Molecular and Clinical Features of Adrenocortical Tumors in Beckwith-Wiedemann Spectrum

Background/Objectives: Adrenocortical tumors (ACTs), including adrenocortical adenoma (ACA) and carcinoma (ACC), represent 0.3–0.4% of pediatric tumors. Beckwith–Wiedemann spectrum (BWSp) confer an increased risk of ACTs, but prognosis, management, and associated molecular characteristics are unclear. Methods: This paper combines a literature review of 54 published cases of BWSp-ACT with a report of one newly identified patient, totaling 55 cases with a confirmed BWSp clinical and/or molecular diagnosis. Results: Nineteen patients with ACA, 33 with ACC, and 3 with ACT of uncertain malignant potential (umACT) were included. Twenty patients had uniparental disomy of chromosome 11p15.5 (patUPD11), 11imprinting Center 2 Loss-of-methylation (IC2-LoM), and had 2 11p15 locus duplication. Eleven patients were diagnosed during cancer screening procedures, including two metastatic at diagnosis ACC. Conclusions: Almost half of ACC patients reached the minimum score for clinical BWSp diagnosis only after ACC onset, suggesting that the BWSp score has limited value for the early diagnosis in such a setting. Two patients with metastatic ACC had a histopathological Wieneke score ≤2, not correlating with clinical malignancy and confirming limitations of the current histopathological classification, as previously documented. Ultrasound screening failed identifying the ACC before metastasis in two cases, indicating an urgent need to develop new strategies for screening of ACTs in BWSp. Furthermore, some cases of metastatic ACC exhibited unexpectedly indolent behavior despite being malignant.