Introduction

Incidental adrenal masses are a relatively common finding on cross-sectional imaging. An adrenal incidentaloma is an adrenal mass measuring 1 cm or larger discovered on an imaging examination that has been obtained for an unrelated indication [1]. The prevalence of adrenal incidentalomas on computed tomography (CT) is estimated to be 4.2% [2]. The vast majority of adrenal incidentalomas are benign, with non-functioning adrenocortical adenomas (ACAs) representing approximately 75% of all incidentalomas [3, 4]. Unlike incidentalomas, adrenal malignancies are not common and typically follow an aggressive course with rapid growth and metastases [5]. A wide spectrum of other pathologies can occur in the adrenal gland, leading to a relatively long list of differential diagnoses. In addition, several pseudolesions can falsely mimic an adrenal lesion on imaging.

In this article, we review imaging features of pitfalls and mimics that are related to various abnormalities within or adjacent to the adrenal glands and can potentially lead to erroneous diagnosis. We also provide clues to help reach a specific diagnosis and avoid potential misinterpretation of these entities.

Pitfalls related to imaging technique

Dedicated adrenal washout protocol typically comprises three phases acquired at specific times in relation to intravenous contrast administration for CT of the adrenal gland. The unenhanced phase is obtained prior to contrast administration, while the early and delayed enhanced phases are obtained at 60–80 s and 15 min, respectively, after contrast administration. Suboptimal imaging technique can result in misdiagnosis of adrenal masses [6].

Suboptimal delayed phase

The precise timing of contrast administration and image acquisition is crucial for the characterization of adrenal lesions relying on their typical contrast enhancement and washout patterns. For example, ACA demonstrates characteristic rapid contrast enhancement followed by rapid washout [7]. A dedicated adrenal CT protocol allows for the calculation of washout percentages, especially absolute percentage washout (APW); APW ≥ 60% is highly sensitive for ACA, with a reported range of 96–100% [8,9,10].

$${\text{APW}} = \frac{{{\text{Early}}\;{\text{Attenuation}}\;{\text{Value}} - {\text{Delayed}}\;{\text{Attenuation}}\;{\text{Value}}}}{{{\text{Early}}\;{\text{Attenuation}}\;{\text{Value}} - {\text{Unenhanced}}\;{\text{Attenuation}}\;{\text{Value}}}} \times 100$$

Care should be taken, when calculating washout percentages, that the delayed scans are acquired 15 min after intravenous contrast administration. Although early image acquisition is more convenient for both the patient and the imaging facility, it results in a significant decrease in diagnostic sensitivity, from 96–100 to 55–79%, depending on the threshold used (Fig. 1) [8, 11, 12]. A recent study showed no diagnostic advantage in acquiring 10-min-delayed contrast-enhanced images over non-enhanced CT images [6]. This finding can be attributed to insufficient time for the washout of the adrenal lesion to adequately manifest; resulting in potentially higher attenuation values on delayed images and lower washout percentages [13]. Another recent study showed that early enhanced CT (~ 70 s postcontrast) in combination with quantitative CT image features could be used to accurately characterize adrenal lesions as benign or malignant without the need for delayed images; however, this approach is still under investigation and has not been implemented clinically [14]. In summary, a suboptimal delayed phase could fail to confirm the diagnosis of an ACA.

Fig. 1
figure 1

An example of suboptimal delay time in a 60-year-old woman with left adrenocortical adenoma. Contrast-enhanced axial CT a and b shows an oval-shaped nodule (arrow) within the left adrenal gland with precontrast (not shown) attenuation of 45 HU, venous phase a attenuation of 75 HU, 5-min-delayed phase b attenuation of 61 HU, and absolute washout of 47%, which is not typical for adrenal adenoma. Contrast-enhanced axial CT c and d was repeated with an optimal 15-min delay and again showed the left adrenal nodule with precontrast (not shown) attenuation of 41 HU, venous phase c attenuation of 115 HU, 15-min-delayed phase d attenuation of 54 HU, and absolute washout of 82%, which is consistent with adrenal adenoma; the lesion was later resected and confirmed to be an adrenocortical adenoma. This case illustrates an important pitfall as the nodule was considered indeterminate based on suboptimal delay time

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Key point

  • A dedicated adrenal CT protocol with 15-min delay should be used when calculating washout percentages for adrenal masses. Suboptimal delay can lead to erroneous diagnosis.

Pitfalls related to the utility of CT and MRI

Understanding the utility of the various imaging modalities and their limitations is important in accurately characterizing adrenal lesions. Various imaging modalities exist for imaging the adrenal glands, including CT, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT.

