man with non–small cell lung cancer. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 34-mm ovoid mass (arrow) in the left adrenal gland. The calculated percentage washout was 68%, a finding that suggested adrenal adenoma. (c) Integrated PET-CT scan shows little FDG uptake in the mass (arrow) (maximum SUV, 2.1), a finding that helped confirm a benign adrenal lesion. The lesion showed no interval growth over a period of more than 12 months (cf Fig 2).
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Figure 4a. Metastatic adrenal nodule from renal cell carcinoma in a 61-year-old man. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show an inhomogeneous small nodule (arrow) in the right adrenal gland. The calculated absolute percentage washout was 49%, a finding that suggested a metastatic nodule. (c) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the right adrenal gland (arrow), a finding that is consistent with a malignant lesion. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of the adrenalectomy specimen shows malignant cells of the adrenal gland identical to those of hypernephroma.
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Figure 4b. Metastatic adrenal nodule from renal cell carcinoma in a 61-year-old man. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show an inhomogeneous small nodule (arrow) in the right adrenal gland. The calculated absolute percentage washout was 49%, a finding that suggested a metastatic nodule. (c) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the right adrenal gland (arrow), a finding that is consistent with a malignant lesion. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of the adrenalectomy specimen shows malignant cells of the adrenal gland identical to those of hypernephroma.
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Figure 4c. Metastatic adrenal nodule from renal cell carcinoma in a 61-year-old man. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show an inhomogeneous small nodule (arrow) in the right adrenal gland. The calculated absolute percentage washout was 49%, a finding that suggested a metastatic nodule. (c) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the right adrenal gland (arrow), a finding that is consistent with a malignant lesion. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of the adrenalectomy specimen shows malignant cells of the adrenal gland identical to those of hypernephroma.
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Figure 4d. Metastatic adrenal nodule from renal cell carcinoma in a 61-year-old man. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show an inhomogeneous small nodule (arrow) in the right adrenal gland. The calculated absolute percentage washout was 49%, a finding that suggested a metastatic nodule. (c) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the right adrenal gland (arrow), a finding that is consistent with a malignant lesion. (d) Photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of the adrenalectomy specimen shows malignant cells of the adrenal gland identical to those of hypernephroma.
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Chemical Shift MR Imaging
The results of initial MR imaging studies showed considerable overlap between the signal intensity characteristics of malignant and benign lesions on conventional spin-echo and gradient-recalled echo images. The ability to distinguish metastases from adenomas has improved considerably with the introduction of more sophisticated MR imaging techniques such as fat-saturated, chemical shift, and dynamic gadolinium-enhanced MR imaging (10,14,37–40). On fat-saturated spin-echo MR images, adrenal adenomas have a characteristic hyperintense rim. In one study of 48 patients, this sign was seen in 26 (93%) of 28 adenomas and in only one (5%) of 20 metastases (39). One group of investigators correlated the MR imaging findings with histologic results in 114 patients with 134 adrenal masses. Combined chemical shift and dynamic gadolinium-enhanced MR imaging was found to have a sensitivity of 91% and a specificity of 94% for differentiating benign from malignant adrenal masses (37).
For chemical shift MR imaging, we use dual-echo acquisition, in which both the in-phase and opposed-phase MR images are obtained during a single breath hold. Regions of interest are indicated on each adrenal lesion with a circle that covers more than two-thirds of the largest diameter of the lesion. Care is taken to avoid lesion edges due to chemical shift artifact. Identical regions of interest are drawn on both in-phase and opposed-phase MR images using the workstation "copy" and "paste" functions. A similar method is used to measure the signal intensities of the kidneys or spleen. The percentage decreases in signal intensity caused by phase differences (in phase versus opposed phase) are calculated, and signal intensities are normalized versus kidney or the spleen parenchyma. Malignant nodules usually show a signal intensity decrease of 20% or less (Fig 5).
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Figure 5a. Metastatic adrenal nodule from ovarian cancer in a 56-year-old woman. (a) Transverse contrast-enhanced CT scan shows a homogeneously enhancing nodule (arrow) in the left adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases. (d) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 5.2) in the left adrenal gland (arrow), a finding that is consistent with a malignant lesion.
