Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards
Ryan Chung, MD* · Joanie Garratt, MD* · Erick M. Remer, MD · Patrick Navin, MB BCh · Michael A. Blake, MB, BCh · Myles T. Taffel, MD · Caitlin E. Hackett, MD . Kedar G. Sharbidre, MD . Wendy Tu, MD, FRCPC . Gavin Low, MB, ChB, MPhil, MRCS, FRCR . Meredith Bara, MD . Benjamin W. Carney, MD, MS . Michael T. Corwin, MD . Michael J. Campbell, MD . James T. Lee, MD . Cortney Y. Lee, MD . Julie C. Dueber, MD . Mostafa A. Shehata, MD · Elaine M. Caoili, MD · Nicola Schieda, MD · Khaled M. Elsayes, MD
Author affiliations, funding, and conflicts of interest are listed at the end of this article. *R.C. and J.G. contributed equally to this work.
The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and ma- lignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appear- ances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided.
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RadioGraphics 2023; 43(7):e220191 https://doi.org/10.1148/rg.220191
Content Codes: CT, GU, MR
Abbreviations: ACC = adrenocortical carci- noma, ACTH = adrenocorticotropic hormone, FDG = fluorine 18 fluorodeoxyglucose, HCC = hepatocellular carcinoma, RCC = renal cell carcinoma
TEACHING POINTS
More recent data have shown that these values are not as specific for adeno- ma as previously believed, since other adrenal tumors such as pheochromo- cytoma, hypervascular metastases, and ACC also can meet these washout thresholds. Other features such as mass size, heterogeneity, and clinical con- text (eg, history of hypervascular malignancy or suspicion for pheochromocy- toma) must be taken into account when using washout CT.
Lipomatous and myelolipomatous degeneration occurs in primary adrenal tu- mors such as adenoma and rarely ACC. It is much less common than adrenal myelolipomas, which have a reported prevalence of up to 6%. At imaging, these areas of degeneration manifest as foci of macroscopic fat within an ad- renal lesion, but they comprise a small percentage of the nodule (mean, 14% of the tumor in one series).
” In a relatively recent study, nearly one-third of adenomas grew over time, all at a rate of less than 3 mm per year, as compared with all malignant nodules, which grew at a rate of greater than 5 mm per year. A growth rate of less than 3 mm per year distinguished the adenomas from the malignant nodules with a sensitivity and specificity of 100%.
Because the attenuation of simple fluid is less than or equal to 10 HU, a ho- mogeneous unilocular cystic adrenal lesion can mimic adenoma at nonen- hanced CT. Owing to their central hypoattenuation, cysts and pseudocysts may also mimic pheochromocytomas with cystic and/or necrotic change. A key feature of an adrenal cyst is its lack of enhancement.
Multiple prior studies have shown that between 17% and 67% of pheochromo- cytomas demonstrate an absolute washout of greater than or equal to 60% and a relative washout of greater than or equal to 40%. A nonenhanced CT attenuation of less than or equal to 10 HU in the solid portion of the tumor is highly specific for adenoma, rarely occurring in pheochromocytoma. In ad- dition, pheochromocytoma is characteristically hypervascular, manifesting as hyperenhancement during the portal venous phase.
Introduction
Adrenal tumors or tumor-like conditions are common in adults. An incidentally detected adrenal mass, or inciden- taloma, is found in approximately 5% of imaging examina- tions performed for reasons not attributable to adrenal disease (1). In the absence of known malignancy, adrenal incidentalo- mas are overwhelmingly benign, with fewer than 1% of them representing malignancy (2,3). However, because the adrenal gland is a common site of metastasis and primary adrenal tu- mors other than benign nonhyperfunctioning adenomas do occur, correctly diagnosing these other entities can be chal- lenging without an awareness of their common imaging ap- pearances or when there is overlap in imaging features.
The American College of Radiology (ACR) white paper on incidental adrenal masses (1) recommends against pursuing any adrenal mass measuring less than 1 cm in short axis to avoid ambiguity regarding the possibility of a mass in the set- ting of nodularity or thickening and the potential for overdi- agnosis and overtreatment of benign disease. In addition, the ACR white paper (1) provides guidance on the evaluation of adrenal masses based on their size, imaging features, and
presence or absence of malignancy. When measuring the size of an adrenal mass, we recommend measuring its longest axis in any plane to determine management.
In this article, we discuss the common and atypical im- aging appearances of adrenal adenoma, adrenocortical car- cinoma (ACC), adrenal cyst, pheochromocytoma, myeloli- poma, metastasis, bilateral adrenal disease, and select rare adrenal tumors and provide clues to the correct diagnosis. In addition, we highlight specific cases presented at multidisci- plinary tumor boards and discuss the roles of different imag- ing modalities, biopsy, and surgery in select cases to further guide appropriate management.
Adrenal Adenoma
Adrenal adenoma is the most common adrenal tumor (4). Lipid-rich adenomas, accounting for approximately 70% of adrenal adenomas, contain microscopic fat, resulting in an attenuation value of less than or equal to 10 HU on conven- tional nonenhanced CT images when a region of interest is placed on the central two-thirds of a homogeneous lesion (5). The less than or equal to 10 HU threshold holds true for ad- renal masses identified on virtual nonenhanced dual-energy CT images. Multiple studies (6-9) have shown that the atten- uation on virtual nonenhanced images is higher than that on true nonenhanced images across dual-energy CT platforms, allowing the radiologist to be confident that an attenuation of less than or equal to 10 HU on virtual nonenhanced images is diagnostic of adenoma. However, this comes with a decrease in sensitivity for the detection of adenoma.
A lipid-rich adenoma demonstrates qualitative and quan- titative loss of signal between in-phase and opposed-phase chemical shift imaging at MRI (10). There are multiple meth- ods of calculating quantitative signal loss, with the simplest and most widely used method known as the adrenal signal in- tensity index, with which regions of interest are placed over the adrenal mass on the in-phase and opposed-phase MR images. The adrenal signal intensity index is a ratio and is defined as [(SI - SI_)/SI_ _ ] x 100, where SI, is the in-phase signal inten- sity and SI „ is the opposed-phase signal intensity, with cutoff values of greater than 16.5% at 1.5 T and greater than 1.7% at 3T diagnostic of adenoma (10). Fat-containing adrenal masses are summarized in Table 1.
