Diagnosis of sarcomatoid adrenal cortical carcinoma in the era of personalized medicine

Sarcomatoid adrenal cortical carcinoma (SACC) is an uncommon variant of adrenocortical carcinoma (ACC incidence 0.5-2 cases/million population), with an aggressive nature and poor prognosis. We present a case of SACC in a 54-year-old woman, followed since 2019 for an incidentally found 2.8 cm right adrenal nodule, which increased in size to 10.6 cm in 1/2022. Biochemical work-up was unremarkable except a mildly elevated dopamine. An adrenalectomy specimen revealed a 484 gram, 12x9.6x7.1 cm, biphasic, mostly MFH-like sarcomatoid high-grade neoplasm with morphology and immunoprofile compatible with SACC. SACC invaded into the adherent fragment of the diaphragm, liver parenchyma, and IVC wall. 1/2 lymph nodes were positive (Stage III, pT4 pN1 cM0). NGS performed at Tempus revealed one genomic potentially actionable variant, three biologically relevant variants, one FDA-approved therapy and one potential therapeutic option. The patient underwent 6 cycles 1st-line cisplatin/etoposide combined with pembrolizumab immunotherapy and is on maintenance pembrolizumab q21d since 08/2022. CT scan in 7/2024 showed no evidence of disease, 2.5 years post SACC diagnosis. We are the first to report a case of SACC with actionable genomic features, and subsequent successful novel personalized treatment, a premise of personalized medicine. Further studies are needed to examine the influence of personalized treatment on the outcome of patients with this rare aggressive carcinoma.