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Figure 5b. Metastatic adrenal nodule from ovarian cancer in a 56-year-old woman. (a) Transverse contrast-enhanced CT scan shows a homogeneously enhancing nodule (arrow) in the left adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases. (d) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 5.2) in the left adrenal gland (arrow), a finding that is consistent with a malignant lesion.
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Figure 5c. Metastatic adrenal nodule from ovarian cancer in a 56-year-old woman. (a) Transverse contrast-enhanced CT scan shows a homogeneously enhancing nodule (arrow) in the left adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases. (d) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 5.2) in the left adrenal gland (arrow), a finding that is consistent with a malignant lesion.
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Figure 5d. Metastatic adrenal nodule from ovarian cancer in a 56-year-old woman. (a) Transverse contrast-enhanced CT scan shows a homogeneously enhancing nodule (arrow) in the left adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases. (d) Integrated PET-CT scan shows increased FDG uptake (maximum SUV, 5.2) in the left adrenal gland (arrow), a finding that is consistent with a malignant lesion.
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Integrated PET-CT
Before undergoing PET-CT, patients fast for at least 6 hours, although oral hydration with glucose-free water is allowed. After a normal blood glucose level in peripheral blood has been ensured, patients receive an intravenous injection of 370 MBq (10 mCi) of FDG and then rest for about 45 minutes before undergoing scanning. Scans are acquired with a PET scanner combined with a multisection CT scanner. The axes of the two systems are mechanically aligned such that a patient can be moved from the CT to the PET gantry by moving the examination table.
CT is performed from the head to the pelvic floor according to a standardized protocol. Patients maintain normal shallow respiration during CT, and immediately afterward, PET is performed with the identical transverse field of view. Acquisition time for PET is 5 minutes per table position (each frame). The CT data are resized from a 512 x 512 matrix to a 128 x 128 matrix to match the PET data so that scans can be fused and CT-based transmission maps generated. PET data sets are reconstructed iteratively using an ordered subset expectation maximization algorithm with segmented attenuation correction. Coregistered scans are then displayed on a workstation with commercially available software.
PET findings are interpreted as positive if the FDG uptake in an adrenal lesion is greater than or equal to that in the liver and as negative if lesion uptake is less than that in the liver. Because the liver often shows heterogeneous FDG uptake, the average visual liver uptake is used for comparison (Fig 6) (3,17,32). Recently, Metser et al (22) suggested that a maximum SUV of 3.1 or more is useful for differentiating malignant from benign adrenal lesions. However, a maximum SUV of 3.1 as a cutoff for malignant adrenal nodule detection is only a guideline, and care must be taken when the interpretation is based solely on the SUVs because this approach may produce false-negative results, especially in subcentimeter metastatic adrenal nodules.
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Figure 6a. Metastatic adrenal nodule from gastric cancer in a 61-year-old man. (a) PET scan demonstrates greater FDG uptake (maximum SUV, 5.7) in the left adrenal gland (arrow) than in the liver. (b) Photomicrograph (original magnification, x100; H-E stain) of the pathologic specimen shows malignant cells in the adrenal gland identical to those of gastric cancer.
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Figure 6b. Metastatic adrenal nodule from gastric cancer in a 61-year-old man. (a) PET scan demonstrates greater FDG uptake (maximum SUV, 5.7) in the left adrenal gland (arrow) than in the liver. (b) Photomicrograph (original magnification, x100; H-E stain) of the pathologic specimen shows malignant cells in the adrenal gland identical to those of gastric cancer.
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Relative Diagnostic Efficacies of PET (Integrated PET-CT), Dynamic CT, and Chemical Shift MR Imaging
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The diagnostic efficacies of helical dynamic CT with calculation of washout percentage on delayed scans are as follows: sensitivity, 61%–100%; specificity, 82%–97%; and accuracy, 81%–99% (Table 1) (1–7).
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Table 1. Reported Results of Dynamic CT in Differentiating Nonadenomatous Adrenal Lesions from Benign Adrenal Adenomas
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Chemical shift MR imaging with variable cutoff values for signal intensity decreases yielded sensitivities of 79%–100%, specificities of 82%–100%, and accuracies of 89%–100% for malignant adrenal lesions (Table 2) (8–13). However, chemical shift MR imaging had a specificity as low as 75% in lesions with high attenuation (20–30 HU) at unenhanced CT (14).
