Management of adrenocortical carcinoma (ACC) is challenging and debulking has been advocated to improve survival and quality of life in advanced disease. We report a remarkable case in a 60-year-old female without relevant cancer family history presenting with abdominal pain.

CT and MR revealed right adrenal neoplasm, liver metastases, inferior vena cava thrombosis. Laboratory data revealed hypercortisolism, and hyperandrogenism. She underwent adrenalectomy with intracaval thrombectomy and multiple liver metastasectomies, with high-dose mitotane for symptomatic relief. Pathological data and immunohistochemistry confirmed high-grade ACC, mENS@T stage pIVa. Despite treatment, CT scans at one month showed oncological progression with a rapid deterioration of the hormonal and clinical picture. Her death ensued 40 days after surgery

Our case, classified as conventional ACC on pathological and immunohistochemical grounds, met all the adverse prognostic factors. Additionally, we found a tumor-associated missense TP53 variant, c.843C>A, at codon 281, within the conserved DNA-binding region. TP53 mutation is associated with chromosomal instability and rapid disease progression. The mutant allele had a relatively low VAF (~27%), strikingly conserved in the primary tumor and in the hepatic metastasis. In our case, the distinctive mitochondrial hyperplasia and hypertrophy, with cristae expansion, was consistent with the clinical evidence of hypercortisolism and hyperandrogenism.

In conclusion, this case highlights the lack of criteria predictive of benefit or harm in the management of advanced stage ACC and challenges the utility of debulking surgery. New therapeutic protocols and new paradigms of care for this rare and aggressive cancer are clearly needed.