(8.05) Lack of Tumor Localization on 68Ga DOTATATE PET/CT in Cushing's Syndrome due to Ectopic ACTH Secretion from Atypical Pulmonary Carcinoid Tumor

Localization of ectopic ACTH secreting tumors causing Cushing's syndrome is essential for clinical management but is often difficult.  68Ga DOTATATE PET/CT is a sensitive and high-resolution diagnostic tool for localization of ectopic ACTH secreting tumors. 68Ga DOTATATE PET/CT can however be negative in less differentiated neuroendocrine tumors such as atypical carcinoids.

Case(s) Description :

A 69-year-old female with history of hypertension, type 2 diabetes, and a hospitalization with severe hypokalemia was diagnosed with Cushing's syndrome due to ectopic ACTH secretion based on 24-hour urine cortisol of 720 mcg/24 hr (NL range 3.5-45 mcg/24), a.m. cortisol of 85 mcg/dL following a low dose dexamethasone suppression test and ACTH of 168 pg/mL (NL range 7.2-63 pg/mL). Pituitary MRI showed a nonspecific less than 1 mm focus of hypoenhancement in the sella region. Bilateral inferior petrosal sinus sampling (IPSS) was compatible with ectopic source of ACTH.

Chest CT scan showed an indeterminate 4 mm right lower lobe lung nodule with no concerning features for malignancy. Abdominal CT scan was unremarkable. 68Ga DOTATATE PET/CT was negative for any tracer avid neuroendocrine tumor.  Patient subsequently underwent a right lower lobe wedge resection given the findings on chest CT.  Pathology showed a 4 mm atypical carcinoid tumor with 2 adjacent carcinoid tumorlets measuring 1 and 2 mm.  Immunostains were positive for synaptophysin, chromogranin, and TTF-1; Ki-67 showed a proliferative rate of less than 1%. ACTH immunostaining was positive in the atypical carcinoid tumor. The mitotic index in the tumor was two mitoses per 2 mm2. Hypercortisolism and hypokalemia resolved after surgery and patient’s hyperglycemia significantly improved.  

Discussion :

Ectopic ACTH secreting neuroendocrine tumors can often be challenging to localize. 68Ga DOTATATE PET/CT scan is a helpful and highly sensitive tool to localize the neuroendocrine tumors including carcinoid tumors of the lung. Although typical pulmonary carcinoid tumors are often easily identified on these scans, less differentiated neuroendocrine neoplasms such as atypical carcinoids may have lost their expression of somatostatin receptors (SSTR) resulting in lower or no uptake of 68 Ga -DOTA- peptides. Further histopathological analysis on the diverse SSTR subtype expression may clarify the different clonal behavior of these tumors and explain negativity of these tumors on 68Ga DOTATATE PET/CT.