Genitourinary Imaging Review

Transcription

1 Genitourinary Imaging Review lake et al. drenal Imaging Genitourinary Imaging Review FOCUS ON: Michael. lake 1 Carmel G. Cronin Giles W. oland lake M, Cronin CG, oland GW Keywords: adrenal cortical carcinoma imaging, adrenal CT, adrenal imaging, adrenal lymphoma imaging, adrenal MRI, adrenal PET/CT, pheochromocytoma imaging DOI: /JR Received March 2, 2010; accepted without revision March 6, ll authors: Division of bdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., oston, M ddress correspondence to M.. lake (mblake2@partners.org). JR 2010; 194: X/10/ merican Roentgen Ray Society drenal Imaging OJECTIVE. drenal nodules are frequently encountered on current high-resolution imaging, and accurate characterization of such lesions is critical for appropriate patient care. Our article highlights how imaging techniques such as CT densitometry, CT washout characteristics, chemical shift MRI, PET, and PET/CT help characterize most adrenal lesions. We focus on these techniques as well as specifically, because of space constraints, the varied imaging appearances of adrenocortical carcinoma, pheochromocytoma, and lymphoma on these techniques. CONCLUSION. The imaging characterization of adrenal lesions has continued to advance over the past decade as new technologies have evolved. CT, MRI, PET, and PET/CT are now established clinical techniques capable of differentiating benign from malignant adrenal lesions. T he widespread use of imaging has led to increased detection of adrenal lesions and has underlined the importance of accurate adrenal lesion characterization [1, 2]. Indeed, it is essential to characterize any adrenal lesion in patients with a known cancer because many tumors may metastasize to the adrenal glands [3], and a metastasis might contraindicate a curative treatment of the patient and affect survival [4]. However, incidental adrenal nodules in patients with no known malignancy or endocrine abnormality are present in approximately 5% of all abdominal CT examinations [5, 6]. The incidence of an adrenal nodule further increases to 9 13% in patients being scanned for a known malignancy [5], but only 26 36% of such adrenal lesions are metastatic [7]. Furthermore, adrenal adenomas are seen more frequently in patients with certain inherited diseases, including multiple endocrine neoplasia type 1 and the Carney complex. The incidence of adenomas also increases with patient age, and about 6% of patients more than 60 years old have an adrenal adenoma [8]. The incidence of metastasis increases to 71%, however, if the adrenal lesion is larger than 4 cm or significantly increases in size within 1 year [9]. ccurate adrenal characterization in patients with a known primary carcinoma has major clinical importance because, for example, an isolated ipsilateral adrenal metastasis in a patient with resectable primary non small cell lung cancer is treated as localized disease. In these patients, resection of isolated adrenal metastasis has been shown to extend disease-free survival [10]. CT, MRI, and PET readily characterize many benign adrenal lesions from their characteristic diagnostic imaging features, including lipid-poor adenomas that can be identified by washout techniques and PET. small minority of adrenal masses, however, remain indeterminate after imaging. These may include metastases (however characterizable by follow-up), adrenocortical carcinoma (CC), lymphoma, and pheochromocytoma. variety of imaging techniques have been advocated in the literature to distinguish between benign and malignant adrenal lesions, and these techniques, along with the sometimes challenging appearances of CC, pheochromocytoma, and lymphoma on these techniques, are highlighted in this article. General morphologic imaging principles are also emphasized. General Morphologic Features The structural features of most adrenal lesions are usually not specific enough to allow them to be characterized with imaging alone. On unenhanced CT, imaging findings that are 1450 JR:194, June 2010

2 drenal Imaging more suspicious for malignancy include large lesion size, irregular margins, heterogeneous appearance, and growth in size. Lesions greater than 4 cm in diameter are more likely to be malignant, and if the patient has no other history of malignancy, an CC should be considered [11] (Fig. 1). Some myelolipomas also are large but are confidently recognized owing to the presence of macroscopic fat [12, 13] (Figs. 2 and 3). lthough adenomas tend to have a smooth contour and large malignant C Fig year-old woman who presented with left lower quadrant pain. C, rterial phase (), portal venous phase axial (), and coronal (C) images show well-encapsulated large 13.5-cm mass lesion arising from left adrenal gland with internal calcifications but containing no focal fat. Pancreas and left kidney are displaced by mass, but there is no evidence of invasion into adjacent vascular structures. On resection this mass represented adrenocortical carcinoma. lesions to have an irregular border, there is a very large overlap; some adenomas also show irregularity, and adrenal multinodularity is usually associated with benignity [14]. Shape is therefore not usually helpful for diagnosis. However, stability of a lesion signifies benignity because it is highly unusual for untreated malignant lesions to remain stable for more than 6 months [2, 15]. In contrast, any adrenal lesion that significantly increases in size over time can usually be considered malignant; some pitfalls include certain benign lesions (adenomas and myelolipomas) that rarely can increase in size but usually do so very slowly unless due to elevated levels of adrenocorticotropic hormone (CTH) as in patients with ectopic CTH secretion. In addition, hemorrhage into the adrenal gland will cause abrupt adrenal enlargement [13]. Many adrenal lesions, both benign and malignant, can be heterogeneous in attenuation, particularly after the JR:194, June

3 lake et al. administration of IV contrast medium. However, large areas of necrosis in a lesion usually signify malignancy. Most adrenal cysts can be characterized from their simple morphology, although some can be complex and are occasionally confused with necrotic malignancies [2, 15, 16]. CT Unenhanced CT adrenal densitometry takes advantage of the fact that around 70% of adrenal adenomas contain significant intracellular lipid (mainly cholesterol, fatty acids, and neutral fat), in contrast to almost all malignant lesions that do not [17 19]. The high intracellular lipid content lowers the unenhanced CT density of most adenomas. Lee et al. [17] first reported that unenhanced CT densitometry could effectively differentiate many adrenal adenomas from nonadenomatous disease. They found that the mean attenuation of adenomas ( 2.2 HU) was significantly lower than that of nonadenomas (28.9 HU). y using a threshold of 0 HU, these lesions could be then differentiated with sensitivity and specificity of 47% and 100%, respectively. Later, Korobkin et al. [18] showed that there is an inverse linear relationship between fat concentration and attenuation on unenhanced CT images. Conversely, almost all nonadenomatous lesions are low in intracellular fat, and their CT attenuation is consequently higher. meta-analysis [20] of published studies later found that if the CT attenuation threshold is raised to 10 HU, the test sensitivity becomes far higher (71%) while high specificity (98%) is maintained. In clinical practice therefore, 10 HU is the most widely used threshold value for the diagnosis of a lipid-rich adrenal adenoma. Song et al. [6] have shown that in 973 consecutive patients with 1,049 incidental adrenal masses adenomas accounted for 75% of incidental masses, of which 78% were lipidrich adenomas with native CT attenuation values of less than 10 HU. There are several limitations to unenhanced CT densitometry, however. Most standard CT scans are now obtained after IV contrast. Thus, unenhanced attenuation measurements cannot be made unless performed at dual-kilovoltage scanning, which provides the potential for a virtual unenhanced CT from an IV contrast-enhanced CT study. Furthermore, up to 30% of adenomas are lipid poor and have an attenuation value greater than 10 HU on unenhanced CT scans, as do almost all malignant lesions [2, 15, 17, Fig year-old woman with history of adrenal mass. CT image shows 3.4-cm partially calcified right adrenal mass containing small focus of macroscopic fat (measuring 40 HU), consistent with myelolipoma. 