THU521 A Case Of Multifocal Pancreatic Neuroendocrine Tumor With Multiple Twists

Disclosure: A. Syeda: None. V. Kantorovich: None. Background: Multifocal pancreatic neuroendocrine tumors (PNETs) are rare and are usually associated with genetic syndromes like Multiple Endocrine Neoplasia 1 (MEN1). Sporadic multifocal PNETs have been infrequently reported. Case: A 68-year-old Caucasian female with a past medical history of hypertension, hyperlipidemia, type 2 diabetes mellitus, morbid obesity, multiple renal cysts, and Barrett’s esophagus presented to endocrinology for evaluation of PNET. An MRI performed for evaluation of renal cysts demonstrated pancreatic lesions suspicious for neoplasm. An endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (FNAB) of the largest lesion was consistent with low grade PNET positive for chromogranin A (CgA) and synaptophysin. Biochemical workup was remarkable for elevated CgA of 4800 ng/mL (n: <311 ng/mL) and elevated gastrin level of 700 pg/mL (n: <100 pg/mL); however, the patient was on proton pump inhibitors. A Ga-68 DOTATATE scan revealed 4 DOTATATE avid masses in the pancreatic head, neck, body and tail, the largest measuring 2.3 cm in the pancreatic head. No metastatic lesions were identified. Family history is significant for hyperparathyroidism in one sister and endometrial cancer in another sister. Genetic testing was negative for 86 genetic mutations including MEN1, VHL, TSC1 and TSC2. The patient underwent a successful total pancreatectomy, splenectomy and duodenectomy with a hepaticojejunostomy and gastrojejunostomy. Surgical pathology revealed 5 multifocal tumors, measuring 0.4-2.2 cm in diameter, with clear margins, without any lymphovascular invasion and 19 lymph nodes negative for malignancy. Mitotic rate was <2 mitoses per mm2 and Ki-67 index was < 3 %. Next Generation Sequencing of the surgical specimen was positive for ATM gene deletion. Interestingly, immunohistochemistry stained strongly for insulin, glucagon and INSM1 suggestive of nesidioblastosis although the patient did not have preoperative hypoglycemia that would raise a clinical suspicion. Discussion: This case highlights several unique features in a multifocal PNET. A recent study suggested that multifocality is not associated with worse prognosis or increased risk of recurrence. Another distinctive finding in our patient is the ATM gene mutation. Heterozygous pathogenic variants in ATM gene are known to be associated with hereditary pancreatic cancer but there has been no reported association with PNETs. ATM gene down regulation is linked with metastatic NETs and was proposed as a potential predictive marker for metastasis and as a novel target in metastatic gastroenteropancreatic NETs. Concurrent occurrence of nesidioblastosis and PNET has been rarely reported in the literature, however, it was a clinically silent phenomenon in our case. Presentation: Thursday, June 15, 2023