In the absence of the above imaging features, long-term (≥12 months) stability of a solid adrenal mass or slow growth (≤3 mm/year) is most suggestive of a benign tumor, most commonly adenoma (1,11,12). The diagnosis of an adrenal ad- enoma can be challenging when typical imaging features are absent, and stability cannot be established. Atypical imaging features of adenomas include lipid-poor adenoma, macroscopic fat, hemorrhage, iron, heterogeneity, large size, and growth.
Lipid-Poor Adrenal Adenoma
An adenoma with a paucity or absence of microscopic fat has a nonenhanced CT attenuation of 10 HU or greater and is inde- terminate. For some lipid-poor adenomas with a nonenhanced CT attenuation of 10-30 HU, MRI is useful for detecting micro- scopic fat on the basis of the signal loss on opposed-phase chem- ical shift MR images (13). However, MRI often does not show
| Fat Type Typical Masses | Atypical Masses | Tips |
|---|---|---|
| Microscopic Adenoma fat | Fat-containing metastasis (eg, RCC, HCC) ACC Pheochromocytoma | Fat-containing extra-adrenal malignancy may be present; in- creased T2-weighted signal intensity and heterogeneity are suggestive of RCC metastasis rather than adenoma ... ... |
| Macroscopic Myelolipoma fat | Adenoma with myelolipomatous degen- eration ACC with myelolipomatous degeneration Extra-adrenal fat-containing mass (lipo- sarcoma, RCC) | Consider biochemical testing for hypercortisolism for a mass with <50% macroscopic fat, as it may represent an adenoma ... Identify organ of origin |
| Note .- HCC = hepatocellular carcinoma, RCC = renal cell carcinoma. | ||
this signal loss when a lipid-poor adenoma has a nonenhanced CT attenuation of greater than 30 HU (Fig S1) (13-15). In this scenario, washout CT has generally been recommended to con- firm adenoma in homogeneous nodules larger than 2 cm, and follow-up CT has been recommended for nodules 1-2 cm (1).
On nonenhanced, 60- to 90-second postcontrast por- tal venous phase, and 15-minute postcontrast delayed phase adrenal washout CT images, most adrenal adeno- mas demonstrate an absolute percentage washout of 60% or greater and a relative percentage washout of 40% or greater (16,17). Absolute percentage washout is defined as [(HUDv- HUM)/(HUDv - HUnon)] x 100, and relative percentage washout is defined as [(HU - HU_)/(HU_)] x 100, where pv
pv
pv HU Dy HU ay, and HU , are the attenuations during the portal non venous, delayed, and nonenhanced phases, respectively (16). However, more recent data have shown that these values are not as specific for adenoma as previously believed, since other adrenal tumors such as pheochromocytoma, hypervascular metastases, and ACC also can meet these washout thresholds (18-20). Other features such as mass size, heterogeneity, and clinical context (eg, history of hypervascular malignancy or suspicion for pheochromocytoma) must be taken into account when using washout CT. Recent evidence has shown that the sensitivity of washout CT for an incidentally detected adrenal adenoma is lower than previously believed, ranging from 64% to 75% (18). In this instance, an adrenal mass that has been sta- ble for 12 months or longer is most likely to be benign (1,11,12).
If stability cannot be confirmed and the patient has no history of malignancy, then the mass is still most likely to be benign (2,3), and follow-up CT in 6-12 months is suitable for an adrenal mass with indeterminate attenuation and washout characteristics. However, due to its relatively low sensitivity for incidental lesions, washout CT may best be used for distin- guishing adenoma from metastasis in patients with a known history of nonhypervascular malignancy (21).
Metabolic imaging with fluorine 18 (18F) fluorodeoxyglu- cose (FDG) PET/CT is both sensitive and specific for differenti- ating benign from malignant lesions (22,23). On FDG PET/CT images, adrenal adenoma is mildly FDG avid (22). Although higher mean and maximal standardized uptake value (SUV) (SUV ___ and SUV_„, respectively) measurements for an ad- mean max’
renal lesion are sensitive for malignancy, they are less spe- cific because SUVs are susceptible to variability (22). Higher liver SUV ratio (adrenal lesion SUV _: liver SUV_) values
max mean and the blood pool SUV ratio (adrenal lesion SUV _: blood max® pool SUVman) are sensitive and specific for malignant adrenal lesions; a history of malignancy further increases specificity (23). Investigators in a relatively recent study (23) reported optimal liver SUV and blood pool SUV ratios of 2.5 and 3.4, respectively. Potential pitfalls include false-negative results for subcentimeter lesions, primary malignancies with low FDG avidity, and hemorrhagic or necrotic metastasis (22,23).
Adrenal Adenoma with Macroscopic Fat
On CT images, macroscopic fat has an attenuation of less than or equal to -20 HU. MRI shows loss of signal following the use of chemical selective fat-suppression sequences and India ink artifact at the interfaces between macroscopic fat and wa- ter on opposed-phase chemical shift images (24). Macroscopic fat within an adrenal mass is a classic feature of adrenal my- elolipoma (25). However, the amount of fat within a myelo- lipoma can vary considerably, and small foci of macroscopic fat are not necessarily diagnostic of a myelolipoma. In some instances, they represent lipomatous or myelolipomatous de- generation within an adenoma (Fig 1) (26).
Lipomatous and myelolipomatous degeneration occurs in primary adrenal tumors such as adenoma and rarely ACC (24,26,27). It is much less common than adrenal myelo- lipomas, which have a reported prevalence of up to 6% (3). At imaging, these areas of degeneration manifest as foci of macroscopic fat within an adrenal lesion, but they comprise a small percentage of the nodule (mean, 14% of the tumor in one series) (26,28). Compared with myelolipoma, which is overwhelmingly nonfunctioning, myelolipomatous degenera- tion within an adrenal lesion has been suggested in some case series to possibly be associated with adrenal corticosteroid ex- cess (26), although this requires validation in larger studies.
Adrenal Adenoma with Hemorrhage
Adrenal hemorrhage is most often unilateral, secondary to blunt trauma, or it may be bilateral, secondary to stress (eg, related to hypotension, sepsis, surgery, or burn), bleeding
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diatheses, or hypercoagulable states (4). In addition, unilat- eral hemorrhage can occur within an adrenal mass (primary or metastatic); this may be difficult to identify during the acute presentation, which commonly involves abdominal pain.
