Mucormycosis is a frequently lethal fungal infection that most commonly affects patients with poorly controlled diabetes or other immunosuppressed states. We report the case of a suspected disseminated Rhizopus infection in a patient who was pursuing naturopathic treatment including mud baths for metastatic adrenocortical carcinoma. He was empirically treated with liposomal amphotericin B but opted to stop treatment following multiorgan failure. The patient passed away on the tenth day of his hospital admission.

BACKGROUND: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown.
METHODS: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics.
RESULTS: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032).
CONCLUSIONS: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

Metastatic adrenocortical carcinoma (ACC) often has a poor outcome, with a five-year survival of less than 25%. We report a rare case of metastatic ACC with a myxoid variant with chromothripsis. We review the histologic variants of ACC, including myxoid type, molecular drivers, and current and investigational therapies for adrenocortical carcinoma. We also discuss the mechanism of chromothripsis, chromothripsis in ACC tumorigenesis, and propose potential therapies targeting chromothripsis.

Adrenocortical carcinoma (ACC) is a very rare and challenging malignancy with a dismal prognosis. The patients usually suffer from primary or metastatic tumors, and about half of the tumors have hormone secretion function to cause Cushing\'s syndrome (CS) and hypercortisolism. The optimal management and clinical outcomes of ACC remain ill-defined due to the rarity of the disease. Due to the failure of effective treatment, surgery remains the main treatment for ACC, which includes distant resectable metastases and ACC recurrent. We reported a 34-year-old woman who was diagnosed with left-sided ACC at another hospital and then underwent left adrenalectomy for ACC 2 years ago. Then she was admitted to our hospital with CS caused by adrenocorticotropic hormone (ACTH) secretion from an ACC metastatic to the liver. She underwent a complete resection of the tumors in the liver and was discharged without any severe complications after hormone replacement therapy. Unfortunately, six months after the hepatectomy, she eventually died due to progressive deterioration and the refusal of further treatment. ACC is a rare and challenging disease with few durable systemic options. Due to the difficulty of full cure, prompt serial follow-up after the operation is probably crucial for a better prognosis.

Surgery remains the only potential option for prolonging survival in synchronous metastatic adrenocortical carcinoma (ACC). The purpose of this study is to identify patients who may benefit from adrenalectomy. Using the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), we identified synchronous metastatic ACC patients who underwent adrenalectomy. Cox regression analysis was performed to identify prognostic factors associated with overall survival. A clinical scoring system was created to predict survival after surgery. Sixty-two patients underwent adrenalectomy for synchronous metastatic ACC. Median age was 54.5 years. Median overall survival was 12 months. In univariable analysis revealed that age 65≥years, tumor stage: T3/4, multiple metastases, liver metastases, and no chemotherapy were associated with poor survival. In the multivariable Cox analysis, liver metastases (P = .017) and no chemotherapy (P = .039) remained independent predictors of worse prognosis. A clinical scoring system including of 1-point each for the 2 predictors demonstrated good discrimination in predicting survival after adrenalectomy (3-year survival: 45.9% for 0 points and 0% for 1 or 2 points; P < .001, area under the curve = .78). Prolonged survival after adrenalectomy combined with chemotherapy can be potentially achieved in synchronous metastatic ACC patients without liver metastases. Patients with liver metastases should be carefully evaluated for surgery.

Adrenocortical carcinoma (ACC) is rare but one of the most malignant endocrine tumors. This article reviews and summarizes the current knowledge about the treatment of ACC. The epidemiology and molecular events involved in the pathogenesis of ACC are briefly outlined. The different diagnostic tools to distinguish benign from malignant adrenocortical tumors, including biochemical analysis and imaging, are discussed. The surgical treatment of ACC has evolved in the last 2 decades. The different surgical alternatives for the treatment of ACC in the context of primary, recurrent, or metastatic disease are reviewed, and the remaining challenges and controversies are discussed.

Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated dose (MTD), safety, and pharmacokinetics (PK) of IL-13-PE in patients with metastatic ACC. Eligible patients had confirmed IL-13 receptor alpha 2 (IL-13Rα2) expressions in their tumors. IL-13-PE at dose of 1-2 μg/kg was administered intravenously (IV) on day 1, 3, and 5 in a 4-week cycle. Six patients received 1 μg/kg and two patients received 2 μg/kg of IL-13-PE. Dose-limiting toxicity was observed at 2 μg/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis demonstrated that at MTD, the mean maximum serum concentration (Cmax ) of IL-13-PE was 21.0 ng/mL, and the terminal half-life of IL-13-PE was 30-39 min. Two (25%) of the eight patients had baseline neutralizing antibodies against PE. Three (75%) of the remaining four tested patients developed neutralizing antibodies against IL-13-PE within 14-28 days of initial treatment. Of the five patients treated at MTD and assessed for response, one patient had stable disease for 5.5 months before disease progression; the others progressed within 1-2 months. In conclusion, systemic IV administration of IL-13-PE is safe at 1 μg/kg. All tested patients developed high levels of neutralizing antibodies during IL-13-PE treatment. Use of strategies for immunodepletion before IL-13-PE treatment should be considered in future trials.