Leptomeningeal Metastasis From Adrenocortical Carcinoma

A Case Report

Anna R. Schreiber; Adwitiya Kar; Andrew E. Goodspeed; Nikita Pozdeyev; Hilary Somerset; Christopher D. Raeburn; Aik-Choon Tan; Stephen Leong; Margaret E. Wierman; Katja Kiseljak-Vassiliades


J Endo Soc. 2020;4(3) 

In This Article

Abstract and Introduction


Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy with limited treatment options. While the overall 5-year survival rate in patients with ACC is 35%, the disease is often rapidly progressive with long-term survival in only 5% of patients. Although tumor stage, grade, and excess hormonal activity predict unfavorable prognosis, additional biomarkers are needed to identify patients with aggressive disease. A 23-year-old woman presented with rapidly progressing signs and symptoms of Cushing's syndrome, with associated abdominal pain and fullness. Evaluation revealed a large left adrenal mass which had developed over 8 months. En bloc surgical resection was performed by an endocrine surgeon, and pathology revealed adrenocortical carcinoma with Ki67 of 60%. Despite adjuvant treatment with mitotane and etoposide–doxorubicin–carboplatin chemotherapy, the patient had rapid disease progression with metastatic spread to liver, lung, bone, brain, and leptomeningies, and she died 11 months after the initial diagnosis. Subsequent analysis of the patient's tumor revealed mutations in TP53 and MEN1. RNA sequencing was compared against the the Cancer Genome Atlas data set and clustered with the high steroid, proliferative subtype, associated with the worst prognosis. The tumor also demonstrated a low BUB1B/PINK1 ratio and G0S2 hypermethylation, both predictive of very aggressive ACC. This case represents a subset of ACC characterized by rapid and fatal progression. Clinically available predictors as well as recently reported molecular signatures and biomarkers correlated with this tumor's aggressiveness, suggesting that development and validation of combinations of biomarkers may be useful in guiding personalized approaches to patients with ACC.


Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with incidence of 0.7 to 2 cases per million annually.[1] ACC presents across the age spectrum with peaks in children less than 5 years and in adults in their fourth and fifth decade of life.[1] The prognosis is poor, as the majority of patients present with regional and distant metastasis at the time of diagnosis. Long-term survivors, however, are occasionally reported. Clinically, Ki67 immunohistochemistry has been used as the primary prognostic biomarker. Recent global profiling of ACC tumors has demonstrated that comprehensive genomic and genetic signature clusters correlate with ACC tumor aggressiveness, but this clustering has not been used prospectively and may be cumbersome for clinical practice.[2]

Common sites of metastasis for ACC include the liver, lungs, and bone.[1] Rarely ACC metastasizes to skin and brain.[1] Leptomeningeal carcinomatous metastases (LM) across all tumor types typically present as multifocal lesions in the leptomeninges in less than 5% of patients with advanced cancer.[3] The most common solid tumors to result in LM include breast, lung, melanoma, and gastrointestinal malignancies.[3] There have been few case reports of ACC resulting in brain metastasis[4–16] and there are only 2 previous ACC cases with leptomeningeal metastases reported in the literature.[17,18]

Here we present the case of a young woman who presented with severe Cushing's syndrome due to ACC with rapid disease progression and LM despite conventional therapy.