OC36 - Analysis of predictive factors of malignancy in adrenal masses: findings from a large single-center surgical cohort

Background/Introduction Risk stratification for malignancy in adrenal masses is crucial to either avoid unnecessary surgery or reduce the risk of missing aggressive lesions. Purpose This study aims to investigate predictors of malignancy in patients with adrenal masses. Methods Retrospective single-center study on 573 adult patients who underwent adrenalectomy at San Luigi Gonzaga Hospital (2005–2023 period). Exclusion criteria: biochemical diagnosis of pheochromocytoma (plasma/urinary metanephrines >2 times the upper normal limit), bilateral adrenalectomy for ACTH-dependent Cushing syndrome, and recurrence of adrenocortical carcinoma (ACC). The final cohort included 191 adrenal masses, preoperatively classified as indeterminate [if ≥1 of the following: i) >10 Hounsfield unit (HU) density on unenhanced CT or loss of signal intensity on out-phase MRI; ii) radiological heterogeneity; iii) diameter ≥40 mm; iv) ≥30% growth at follow-up; v) FDG-PET uptake] or likely-benign (none of the above). Results Among the 191 masses, 56 (29.3%) were considered likely benign, and 135 (70.7%) indeterminate. Patients with indeterminate lesions were older [61 (IQR 52-69) vs 51 (IQR 45-58) years, p<0.001] and more frequently had a history of extra-adrenal cancer (24% vs 11%, p=0.039) or elevated DHEAS levels (14% vs 0%, p=0.062), compared to those with likely-benign lesions. Histopathology revealed 33 malignancies (17.3%, 21 ACC and 12 metastases), all within the indeterminate group. Multivariate analysis identified tumor diameter [OR 1.05, 95%CI 1.03–1.07, p<0.001], HU (OR 1.09, 95%CI 1.04-1.15, p<0.001), and a history of extra-adrenal tumors (OR 5.78, CI 1.95-18.39, p=0.002) as independent predictors of malignancy. Conversely, an incidental presentation was significantly associated with a lower likelihood of malignancy (OR 0.08, CI 0.02-0.26, p<0.001). The optimal size cut-off was 54.5 mm at ROC analysis (specificity 84%, sensitivity 74%, AUC 0.77). Elevated DHEAS was associated with malignancy in univariate analysis (OR 17.7, CI 4.23–93.4, p<0.001), but not in multivariate analysis. Conclusion(s) Our study confirms the predictive value of radiological features traditionally associated with malignancy, and shows that clinical factors, such as history of prior malignancy and mode of presentation, are important. Integrating this information may improve individualized risk stratification. The potential utility of biochemical markers such as DHEAS, although appealing, remains to be confirmed.