CT, because of its low cost and high accuracy, is recommended as the initial imaging modality for evaluating an incidental adrenal mass [15, 16]. Unenhanced CT readily identifies ACA, as most ACAs have low attenuation due to their abundant intracellular lipid content [17]. By using a threshold of 10 Hounsfield units (HU), unenhanced CT achieved a sensitivity ranging from 40 to 70% and a specificity ranging from 98 to 100% in distinguishing lipid-rich adenomas [17, 18]. No further testing is required if the adrenal mass is < 10 HU with imaging features suggesting benignity (e.g., homogeneity, well-defined borders, stability over time). Approximately 30% of adenomas are lipid poor which demonstrate attenuation values > 10 HU. Lipid-poor adenomas exhibit characteristic enhancement and washout patterns that can be exploited on adrenal CT protocol, as discussed previously.

MRI also has the ability to differentiate adrenal adenomas from non-adenomas based on their inherent tissue characteristics [19]. Chemical shift MRI (CSI) is particularly useful in the diagnosis of adenomas because of its characteristic loss of signal intensity on out-of-phase (OP) compared to in-phase (IP) images based on the difference in precession frequency of water and fat molecules [7, 20]. The percentage of signal loss is referred to as the adrenal signal intensity index (ASII); an ASII of > 16.5% on 1.5 Tesla (T) MR scanners is diagnostic of adrenal adenomas [21]. \({\text{ASII}} = \frac{{\left( {{\text{lesion}}\;{\text{IP}}} \right) - \left( {{\text{lesion}}\;{\text{OP}}} \right)}}{{\left( {{\text{lesion}}\;{\text{IP}}} \right)}} \times 100\). Studies have shown the ability of CSI to characterize 89% of adenomas with attenuations of 10–30 HU on unenhanced CT [22]. However, 8% of ACAs do not demonstrate loss of signal intensity on CSI, due to their insufficient intracellular lipid content (Fig. 2) [23,24,25]. This has been proven to be a limitation of CSI and could be problematic, especially in ACAs with precontrast CT attenuation > 30 HU [22, 24].

Fig. 2
figure 2

An example of a lipid-poor adrenocortical adenoma without signal loss on opposed-phase compared to in-phase MR images in a 26-year-old man. T1-weighted axial MRI shows a round-shaped nodule (arrow) measuring 2.5 cm involving the right adrenal gland with no drop in signal intensity on out-of-phase b compared to in-phase a pulse sequences. Contrast-enhanced CT was performed 1 month later and demonstrated the same nodule with precontrast c attenuation of 25 HU, venous phase d attenuation of 95 HU, 15-min-delayed phase e attenuation of 43 HU, and absolute percentage washout of 74%, which is consistent with an adrenocortical adenoma. The adrenal mass was surgically resected and proven to be an adrenocortical adenoma. Caution should be exercised when evaluating lipid-poor adenomas on MRI, as 8% of lipid-poor adenomas do not show signal loss on out-of-phase compared to in-phase pulse sequences

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A potential pitfall when evaluating an adrenal mass on MRI is calculating the washout percentages based on their signal intensity on the precontrast and contrast-enhanced phases. To our knowledge, studies for adapting washout thresholds for MRI have been limited and had conflicting results [21]. Therefore, the calculation of washout percentages for diagnosis of adrenal adenomas should be limited to CT with adrenal protocol.

During the interpretation of an imaging study of the adrenal glands, care should be taken that scan parameters were kept the same among all phases of CT or MRI. Scan parameters, including both acquisition and reconstruction parameters, can potentially affect attenuation values and lead to misinterpretation of the imaging study.

Key points

  • An adrenal mass with precontrast attenuation of < 10 HU on CT is diagnostic for lipid-rich adenoma and obviates the need for washout study.

  • On MRI, significant drop of signal intensity on OP compared to IP images is diagnostic for adrenal adenoma.

  • Calculation of washout should be limited to contrast-enhanced CT with adrenal protocol.

  • Scan parameters should be the same among different phases.

Inaccurate placement of the region of interest

A common pitfall that can occur when evaluating a CT or MRI study is the inaccurate placement of the region of interest (ROI) for calculation of attenuation values. It is essential to place the ROI tool to cover at least one-half to two-thirds of the adrenal mass, excluding any necrotic area, when applicable [26]. It should also be noted that the ROI is to be placed over a homogeneous region for accurate measurement. Incorrect placement can lead to the underestimation or overestimation of the attenuation values.

Key point

  • The ROI should cover one-half to two-thirds of the adrenal mass and be placed over a homogeneous region of the mass, excluding any necrotic areas.

Pitfalls related to anatomy

The adrenal glands are inverted Y-shaped organs with a body and two limbs: a medial limb and a lateral limb [27]. The adrenal glands are located in the retroperitoneum, anteromedially and superiorly to the kidneys. The right adrenal gland is adjacent to the right lobe of the liver, crus of the right hemidiaphragm, duodenum, inferior vena cava, and right kidney; whereas the left adrenal gland is adjacent to the spleen, pancreatic tail, stomach, and left kidney [28]. Masses arising from adjacent structures can potentially be mistaken for adrenal lesions. Multiplanar reformats can help distinguish the adrenal glands from adjacent structures and allow the vast majority of these lesions to be distinguished from true adrenal lesions.

