Leptomeningeal metastasis from Adrenocortical carcinoma: a case report

Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy with
limited treatment options. While 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 eleven
months after the initial diagnosis. Subsequent analysis of 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 as well as 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.