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SUN-333 Expression of Type 2 Somatostatin Receptors and Low Tumor Markers of Aggressiveness Correlate with Positive 68Ga-DOTATATE Findings in Ectopic ACTH-Producing Tumors

Abstract Background: Ectopic ACTH Syndrome (EAS) is caused by over production of ACTH from non-pituitary neuroendocrine tumors (NET). Tumor localization is challenging; lesions are often < 1 cm in diameter or slow growing so that they are not seen on thin-cut CT or FDG-PET. The use of functional imaging such as 68Ga-DOTATATE PET/CT (DOTATATE) and 6 mCi Octreoscan (OCT) takes advantage of somatostatin receptor expression on these NETs [1-3]. Here, we studied the type 2 somatostatin receptor (SSTR2) expression in ectopic ACTH-producing tumors by immunohistochemistry (IHC) and correlated it with DOTATATE and OCT findings. Methods: All 17 patients (pts) had anatomic and functional imaging and histologic confirmation of EAS. IHC of tumors included evaluation of ACTH, SSTR2 and Ki67; pancreatic tissue islets were the positive SSTR2 control. An experienced research pathologist scored positive staining by the distribution of staining throughout the tumor (diffuse or patchy/focal), the % of cells that were positive (as 1 – 30%, >30-<60% or >60%), and staining intensity (as 1-3). We correlated the IHC findings with imaging (positive or negative in tumor site) and aggressiveness markers in the area of greatest IHC staining, defined as the Ki67 index (<3%, >3-20%, or >20% positive), mitotic count in 10-25 high power fields (HPF), or presence of tumor necrosis or metastasis. Results: The median age at diagnosis was 50 ± 12 years, 65% were females (n:11/17), median tumor size 9 mm (range 4-67 mm). Tumor was identified by DOTATATE in 13/16 pts and by OCT in 3/17. All 17 resected tumors stained for ACTH. Tumor type and location included 11 pulmonary NETs (64%), and 1 each of pulmonary tumorlets, appendiceal NET, ovarian teratoma, mediastinal NET, pheocromocytoma and a NET in a lymph node with unknown primary. Ten tumors had 3+ SSTR2 staining in >75% cells; DOTATATE was positive for all, OCT detected only 3. Four tumors had 0 – 1% of SSTR2 positive cells; DOTATATE was positive in 2 and OCT in none. Three tumors had <10, <25 and 50% staining and 1-2+ intensity; DOTATATE detected 1 and OCT none. Both scans were negative in a mediastinal NET with necrosis, Ki67 >20%, 25 mitoses/10 HPF and <1% SSTR2+ cells, and a metastatic ovarian teratoma with Ki67 21%, mitotic count 21/10HPF and <25% SSTR2+ cells. Conclusions: Most EAS tumors in our cohort were small, expressed SSTR2, and lacked markers of aggressiveness. Strong SSTR2 expression correlated with positive 68Ga-DOTATATE findings in 100% of cases but only 33% of OCT cases. Negative or limited SSTR2 receptor distribution was associated with 43% rate of DOTATATE positivity. Further investigation is needed into expression of other SSTRs to understand this finding. We speculate that positive imaging is a complex reflection of tumor size, SSTR expression, and malignancy potential.