Before IV contrast injection, a density ≤10 Hounsfield Units (HU), a homogenous appearance, and neat contours are features of a benign tumour, while malignant cortical adrenal tumours generally have a consistent density value ≥18 HU. Another characteristic feature seen in primary ACC, pheochromocytomas and metastatic tumours is the relatively slow contrast wash out [2]. A decrease of more than 40 % of the maximal enhancement 10 min after the injection has been reported to be pathognomonic of an adenoma [3].

The tumour size is another important feature to differentiate between a benign mass and an ACC. According to statistical data collected from a large series, the likelihood of malignancy doubles (to 10 %) at a threshold of ≥4 cm and rises to more than ninefold (47 %) for tumours ≥8 cm [4, 5] (Fig. 26.2a, b).

Gadolinium-enhanced MRI may be an alternative in patients allergic to iodinated contrast.

Once suspicion of an ACC is raised by other investigations, 18F-FDG PET appears to be the standard imaging means to “ascertain” the diagnosis because of its reported 100 % sensitivity and negative predictive value (Fig. 26.3a–d) [6]. A threshold ratio of 1.8 between the maximum standardized uptake values (SUVmax) of the tumour and that of the liver demonstrated 100 % sensitivity and specificity after correlation with the final histological diagnosis [6]. A cutoff SUV of 3.1 was also proposed as a reliable demarcation point between malignant lesions and adrenal adenomas with sensitivity, specificity, positive predictive value and negative predictive value of 98.5 %, 92 %, 89.3 %, 98.9 %, respectively [7].

Nine histological criteria of Weiss were used to predict tumour malignancy and prognosis: Fuhrman nuclear grade III or IV (see Chap. 13, Table 13.​2), >5 mitosis/50 HPF, atypical mitosis, cytoplasm characteristics (less than 25 % of clear vacuolated cells being an unfavourable factor), diffuse architecture, tumour necrosis, venous invasion, sinusoid invasion and capsular invasion [8]. Each criterion is scored 1 when present. A total score >3 is predictive of malignancy. In view of the possible subjectivity inherent to the interpretation of some criteria of Weiss, a retrospective study proposed to double the weight of the 2 most reliable ones, i.e. the mitotic rate and the cytoplasm characteristics. In this modified Weiss criteria, presence of atypical mitosis, tumour necrosis and capsular invasion are still considered with a score 1 while the remaining has been abandoned [9].

However, histopathological diagnosis of ACC remains challenging as the distinction from a benign adenoma is generally difficult. A French study has identified 3 molecular predictors using tumour RNA micro-arrays as novel tools for the detection of malignancy and for predicting survival [10]: the combination of DLG7 and PINK1 for malignancy signature and the combined expression of BUB1B and PINK1 as predictors of survival.

More recently a novel steroid metabolomics¹ approach was proposed to help in the differential diagnosis between an ACC and an adrenal adenoma [11]. This is a simplified diagnostic tool based on the identification of only 9 adrenal steroids from a 24-h urinary collection with properties that are most helpful in differentiating the malignant from the benign variety. This investigation is virtually equal in sensitivity and specificity to the currently used fastidious 32 steroid-based study.

Transcutaneous biopsy of the ACC is currently not recommended for the diagnosis of a primary ACC because of poor diagnostic value and possible complications (bleeding, tumour cell spillage), although a recent retrospective study has shown that it does not affect the recurrence-free or overall survival [12].

The use of a fine-needle biopsy should be restricted to [13]: