Transformation of a Benign Adrenocortical Adenoma to a Metastatic Adrenocortical Carcinoma Is Rare But It Happens

Abstract

The transformation of an adrenocortical adenoma (ACA) to an adrenocortical carcinoma (ACC) is extremely rare. Current guidelines suggest against further imaging studies and follow-up in patients with nonfunctional adrenal incidentalomas (NFAIs) with benign imaging characteristics. Herein, we present a 64-year-old male patient diagnosed initially with a NFAI of 3 cm in size with imaging characteristics consistent with an ACA. However, 13 years after initial diagnosis, this apparent ACA developed into a high-grade cortisol and androgen-secreting ACC with synchronous metastases. The literature review revealed a further 9 case reports of adrenal incidentalomas initially characterized as ACA that subsequently developed into ACC within a period ranging from 1 to 10 years. The pathogenesis of transformation of an initially denoted ACA to ACC is not fully delineated, although the existing literature focuses on the preexisting or changing genetic background of these lesions, highlighting the need to develop robust prognostic markers to identify patients at risk and individualize the follow-up of these unique cases.

Keywords: adrenal adenoma; adrenal incidentaloma; adrenal incidentalomas; adrenocortical carcinoma; malignant evolution; malignant transformation.

Figure 1.

Axial unenhanced Computerised Tomography (CT) image of the upper abdomen demonstrates a nodular left adrenal lesion of 3 cm in size with low attenuation values <10 HU consistent with adenoma (A). Follow-up CT images of the same patient show no significant change of the lesion's size or density with mean ± SD density values equal to 7 ± 16.37 HU (max = 46, min = −35) (B) and 3.4 ± 27.85 HU (max = 68, min = −76) (C). On the follow-up CT performed one year before adrenocortical carcinoma (ACC) diagnosis the lesion remains stable in size but demonstrates higher mean ± SD density values equal to 24 ± 19.83 HU (D). Red circle: region of interest (ROI), HU: Hounsfield unit, Mean: mean HU, Max: maximum HU, Min: minimum HU, SD: standard deviation, Area: area of a square (cm²).

Figure 2.

Axial computed tomography of the abdomen of the same patient before (A) and after (B) intravenous contrast administration shows a heterogeneous mass with central necrotic foci involving the left adrenal gland and extending to the surrounding tissues (arrows). On ¹⁸FDG-PET images (C-D), the lesion demonstrates avid ¹⁸FDG uptake (small arrow) and high metabolic activity lesions in the liver (long arrow) and the lungs (arrowheads) suspicious of metastases. Abbreviations: ¹⁸FDG-PET, 18F-fluorodeoxyglucose positron emission tomography.

Figure 3.

Pre-and 6 months posttreatment MRI of the same patient. Axial T2W STIR (A), T1-opposed phase (B), and contrast-enhanced T1W SPIR (C) images on pretreatment MRI demonstrate a heterogeneous left adrenal mass (arrow in A and B) with intense contrast enhancement (arrow in C). A hepatic metastasis is also seen in the right liver lobe (arrowheads in A-C). Corresponding posttreatment MRI exhibits a significant decrease in the adrenal lesion size (arrows in D-F). Note the minimal enhancement of the lesion on the postcontrast image (arrow in F), another finding indicative of the tumor's response to treatment. Liver lesion is also decreased (arrowheads in D and E) and less enhanced (arrowhead in F) on posttreatment MRI. Abbreviations: MRI, magnetic resonance imaging.

Figure 4.

Pre-and posttreatment CT of the lung of the patient. Axial CT image at the initial presentation (A) demonstrates 2 well-circumscribed pulmonary nodules in the right lower lobe (arrows) consistent with metastases. Corresponding CT image at the same level (B), 6 months posttreatment, shows complete resolution of the metastatic nodules. Abbreviations: CT, computed tomography.

Figure 5.

Transcriptome classification. Patient's sample (*) was projected on the two principle components (Dim1, Dim2) of a principal component analysis (PCA) in a reference cohort of 95 patients (14). Samples from this reference cohort are presented as faint circles colored by transcriptome class: blue for adrenocortical adenomas “C2”, red for adrenocortical carcinoma of poor prognosis “C1A” and yellow for adrenocortical carcinoma of better prognosis “C1B”.