19, 21 26]. Therefore, lesions with an unenhanced CT attenuation greater than 10 HU require further evaluation to characterize them. further caveat is that two independent studies by Hahn et al. [27] and Stadler et al. [28] reported that different single-detector and MDCT helical scanners produce slightly different but statistically significant unenhanced attenuation levels, which sometimes could conceivably lead to erroneous categorization [29]. More recently, CT histogram analysis has been applied to both unenhanced CT and contrast-enhanced CT images [30 34]. ae et al. [30] have advocated this method as being more sensitive than the 10-HU threshold method for the diagnosis of adrenal adenoma. The technique involves placement of a region of interest (ROI) over approximately one half to two thirds of the adrenal surface area excluding areas of necrosis as is done for standard attenuation measurement. This ROI is further processed with a histogram analysis tool, which is now standard on most CT viewing workstations [30]. The individual attenuation values of all the pixels in the ROI are then plotted against their frequency. The amount of lipid in the mass is proportional to the number of negative pixels (less than 0 HU) within it. The study by ae et al. [30] showed that 97% of adenomas contain negative pixels. Eighty-five percent have more than 5% negative pixels, and 83% have more than 10% negative pixels. No metastases had negative pixels [34]. However, results of subsequent histogram analysis studies have varied, reporting negative pixels in both adenomas and nonadenomas, including metastases, pheochromocytomas, and CC [31, 32]. Ho et al. [33] reported a much lower percentage of lipid-poor adenomas (50%) exceeding 10% negative-attenuation pixels, compared with 100% of lipid-rich adenomas. Other authors report improved sensitivities of 85 91% while maintaining perfect specificity for adenomas [33, 34]. CT histogram analysis on unenhanced CT images can therefore be used as an adjunct to the CT attenuation values because the combination of CT attenuation value less than 10 HU or greater than 10% negative pixel content would correctly identify 91% of adenomas compared with 66% using CT attenuation values alone [33, 34]. On contrast-enhanced CT, a 10% or greater negative pixel threshold indicates an adenoma with sensitivity of 12% and specificity of 99%. lthough histogram analysis specificity for the diagnosis of adenomas on contrast-enhanced CT scans was high using a 10% negative pixel threshold, its low sensitivity limits its clinical usefulness [31, 32]. However, certainly it may occasionally obviate further imaging. The most practical clinical application of histogram analysis appears to be as an adjunct to unenhanced CT, where it can improve the sensitivity to almost 90% while maintaining high specificity for adenomas. Nevertheless, this methodology is scanner- and techniquedependent, and most departments do not yet routinely use this analysis method [31]. CT Washout Several authors [23, 26, 35] reported that although the CT densitometry method was unable to characterize adrenal lesions during the dynamic phase of a contrast-enhanced CT examination, it could be used on delayed (15 minutes to 1 hour) images. It was 1452 JR:194, June 2010

4 drenal Imaging C E Fig year-old man with some abdominal discomfort., CT image shows 12.3-cm well-defined heterogeneous mass arising from left adrenal that contains several areas of macroscopic fat. D, Fat manifests as T2 and T1 hyperintensity similar to extraadrenal fat on T2- weighted () and T1-weighted in-phase (C) images and shows loss of signal on fatsaturation (C) and out-of-phase (D) images. Mass contains areas of mild internal enhancement. Findings are consistent with large left adrenal myelolipoma. E, IV gadolinium-enhanced T1-weighted image shows that mass contains areas of mild internal enhancement. D JR:194, June

5 lake et al. TLE 1: bsolute Percentage Washout and Relative Percentage Washout Formulas Parameter found that adenomas enhance rapidly and also show a rapid loss of contrast medium a phenomenon termed contrast washout. Malignant lesions also enhance rapidly but usually show a slower washout of contrast medium due to leaky capillaries. It was further discovered that the ratio of attenuation values on the washout-delayed scan when compared with the initial dynamic contrast-enhanced study could help accurately characterize adrenal lesions [23]. lthough these findings were first reported on MRI, the technique was considered insufficiently reliable to be used in clinical practice [36]. Several studies, however, then described a more clinically robust CT method using percentage washout threshold values (Table 1) with high accuracies for the diagnosis of both lipid-rich and lipid-poor adrenal adenomas [2, 19, 26, 37, 38]. If a 15-minute delay after contrast administration protocol is used, an absolute percentage washout of 60% or higher has reported sensitivity of 86 88% and specificity of 92 96% for the diagnosis of an adenoma [19, 22]. In similar fashion, if a 10-minute delayed protocol is used, sensitivity of 100% and