Hemorrhage within an adrenal adenoma is uncommon but is suggested by interval enlargement of a previously characterized adenoma (Fig 2). CT generally shows hetero- geneous enlargement, with areas of hemorrhage demonstrat- ing hyperattenuation (50-90 HU) on nonenhanced images and no enhancement following contrast material adminis- tration (4,29). With dual-energy CT, areas of hemorrhage, as opposed to soft tissue within a mass, do not enhance be- tween virtual nonenhanced images and postcontrast images or demonstrate uptake on iodine-enhanced images (30).
Hemorrhage depicted at MRI is age dependent, but it is generally recognizable as nonenhancing T1-hyperintense
and T2-hypointense signal (4,29). Areas of hemorrhage can obscure enhancing soft tissue because of intrinsic T1-hyper- intense signal. Subtraction images are key to identifying en- hancing soft tissue that is diagnostic of an underlying mass with hemorrhage (4,29).
Identifying enhancing soft tissue can be challenging in the acute setting. Furthermore, rapid or marked enlarge- ment of an adrenal mass due to hemorrhage can be difficult to distinguish from growth of a malignant mass. There are no established guidelines for follow-up to assess for an un- derlying mass after resolution of hemorrhage (31); however, follow-up imaging is often warranted, and 6-12 weeks after resolution of the hemorrhage is reasonable. Of note, mild elevation of plasma normetanephrine levels can occur sec- ondary to hemorrhage and irritation of medullary cells (32). The adrenal masses that may have hemorrhage are summa- rized in Table 2.
Adenoma with Iron Deposition
Iron deposition within the reticuloendothelial system (eg, liver, spleen, and bone marrow) results in decreased signal intensity with all MRI pulse sequences, is most pronounced on T2 *- weighted MR images, and demonstrates loss of signal on in-phase (sequence with the longer echo time) compared with opposed-phase MR images (33). Iron deposition can oc- cur within a normal adrenal cortex following red blood cell transfusion and intravenous administration of ultrasmall superparamagnetic iron oxide particles (34). Iron deposition can also occur within an adrenal adenoma and result in sig- nal loss with all MRI sequences, particularly on in-phase and opposed-phase chemical shift MR images (Fig 3) (20). This dis- rupts the typical signal loss at opposed-phase imaging that is
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Table 2: Adrenal Masses with Hemorrhage
Atypical masses
Pheochromocytoma (most common) Metastasis Adrenocortical carcinoma
Myelolipoma
Adenoma
Tips
Perform dual-energy CT or MRI to identify un- derlying mass
Perform follow-up imaging in 6-12 weeks to assess for underlying mass after hemorrhage has resolved
No adrenal masses typically have hemorrhage
characteristic of microscopic fat within an adenoma and may mimic chronic hemorrhage or calcifications. Prior imaging findings, the clinical history, and iron deposition in the retic- uloendothelial system are important clues to the diagnosis. Adrenal washout CT may help identify an adenoma with iron deposition because the washout characteristics are not affected by iron deposition; however, to our knowledge, this has not been demonstrated.
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Heterogeneous Adrenal Adenoma
Adenomas classically demonstrate homogeneity on CT and MR images; heterogeneity of an adenoma is atypical. Hetero- geneity within an adenoma may arise owing to macroscopic fat or hemorrhage (Fig 1). Prospectively, heterogeneous ad- enomas may be difficult to differentiate from metastasis, pheochromocytoma, or ACC, particularly when they are large (35). Heterogeneous microscopic fat, seen as signal loss in less than 80% of the mass at opposed-phase chemical shift MRI, indicates a high likelihood of benignancy in patients with- out prior cancer. This also holds true for adrenal nodules in patients with most malignancies. However, the radiologist should be cautious in the setting of patients with fat-contain- ing malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) or when the morphologic pat- tern of signal loss is suggestive of a collision tumor (with two distinct parts or peripheral signal loss) (35). It is reasonable to perform short-interval follow-up CT to demonstrate stability that supports a benign lesion.
Large Adrenal Adenoma
A 4-cm or larger adrenal adenoma is atypical, but it often has imaging features that are seen in smaller adenomas, includ- ing homogeneity and well-circumscribed margins without lo- cal invasion (36). However, a 4-cm or larger adrenal mass has a higher rate of malignancy than a mass smaller than 4 cm (4,37). A 4-cm threshold is sensitive (up to 93%) but less spe- cific for malignancy than a 6-cm cutoff (38). In one study in- volving 705 adrenal tumors (39), the prevalence of malignancy in adrenal lesions larger than 4 cm was 31%, and the risk of malignancy increased proportionally with tumor size. How- ever, malignancy cannot be determined by size alone; older age at diagnosis and higher attenuation at nonenhanced CT (>20 HU) are additional predictors of malignancy (39). In ad- dition, ACC is often heterogeneous with cystic and/or necrotic
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change, hemorrhage, or invasion of adjacent organs or veins, and nearly 70% of ACCs are 6 cm or larger (4,37).
It may be impossible to distinguish a large atypical adenoma from an ACC or other malignant mass with imaging because of overlapping imaging features. If there are no benign diag- nostic features, evaluation of the clinical context, including hormonal assessment, is essential for assessing the need for surgical resection of a 4-cm or larger adrenal mass (Fig 1) (39). Patients with a large adrenal mass should be managed by a multidisciplinary team that includes surgeons, endocri- nologists, and radiologists (39).
Slow Growth of Adenoma
Stable size of an adrenal mass for 12 months or longer is sug- gestive of benignity, whereas significant growth is suggestive of malignancy (1,11,12). Because adrenal adenoma is over- whelmingly the most common benign adrenal neoplasm, it is the presumed diagnosis in cases of a stable adrenal mass (40). Conversely, growth of an adrenal mass is suspicious for a nonadenoma. However, in a relatively recent study (11), nearly one-third of adenomas grew over time, all at a rate of less than 3 mm per year, as compared with all malignant nodules, which grew at a rate of greater than 5 mm per year. A growth rate of less than 3 mm per year distinguished the adenomas from the malignant nodules with a sensitivity and specificity of 100% (Fig S2) (11). The growth rates of adrenal masses are summarized in Table 3.