Adrenal pseudonodule

In some instances, a completely normal adrenal gland can be misidentified as a pathological adrenal nodule; such misidentification can be attributed to the gland’s appearance when viewed on a single plane, most commonly the axial plane. Due to the normal variations in the shape, orientation, and location of the adrenal glands, a horizontally oriented limb of the adrenal gland can mimic an adrenal nodule in the axial plane. However, upon examination of the multiplanar reformatted (MPR) images in the coronal and sagittal planes, the normal adrenal gland can be clearly identified (Fig. 3). Likewise, a vertically oriented limb can be easily recognized in the axial plane, but it may mimic an adrenal nodule on the coronal plane. Therefore, it is useful to make use of MPR on CT or alternate imaging planes on MRI to confirm suspected nodules.

Fig. 3
figure 3

An adrenal pseudonodule in a 24-year-old woman with hyperparathyroidism. Contrast-enhanced axial CT a shows an oval structure (arrow) in the left suprarenal region that was suspected to be an adrenal nodule. However, coronal reformatted images b did not show the structure, and a normal left adrenal gland was noted

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Exophytic gastric lesions

Gastric diverticula are rare outpouchings of the gastric wall that commonly arise from the gastric fundus, with a prevalence of 0.02% in autopsies and 0.04% on upper gastrointestinal series [29]. Gastric discomfort and post-prandial fullness are unusual manifestations, as symptomatic gastric diverticula are rare and are most often discovered incidentally [30, 31]. Occasionally, a gastric fundal diverticulum (Fig. 4) can be misinterpreted as a left adrenal mass, especially when filled with fluid [32]. MPR images can be helpful in such cases, especially with oral contrast, to visualize the communication between the gastric cavity and the diverticulum. A key finding, in such cases, is the identification of gas within the suspected lesion (gas may not be present or can be very minimal in amount). On MRI, the presence of gas inside the diverticulum can cause susceptibility artifacts.

Fig. 4
figure 4

An example of gastric diverticulum mimicking an adrenal nodule in a 69-year-old man. Contrast-enhanced axial CT a shows a hypoattenuating nodule (arrow) in the left suprarenal region that was suspected to be a left adrenal nodule. Follow-up intravenous and oral contrast-enhanced axial CT b shows the communication (black arrow) between the structure (white arrow) and the gastric fundus, with layering of the oral contrast material within the gastric diverticulum

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Other exophytic gastric lesions that are adjacent to the adrenal glands, including gastrointestinal stromal tumors, can potentially be mistaken for adrenal lesions [33].

Exophytic hepatic lesions

Occasionally, exophytic hepatic lesions can appear inseparable from the right adrenal gland and may pose a diagnostic challenge due to unclear origin [34, 35]. Hemangioma is the most common benign mesenchymal tumor of the liver. Pedunculated hemangiomas represent 12% of hepatic hemangiomas and tend to be larger in size [36, 37]. Typical imaging features of hemangiomas are diagnostic, and MPR is helpful in detecting a mass attached to the liver and identifying the adrenal gland separate from the exophytic hepatic lesion (Fig. 5).

Fig. 5
figure 5

An example of an exophytic hepatic mass mimicking an adrenal nodule in a 50-year-old man with hepatic hemangioma. Contrast-enhanced axial CT a in the delayed phase shows a hypoattenuating nodule (arrow) in the right suprarenal region suspected to be a right adrenal nodule. However, coronal reformation b shows the lesion (white arrow) to be arising from the right hepatic lobe. The right adrenal gland (black arrow) is seen separate from the lesion

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Pitfalls related to adjacent vascular structures

Extrahepatic portosystemic shunts in the setting of portal hypertension may give rise to several collaterals or varices in the upper abdomen. For example, the inferior phrenic vein, which runs immediately anterior to the adrenal gland, connects the splenic vein (portal system) to the left renal vein (systemic) and can result in adrenal or periadrenal varices [38, 39]. A periadrenal varix could be interpreted as an adrenal tumor, and an attempted excision or biopsy could be catastrophic. On CT, early intense enhancement is not uncommon; the left inferior phrenic vein can be seen draining into the left renal vein on MPR images [39, 40]. While on MRI, vascular structures tend to exhibit the flow void phenomenon, appearing as loss of signal on spin-echo techniques (Fig. 6). It should be noted, however, that flow void is dependent upon vascular patency and blood flowing at a sufficient velocity [41].

Fig. 6
figure 6

An example of a vascular structure mimicking an adrenal nodule in a 67-year-old man with hepatocellular carcinoma. Axial T2-weighted MRI shows an enlarged retroperitoneal collateral (arrow) in the expected location of the left adrenal gland with a flow void consistent with a vessel. The left adrenal gland cannot be definitely visualized

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Other vascular structures, including venous and arterial aneurysms and pseudoaneurysms, abutting the adrenal glands are rare but can be potentially mistaken for adrenal lesions [42].

