Ectopic adrenocorticotropic hormone syndrome associated with olfactory neuroblastoma: acquirement of adrenocorticotropic hormone expression during disease course as shown by serial immunohistochemistry examinations

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of endogenous hypercortisolism sustained by an extrapituitary ACTH-secreting tumor. Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract and is derived from the olfactory epithelium. Because the paranasal sinus is not a common site of EAS, the development of ONB in patients with EAS is rare. We herein report the first known case of ONB with acquirement of ACTH production during the clinical course as proven by immunohistochemistry. A 50-year-old man diagnosed with ONB was referred to our department in July 2015 because of hypokalemia, hyperglycemia, decreased eosinophil and granulocyte counts, and elevated serum levels of ACTH and cortisol. Although two previous ONB biopsy specimens (2011 and 2014) showed no ACTH immunoreactivity, a newly obtained specimen in August 2015 clearly showed ACTH immunoreactivity. This is the first case of ectopic ACTH syndrome associated with an ONB that acquired the ability to express ACTH during its clinical course as shown by serial immunohistochemical examinations.