Adrenocortical Carcinoma
ACC is a rare malignant tumor of the adrenal cortex with a bimodal distribution, affecting children younger than 5 years and adults in their 4th to 5th decade of life (37). Pa- tients may present with abdominal pain, distention, or a palpable mass. ACC may produce excess cortisol, androgen, estrogen, or aldosterone levels, although hormonal excess may be absent (39).
ACC is typically a large circumscribed mass with hetero- geneous attenuation due to cystic and/or necrotic change, hemorrhage, and calcification (37,41). Smaller ACCs may be homogeneous and difficult to distinguish from adenomas, particularly if they are smaller than 4 cm. On nonenhanced CT images, ACC rarely has an attenuation lower than 20 HU, which helps differentiate it from adenoma (2). ACC en- hances heterogeneously, with areas of central nonenhance- ment due to necrosis or hemorrhage (37,41). Although data are limited, ACC often shows an absolute washout of less than 60%, but it may exceed washout thresholds that are compatible with adenoma (Fig S3) (37,41).
On MR images, ACC demonstrates heterogeneous signal intensity with variable amounts of nonenhancing central T2-hyperintense signal (cystic and/or necrotic change) and intrinsic T1-hyperintense signal (hemorrhage) (42,43).
On both CT and MR images, a 4-cm or larger adrenal mass increases the likelihood of ACC, with up to 70% of ACCs presenting as a 6-cm or larger mass (37). Kahramangil
| Growth Rate | Typical Masses | Atypical Masses | Tips |
|---|---|---|---|
| <3 mm/y | Adenoma, myelolipoma, cyst or pseudocyst | Not applicable | Adenomas can grow up to 3 mm/year |
| >5 mm/y | Metastasis, ACC, pheo- chromocytoma | Myelolipoma (in the setting of congen- ital adrenal hyperplasia and medica- tion nonadherence) | Malignancies tend to grow 5 mm or more per year; rapid growth can cause or result from acute hem- orrhage |
| Table 4: Adrenal Masses with Cystic and/or Necrotic Change | |
|---|---|
| Typical Masses | Tips |
| Cyst | Perform adrenal washout CT, dual-energy CT, or gadolinium-enhanced MRI to assess for enhancement |
| Metastasis | Masses should be suspected in the presence of extra-adrenal malignancy, new or rapid growth of an adrenal mass, multiple adrenal masses, or other metastases |
| Pheochromocytoma (common) ACC | Perform biochemical evaluation for adrenal mass <4 cm with cystic and/or necrotic change and hyperenhancement, even if absolute washout is ≥ 60%, because these features are common in pheochromocytoma; look for a thick- ened rind of enhancing soft tissue to distinguish cyst from cystic and/or necrotic change |
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et al (2) reported an ACC prevalence of 1.7% among 2219 ad- renal incidentalomas, with ACC rates by size of 0.1%, 2.4%, and 19.5% for adrenal incidentalomas smaller than 4 cm, 4-6 cm, and 6 cm or larger, respectively. Another group of authors (44) reported prevalences of 0.2%, 4.8%, and 37.7%, respectively, in their cohort of 2498 adrenal incidentalomas, in which 18 of 214 resected tumors were ACCs. Additional clues to the diagnosis of ACC include irregular margins, lo- cal invasion of adjacent organs, venous invasion or tumor thrombus, and metastases. The adrenal masses with cystic and/or necrotic change are summarized in Table 4.
ACC rarely contains microscopic fat (45) or macroscopic fat (37,41,46). ACC with macroscopic fat usually occurs in a mass larger than 6 cm that is heterogeneous and invasive, with macroscopic fat comprising less than 5% of the mass
(46). Furthermore, patients are often symptomatic, or there are other factors that herald the correct diagnosis (46).
ACC is an FDG-avid tumor, and FDG PET/CT may help in identifying the primary tumor or evaluating for local recur- rence or metastasis (42). The role of biopsy for indeterminate adrenal lesions is controversial. Percutaneous biopsy of ACC in particular is often avoided because of the risk of tumor seeding along the needle track, capsule breakdown, and dif- ficulty reliably distinguishing ACC from adenoma in biopsy specimens (21). However, the benefits of biopsy may exceed the risks in patients who are poor surgical candidates (37).
Adrenal Cyst
Adrenal cyst is a differential diagnosis for a low-attenuation (0-20-HU) adrenal lesion (Fig S2). There are four types of adrenal cysts: endothelial-vascular, pseudocyst, epithelial, and parasitic (4). Endothelial cysts and pseudocysts make up more than 80% of all adrenal cysts (4). All adrenal cysts demonstrate simple fluid attenuation with varying degrees of loculation, septa, and calcification. Endothelial and ep- ithelial cysts are usually thin walled and multilocular and can contain septal calcifications, whereas pseudocysts have a slightly thicker wall, are unilocular, and can contain pe- ripheral calcifications (Fig 4). A pseudocyst arises from prior hemorrhage. Parasitic (echinococcal) cysts have the thickest walls, are unilocular or multilocular, and can contain pe- ripheral calcifications and daughter cysts.
Because the attenuation of simple fluid is less than or equal to 10 HU, a homogeneous unilocular cystic adrenal lesion can mimic adenoma at nonenhanced CT. Owing to their central hypoattenuation, cysts and pseudocysts may also mimic pheochromocytomas with cystic and/or ne- crotic change. A key feature of an adrenal cyst is its lack of enhancement.
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On US images, a cyst is anechoic with varying degrees of wall thickening, septation, and echogenic shadowing calcifications. With adrenal washout CT, one can easily dis- tinguish a cyst from an adenoma, because an adenoma en- hances while a cyst does not. MRI shows hyperintensity on T2-weighted images (Fig 5), hypointensity on T1-weighted images, and no enhancement on gadolinium-enhanced im- ages. Macroscopic fat and microscopic fat are absent. There is a paucity of data on whether follow-up imaging is needed, and there are no guidelines for determining the frequency and duration of follow-up imaging (47,48).
Pheochromocytoma
Pheochromocytoma is a rare catecholamine-secreting neuro- endocrine tumor that develops from the chromaffin cells of the adrenal medulla, and it occurs most often in middle-aged adults. As most pheochromocytomas are hormonally active, patients may present with symptoms such as palpitations, headache, diaphoresis, and signs of hypertension (49). How- ever, these tumors are incidentally diagnosed with imaging, ac- counting for up to 3%-5% of adrenal incidentalomas (10,21,43).