Splenules and splenosis

Ectopic splenic tissue (EST) is a benign incidental finding seen in up to 16% of abdominal CT examinations [43]. Splenules (accessory spleens, or splenunculi) represent a congenital subtype of ectopic normal splenic tissue that occurs as a result of failure of fusion during embryogenesis [43], whereas splenosis represents the acquired form of EST seen after trauma or surgery. EST can be located almost anywhere in the abdomen—usually near the splenic hilum—with the exception of splenosis, which can also be located in the thorax [44]. EST situated in the suprarenal region has been reported to mimic adrenal masses (Fig. 7) [45, 46]. ESTs typically appear as well-marginated, round nodules exhibiting the same density/intensity and enhancement characteristics of the spleen. Diagnosis can be confirmed with technetium 99 m (Tc 99 m) sulfur colloid scintigraphy, which demonstrates high uptake in the splenic tissue [43]. However, Tc 99 m heat-denatured red blood cell scintigraphy, with its greater specificity, remains the gold standard for detecting splenic tissue [47]. It is worth noting that the addition of single-photon emission CT and CT (SPECT/CT) to either of the previously mentioned nuclear scans significantly improves sensitivity [48]. The diagnosis of EST should be excluded, using the appropriate imaging modalities and clinical correlation (i.e., history of abdominal trauma, or splenic rupture), when evaluating a suprarenal mass with suspicious imaging features.

Fig. 7
figure 7

An example of a splenule mimicking a left adrenal mass. Contrast-enhanced axial CT shows a well-circumscribed, round 1.6-cm nodule (arrow) in the left suprarenal region. Relative washout was 42.5% (no precontrast images were available for calculation of the APW), which is consistent with an adrenocortical adenoma. However, biopsy confirmed the diagnosis of a splenule

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Celiac ganglion

The celiac ganglia are the largest of the autonomic celiac plexus, innervating most of the gastrointestinal tract. They are located in the upper abdomen, with one on each side of the aorta and medial to the adrenal glands [49]. The celiac ganglia measure approximately 0.5 cm in diameter, and the left ganglion is usually visualized more than the right ganglion (89% vs 67%) [50]. This structure can be potentially misinterpreted for an adrenal mass, given its location and morphology. The celiac ganglia are multilobular or, less commonly, discoid in shape [51]. On CT, soft-tissue attenuation is seen, similar to adenomas, in the unenhanced and early enhanced phases; however, in the delayed phase, celiac ganglia typically exhibit progressive enhancement [50]. Evaluation on MPR allows the recognition of a celiac ganglion as a separate structure from the adrenal gland (Fig. 8).

Fig. 8
figure 8

An example of celiac ganglion mimicking an adrenal nodule in a 38-year-old woman with lung cancer. Contrast-enhanced axial CT a shows a sub-centimeter nodule (arrow) in the left suprarenal region suspected to be an adrenal adenoma. Coronal reformatting b shows the nodule (arrow) separate from the left adrenal gland and revealed it as the left celiac ganglion

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Key point

  • Thorough evaluation of the sagittal and coronal planes is crucial in avoiding pitfalls related to adjacent anatomical structures or pathologies.

Mimics of adrenal adenoma

Simple adrenal cyst

Adrenal cysts are uncommon, with a prevalence estimated from 0.064 to 0.18% and constituting around 5.7% of adrenal incidentalomas [52, 53]. They are three times more common in women than in men and tend to be unilateral, occurring with equal frequency on each side. Adrenal cysts are usually discovered incidentally but can present with abdominal pain, hemorrhage, or cyst rupture. They are classified into four histological subtypes, in decreasing order of incidence: endothelial cysts, pseudocysts, epithelial cysts, and parasitic cysts. Endothelial cysts are the most common subtype, accounting for nearly 45% of all adrenal cysts. Uncomplicated adrenal cysts demonstrate typical imaging features. However, because they are filled with fluid, they show low attenuation on unenhanced CT ≤ 20 HU. Therefore, an adrenal cyst can mimic a lipid-rich adenoma if its attenuation value is < 10 HU. Adrenal cysts lack the characteristic postcontrast enhancement of ACAs (Fig. 9) [54, 55]. MRI easily confirms an adrenal cyst, with marked hyperintensity on T2-weighted sequences and lack of signal loss on opposed-phase gradient echo T1-weighted images.

Fig. 9
figure 9

An example of a simple adrenal cyst mimicking an adrenal adenoma in a 54-year-old woman. Precontrast axial CT shows a nodule (arrow) that was suspected to be an adrenal lipid-rich adenoma within the left adrenal gland with attenuation of 6 HU. The nodule was found to demonstrate no enhancement on postcontrast CT with a thin, imperceptible wall, and markedly increased signal intensity on T2-weighted MRI, consistent with a simple cyst

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Key points

  • Simple adrenal cysts show fluid attenuation on precontrast CT and thus can mimic lipid-rich adenomas on unenhanced CT.

