Differentiation between adrenocortical carcinoma and lipid-poor adrenal adenoma using a multiparametric MRI-based diagnostic algorithm

Adrenal incidentaloma is depicted in 2% to 7% of patients in the general population and defined as an adrenal lesion (AL) larger than 10 mm that is incidentally discovered on an imaging examination [1], [2], [3]. At the time of initial detection, assessment of the risk of malignancy is one important concern. Approximately 80% of adrenal incidentalomas are benign adrenal adenomas (AA) [2,3]. Identification of benign AA is relatively straightforward for homogenous and lipid-rich AA (i.e., < 10 Hounsfield units [HU]) smaller than 4 cm on non-contrast computed tomography (CT) [1]. Apart from these benign features, additional imaging is generally recommended [1]. The characterization of lipid-poor AA (LPAA) was historically based on washout calculation on contrast-enhanced CT, that is now being debated, or using chemical-shift magnetic resonance imaging (MRI) sequences, but the accuracy for the diagnosis of LPAA remains unperfect, with reported values under 90% [4], [5], [6], [7], [8], [9], [10].

Characterization of AL also relies on the assessment of adrenal hormonal excess, and for patients with oversecretion, the diagnosis is obtained on the basis of the results of laboratory tests. In other situations, the diagnosis of primary adrenal malignancy (i.e., adrenocortical carcinoma [ACC]) is relatively straightforward when loco-regional involvement (i.e., European Network for the Study of Adrenal Tumors [ENSAT] stage III or IV tumors) or distant metastases are present. Similarly, when a patient with a known cancer develops AL during the follow-up, the diagnosis of adrenal metastasis is highly likely. However, in the remaining situations, the assessment of malignancy of LPAA can be challenging and surgery remains necessary. In these cases, the distinction mostly concerns LPAA, estimated to represent approximately one third of benign AAs and early stage ACCs (i.e., ENSAT stage I and II) [11,12]. Although, tumor size is a sensitive criterion for the diagnosis of ACC using a cut-off of 4 cm, it yields modest specificity [13]. Similarly, laboratory tests may help differentiate between benign and malignant AL but there is some degrees of overlap and laboratory tests are not accurate enough to discriminate between ACC and LPAA [21]. Consequently, despite improvement in non-invasive diagnosis, it can be estimated that 25% of adrenalectomies, which are performed for atypical benign ALs to rule out malignancy, are futile and could be avoided [14,15].

Despite demonstrated advantages in tissue characterization, MRI is still considered as a second line imaging modality for the assessment of adrenal lesions [6], [7], [8], [9]. In this regard, a consensus on the use of MRI was obtained for chemical shift imaging sequences only. Other MRI sequences such as diffusion-weighted imaging (DWI), with apparent diffusion coefficient (ADC) calculation have led to conflicting results in terms of AL characterization and their use remains debated [15], [16], [17]. Accordingly, the actual capabilities of MRI for the characterization of adrenal malignancy, and more specifically of ACC, must be clarified.

The purpose of this study was to evaluate the capabilities of multiparametric MRI in differentiating between LPAA and ACC using two independent cohorts of patients from two centers.

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