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Table 2. Reported Results of Chemical Shift MR Imaging in Differentiating Nonadenomatous Adrenal Lesions from Benign Adrenal Adenomas
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Preliminary results suggest that FDG PET can help characterize metabolically adrenal masses and help differentiate metastatic from benign adrenal lesions (15,16). Over the past 5 years, diagnostic sensitivities of 93%–100%, specificities of 90%–96%, and accuracies of 92%–96% have been achieved with FDG PET (17–20). Because FDG PET can be used to evaluate primary lesions as well as metastases, it can be cost effective and is the modality of choice for the characterization of adrenal lesions, especially in patients with a malignancy.
FDG PET–CT is better able to help differentiate benign from malignant adrenal lesions than is 18F-FDG PET alone. In one study of 175 adrenal masses in 150 patients (22), PET data alone (maximum SUV, 3.1) yielded a sensitivity, specificity, and accuracy of 99% (67 of 68 nodules), 92% (98 of 107), and 94% (165 of 175), respectively, and combined PET-CT data yielded corresponding values of 100% (68 of 68 nodules), 98% (105 of 107), and 99% (173 of 175). Moreover, specificity was significantly higher for PET-CT (P < .01) (Table 3).
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Table 3. Reported Results of PET or PET-CT in Differentiating Metastatic Adrenal Lesions from Benign Adrenal Lesions in Oncologic Patients
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PET-CT has somewhat higher and more consistent accuracy than dynamic CT or chemical shift MR imaging.
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Lesions That May Produce False-Negative Results at Integrated PET-CT
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Jana et al (20) reported two cases of false-negative adrenal lesions at FDG PET (maximum SUV, 2.1 and 2.3, respectively) in patients with a pulmonary carcinoid tumor. Metastatic lesions from pulmonary adenocarcinoma with a predominantly bronchioloalveolar carcinoma component may also show little FDG uptake at PET-CT (Fig 7). Hemorrhage and necrosis have been reported to be the other common causes of false-negative FDG PET results (17,20,22). Nodule size is another factor that contributes to a false-negative interpretation. According to a previous report (19) and in our experience, most metastatic adrenal nodules 10 mm or less in diameter showed lower uptake than the liver (Figs 8, 9). Subcenti-meter metastatic lesions will have less FDG uptake than large lesions because of the limited resolution of PET (currently in the range of 4–6 mm). Different criteria may be required for small lesions than for large lesions in the characterization of lesions as malignant.
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Figure 7a. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 7b. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 7c. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 7d. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 7e. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 7f. False-negative adrenal nodule at integrated PET-CT performed in a 59-year-old man with lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component. (a) Transverse contrast-enhanced CT scan shows a 15-mm ovoid nodule (arrow) in the right adrenal gland. (b, c) Transverse chemical shift in-phase (b) and out-of-phase (c) MR images show no signal intensity change in the nodule (arrow) between phases, a finding that indicates a high probability of metastasis. (d) Integrated PET-CT scan shows little FDG uptake (maximum SUV, 1.7) in the nodule (arrow), a finding that suggests a benign lesion. (e) Photograph of the right adrenalectomy specimen shows a solid, whitish, ovoid adrenal lesion (arrow). (f) Photomicrograph (original magnification, x100; H-E stain) of the specimen shows a metastatic lesion from lung adenocarcinoma with a predominantly bronchioloalveolar carcinoma component.
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Figure 8a. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 55-year-old man with hepatocellular carcinoma. (a) Transverse unenhanced CT scan shows a 7-mm round nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.1) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows a metastatic lesion from hepatocellular carcinoma.
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Figure 8b. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 55-year-old man with hepatocellular carcinoma. (a) Transverse unenhanced CT scan shows a 7-mm round nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.1) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows a metastatic lesion from hepatocellular carcinoma.
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Figure 8c. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 55-year-old man with hepatocellular carcinoma. (a) Transverse unenhanced CT scan shows a 7-mm round nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.1) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows a metastatic lesion from hepatocellular carcinoma.
