SUN-927 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor to the Breast

Abstract

Introduction:We present a rare case of ectopic Cushing syndrome (CS) due to a neuroendocrine tumor (NET) metastatic to the breast.Case:A 38-year-old female was referred for ACTH-dependent CS. She had rapid development of cushingoid features and hypertension three months prior to presentation. A 24-hour urinary free cortisol (UFC) was elevated to 2548 μg (0-50 μg/24hr), and ACTH was 228 pg/mL (10-60 pg/mL). A pituitary MRI was normal, and inferior petrosal sinus sampling was not consistent with a central ACTH source. A DOTA-TATE scan showed mediastinal lymphadenopathy and a 0.8cm area of uptake in the right breast. The patient was placed on ketoconazole and UFC normalized. Following biopsy, she underwent breast lumpectomy at an outside hospital, and pathology showed triple negative invasive carcinoma of the breast. Chemotherapy was initiated.However, her CS rapidly worsened: repeat UFC was 4867 μg, and ACTH was 369 pg/mL. Re-review of her pathology slides at our facility showed that the tumor stained negative for breast markers and positive for markers of NET and ACTH. Ki67 staining was approximately 30%. Chemotherapy for breast cancer was immediately stopped. A follow-up PET-CT continued to show uptake in the mediastinal lymph nodes. FNA of these lymph nodes revealed metastatic NET. In order to maximize control of her CS prior to chemotherapy, she underwent bilateral adrenalectomy (BLA). Afterwards, the patient received 10 cycles of chemotherapy with modified FOLFOX-7 for her NET. Thus far, the tumor burden appears stable, and she has been recommended to hold off on radiation therapy. She is currently taking replacement doses of hydrocortisone and fludrocortisone.Conclusion:In this challenging case, determination of source of ACTH hypersecretion led to an initial diagnosis of breast cancer. Primary breast carcinoma with neuroendocrine differentiation has been reported to show significant overlap in pathology with NET metastatic to the breast1. However, worsening of the CS in this case led to consideration of an alternative diagnosis, resulting in diagnosis of an ACTH producing NET metastatic to the breast. Prior to chemotherapy, she underwent BLA, which may lower morbidity and mortality associated with ACTH-dependent CS2, particularly given plan for further chemotherapy.Reference:1. Mohanty SK, Kim SA, DeLair DF, et al. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016;29(8):788-798. doi:10.1038/modpathol.2016.69.2.2. Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing’s syndrome. Surgery. 2013;154(6):1174-1183; discussion 1183-1184.