  • Lack of postcontrast enhancement and markedly increased signal intensity on T2-weighted MRI are characteristics of simple cysts.

Adrenal metastases containing intracellular lipid

The most common malignant lesions involving the adrenal gland are metastases. In fact, the adrenal gland is a common site for metastases, which are seen in up to 27% of autopsies of patients with known primary malignancies [56]. Tumors known to metastasize to the adrenal glands include breast cancer, lung cancer, colorectal cancer, pancreatic cancer, renal cell carcinoma, melanoma, and hepatocellular carcinoma [57]. Adrenal metastases are usually solitary and asymptomatic, with a variable CT appearance and sluggish washout of contrast. Metastases from clear cell renal cell carcinoma (CRCC) and hepatocellular carcinoma (HCC) may contain an abundant amount of intracellular lipid and can, thereby, demonstrate low attenuation on non-contrast CT [58]. On contrast-enhanced CT, APW of more than 60% can be seen, mimicking adrenal adenomas (Fig. 10) [58]. A drop of signal intensity on OP compared to IP pulse sequences can be seen on MRI, mimicking adenoma.

Fig. 10
figure 10

An example of adrenal metastasis demonstrating washout in a 67-year-old man with clear cell renal cell carcinoma. Contrast-enhanced axial CT shows an oval-shaped nodule (arrow) within the left adrenal gland with precontrast a attenuation of 26 HU, venous phase b attenuation of 228 HU, 15-min-delayed phase c attenuation of 86 HU, and absolute washout of 70%, which is typical of adrenocortical adenoma. However, the high attenuation on the venous phase (228 HU) is not consistent with adrenocortical adenoma. The mass was later resected and proven to be an adrenal metastasis from clear cell renal cell carcinoma

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Although lipid-rich metastases exhibit washout characteristics similar to adrenal adenomas, an attenuation of > 140 HU in the venous phase should raise the suspicion of vascular metastases such as CRCC or HCC [58]. Ancillary imaging features favoring metastases include local invasion, cystic changes, necrosis, and hemorrhage [59]. Positron emission tomography (PET)/CT can show avid FDG uptake by the metastatic deposits, and is highly sensitive and specific in this regard, when the lesion in question has a standardized uptake value (SUV) of > 3.1 [60, 61].

Key points

  • Adrenal metastasis from HCC and CRCC can demonstrate washout characteristics similar to ACA.

  • Venous phase attenuation of > 140 HU should raise suspicion of vascular metastases.

  • Metastases containing intracellular lipid (such as those from HCC and CRCC) can demonstrate signal drop on OP compared with IP pulse MRI sequences, thus mimicking adenoma.

  • Avid FDG uptake on PET/CT can help confirm the diagnosis of metastasis.

Pheochromocytoma demonstrating washout

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors arising from the chromaffin cells, mostly of the adrenal medulla, with a reported incidence of 0.05% [62]. Asymptomatic pheochromocytoma is increasingly diagnosed as an incidental adrenal mass [63]. It typically appears on CT as a heterogeneously enhancing mass ranging in size from 4 to 6 cm [64, 65]. Pheochromocytomas show inconsistent washout patterns on adrenal CT protocol; up to one-third of pheochromocytomas demonstrate washout characteristics similar to ACA on delayed CT scans, and hence could be confused with adenomas [66,67,68].

A valuable clue to differentiating pheochromocytoma from adenoma on enhanced CT is the characteristic intense enhancement of pheochromocytoma in the venous phase; pheochromocytomas demonstrate venous phase attenuation values of up to 190 HU, whereas the maximum venous phase attenuation of ACA is 133 HU [69, 70]. Another crucial pitfall is the notion that all demonstrate marked hyperintensity on T2-weighted MRI (light bulb sign); in fact, pheochromocytomas can also present with isointensity or even hypointensity on T2-weighted images and therefore can possibly mimic other pathologies [71,72,73]. Careful imaging correlation to the clinical and biochemical testing is crucial for accurate diagnosis in the evaluation of a suspected pheochromocytoma.

Key points

  • Up to one-third of pheochromocytomas demonstrate washout characteristics similar to ACA.

  • Pheochromocytomas are vascular tumors and exhibit high attenuation, up to 190 HU, in the venous phase.

  • Pheochromocytomas can present as iso- or hypointense on T2-weighted images, contrary to the notion that they always appear markedly hyperintense on T2-weighted images.