specificity of 98% have been obtained for a threshold absolute percentage washout value of 52% [38] (Fig. 4). If a 10-minute delay protocol is used, a relative percentage washout of 38 40% or higher has had reported sensitivity and specificity of 98% and 100% for the detection of adenoma [38]. fter 15 minutes, if a relative percentage washout of 40% or higher is achieved, sensitivity is 96% and specificity is 100% for the diagnosis of an adenoma [19]. lake et al. [38] also highlighted that an unenhanced CT attenuation value of 0 HU or lower should supersede the contrast washout characteristics and that noncalcified, nonhemorrhagic adrenal lesions with a native density of 43 HU or more should be considered indeterminate and suspicious for malignancy irrespective of their contrast washout characteristics [38]. Pheochromocytomas, although rare, may mimic both adenomas and malignant masses on both CT densitometry and washout [38], and some authors strongly advise considering a pheochromocytoma if the contrast-enhanced CT value is very high, for example, more than 150 HU [26]. However, in general, a combination of unenhanced CT, contrast enhancement, and washout characteristics correctly discriminates nearly all adrenal adenomas from malignant lesions. drenal PET/CT PET and PET/CT also have been shown to be valuable in the differentiation of adrenal masses [39]. drenal glands are larger than the spatial resolution of PET (about 5 mm), and, although rich in vascularity and metabolically active, they are usually not visible on PET alone. Combined PET/CT can assign adrenal tracer uptake to the location of the adrenal gland when present. agheri et al. [40] found only 5% (2/40) of normal adrenal glands could be visualized with PET alone, whereas 68% (27/40) were identified with integrated PET/ CT. With regard to standardized uptake value (SUV), the average maximum and mean SUVs are recorded in Table 2 [40]. drenal FDG uptake is considered to be of malignant origin when intensity is higher than hepatic uptake. lake et al. [41] found that of 32 benign adrenal masses, 30 showed 18 F-FDG activity on visual analysis of PET/CT that was less than that of the liver (specificity, 94%). However, the maximum SUV of normal adrenal glands ranged from 0.95 to 2.46, and given that normal liver tissue has an average mean SUV between 1.5 and 2.0, physiologic adrenal uptake might in some cases be in the range of malignant lesions. Caoili et al. [42] found significant differences only in SUV ratios (adrenal/ liver) but not in absolute SUVs in differentiating adrenal adenomas and metastases. Metser et al. [43] found using a maximum SUV of 3.1 for differentiating malignant from benign adrenal lesions had sensitivity and specificity of 98.5% and 92% for this Formula bsolute percentage washout 100 x (contrast-enhanced CT HU delayed CT HU) / (CT HU unenhanced CT HU) Relative percentage washout 100 x (contrast-enhanced CT HU delayed CT HU) / (CT HU) Note If unenhanced CT has been obtained, absolute percentage washout can be calculated by the formula shown. If no unenhanced CT is available, then relative percentage washout can be calculated by the formula shown. Contrast-enhanced scan performed at seconds. semiquantitative threshold. When they combined the SUV threshold with attenuation analysis from unenhanced CT (< 10 HU positive for adenoma), they found sensitivity of 100% and specificity of 98%. Furthermore, they found that FDG uptake was not significantly different between lipid-rich and lipidpoor adenomas sensitivity and specificity were 98.5% and 92% for differentiating lipid-poor adenomas and 98.5% and 93% for all adenomas. oland et al. [39] found that PET/ CT had sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 99%, 100%, 100%, 93%, and 99% for the detection of benign lesions and 100%, 99%, 93%, and 100%, respectively, for the detection of malignancy. In the study of Metser et al. [43], PET alone (maximum SUV, 3.1) achieved sensitivity, specificity, and accuracy of 99% (67 of 68 nodules), 92% (98 of 107), and 94% (165 of 175), respectively, compared with integrated PET/CT with values of 100% (68 of 68 nodules), 98% (105 of 107), and 99% (173 of 175), respectively. lso described were added advantages of small adrenal lesions detected on CT, which were correctly diagnosed on the PET component by evaluating tracer uptake [43]. Five percent of adrenal abnormalities interpreted as positive at PET are false-positive for malignancy. This is secondary to inflammatory lesions (sarcoidosis, tuberculosis [44]), adrenal endothelial cysts, some adrenal adenomas, and periadrenal abnormality [45], and adrenal cortical hyperplasia may all mimic metastases because they have been associated with increased FDG uptake. Metastasis detection at PET/CT, however, depends on the primary tumor, metastasis size, and differentiation. PET scanners have a spatial resolution of about 5 mm. Hemorrhage and necrosis are also known to cause TLE 2: verage Maximum and Mean Standardized Uptake Value (SUV) [40] drenal Gland verage Maximum SUV verage Mean SUV Right Left Note Data are range of indicated value JR:194, June 2010