Although most pheochromocytomas develop sporadically, approximately one-third of them are associated with germline mutations (19). Compared with sporadic pheochromocytoma, hereditary pheochromocytoma is more often asymptomatic and associated with lower 24-hour urinary normetanephrine levels, smaller size at detection, and detection in younger pa- tients (19).
A suspected diagnosis of pheochromocytoma must be confirmed with biochemical testing, including analysis of elevated plasma or 24-hour urine fractionated metanephrine levels (43,49). Biopsy is not recommended; instead, surgical resection is required to avoid the sequelae from excess cate- cholamine levels (21,43).
Patients who have bilateral adrenal masses without diag- nostically benign features (eg, nonenhanced CT attenuation of ≤10 HU) or other cysts or tumors associated with a pheochro- mocytoma syndrome should be evaluated with biochemical testing for pheochromocytoma (Fig 6). This workup should be performed regardless of whether the adrenal masses demon- strate washout consistent with adenoma, as pheochromocy- toma may meet these thresholds.
At MRI, approximately two-thirds of pheochromocytomas show increased signal intensity, described as being “light-bulb bright,” on T2-weighted images (20). This imaging feature overlaps with the T2 hyperintensity from cystic changes in adenomas and pheochromocytomas. Use of the quantitative T2-weighted signal intensity ratio has been shown to improve sensitivity and specificity in differentiating pheochromocy- toma from other lesions (20,50). For instance, Borhani and Hosseinzadeh (50) reported that an adrenal-to-muscle signal intensity ratio of at least 3.95 at 1.5-T MRI was 81% sensitive and 88% specific for diagnosing pheochromocytoma.
Between 22% and 97% of pheochromocytomas demon- strate cystic and/or necrotic change (19,21,51). Cystic and/or necrotic change is defined as a focal central area of low atten- uation subjectively similar to fluid attenuation within a solid mass or nodule on CT images and hyperintense signal on T2- weighted MR images, without corresponding enhancement. It is an imaging appearance, but it does not imply a patho- logic diagnosis of necrosis (52). On images, the distinguishing feature of pheochromocytoma with a cystic and/or necrotic appearance is a thick enhancing wall that retains contrast en- hancement on delayed postcontrast images (Fig 7) (49); septa may or may not be present (52). In the case of an incidental solid adrenal mass with cystic and/or necrotic change, pheo- chromocytoma should be strongly considered (21). Labora- tory evaluation is recommended to confirm the diagnosis.
A large pheochromocytoma can exert mass effect or in- vade adjacent structures; this may make distinguishing pheochromocytoma from ACC difficult, as cystic and/or ne- crotic change, heterogeneity, and enhancement can be seen in both of these tumors (Fig 8). Metastases can occur with
both pheochromocytoma and ACC. It should be noted that all pheochromocytomas have metastatic potential, diagnosed on the basis of the presence of chromaffin cells at sites outside of their normal location (adrenal gland and sympathetic and para- sympathetic ganglia) (53). Although both pheochromocytoma and ACC may develop sporadically, a predisposing hereditary mutation may favor one diagnosis over the other. Additional clues include elevated metanephrine levels (for pheochromo- cytoma) or elevations of other hormones such as cortisol, an- drogen, estrogen, and aldosterone (for ACC) (37).
Pheochromocytoma with Greater than 60% Contrast Material Washout
Multiple prior studies have shown that between 17% and 67% of pheochromocytomas demonstrate an absolute washout of greater than or equal to 60% and a relative washout of greater than or equal to 40% (Fig 9) (18-20,54,55). A nonenhanced CT attenuation of less than or equal to 10 HU in the solid portion of the tumor is highly specific for adenoma, rarely occurring in pheochromocytoma (19). In addition, pheochromocytoma is characteristically hypervascular, manifesting as hyperen- hancement during the portal venous phase. Several portal venous phase attenuation thresholds to distinguish pheochro- mocytoma from adenoma have been studied: greater than or equal to 130 HU was 38% sensitive and 100% specific (55), and greater than or equal to 85 HU was 88% sensitive and 84% specific (54). In addition to the aforementioned features, a proposed modified criterion to distinguish adenoma from pheochromocytoma includes one of the following: (a) lesion attenuation of greater than or equal to 40 HU at nonenhanced CT, (b) lesion attenuation of greater than or equal to 160 HU at portal venous phase CT, (c) lesion attenuation of greater than or equal to 70 HU at 15-minute delayed CT, or (d) in- tralesional cystic degeneration at portal venous phase CT and 15-minute delayed phase CT (56). We recommend biochem- ical testing for pheochromocytoma when an adrenal mass demonstrates cystic and/or necrotic change or has a portal venous phase CT attenuation of greater than or equal to 130 HU, even if the washout threshold is suggestive of adenoma.
If there is ongoing high clinical suspicion for pheochro- mocytoma despite negative biochemical testing results, mo-
lecular imaging with gallium 68 (68Ga)-labeled somatostatin analogs (68Ga-DOTA Phel-Tyr3-octreotide, 68Ga-tetraazacy- clododecane tetraacetic acid-octreotate, and 68Ga-DOTA NaI3-octreotide), 18F-fluorodopamine, 18F-fluorodihydroxy- phenylalanine (18F-DOPA), or 123I-metaiodobenzylguanidine (123I-MIBG) may confirm pheochromocytoma. Note that the reported sensitivities of 68Ga-labeled somatostatin analogs are greater than those of 18F-fluorodopamine and 18F-DOPA, and the reported sensitivities of 18F-fluorodopamine and 18F-DOPA are greater than those of 123I-MIBG (57). In ad- dition to aiding in the diagnosis of pheochromocytoma in the setting of equivocal biochemical or anatomic imaging results, molecular imaging can be used to assess the local-re- gional extent of disease, identify tumor multiplicity and me- tastasis, and detect therapeutic molecular targets (57).