Small adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is the most common primary malignant tumor involving the adrenal glands, with an estimated annual incidence of approximately 0.72 cases per million and accounting for 0.2% of all cancer-related deaths in the United States [74]. Approximately 30% of ACCs are incidentally seen on imaging [4]. ACC tends to be large (> 5 cm) at diagnosis and measures approximately 13 cm on average [75]. However, at least 9% of tumors are < 6 cm, and 3% are < 4 cm [76, 77]. These cases can be confused with adenomas because of their small size at diagnosis (Fig. 11). A case series has shown a number of ACCs that had a median size of 2.8 cm at diagnosis and were presumed benign, which led to delayed diagnosis and poor survival outcomes [78]. Adrenal CT protocol is helpful in this regard, as ACCs tend to demonstrate slow washout of contrast on delayed phases (< 40% at 15 min) [79].

Fig. 11
figure 11

An example of small adrenocortical carcinoma (ACC) mimicking an adrenal adenoma in a 43-year-old woman. Contrast-enhanced CT in the venous phase demonstrating a 1.5-cm nodule (arrow) within the right suprarenal region. This lesion was incidentally discovered on imaging and diagnosed as an adrenal adenoma based on size. It was followed up for a year and remained stable; however, follow-up CT, 2 years later, showed interval growth (not shown). The mass was surgically resected and pathological examination revealed an ACC

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Key points

  • Three percent of ACCs are < 4 cm and can mimic ACAs on imaging based on their small size.

  • ACCs typically demonstrate slow washout of contrast, with APW < 60%.

Mimics of adrenocortical carcinoma

Large adrenocortical adenoma

ACA is classically described as a small homogeneous adrenal nodule. ACAs have an average maximum dimension of 3 cm, whereas ACCs have an average maximum dimension of 6 cm. Although infrequent, ACAs can grow to be > 4 cm and occasionally even > 10 cm (Fig. 12) [80]. They can, rarely, demonstrate calcification, necrosis, and hemorrhage, mimicking malignancy [81]. A diagnosis of ACA could be suspected in the presence of an unremarkable clinical presentation, stability over time, characteristic rapid washout patterns, lack of absolute features of malignancy such as invasion, and minimal FDG uptake on PET/CT. Nevertheless, surgical resection should be the standard of care for all adrenal masses measuring > 4 cm.

Fig. 12
figure 12

An example of an adrenocortical adenoma mimicking an adrenocortical carcinoma in a 36-year-old man. Contrast-enhanced axial CT shows a well-circumscribed homogeneous mass (arrow) within the left adrenal gland with maximum axial dimension of 5.1 cm and attenuation of 58 HU on the venous phase. The mass was surgically resected and proven to be left adrenocortical adenoma despite being larger than 4 cm

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Key points

  • ACA can grow in size > 4 cm and—rarely—can demonstrate calcifications, necrosis, and hemorrhage, mimicking ACC.

  • ACA lacks the absolute features of malignancy such as invasion and metastases, and its stability over time can suggest diagnosis of a benign lesion.

  • Surgical resection should remain the standard of care for large masses measuring > 4 cm.

Adrenal pseudocyst

Adrenal pseudocyst is the second most common cystic lesion involving the adrenal glands, constituting nearly 39% of all adrenal cysts [82]. Unlike true cysts, pseudocysts possess a fibrous capsule and lack a cellular lining; their etiology is unclear [83]. The majority of these cysts present with symptoms related to their large size are discovered incidentally on imaging [84]. The appearance of an adrenal pseudocyst on imaging can be similar to those of malignant lesions, especially ACC, because of the large size at diagnosis and the presence of intralesional hemorrhage, septations, and/or soft tissue component (Fig. 13). A thin, smooth wall enhancement can be frequently seen on MRI and CT [85]. Calcifications can also be seen in both adrenal pseudocysts and adrenal tumors. However, when compared with the central and irregular calcifications in adrenal tumors, pseudocysts tend to show more peripheral (mural) and regular curvilinear calcifications [55]. Intralesional hematomas appear as soft-tissue attenuation within the adrenal mass, mimicking ACC. Given the characteristic features of hematomas, attenuation values are variable on precontrast CT, depending on the age of the hematoma, and enhancement is typically absent in contrast-enhanced phases, although enhancement can be rarely encountered secondary to fibrosis [86].

Fig. 13
figure 13

An example of an adrenal pseudocyst mimicking an adrenocortical carcinoma in a 46-year-old man. T2-weighted coronal MRI shows a well-circumscribed large heterogeneous mass (arrow) within the left adrenal gland that was suspected to be an adrenocortical carcinoma. However, the mass was surgically resected and proven to be a left adrenal pseudocyst with intracystic hemorrhage

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Pseudocysts may also demonstrate low signal intensity on T1-weighted MRI sequences and high signal intensity on T2-weighted sequences. Due to their absence of metabolic activity, pseudocysts do not show FDG uptake on PET/CT, which is a helpful clue in differentiating an adrenal pseudocyst from ACC.

Key points

  • Adrenal pseudocysts may contain calcifications that are typically peripheral and regular, compared with central and irregular calcifications in ACC.

  • A thin, enhancing wall can be identified on contrast-enhanced studies.