6 drenal Imaging false-negative results in FDG PET [42, 46, 47]. Metastases from primary carcinomas that are non-fdg avid have been found to be false-negative on PET, including carcinoid (neuroendocrine tumors) and pulmonary carcinoma of the bronchioloalveolar type [46 48]. FDG PET cannot differentiate among malignant lesions, for example, among metastases, CC, malignant pheochromocytoma, and lymphoma. CC, Pheochromocytoma, and Lymphoma on drenal PET/CT CC echerer et al. [49] showed sensitivity and specificity of 100% and 95%, respectively, C D E Fig year-old woman with incidental adrenal mass. F, Right adrenal gland shows 1.1-cm lesion measuring 8 HU on unenhanced ( and ), 40 HU on dynamic phase (C and D), and 18 HU on 10-minute delayed phase images (E and F). These density and washout properties are consistent with adrenal adenoma. F JR:194, June

7 lake et al. (n = 10) for CC with FDG PET. They also found that PET detected additional lesions in 30% of cases. Leboulleux et al. [50] reported sensitivities of 90% and 93% for the detection of distinct lesions and the diagnosis of metastatic organs, respectively. With the recent use of 11 C-metomidate (METO), a marker of 11 beta-hydroxylase, Hennings et al. [51] found that METO PET had sensitivity and specificity of 89% and 96% for the identification of tumors of adrenocortical origin (n = 73). METO can distinguish adrenal metastases and pheochromocytomas from adrenocortical tumors (adenomas and CC); however, it cannot differentiate adenomas from CC. FETO, (R)- 1-(1-phenylethyl)- 1 H-imidazole-5-carboxylic acid 2-[ 18 F] fluoroethylester, has a longer halflife, allows longer imaging protocols, and is currently under investigation. However, presently FDG PET/CT remains the functional study of choice because it also may show additional sites of metastatic disease. Fig year-old man with extranodal marginal zone type -cell lymphoma now with transformation to diffuse large cell lymphoma of adrenals. and, There is nodular thickening measuring approximately 2.3 cm in thickness involving entire left adrenal gland with some preservation of its shape on CT image () with corresponding abnormal 18 F-FDG uptake on overlaid PET/CT image (). Pheochromocytoma The imaging technique of choice in localizing pheochromocytomas has been metaiodobenzylguanidine (MIG), which has high sensitivity (95 100%) and specificity (100%) [52]. Pheochromocytoma, whether benign or malignant, might accumulate FDG. It was reported, however, that among malignant pheochromocytomas, the percentage with increased uptake is higher than among benign pheochromocytomas [46]. Shulkin et al. [52] compared FDG PET with MIG and found sensitivity of 83% for the detection of benign pheochromocytomas, whereas FDG PET had sensitivity of 58%. For malignant pheochromocytomas, MIG had sensitivity of 88%, whereas FDG PET had sensitivity of 82%. lthough MIG had better sensitivity, all of the MIG-negative lesions showed avid FDG uptake. These authors concluded that most pheochromocytomas accumulate FDG, uptake is found in a greater percentage of malignant than benign pheochromocytomas, and FDG PET is especially useful in defining the distribution of those pheochromocytomas that fail to concentrate MIG. Newer PET-specific tracers for the sympathetic system, 11 C-hydroxyephedrine (HED) and 18 F-dihydroxyphenylalanine (F-DOP), are under investigation and have shown promising results [1]. Lymphoma PET/CT has been found to be valuable in distinguishing nonfunctioning adrenal neoplasm or hyperplasia from lymphomatous involvement (Fig. 5). The degree of FDG avidity in adrenal lymphoma tends to parallel that in other involved areas so that the resolution of adrenal gland uptake after treatment often follows that of uptake in other regions [43]. It should be remembered, however, that certain subtypes of lymphoma (for example, marginal zone and peripheral T-cell) and low-grade lymphomas may not show reliable FDG tumor uptake on the PET component. MRI and