PMC9895772_01
(A) Computed tomography (CT) scan of abdomen 6 months before admission. (B) CT scan at the time of admission. (C)
68Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe1-Tyr3-octreotide positron emission tomography/CT (DOTATOC-PET/CT) at abdominal level on admission. (D) DOTATOC-PET/CT at pelvic level on admission. CT scan of multiple intra-abdominal tumors of increasingly large size (blue dotted circle). DOTATOC PET/CT showing uptake of radiotracer in the tumors.
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The tumors were increased in size compared to six months before ( Figures 1A, B ). DOTATOC-PET/CT showed high uptakes of the radiotracer in all of the intraabdominal and subcutaneous lesions, indicating the expression of somatostatin receptors (SSTRs), mainly SSTR 2 and 5 ( Figures 1C, D ).
(A) Immunoblot analysis of insulin-like growth factor 2 (IGF2) in serum, tumors (T1-7 representing tumor #1-7) and their nearby normal tissue (N2-4 corresponding to tumor #2-4). Big IGF2 (11-18 kDa) was detected in preoperative serum and all tumor samples. The lane on the right is the IGF2 standard product. T: tumor; N: nearby normal tissue. (B, D) Preoperative and (E) 20 days postoperative continuous glucose monitoring results. (B) Without octreotide administration. (C) 50 mug Octreotide administration at 7 am (blue arrow). (D) 100 mug octreotide administration at 7 am (blue arrow). The red square indicates comparable period of blood glucose levels after octreotide administration. Each black triangle represents meal intake. The green lines indicate the period during which 9 g/h of glucose was intravenously administered.
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IGF2 to cause hypoglycemia. Immunoblot analysis revealed serum big IGF2, which established a clinical diagnosis of NICTH ( Figure 2A ). Single-dose subcutaneous octreotide administration was found by continuous glucose monitoring (CGM) system to increase the postprandial blood glucose level ( Figures 2B-D ). The immunoblot analyses of 7 of the 11 resected tumors, for which samples were available, revealed big IGF2 production in all of them ( Figure 2A ). After the surgery, hypoglycemia was resolved even after discontinuation of glucose infusion ( Figure 2E ). IGF2 was null one week after the surgery ( Figure 2A ). In addition, two weeks after the surgery, 72-hour fasting showed that plasma glucose levels no longer dropped to 55 mg/dL (3.06 mmol/L) with high ketone body levels; acetoacetate was 596 mumol/L and beta-hydroxybutyrate was 2,170 mumol/L ( Table 1 ).
(A) Macroscopic view of resected tumors. T1-11 represent tumor #1-11. (B-G) Microscopic findings of the representative resected tumor. (B, C) Hematoxylin and eosin staining showed that the tumor was composed of spindle to ovoid cells forming the patternless pattern. Immunohistochemical stains of tumor #10 show tumor cells to be positive for (D) signal transducer and activator of transcription 6 (STAT6), (E) IGF2, (F) somatostatin receptor 2 (SSTR2) and negative for (G) SSTR5. Scale bar: 50 mum.
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In the surgery, five of the largest intraabdominal tumors (tumor #1-4, #8 in  Figure 3A ) and six small tumors accessible from the abdominal operative field (tumor #5-7, #9-11 in  Figure 3A ) were resected. Histopathological examination revealed spindle to ovoid shaped signal transducer and activator of transcription 6 (STAT6)-positive tumor cells, compatible with the metastatic SFTs ( Figures 3B-D ). Additional immunohistochemical studies showed positive immunostaining for IGF2 and SSTR2 and negative immunostaining for SSTR5 in the tumor cells ( Figures 3E-G ).