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Figure 9a. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 58-year-old man with lung carcinoma. (a) Initial transverse contrast-enhanced CT scan shows a 6-mm ovoid nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.8) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) On a follow-up CT scan obtained 15 months after a, the nodule (arrow) is 17 mm in diameter, a finding that strongly suggests a metastatic nodule.
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Figure 9b. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 58-year-old man with lung carcinoma. (a) Initial transverse contrast-enhanced CT scan shows a 6-mm ovoid nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.8) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) On a follow-up CT scan obtained 15 months after a, the nodule (arrow) is 17 mm in diameter, a finding that strongly suggests a metastatic nodule.
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Figure 9c. False-negative metastatic adrenal nodule at integrated PET-CT performed in a 58-year-old man with lung carcinoma. (a) Initial transverse contrast-enhanced CT scan shows a 6-mm ovoid nodule (arrow) in the left adrenal gland. (b) Integrated PET-CT scan shows lower FDG uptake (maximum SUV, 2.8) in the left adrenal gland (arrow) than in the liver, a finding that suggests a benign lesion. (c) On a follow-up CT scan obtained 15 months after a, the nodule (arrow) is 17 mm in diameter, a finding that strongly suggests a metastatic nodule.
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Lesions That May Produce False-Positive Results at Integrated PET-CT
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Occasionally, adrenal adenomas demonstrate positive FDG uptake, at levels even higher than those in the liver; consequently, false-positive results can be expected in about 5% of adrenal adenomas (Fig 10) (4). It is not fully understood why some adenomas show increased FDG uptake, thereby simulating metastatic nodules. The functional state of an adenoma is presumed to be a factor in determining the intensity of FDG uptake, with increased uptake in functioning adrenal adenomas (41). In addition, pheochromocytoma of the adrenal gland (Fig 11) has been reported to show increased FDG uptake at PET (17). In our experience, an adrenal cortical hyperplasia without chronic inflammatory cell infiltration (Fig 12) and an adrenal endothelial cyst (Fig 13) also simulated metastatic nodules and showed increased FDG uptake.
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Figure 10a. False-positive adrenal adenoma at integrated PET-CT performed in a 63-year-old woman with lung adenocarcinoma. (a) Transverse contrast-enhanced CT scan shows a 21-mm heterogeneous nodule (arrow) in the left adrenal gland. (b) CT, FDG PET, and integrated PET-CT scans show increased FDG uptake (maximum SUV, 7.5) in the left adrenal gland (arrows). The adrenalectomy specimen showed adrenal adenoma.
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Figure 10b. False-positive adrenal adenoma at integrated PET-CT performed in a 63-year-old woman with lung adenocarcinoma. (a) Transverse contrast-enhanced CT scan shows a 21-mm heterogeneous nodule (arrow) in the left adrenal gland. (b) CT, FDG PET, and integrated PET-CT scans show increased FDG uptake (maximum SUV, 7.5) in the left adrenal gland (arrows). The adrenalectomy specimen showed adrenal adenoma.
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Figure 11a. Adrenal pheochromocytoma with increased FDG uptake at integrated PET-CT performed in a 33-year-old woman with multiple endocrine neoplasia type IIA. (a) Transverse contrast-enhanced CT scan shows a 4.5-cm mass (arrows) in the left adrenal gland. (b) CT, FDG PET, and integrated PET-CT scans show increased FDG uptake (maximum SUV, 5.6) in the left adrenal gland (arrows). The adrenalectomy specimen showed pheochromocytoma.
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Figure 11b. Adrenal pheochromocytoma with increased FDG uptake at integrated PET-CT performed in a 33-year-old woman with multiple endocrine neoplasia type IIA. (a) Transverse contrast-enhanced CT scan shows a 4.5-cm mass (arrows) in the left adrenal gland. (b) CT, FDG PET, and integrated PET-CT scans show increased FDG uptake (maximum SUV, 5.6) in the left adrenal gland (arrows). The adrenalectomy specimen showed pheochromocytoma.
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Figure 12a. False-positive adrenal cortical hyperplasia at integrated PET-CT performed in a 70-year-old man with squamous cell lung carcinoma. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 25-mm, ovoid nodular lesion (arrow) in the left adrenal gland. The calculated absolute percentage washout was 75%, a finding that suggested adrenal adenoma. (c) Coronal integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the nodule (arrow), a finding that suggests that the nodule is malignant. (d) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows cortical hyperplasia with no evidence of malignant cellular infiltration.
