Adrenocortical carcinoma with circulating tumor DNA analysis at post-operative recurrence: a case report with review of literature.

Recently, the usefulness of circulating tumor DNA (ctDNA) analysis in various malignancies has been reported. However, reports on ctDNA analysis in adrenocortical carcinoma (ACC) are few. Therefore, this study aimed to examine the detectability of genetic mutations in ctDNA and the association between ctDNA allelic ratio and disease progression in a patient with post-operative recurrence of ACC. A 77-year-old woman presented with a 5.4 cm left adrenal mass, which was clinically diagnosed as subclinical cortisol-producing ACC on close examination. She underwent left adrenalectomy and was diagnosed with stage II (T2N0M0) ACC. Post-operatively, adjuvant chemotherapy with mitotane was commenced because of histologically high-grade ACC. However, 17 months post-operatively, she had a local recurrence at the left adrenalectomy site. FoundationOne® CDx Cancer Genome Profile showed CTNNB1 G34A mutation in the resected adrenal tumor. She had heart failure and interstitial pneumonia and was treated with radiotherapy for local recurrence. Subsequently, lung and liver metastasis appeared post-operatively at 21 and 23 months, respectively. Serum dehydroepiandrosterone sulfate and computed tomography findings at 27 months post-operatively showed disease progression. We collected the peripheral blood at 23 and 27 months post-operatively and analyzed 18 genes associated with adrenal disease in plasma cell-free DNA and the resected adrenal tumor using a next-generation sequencer. At both time-points, CTNNB1 mutations consistent with the primary tumor were observed in ctDNA, with the allelic ratio increasing over time from 8% to 27%. In conclusion, monitoring the ctDNA allelic ratio may be useful for evaluating disease progression in advanced ACC.