Endocrine Abstracts

JOINT2770

It remains debated whether adrenocortical adenomas (ACAs) might represent a precursor to adrenocortical carcinomas (ACCs) or whether ACCs arise ‘de novo’ from adrenocortical tissue. Sporadic cases of malignant transformation of pre-existing ACA after prolonged latency have been reported, highlighting the unpredictable malignant potential of few benign tumors. This study retrospectively investigates the prevalence of prior imaging-based ACA diagnosis in the largest single-center ACC cohort, including 1516 patients referred to our center since January 2000. We identified 3 patients (0.2%) with documented ACA that remained stable for ≧2 years but were later histologically confirmed as ACC. All 3 patients were female, with a median age of 33 years at ACA diagnosis and 40 years at surgery. Tumors averaged 3.3 cm initially, and median follow-up was 7 years (range:4–14 years).

Case 1: A 39-year-old woman was diagnosed with a 4.5 cm left ACA in 2003. The lesion remained stable during the first 8 years of regular follow-up. However, following a 5-year gap in surveillance, the lesion grew to 6 cm and exhibited a new inhomogeneous appearance at CT imaging. Surgical tumor resection confirmed a high-grade ACC (Ki67:20%; Weiss score:9) with p53 positivity at immunohistochemistry. She died 2 years later from synchronous lung adenocarcinoma.

Case 2: A 33-year-old woman had a diagnosed of 3.7 cm non-functioning right ACA in 2014. After 3 years, although the lesion did not significantly change in size, the patient underwent adrenalectomy because of the development of hypercortisolism (cortisol after 1 mg-DST:16.6 μg/dl). Histology revealed low-grade ACC (Ki67:2–5%; Weiss score:3). She remains disease-free under active surveillance.

Case 3: A 33-year-old woman was diagnosed with a 1.6 cm left ACA in 2014, which remained stable until 2016. Hormonal evaluation was incomplete at diagnosis. By 2021, the lesion had grown significantly to 7.5 cm and hypercortisolism was detected (cortisol after 1-mg-DST:17 μg/dl). Adrenalectomy confirmed a high-grade ACC (Ki67:10–40%; Weiss score:8). A somatic pathogenic variant in CTNNB1 (p.Ser45Ala) was found. Since 2021, she has been undergoing mitotane and systemic therapies due to disease progression. Determining whether these ACCs arose from the malignant transformation of pre-existing ACAs, developed de novo, or were initially misdiagnosed remains challenging. However, these cases emphasize the exceptionally low likelihood of malignant transformation in benign-appearing, size-stable adrenal lesions, despite the high prevalence of benign adrenal tumors. Additionally, one case describes a rare occurrence of hormonal hypersecretion developing over time.