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Figure 12b. False-positive adrenal cortical hyperplasia at integrated PET-CT performed in a 70-year-old man with squamous cell lung carcinoma. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 25-mm, ovoid nodular lesion (arrow) in the left adrenal gland. The calculated absolute percentage washout was 75%, a finding that suggested adrenal adenoma. (c) Coronal integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the nodule (arrow), a finding that suggests that the nodule is malignant. (d) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows cortical hyperplasia with no evidence of malignant cellular infiltration.
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Figure 12c. False-positive adrenal cortical hyperplasia at integrated PET-CT performed in a 70-year-old man with squamous cell lung carcinoma. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 25-mm, ovoid nodular lesion (arrow) in the left adrenal gland. The calculated absolute percentage washout was 75%, a finding that suggested adrenal adenoma. (c) Coronal integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the nodule (arrow), a finding that suggests that the nodule is malignant. (d) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows cortical hyperplasia with no evidence of malignant cellular infiltration.
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Figure 12d. False-positive adrenal cortical hyperplasia at integrated PET-CT performed in a 70-year-old man with squamous cell lung carcinoma. (a, b) Dynamic contrast-enhanced early-phase (a) and delayed-phase (b) adrenal CT scans show a 25-mm, ovoid nodular lesion (arrow) in the left adrenal gland. The calculated absolute percentage washout was 75%, a finding that suggested adrenal adenoma. (c) Coronal integrated PET-CT scan shows increased FDG uptake (maximum SUV, 4.6) in the nodule (arrow), a finding that suggests that the nodule is malignant. (d) Photomicrograph (original magnification, x100; H-E stain) of the left adrenalectomy specimen shows cortical hyperplasia with no evidence of malignant cellular infiltration.
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Figure 13a. False-positive adrenal endothelial cyst with hemorrhage at integrated PET-CT performed in a 55-year-old man with squamous cell lung carcinoma. (a) Transverse contrast-enhanced CT scan shows a 7-mm enhancing nodule (arrow) in the left adrenal gland. (b, c) Coronal FDG PET (b) and integrated PET-CT (c) scans show increased FDG uptake in a lung mass (maximum SUV, 33.5) (arrowhead) and the left adrenal gland nodule (maximum SUV, 4.3) (arrow), findings that suggest that the nodule is malignant. The patient underwent left lower lobectomy and left adrenalectomy. At histopathologic examination, the adrenal lesion proved to be an endothelial cyst with hemorrhage.
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Figure 13b. False-positive adrenal endothelial cyst with hemorrhage at integrated PET-CT performed in a 55-year-old man with squamous cell lung carcinoma. (a) Transverse contrast-enhanced CT scan shows a 7-mm enhancing nodule (arrow) in the left adrenal gland. (b, c) Coronal FDG PET (b) and integrated PET-CT (c) scans show increased FDG uptake in a lung mass (maximum SUV, 33.5) (arrowhead) and the left adrenal gland nodule (maximum SUV, 4.3) (arrow), findings that suggest that the nodule is malignant. The patient underwent left lower lobectomy and left adrenalectomy. At histopathologic examination, the adrenal lesion proved to be an endothelial cyst with hemorrhage.
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Figure 13c. False-positive adrenal endothelial cyst with hemorrhage at integrated PET-CT performed in a 55-year-old man with squamous cell lung carcinoma. (a) Transverse contrast-enhanced CT scan shows a 7-mm enhancing nodule (arrow) in the left adrenal gland. (b, c) Coronal FDG PET (b) and integrated PET-CT (c) scans show increased FDG uptake in a lung mass (maximum SUV, 33.5) (arrowhead) and the left adrenal gland nodule (maximum SUV, 4.3) (arrow), findings that suggest that the nodule is malignant. The patient underwent left lower lobectomy and left adrenalectomy. At histopathologic examination, the adrenal lesion proved to be an endothelial cyst with hemorrhage.
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Suggested Diagnostic and Therapeutic Algorithm for Adrenal Lesions in Patients with an Extraadrenal Malignancy
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Abstract
Introduction