Developing MR Techniques MRI, with its inherent tissue characterizing ability, offers utility in the assessment of adrenal disorders. The normal adrenal is of low to intermediate signal on T1- and T2- weighted imaging. drenal adenomas usually show relatively uniform enhancement on immediate gadolinium-enhanced images [53]. Small, rounded foci of altered signal intensity may be seen within an adenoma owing to cystic changes, hemorrhage, or variation in vascularity. Chemical shift imaging (CSI) is the mainstay of MR evaluation of solid adrenal lesions. Visual analysis of CSI compared with splenic intensity is the most common mode of adrenal lesion analysis and has been reported to be as effective as quantitative assessments (defined at the end of this section) [54]. MRI identifies intracellular lipid because of the different resonant frequencies of fat and water protons in a given voxel [15, 54 59]. Fat protons precess at a lower frequency than water protons, and they thus cancel each other out during out-of-phase breath-hold gradient-echo MRI [59 62]. This phenomenon results in loss of signal intensity on out-of-phase imaging when compared with in-phase images (Fig. 6.). Korobkin et al. [18, 58] found an inverse linear relationship between the percentage of lipid-rich cells and the relative change in MR signal intensity on CSI. When there are almost equal concentrations of fat and water protons in most voxels, as is seen with lipid-rich adenomas, there will be almost complete signal intensity loss on out-of-phase images. Conversely, with a low lipid-to-water proton ratio, as may be seen in lipid-poor adrenal adenomas, 1456 JR:194, June 2010

8 drenal Imaging the signal intensity is essentially unchanged on out-of-phase images; such lesions remain indeterminate by CSI methods. Important caveats to be aware of, however, are CC, pheochromocytoma, and clear cell renal cell cancer metastasis, all of which may sometimes show signal loss on out-of-phase images. The sensitivity and specificity of CSI for the differentiation of incidental adrenal lesion are similar to those of unenhanced CT densitometry, at % and %, respectively [57, 59, 60]. Studies have shown that for lipid-rich adenomas, there is effectively no difference between CT and MRI, but CSI might be superior when evaluating lipid-poor adenomas [60]. However, one study [61] showed that CSI might be useful only when the unenhanced CT attenuation is less than 30 HU. In terms of quantitative analysis, calculation of the adrenal-to-spleen CSI ratio or the signal intensity index allows quantification of the chemical phenomenon (Table 3). CSI ratio of less than 0.71 or a signal intensity index of more than 16.5% both indicate a lipid-rich adenoma [62]. Diffusion MRI for drenal Lesions Published reports of diffusion analysis have so far been disappointing for adrenal assessment. Tsushima et al. [63] in a review of 43 adrenal tumors found no difference in apparent diffusion coefficient (DC) values between adenomas and metastatic tumors. Miller et al. [64] found similar results of DC values not being useful in distinguishing benign from malignant adrenal lesions (n = 160 lesions). MR drenal Spectroscopy Faria et al. [65] showed that using threshold values of 1.20 for the choline creatine TLE 3: Quantitative MRI drenal Chemical Shift Imaging nalysis Parameter ratio (92% sensitivity, 96% specificity; p < 0.01), 0.38 for the choline lipid ratio (92% sensitivity, 90% specificity; p < 0.01), and 2.10 for the lipid creatine ratio (45% sensitivity, 100% specificity) enabled adenomas and pheochromocytomas to be distinguished from carcinomas and metastases ppm/creatine ratio greater than 1.50 enabled distinction of pheochromocytomas and carcinomas from adenomas and metastases (87% sensitivity, 98% specificity; p < 0.01). The best distinction was obtained by comparing choline creatine and ppm/ creatine ratios. Further larger studies will be needed to validate these promising spectroscopic findings. CC, Pheochromocytoma, and Lymphoma on drenal MRI CCs are seen as heterogeneous on both T1- and T2-weighted imaging because of hemorrhage and necrosis [66]. Necrotic areas can have high signal intensity on T2- weighted imaging, and blood products can result in areas of high signal intensity within the lesion on T1-weighted imaging. CC can contain foci of intracytoplasmic lipid, which results in a loss of signal intensity on out-ofphase images a feature that could cause them to be erroneously diagnosed as benign adenomas (even at pathology [67]), although their usually large size