  • Postcontrast intralesional enhancement is not typically seen, although it can, rarely, be encountered due to fibrosis.

  • Adrenal pseudocysts show no or minimal FDG uptake on PET/CT.

Ganglioneuroma

Ganglioneuroma is a rare benign tumor arising from neural crest tissue. Ganglioneuromas arising from the adrenal glands are uncommon and usually occur in patients younger than 20 years [87, 88]. Patients are typically asymptomatic, but some present with symptoms due to hormonal hypersecretion or abdominal/back pain attributed to mass effect by the tumor [89]. Adrenal ganglioneuroma is usually large at diagnosis, with a median maximum dimension of 8 cm. The classic CT appearance is a well-circumscribed mass with low attenuation on unenhanced images and progressive enhancement after intravenous contrast administration (Fig. 14) [89]. Familiarity with the typical imaging features of ganglioneuroma is crucial in distinguishing ganglioneuroma from ACC, as a ganglioneuroma could be mistaken for ACC because of its large size. MRI usually shows a homogeneous hypointense mass on T1-weighted images and a heterogeneous hyperintense mass on T2-weighted images.

Fig. 14
figure 14

An example of a surgically proven adrenal ganglioneuroma mimicking adrenocortical carcinoma in a 58-year-old woman. Contrast-enhanced axial CT shows a large homogeneous mass (arrow) in the right suprarenal region measuring 12.2 cm in maximal dimension with precontrast a attenuation of 33 HU, venous phase b attenuation of 41 HU, and delayed phase c attenuation of 49 HU showing progressive enhancement typical of adrenal ganglioneuroma

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Key points

  • Ganglioneuroma is typically large at the time of diagnosis, mimicking ACC.

  • The typical imaging features of ganglioneuroma are low attenuation and slight progressive enhancement after intravenous contrast administration.

ACC containing macroscopic fat mimicking myelolipoma

Although extremely rare, ACCs have been reported to contain bulk fat on imaging [90, 91]. The presence of macroscopic fat in an adrenal mass has been considered pathognomonic of an adrenal myelolipoma. However, adrenal tumors, including ACA and ACC, can undergo lipomatous metaplasia and therefore may demonstrate minor foci of bulk fat over time [92]. Fat-containing ACC is rarely encountered and can be mistaken for an adrenal myelolipoma on imaging (Fig. 15).

Fig. 15
figure 15

An example of an adrenocortical carcinoma with bulk fat. Contrast-enhanced axial CT (a, b), and coronal reformatted (c), demonstrating a large heterogeneous mass with central necrosis and a small focus of fat attenuation (− 23 HU) representative of bulk fat. Surgical resection confirmed the diagnosis of adrenocortical carcinoma with bulk fat. Reprinted with permission from BioMed Central (BMC). Egbert et al. [90]

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An important clue to differentiate between both entities is the amount of fat present. Myelolipoma is known to contain major amount of fat, when compared to tumors undergoing lipomatous metaplasia containing minimal fat. Another clue depends on evaluation of prior imaging studies, when present. In fat-containing ACAs or ACCs, the development of the macroscopic fat foci can be seen over time.

Key points

  • The presence of bulk fat within an adrenal mass is characteristic of adrenal myelolipoma.

  • Bulk fat in ACC or ACA, when present, is minimal in amount.

Mimics of adrenal hyperplasia

Adrenocortical hyperplasia refers to the benign thickening of the adrenal glands on imaging; it is an unusual cause of hypercortisolism and hyperaldosteronism. Adrenocortical hyperplasia can be discovered incidentally without associated hormonal hypersecretion [93]. Imaging typically demonstrates diffuse thickening of the gland, which maintains its normal shape; less commonly, nodular enlargement can occur [26]. Bilateral multinodular appearance is typically seen in patients with ACTH-independent macronodular adrenal hyperplasia (Fig. 16); radiologists need to be familiar with this pattern to avoid misinterpreting adrenal hyperplasia as metastatic deposits. Some primary malignancies can secrete ACTH, leading to the development of ACTH-dependent adrenal hyperplasia, which can mimic metastases—especially in the context of underlying primary malignancy (Fig. 17).

Fig. 16
figure 16

An example of ACTH-independent macronodular adrenal hyperplasia (AIMAH) mimicking metastases in a 42-year-old man. Contrast-enhanced axial CT shows bilateral multinodular enlargement of both adrenal glands (arrows), with more enlargement on the left side and CT attenuation ranging between 72 HU and 81 HU, compatible with bilateral adrenal metastases. Biochemical evaluation and surgical resection proved the mass to be AIMAH

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Fig. 17
figure 17

An example of ACTH-dependent adrenal hyperplasia mimicking adrenal metastases in a 33-year-old woman with Cushing syndrome. Contrast-enhanced axial CT a shows diffusely enlarged adrenal glands (black arrows) secondary to ectopic ACTH production in the setting of a metastatic neuroendocrine tumor (NET) of the pancreas (white arrow). Follow-up contrast-enhanced axial CT at 9 months b shows progressive enlargement of the pancreatic NET (white arrow) with parallel enlargement of the adrenal glands. Thus, ACTH-dependent adrenal hyperplasia can mimic metastatic deposits due to the enlargement of the adrenal glands in the setting of an enlarging primary tumor

