MON-509 The Paradox of Size: A Case of Indolent Oncocytic Adrenocortical Carcinoma

Abstract Disclosure: S. Ojha: None. Y. Abdullah: None. P.V. Kumar: None. A. Mody: None. M.N. Kulkarni-Date: None. Introduction: Oncocytic adrenocortical carcinoma (OAC) is a rare morphologic variant of adrenocortical carcinoma (ACC), characterized by tumor cells with abundant granular, eosinophilic cytoplasm, often reflecting high mitochondrial density. Fewer than 150 cases have been reported, limiting consensus on optimal diagnostic and therapeutic pathways. Case Presentation: A 45-year-old female presented with progressive left-sided abdominal pain, 79-pound weight loss, and mild endocrine abnormalities. Imaging revealed a large left adrenal mass measuring 26.0 x 25.0 x 16.0 cm with central necrosis, features typically associated with high-grade ACC. Histopathological evaluation revealed a low Ki-67 index (2%) and negative lymph nodes, challenging the assumption that size correlates with aggressive behavior. The patient underwent multiorgan en bloc resection, including adrenalectomy, nephrectomy, distal pancreatectomy, splenectomy, and lymph node dissection via a chevron incision, achieving R0 resection. Intraoperatively, the tumor displayed hemorrhage and necrosis but was successfully excised despite significant blood loss. Pathology showed polygonal cells with oncocytic features, retained adrenocortical markers (Melan-A, SF-1, calretinin), and vascular invasion confirming malignancy under Lin-Weiss-Bisceglia (LWB) criteria. Venous invasion emerged as a key diagnostic feature despite low mitotic rates. Postoperatively, the patient’s hypercortisolism and elevated DHEAS resolved, and recovery was uncomplicated apart from transient supraventricular tachycardia and ileus. Next-generation sequencing revealed alterations in TP53-related pathways without classic ACC driver mutations, suggesting unique metabolic signatures in oncocytic variants. The low proliferation index, negative margins, and absence of high-risk genetic alterations led the multidisciplinary team to forgo adjuvant therapy such as mitotane or radiotherapy. Instead, intensive surveillance with regular imaging and endocrine testing was adopted, consistent with the unpredictable recurrence patterns of adrenocortical malignancies. Conclusion: This case highlights that OAC, despite its extraordinary size and necrotic features, can exhibit biologically indolent behavior when characterized by low mitotic indices and non-metastatic profiles. The absence of classic high-risk markers supported a conservative postoperative strategy. TUMOR BIOLOGY, defined by specialized histopathologic and molecular profiling, may override size-based prognostic models. Further research into the genomic and metabolic features of OAC is crucial to refine treatment and surveillance strategies for this rare malignancy. Presentation: Monday, July 14, 2025