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.