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Bilateral adrenal metastases and bilateral adrenal lymphoma

The adrenal gland is a relatively common location for metastatic disease [4]. Adrenal metastases are often bilateral and constitute an estimated 5.7% of bilateral adrenal lesions [94]. Adrenal metastases show inconsistent appearance on imaging; however, they can demonstrate bilateral diffuse or nodular thickening of the adrenal glands and maintain adreniform shape, resembling adrenocortical hyperplasia (Fig. 18). History of known malignancy is crucial in suggesting the possibility of metastatic deposits. Adrenal lymphoma, which rarely occurs, can appear identical to adrenal hyperplasia on imaging and is commonly bilateral [94, 95]. Given their interchangeable imaging appearance, adrenal lymphoma and metastatic lesions both can mimic adrenal hyperplasia and vice versa. Lymphoma and metastatic lesions both commonly exhibit low and moderate signal intensity on T1- and T2-weighted MRI, respectively, with progressive enhancement on contrast-enhanced T1 sequences. PET/CT is useful in such cases and usually shows intense FDG uptake; conversely, adrenal hyperplasia typically demonstrates FDG uptake that is just minimally increased above normal background [96].

Fig. 18
figure 18

An example of adrenal metastasis mimicking adrenal hyperplasia in a 56-year-old man with a history of metastatic melanoma. T1-weighted axial MRI a shows diffuse adreniform thickening of the left adrenal gland (arrow) appearing hypointense on T1, which is thought to represent adrenal hyperplasia. No abnormal diffusion restriction, enhancement, or T2 signal characteristics (not shown) within the left adrenal gland to suggest metastasis. However, PET/CT b shows avid FDG uptake (SUVmax = 18.9) in the left adrenal gland (arrow). The left adrenal gland was surgically resected and proven to have metastatic deposit from melanoma

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Key points

  • Bilateral adrenal metastases and lymphoma may manifest with adreniform thickening of the adrenal gland, mimicking adrenal hyperplasia.

  • History of a primary malignancy highly suggests the possibility of adrenal metastases rather than adrenal hyperplasia.

  • PET/CT can be useful, as it usually shows intense FDG uptake by metastases and lymphoma but not by hyperplasia.

Adrenal collision tumor

A collision tumor is generally defined as a rare condition where two morphologically and pathologically distinct tumors, benign or malignant, co-exist in close proximity to each other within the same organ [97]. Collision tumors have been reported to involve a multitude of organs, including the liver, lungs, stomach, and adrenal glands [98, 99]. Collision tumors pose a diagnostic and therapeutic challenge because collision tumors consisting of a benign and malignant component can result in the malignant component going undiagnosed and possibly untreated. Therefore, accurate identification of these tumors is of utmost importance.

Adrenal collision tumors (ACTs) include a mixture of primary and secondary adrenal tumors and can mimic several adrenal pathologies on imaging (Fig. 19). Given the high prevalence of adenomas, they are the most commonly reported ACTs together with myelolipomas [100]. When an adrenal adenoma is present in an ACT, heterogeneous signal drop can be appreciated on OP compared with IP images [21]. Diagnosis of ACTs on imaging requires a high index of suspicion during evaluation of a heterogeneous adrenal mass. In addition, it is essential to correctly utilize different imaging modalities, as discussed before, to delineate the distinct tumor components based on their individual imaging features [100].

Fig. 19
figure 19

An example of an adrenal collision tumor in a 59-year-old man with history of metastatic melanoma. T1-weighted contrast-enhanced axial MRI shows two distinct masses within the right adrenal gland; a 1.9 × 1.8 cm intracellular fat-containing adrenal adenoma (long arrow) that has been stable compared to prior imaging, showing signal drop on IP/OP (ASII = 38%). The other mass (arrowhead) is a 1.3 cm mildly enhancing adrenal nodule that has not been present on prior imaging, with no drop of signal on out-of-phase compared to in-phase pulse sequences (ASII = 7%). Pathological examination confirmed an adrenal collision tumor consisting of an adenoma and a metastasis

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Key points

  • Identification of collision tumors is essential for appropriate management.

  • A new discernible nodule within a preexisting adrenal mass raises suspicion for ACT.

Conclusion

Pitfalls in adrenal imaging can be encountered due to several reasons; imaging technique-related pitfalls are common and include suboptimal delay during adrenal enhanced CT protocol. Adrenal pseudolesions represent another potential pitfall because of the close anatomical location of the adrenal glands to various abdominal organs. In addition, atypical features of certain pathologies and rare entities can have similar appearances to more common pathologies on imaging.