and associated clinical findings alert the interpreting radiologist to this pitfall. The diagnosis of CC Formula drenal-to-spleen CSI ratio Lesion-to spleen SIIP / lesion-to-spleen SIOP drenal signal intensity index 100 x [(SIIP SIOP) / SIIP] Note SIIP and SIOP are the signal intensities measured on in-phase and out-of-phase images, respectively. also may be suggested on MRI or CT by its known propensity to spread via venous tumor thrombus. Lymphomatous lesions show washout characteristics similar to those of other primary or secondary adrenal malignancies. Lymphoma shows heterogeneous low signal intensity on T1-weighted images and heterogeneous high signal intensity on T2- weighted images [68], with progressive enhancement after administration of contrast material. Lymphoma can sometimes maintain the adreniform shape of the gland and so in its early stage could mimic adrenal hypertrophy or hyperplasia in contour. Up to 70% of pheochromocytomas show relatively high signal intensity on T2-weighted images a feature classically known as the light bulb sign, which was originally thought to be characteristic of pheochromocytoma [56, 69]. Currently, however, that description is not considered accurate, with at least 30% of pheochromocytomas showing moderate or low T2-weighted signal intensity and appearing similar to other adrenal diseases [15, 70]. Pheochromocytomas do not usually have significant cytoplasmic lipid and generally maintain their signal intensity on out-of-phase images, although exceptions are possible because fatty degeneration is sometimes known to occur [70 72]. Most lesions exhibit intense enhancement after contrast injection [73] (Fig. 7). t MR spectroscopy, pheochromocytomas were found to have a unique MR spectral sig- Fig year-old man with Cushing syndrome. and, MRI shows left adrenal nodule on in-phase image (), with marked loss of signal relative to splenic signal on out-of-phase image () consistent with lipid-rich adenoma. JR:194, June

9 lake et al. C Fig year-old woman with neurofibromatosis type 1 and history of resected left adrenal pheochromocytoma. Patient underwent left adrenalectomy. D, On T1-weighted images ( and ), 18-mm right adrenal nodule is heterogeneous in signal; however, on T2-weighted image (C), lesion is predominantly T2 hyperintense. This lesion shows no signal decrease on out-of phase image () and heterogeneous marked enhancement (D), features concerning for pheochromocytoma. nature, showing 6.8-ppm resonance that is not seen in adenomas and is attributed to the presence of catecholamines and catecholamine metabolites [74]. Conclusion The imaging characterization of adrenal lesions has continued to advance over the past decade as new technologies have continued to evolve. CT, MRI, PET, and PET/CT are now established clinical techniques capable of differentiating benign from malignant adrenal lesions. Developments in adrenal imaging, such as spectroscopy, also have shown promise as potentially useful adrenal applications. It is important to be knowledgeable about the imaging appearances of pathology that can affect the adrenal gland. The diminutive size of the adrenal gland belies its pivotal importance in medicine, and imaging now plays a critical role in adrenal pathology detection and characterization. References 1. oland GW, lake M, Hahn PF, Mayo-Smith WW. Incidental adrenal lesions: principles, techniques, and algorithms for imaging characterization. Radiology 2008; 249: Dunnick NR, Korobkin M. Imaging of adrenal incidentalomas: current status. JR 2002; 179: Lam KY, Lo CY. Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 2002; 56: Mitchell IC, Nwariaku FE. drenal masses in the cancer patient: surveillance or excision. Oncologist 2007; 12: ovio S, Cataldi, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 2006; 29: Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy. JR 2008; 190: Oliver TW Jr, ernardino ME, Miller JI, Mansour K, Greene D, Davis W. Isolated adrenal masses in nonsmall-cell bronchogenic carcinoma. Radiology 1984; 153: Libe R, ertherat J. Molecular genetics of adrenocortical tumours: from familial to sporadic diseases. Eur J Endocrinol 2005; 153: Frilling, Tecklenborg K, Weber F, et al. Importance of adrenal incidentaloma in patients with a history of malignancy. Surgery 2004; 136: Kocijancic I, Vidmar K, Zwitter M, Snoj M. The significance of adrenal metastases from lung carcinoma. Eur J Surg Oncol 2003; 29: Szolar DH, Melvyn Korobkin M, Reittner P, et al. D 1458 JR:194, June 2010

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