Pheochromocytoma with Hemorrhage
Hemorrhage is a rare complication; however, pheochromo- cytoma is the most common primary tumor to hemorrhage. Although the underlying mechanism of pheochromocy- toma with hemorrhage is unknown, some theories suggest increased intracapsular pressure from trauma, a rapidly enlarging tumor that outgrows its blood supply, and vaso- dilatation and interstitial hemorrhage caused by the use of antihypertensive medications. Patients may present with symptoms of a hypertensive crisis secondary to excessive catecholamine release from a ruptured pheochromocytoma (43). Intratumoral hemorrhage manifests as increased at- tenuation of a pheochromocytoma on nonenhanced CT im- ages or intrinsic T1-hyperintense signal on MR images (41). Bleeding and rupture of a pheochromocytoma may manifest as retroperitoneal hemorrhage (Fig 10). As mentioned ear- lier, adrenal hemorrhage from any cause may lead to tran- sient metanephrine elevation (32).
Myelolipoma
Composed of adipose and hematopoietic tissue, myeloli- poma is an uncommon benign neoplasm that is often hor- monally inactive and mainly found in the adrenal glands (58). The prevalence of adrenal myelolipoma can be as high as 6% (3).
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At imaging, myelolipoma has predominantly macroscopic fat attenuation (less than -20 HU) on CT images or suppressed T1 hyperintensity on inversion-recovery or frequency-selec- tive fat-suppression MR images (10,20). On opposed-phase chemical shift MR images, India ink artifact is present at the interface between normal adrenal tissue or soft-tissue com- ponents of a myelolipoma and the macroscopic fat (10,20). Myelolipoma is typically a well-circumscribed round or ellip- tical mass (59). The majority of adrenal myelolipomas demon- strate no or slow growth, with growth of greater than 1 cm associated with larger myelolipomas and hemorrhage (60). For patients who are symptomatic, often owing to larger my- elolipomas, adrenalectomy should be considered (60).
As mentioned earlier, myelolipomatous degeneration within an adrenal mass (most commonly adenoma) should be considered in cases of nodules with small foci of mac- roscopic fat (26,28); this pathologic entity is often misinter- preted as myelolipoma. Because adenomas, including those with myelolipomatous degeneration, may be functional, hor- monal evaluation may be warranted for patients who have an adenoma with myelolipomatous degeneration (26).
Bilateral Adrenal Myelolipomas in Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia results from 21-hydroxylase de- ficiency, and the absence of this enzyme disrupts the adrenal steroid biosynthesis pathway (61). The adrenal glands enlarge and sometimes develop multiple fat-containing masses owing to excessive adrenal cortical stimulation caused by adrenocorti- cotropic hormone (ACTH) (62). The majority of myelolipomas are unilateral; when they are bilateral, there is a strong correla- tion with congenital adrenal hyperplasia (Fig 11) (27).
Metastasis
Non-Fat-containing Metastasis
Metastases are the most common malignant adrenal tumor. However, adrenal incidentalomas are unlikely to represent metastases (2,3). Cancers of the lung, bowel, breast, and pan- creas are the most common malignancies that metastasize to the adrenal gland (10). The imaging appearance of adrenal metastases is nonspecific, overlapping with that of other ad- renal tumors (Fig 12).
At nonenhanced CT, adrenal metastases have an attenu- ation higher than 10 HU and typically do not wash out on postcontrast images (10). Similar to pheochromocytomas, metastases from clear cell RCC, HCC, melanoma, and neu- roendocrine tumors are hypervascular (63) and may show washout. FDG PET/CT is both sensitive and specific in differ- entiating benign from malignant lesions.
ACC is characteristically a large, heterogeneous, enhanc- ing mass (37,41) that has features that may be seen in metas- tasis (Fig 13). This carcinoma may be suggested in the absence of a primary extra-adrenal malignancy and in the presence of adrenocortical hormone excess and calcifications (37,41). Clues to the diagnosis of a metastasis include the presence or history of an extra-adrenal primary malignancy, bilateral or multifocal tumors, rapid growth, and interval development (4). Differentiating ACC from metastasis with imaging may be difficult but is imperative, as the surgical approach for ACC is adrenalectomy, while adrenal metastasis is most often treated systemically.
Fat-containing Metastasis
Rarely, metastases from microscopic fat-containing extra-adre- nal malignancies can have microscopic fat (Fig 14), presenting
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a diagnostic dilemma because lipid-rich adenomas are diag- nosed on the basis of the presence of microscopic fat. Such pri- mary malignancies include clear cell RCC and HCC (64,65). Clues to the diagnosis of a fat-containing metastasis include presence or history of a primary malignancy with microscopic
fat, a new adrenal mass, multiplicity, other metastases, and hypermetabolism on FDG PET/CT images (66). In addition, increased T2-weighted signal intensity and heterogeneity are features that can differentiate clear cell RCC metastasis from adenoma (20).
Bilateral Adrenal Abnormalities
Adrenal Hyperplasia
Adrenal hyperplasia is characterized by nonneoplastic en- largement of the adrenal glands. At imaging, this manifests as diffuse bilateral thickening with adreniform morphology (67). Occasionally, there is a micronodular or macronodular appearance. Rarely, hyperplasia is unilateral. There are mul- tiple types of adrenal hyperplasia, depending on the inciting factor. A few examples include ACTH-dependent adrenal hy- perplasia, adrenocortical nodular disease, and congenital ad- renal hyperplasia (67).
ACTH-dependent Adrenal Hyperplasia .- The pituitary gland normally secretes ACTH to stimulate the adrenal glands to produce cortisol. Normally, elevated cortisol feeds back on the pituitary gland to decrease ACTH production. The decreased ACTH production, in turn, decreases cortisol production by the adrenal glands. Pituitary tumors that produce excess ACTH can cause adrenal hyperplasia because these hyperse- creting tumors are unaffected by this feedback loop. Similarly, ectopic ACTH production in paraneoplastic syndromes can
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result in adrenal hyperplasia that escapes the normal feed- back mechanism. Nearly half of all of the ectopic ACTH production is from lung malignancies (67,68). Medullary thy- roid carcinoma and malignancies arising from the thymus, bowel, and pancreas less commonly cause ectopic ACTH production. These tumors and their extra-adrenal metastases can cause adrenal hyperplasia, sometimes developing rapidly and mimicking adrenal metastasis. However, diffuse smooth enlargement of both adrenal glands with adreniform mor- phology is suggestive of hyperplasia (Fig 15), although it is similar in appearance to lymphoma.
