Case Report:
A 61 year old female presented to her primary care physician in late December 2020 with increasing right leg/ankle pain unresponsive to conservative therapy, elevated blood pressure, and concerns of new hirsutism. Subsequent MRI of her right leg revealed infiltrative enhancing lesion of the distal tibia concerning for metastatic foci (Figure 1, 2). Follow up PET/CT demonstrated diffuse metastatic disease (Figure 3, 4). An MRI brain was notable for diffuse boney metastasis without overt evidence of intraparenchymal disease. Initially this was thought to be an adrenal gland primary tumor due to noted hirsutism and elevate cortisol, however a full hormonal assessment was completed (Table 1). Ultimately, the results revealed both an elevated cortisol and elevated ACTH, favoring a non-adrenal and suspected pancreatic origin HGNEC (fluorodeoxyglucose [FDG] avid mass seen on PET), given the association of ACTH producing NET arising from islet tumor cells.
In February 2021, the patient had a biopsy of a subcutaneous breast lesion with initial pathology demonstrating malignant infiltrative proliferation within soft tissues that features pleomorphic nests of cells, nucleoli with salt-and-pepper chromatin, higher nuclear:cytoplasmic ratios, and greater than 40 mitoses per 2 mm E^E2 (Image 1, 2). Immunohistochemical stains were performed and positive for Lu-5, CK-7 (patchy), TTF-1, chromogranin, synaptophysin and negative for CK20, SOX10, GATA-3, and p40. These findings were consistent with HGNEC.
Due to the aggressive nature and high burden of her disease, the patient was admitted to the hospital upon receipt of her pathology results. Hematology/Oncology and Endocrinology were consulted. She was initiated on cytotoxic chemotherapy with carboplatin and etoposide. The patient was also initiated on ketoconazole to inhibit steroidogenesis in setting of ectopic ACTH production/Cushing’s syndrome. The patient tolerated chemotherapy administration well without evidence of tumor lysis syndrome. On day 5, however, she developed an ileus requiring placement of a nasogastric tube. Labs demonstrated severe cytopenias with absolute neutrophil count (ANC) < 600. On day 7, she began to experience respiratory distress with imaging notable for diffuse bilateral pulmonary opacities with a pleural effusion. The patient was intubated due to impending respiratory failure. Bronchoscopy and thoracentesis were performed at that time. She was initiated on empiric antimicrobials, daily filgastrim, and stress dose hydrocortisone given concern for relative adrenal insufficiency. Infectious workup including blood cultures, urine cultures, cerebral spinal fluid studies, and BAL returned negative. Unfortunately, the patient continued to deteriorate with development of multi-organ failure and decreasing neurologic response despite sedation holds. In March 2021, the patient was transitioned to comfort care, terminally extubated, and passed shortly thereafter.