Multiple metastatic NET of unknown primary site in a young patient with carcinoid syndrome: Can we treat it as a gastrointestinal NET?

Diana Lambrinoc; Alexandru Morea; Roxana Dușceac; Cătălina Poiană

doi:10.1530/endoabs.70.AEP727

Introduction: Neuroendocrine tumours (NETs) of unknown primary site are relatively uncommon, representing about 10% of all NETs. Of these, particularly the well-differentiated NETs often present initially with liver metastases, and most of these represent gastroenteropancreatic NETs. The presence of carcinoid syndrome is also common.

Case presentation: We describe the case of a 40 years-old patient presented in 2013 with flushing, diarrhea, and back pain. The chest-abdomen-pelvis CT showed several small lung nodules, multiple vertebral sclerotic bone metastasis, along with an osteolytic lesion on sacrum. It also revealed metastatic lesions in both hepatic lobes along with several enlarged abdominal lymph nodes. The upper and lower gastrointestinal endoscopy didn’t show any lesion. A hepatic biopsy was performed, histopathological examination and immunochemistry showing well differentiated G1 NET, with Ki-67 < 3%, positive for chromogranin A, somatostatin receptor type 2 and 5 and also for CDX2, indicating a midgut origin. The serum serotonin, chromogranin A and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were elevated, thereby treatment with somatostatin analogues (SSA) was initiated, improving the carcinoid syndrome. The tumour markers had, however, an oscillating evolution (Table 1). For bone metastasis he received zoledronic acid and radiation therapy for pain control. A 99 mTc-Tektrotyd scintigraphy and SPECT/CT were also performed, still unable to showcase the primary site. Furthermore in December 2019, the patient has undergone the first therapy cycle of ¹⁷⁷Lu-DOTATOC peptide receptor radionuclide therapy (PRRT) and tolerated it well. The second cycle will be administered in February 2020.

**Table 1** Serum Chromogranin A, Serotonin and urinary 5-HIAA/24 h levels during SSA therapy.
Date	5-HIAA mg/24 h (N: 2–9)	Serotonin mg/l (N: 80–400)	Chromogranin A mg/l (N: 27–94)	SSA	Dose of SSA/28 days
09.2014	242	1430	605	Octreotide LAR	20 mg
10.2015	118↓	2185↑	473↓	Octreotide LAR	20 mg
02.2017	149↑	>1000	540↑	Octreotide LAR	60 mg
07.2017	231↑	5.03↓↓	667↑	Lanreotide AG	120 mg
06.2018	285↑	3267↑	566 ↓	Lanreotide AG	120 mg
08.2018	97↓	1457↓	447 ↓	Octreotide LAR	60 mg
01.2019	165↑	2237↑	650 ↑	Octreotide LAR	60 mg
10.2019	145↓	1100↓	1320↑	Lanreotide AG	120 mg

Discussion: We showcase the importance of comprehensively investigating NETs of unknown origins as they are characterized by variable, yet frequently indolent evolution. Patients with abdominal masses on imaging scans and no evidence of the tumour on upper or lower endoscopy can be considered to have small intestinal primary tumours and should be treated according to guidelines.

Endocrine Abstracts

AEP727