Adrenocortical Nodular Disease .- The World Health Orga- nization classifies adrenocortical nodular disease into three subtypes: (a) sporadic nodular, (b) bilateral micronodular,
and (c) bilateral macronodular (53). The latter two entities are associated with germline mutations and are distinguished according to nodule size (<1 cm for micronodular, ≥1 cm for macronodular) and affected patient population (children and young adults for micronodular, adults for macronodular) (53). Bilateral macronodular adrenocortical disease (Fig 16) is a rare cause of bilateral adrenal nodules that can result in clinical hypercortisolism or mild autonomous cortisol secre- tion (previously subclinical hypercortisolism) (53,69). Images show marked diffuse thickening of both adrenal glands, with multiple bilateral nodules. Differential considerations include bilateral metastases or adenomas. Other less common causes of bilateral nodules include pheochromocytoma, congenital adrenal hyperplasia, Cushing disease, and secondary adrenal hyperplasia from ectopic ACTH production (69).
Lymphoma
Adrenal lymphoma is rare and may be primary (less common) or secondary (more common) (4). The most common adrenal lymphoma subtype is non-Hodgkin lymphoma. Adrenal lym- phoma is frequently bilateral, with up to 75% of primary ad- renal lymphomas involving both glands (70). It may occur as focal or multifocal adrenal masses, but it typically occurs as dif- fuse adrenal enlargement (70) from secondary lymphoma asso- ciated with lymphadenopathy and splenomegaly. At CT, these tumors have homogeneous soft-tissue attenuation with mild enhancement. At MRI, they are homogeneous with T1-hy- pointense or T1-isointense signal, T2-hyperintense signal, mild enhancement, and diffusion restriction (4,70). At FDG PET/ CT, there is increased radiotracer uptake (Fig 17) (70).
Rare Adrenal Lesions
Hemangioma
Adrenal hemangioma is a benign mesenchymal neoplasm that arises from the endothelium of blood vessels. The two primary subtypes are capillary and cavernous, although the cavernous subtype is most common (49,71). Affected patients are typically 50-70 years of age, with a slight female predomi- nance (71). Adrenal hemangioma is nonfunctioning and often
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Figure 14. Fat-con- C D taining left adrenal metastasis in a 63-year- old woman with clear cell RCC. (A, B) Axial T1-weighted MR images show a heterogeneous large right renal mass (arrow) with signal loss (arrowheads) between the in-phase (A) and opposed-phase (B) sequences, indicating microscopic fat within a clear cell RCC. (C, D) Axial T1-weighted MR images of a 2.8-cm left adrenal nodule (arrow) show signal loss (arrowhead) be- tween the in-phase (C) and opposed-phase (D) sequences, compatible with microscopic fat.
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incidentally detected (71). It is usually asymptomatic, but if it is larger than 10 cm, it may compress surrounding structures and cause abdominal pain. A known complication is rupture that results in retroperitoneal hemorrhage (71).
On CT images, hemangioma appears as a predominantly solid or mixed cystic and solid lesion with hypoattenuation centrally (41,49,71). Calcifications are common and favored to reflect phleboliths in dilated vascular spaces (71). At MRI, hemangioma is hyperintense on T2-weighted images and hy- pointense on T1-weighted images; focal areas of T1 and T2 hyperintensity indicate hemorrhage and necrosis (49,71). At both CT and MRI, adrenal hemangioma demonstrates periph- eral discontinuous nodular enhancement during the arterial phase and progressive centripetal enhancement during post- contrast delayed phases (Fig 18) (41,49). It may be difficult to differentiate a hemangioma from other adrenal lesions if there is an absence of centripetal filling during postcontrast delayed phases (41). However, classic imaging features may
suggest the possibility of hemangioma, and surveillance im- aging may be an appropriate alternative to surgery.
Oncocytoma
With fewer than several hundred cases reported in the litera- ture, adrenal oncocytoma (oncocytic adrenocortical adenoma or neoplasm) is a rare adrenal cortical tumor (4,72). This neoplasm is more predominant in women and occurs more frequently in the left adrenal gland (72). Most patients are asymptomatic.
At imaging, adrenal oncocytoma is often a large well-cir- cumscribed tumor with mild heterogeneous enhancement (Fig S4). The mild enhancement and absence of lipid allow this lesion to be distinguished from pheochromocytoma and lipid-rich adrenal adenoma, respectively (4,72). While imaging cannot be used to distinguish benign from malignant adrenal oncocytic neoplasms, certain features have been associated with increased malignant potential. These features include
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more intense enhancement, size larger than 10 cm, vascular in- vasion, necrosis, and lymphadenopathy (4,72). Therefore, it may be difficult to differentiate malignant oncocytoma from pheo- chromocytoma. Adrenal oncocytomas are surgically resected.
Ganglioneuroma
Ganglioneuroma is a rare benign tumor comprised of gan- glion and Schwann cells and arises along the sympathetic chain, including the adrenal medulla in 20%-30% of cases (49). Most patients are asymptomatic young adults (41,73).
On CT images, ganglioneuroma is homogeneously hypoat- tenuating (<40 HU) with mild progressive contrast enhance- ment (4). Stippled intralesional calcifications are common, occurring in roughly half of cases (41,49,73). Cystic change is uncommon (49).
At MRI, ganglioneuroma appears homogeneously or heterogeneously hyperintense on T2-weighted images and hypointense on T1-weighted images (Fig 19), probably sec- ondary to ganglion cells and myxoid components. The inter- weaved bundles of collagen fibers and Schwann cells give a
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whorled appearance on T2-weighted images (41,49). Dynamic contrast-enhanced MRI shows mild progressive enhance- ment (41,49). The average size of ganglioneuromas is 6-8 cm at diagnosis, and these neoplasms may be mistaken for ACC (73). In pediatric patients, the differential diagnosis includes neuroblastoma and ganglioneuroblastoma (4).
Conclusion
Atypical presentations of common benign and malignant adrenal masses, mimics of benign and malignant adrenal masses, and rare adrenal disease may pose diagnostic chal- lenges for radiologists. Knowledge of clues to the correct diagnosis is needed to avoid misdiagnosis, suboptimal man-
Figure 19. Ganglioneuroma in a 36-year-old man with a left adrenal mass and negative endocrine workup results. (A-C) Axial contrast-en- hanced arterial (A), portal venous (B), and 3-minute delayed (C) phase T1-weighted MR images show a mass (arrows), with slow progressive central delayed enhancement (arrowhead) seen in C. (D) T2-weighted MR image shows the mass (arrows) with markedly increased signal intensity. FDG PET/CT (not shown) showed minimal radiotracer avidity. This mass was resected because of its size. (E) Gross pathologic spec- imen shows the mass with a homogeneous tan-pink glistening cut sur- face, and the adjacent kidney, which could not be separated at surgery.
agement, and potentially adverse outcomes. The key lessons presented in this article are summarized in Table 5.
