Differentiating between adrenocortical carcinoma and lipid-poor cortical adenoma: A novel cross-sectional imaging-based score

Published:October 13, 2022DOI:



      Discrimination between adrenocortical carcinoma and lipid-poor cortical adenoma preoperatively is frequently difficult as these two entities have overlapping imaging characteristics. Differentiation will allow for the selection of the most appropriate operative approach and may help prevent over-treatment. We aimed to identify imaging features that could preoperatively differentiate adrenocortical carcinoma from lipid-poor cortical adenoma and use them in a novel imaging-based score.


      We conducted a retrospective analysis of patients with pathologically proven adrenocortical carcinoma and lipid-poor cortical adenoma who underwent resection in a single tertiary referral center between March 1998 and August 2020. The inclusion criteria were diameter >1 cm, attenuation >10 Hounsfield units on nonenhanced computed tomography, and histopathologic diagnosis. Patients with metastatic or locally advanced adrenocortical carcinoma adenoma (stages 3–4) were excluded. We developed a score using binary logistic multivariate regression model in 5-fold derivation (∼70%) cohorts with stepwise backward conditional regression as feature selection. Standardized mean regression weight was used as variable score points.


      We identified 232 adrenals resected across 211 patients. By comparing the imaging characteristics of adrenocortical carcinoma (n = 56) and lipid-poor cortical adenoma (n = 156), we revealed statistically significant differences between the groups in 9 parameters: size, attenuation, thin and thick rim enhancement patterns, heterogeneity, calcification, necrosis, fat infiltration, and lymph node prominence. The score mean performance was 100% sensitivity for the exclusion of adrenocortical carcinoma, 80% specificity (95% confidence interval, 68.3–91.5), 66% positive predictive value (95% confidence interval, 52.3–78.7), and 100% negative predictive value with area under the curve of 0.974.


      We defined and evaluated a novel 9-variable, imaging-based score. This score outperformed any single variable and could facilitate safe preoperative discrimination of adrenocortical carcinoma and lipid-poor cortical adenoma.
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        • Ebbehoj A.
        • Li D.
        • Karu R.J.
        • et al.
        Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study.
        Lancet Diab Endocrinol. 2020; 8: 894-902
        • Reimondo G.
        • Castellano E.
        • Grosso M.
        • et al.
        Adrenal incidentalomas are tied to increased risk of diabetes: findings from a prospective study.
        J Clin Endocrinol Metab. 2020; 105: e974-981
        • Song J.H.
        • Chaudhry F.S.
        • Mayo-Smith W.W.
        The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy.
        AJR Am J Roentgenol. 2008; 190: 1163-1168
        • Fassnacht M.
        • Dekkers O.M.
        • Olaf M.
        • et al.
        European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors.
        Eur J Endocrinol. 2018; 179: G1-G46
        • Sharma E.
        • Dahal S.
        • Sharma P.
        • et al.
        The characteristics and trends in adrenocortical carcinoma: a United States population based study.
        J Clin Med Res. 2018; 10: 636-640
        • Bancos I.
        • Taylor A.E.
        • Chortis V.
        • et al.
        Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study.
        Lancet Diab Endocrinol. 2020; 8: 773-781
        • James B.C.
        • Aschebrook-Kilfoy B.
        • Cipriani N.
        • Kaplan E.L.
        • Angelos P.
        • Grogan R.H.
        The incidence and survival of rare cancers of the thyroid, parathyroid, adrenal, and pancreas.
        Ann Surg Oncol. 2016; 23: 424-433
        • Hines J.M.
        • Bancos I.
        • Bancos C.
        • et al.
        High-resolution, accurate-mass (HRAM) mass spectrometry urine steroid profiling in the diagnosis of adrenal disorders.
        Clin Chem. 2017; 63: 1824-1835
        • Boland G.W.
        • Lee M.
        • Gazelle G.S.
        • Halpern E.F.
        • McNicholas M.M.
        • Mueller P.R.
        Characterization of adrenal masses using unenhanced CT: an analysis of the CT literature.
        AJR Am J Roentgenol. 1998; 171: 201-204
        • Israel G.M.
        • Korobkin M.
        • Wang C.
        • Hecht E.N.
        • Krinsky G.A.
        Comparison of unenhanced CT and chemical shift MRI in evaluating lipid-rich adrenal adenomas.
        AJR Am J Roentgenol. 2004; 183: 215-219
        • Korobkin M.
        • Giordano T.J.
        • Brodeur F.J.
        • et al.
        Adrenal adenomas: relationship between histologic lipid and CT and MR findings.
        Radiology. 1996; 200: 743-747
        • Lee M.J.
        • Hahn P.F.
        • Papanicolaou N.
        • Egglin T.K.
        • Saini S.
        • Mueller P.R.
        • Simeone J.F.
        Benign and malignant adrenal masses: CT distinction with attenuation coefficients, size, and observer analysis.
        Radiology. 1991; 179: 415-418
        • Ream J.M.
        • Gaing B.
        • Mussi T.C.
        • Rosenkrantz A.B.
        Characterization of adrenal lesions at chemical-shift MRI: a direct intraindividual comparison of in- and opposed-phase imaging at 1.5 T and 3 T.
        AJR Am J Roentgenol. 2015; 204: 536-541
        • Dinnes J.
        • Bancos I.
        • Di Runnano L.F.
        • et al.
        Management of endocrine disease: Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis.
        Eur J Endocrinol. 2016; 175: R51-R64
      1. Fassnacht M, Arit W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol; 016;175:G1–G34.

