Adrenocortical carcinoma (ACC) is a rare yet aggressive malignancy. Survival rates remain poor, even after complete surgical resection1,2. Monitoring for disease recurrence is challenging. We describe a case where the use of urine steroid profiling and genomics has been employed in monitoring for disease recurrence and identifying potential treatment targets.
A 37-year-old female was diagnosed with stage 2 high-grade ACC (Ki67 75%) after presenting with a 17cm right-sided abdominal mass and symptoms of androgen excess. A right adrenalectomy/nephrectomy was performed. No lymphadenopathy or distant metastases were present. Urine steroid profiling post-operatively showed reduction in the previously elevated metabolites and precursors. The patient completed adjuvant fractionated adrenal bed radiotherapy and commenced mitotane. Therapy was complicated by reversible hepatotoxicity and central hypothyroidism.
One year later single bilateral lung nodules were noted on progress imaging, with subsequent staged wedge resections. At this time there was no elevation in urine steroids. A mild elevation of urinary pregnanetriol alone was detected six months later. However to date, 24-hour urine free cortisol, serum androgens, and serial imaging have not revealed further recurrence.
HiSeq X whole genome sequencing was performed on one of the metastatic tumours. A high rate of single nucleotide variants and indels was observed (48,718 total, 16 per megabase). Loss of function mutations were identified in multiple tumour suppressor genes including TP53 (G245S). No putative driver mutations or germline mutations were identified. Somatic signature analysis revealed the tumour to have microsatellite instability and defective mismatch repair. Subsequently, positive PD-L1 expression was detected by tumour immunohistochemistry, suggesting that PD-1 blockade could be considered for disease recurrence. Finally, we have identified a tumour-specific 11kB deletion on chromosome 16 and designed a specific PCR-assay to identity the presence of circulating tumour DNA in plasma.
Genomic analysis of ACC may provide insight into tumour biology and therapeutic targets.