Author affiliations .- From the Department of Radiology, Division of Abdom- inal Imaging, Massachusetts General Hospital, Boston, MA (R.C., M.A.B.); Department of Radiology, Abdominal Imaging, Hospital of the University of Pennsylvania, Philadelphia, PA (J.G.); Department of Radiology, Imaging Institute and Glickman Urological Institute, Cleveland Clinic, Cleveland, OH (E.M.R.); Department of Radiology, Mayo Clinic, Rochester, MN (P.N.); Department of Radiology, Center for Biomedical Imaging, NYU Grossman School of Medicine, NYU Langone Health, New York, NY (M.T.T.); Depart- ment of Radiology, Ohio State University Wexner Medical Center, Columbus, OH (C.E.H.); Department of Radiology, University of Alabama, Birming- ham, AL (K.G.S.); Department of Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada (W.T., G.L., M.B.); Departments of Radiology (B.W.C., M.T.C.) and Surgery (M.J.C.), UC Davis Medical Center, Sacra- mento, CA; Department of Radiology (J.T.L.), Department of General Surgery (C.Y.L.), and Department of Pathology and Laboratory Medicine (J.C.D.), University of Kentucky, Lexington, KY; Department of Diagnostic Radiol- ogy, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (M.A.S., K.M.E.); Department of Radiology, University of Michigan, Ann Arbor, MI (E.M.C.); and Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada (N.S.). Presented as an education exhibit at the 2021 RSNA Annual Meeting. Received September 27, 2022; revision requested November 9 and received December 21; accepted January 12, 2023. Address correspondence to K.M.E. (email: kmelsayes@mdanderson.org).
| Table 5: Key Lessons for Diagnosis of Adrenal Neoplasms | |
| Neoplasm | Tips |
| Adenoma | An adrenal nodule with homogeneous low attenuation (≤10 HU) on nonenhanced CT images and microscopic fat on chemical shift MR images is diagnostic of an adenoma Adrenal washout CT findings should not be stand-alone features for the diagnosis of lipid-poor adenoma; other features such as a mass size, heterogeneity, and clinical context should be considered to avoid misdiagnosis Adrenal washout CT is most useful for distinguishing adenoma from metastasis in patients with known nonhypervascular Heterogeneous signal loss within an adrenal mass at opposed-phase chemical shift MRI overwhelmingly represents mi- primary malignancy croscopic fat within an adenoma in patients without and with malignancy .; however, one should be cautious in patients who have extra-adrenal malignancies with microscopic fat or when the heterogeneity may signify a collision tumor; follow-up imaging can be pursued in these settings While a mass >4 cm may represent an adenoma, a mass this size is generally resected because of the increased rate of malignancy; however, each patient should be managed individually by a multidisciplinary team |
| ACC | ACC rarely has attenuation <20 HU at nonenhanced CT and is most often >4 cm in size, with a heterogeneous appearance ACC often demonstrates absolute washout <60%; however, the washout may exceed 60% |
| Adrenal cysts | Endothelial cyst and pseudocyst make up the majority of adrenal cystic lesions Adrenal cyst may be confused for adenoma because of a nonenhanced attenuation of ≤10 HU and for pheochromocytoma with cystic and/or necrotic change, because of central hypoattenuation; however, it can be readily distinguished from the latter entities due to the absence of enhancement We do not recommend follow-up for adrenal cysts |
| Pheochromo- cytoma | Cystic and/or necrotic change within an adrenal mass should raise suspicion for pheochromocytoma An adrenal mass with a nonenhanced attenuation of ≤10 HU in the solid portion of the tumor rarely occurs with pheo- chromocytoma An adrenal mass with an absolute percentage washout of >60% may represent pheochromocytoma, particularly if there are other imaging or clinical features that suggest a hypervascular tumor with catecholamine excess; we recommend bio- chemical testing for pheochromocytoma when an adrenal mass demonstrates cystic and/or necrotic change or a portal venous phase attenuation of ≥130 HU, even if it demonstrates an absolute percent washout of >60% Biochemical assessment or molecular imaging may help distinguish pheochromocytoma from ACC; these neoplasms may have overlapping imaging features |
| Myelolipoma | Myelolipomas can be confidently diagnosed at imaging when fat makes up most of the mass An adrenal mass with a proportionally small focus of macroscopic fat should raise suspicion for myelolipomatous degener- ation within an adrenal adenoma; because adenoma may be functional, one should consider hormonal evaluation when the possibility of adenoma with myelolipomatous degeneration is raised |
| Metastasis | Differentiating between ACC and adrenal metastasis is imperative, as ACC is treated with adrenalectomy, while adrenal metastasis is most often treated systemically |
| Metastases from microscopic fat-containing extra-adrenal malignancies can have microscopic fat and mimic adenomas on opposed-phase chemical shift MR images; clues to the diagnosis of a fat-containing metastasis include presence or histo- ry of a primary malignancy with microscopic fat, development of a new adrenal mass, multiplicity, additional metasta- ses, and hypermetabolism at FDG PET/CT | |
| Bilateral adrenal lesions | Adrenal hyperplasia and adrenal lymphoma may be difficult to distinguish from one another, as both may present as dif- fuse bilateral adrenal enlargement or multifocal adrenal nodules; the presence of lymphadenopathy and splenomegaly is more suggestive of lymphoma |
| Rare adrenal lesions | The presence of classic imaging features of adrenal hemangioma (discontinuous peripheral nodular enhancement with progressive centripetal filling) may suggest the possibility of hemangioma, and surveillance imaging may be an appropri- ate alternative to surgery An adrenal mass with mild progressive enhancement may represent ganglioneuroma |
Disclosures of conflicts of interest .- E.M.R. Member of Society of Abdomi- nal Radiology Board of Directors. M.T.C. Consulting fees from Corcept Ther- apeutics. K.M.E. Editorial board member of RadioGraphics. All other au- thors, the editor, and the reviewers have disclosed no relevant relationships.
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