        • Schieda N.
        • Siegelman E.S.
        Update on CT and MRI of adrenal nodules.
        AJR Am J Roentgenol. 2017; 208: 1206-1217
        • Davenport M.S.
        • Neville A.M.
        • Ellis J.H.
        • Cohan R.H.
        • Chaudhry H.S.
        • Leder R.A.
        Diagnosis of renal angiomyolipoma with hounsfield unit thresholds: effect of size of region of interest and nephrographic phase imaging.
        Radiology. 2011; 260: 158-165
        • Corwin M.T.
        • Mitchell A.S.
        • Wilson M.
        • Campbell M.J.
        • Fananapazir G.
        • Loehfelm T.W.
        Accuracy of focal cystic appearance within adrenal nodules on contrast-enhanced CT to distinguish pheochromocytoma and malignant adrenal tumors from adenomas.
        Abdom Radiol. 2021; 46: 2683-2689
        • Pena C.S.
        • Boland G.W.
        • Hahn P.F.
        • Lee M.J.
        • Mueller P.R.
        Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT.
        Radiology. 2000; 217: 798-802
        • Mantero F.
        • Terzolo M.
        • Arnaldi G.
        • et al.
        A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.
        J Clin Endocrinol Metab. 2000; 85: 637-644
        • Iñiguez-Ariza N.M.
        • Kohlenberg J.D.
        • Delivanis D.A.
        • et al.
        Clinical, biochemical, and radiological characteristics of a single-center retrospective cohort of 705 large adrenal tumors.
        Mayo Clin Proc Innov Qual Outcomes. 2018; 2: 30-39
        • Mayo-Smith W.W.
        • Song J.H.
        • Boland G.L.
        • et al.
        Management of incidental adrenal masses: a white paper of the ACR incidental findings committee.
        J Am Coll Radiol. 2017; 14: 1038-1044
        • Garay-Lechuga D.
        • Pérez-Soto R.H.
        • Hernández-Acevedo J.
        • et al.
        Computed tomography (CT) scan identified necrosis, but is it a reliable single para.meter for discerning between malignant and benign adrenocortical tumors?.
        Surgery. 2022; 171: 104-110
        • Thomas A.J.
        • Habra M.A.
        • Bhosale P.R.
        • et al.
        Interobserver agreement in distinguishing large adrenal adenomas and adrenocortical carcinomas on computed tomography.
        Abdom Radiol. 2018; 43: 3101-3108