PMC8826724_01
Coronal and axial CT views at diagnosis (A, B) show an abdominal solid mass (23x13x18 cm), with several necrotic-cystic zones, closely located to the lesser curvature of the stomach, which displaced the duodenum, pancreas, aorta and cave vein. Coronal and axial images of 18-FDG PET/CT scan (C, D) reveal increased metabolic activity in the whole mass. Coronal and axial images of somatostatin receptor scintigraphy SPECT/CT show increased expression of somatostatin receptors (E, F). Coronal and axial images of CT after surgery show complete tumor resection (G, H).
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CT showed a well-localized abdominal solid mass (23x13x18 cm), with necrotic-cystic zones, closely located to the lesser curvature of the stomach, and displacing the duodenum, pancreas, aorta and cave vein ( Figures 1A, B ). The 18-FDG PET/CT scan showed increased metabolic activity in the whole mass ( Figures 1C, D ). Additionally, a somatostatin receptor scintigraphy SPECT/CT revealed increased expression of somatostatin receptors ( Figures 1E, F ). Surgery was performed five months after the diagnosis and total resection of the lesion was achieved ( Figure 1G, H ).
(A) Time-line representation of evaluated biochemical parameters since diagnosis until two years after surgery. Serum values of calcium, phosphate, PTH, PTHrP, 25(OH)D3, 1,25(OH)2D3 are depicted. Medical treatment is also represented. PH, parenteral hydration; ZA, zolendronic acid; IC, intravenous corticoids; IV intravenous furosemide; OC; oral corticoids; OF, oral furosemide; I, imatinib; O, octreotide; C, calcifediol; S, surgery. The gray square represents normal calcium serum levels. Cell proliferation assay of primary cultures of the described GIST tumor after 24, 48 and 72 hours of incubation with denosumab, sorafenib, sunitinib, octreotide, pasireotide and hydrocortisone (B-D). Molecular expression of somatostatin receptors (E), vitamin D- related enzymes and receptors (F) and inflammation related genes (G) using qPCR. *p < 0.05; **p < 0.01; ***p < 0.001.
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The evolution of serum calcium, calcitriol, other biochemical parameters and the respective treatment are depicted in  Figure 2A . During the first 24h, sorafenib significantly decreased cell proliferation ( Figure 2B ), any significant change was observed after 48 hours ( Figure 2C ) but after 72h only sunitinib achieved this effect. Remarkably, denosumab, pasireotide and hydrocortisone increased cell proliferation at 72h ( Figure 2D ). The molecular analysis of tumor cells in the tumor sample reveled mRNA expression of somatostatin receptors (especially SST1, SST2 and the truncated receptor SST5TMD4;  Figure 2E ). Figure 2F ). Furthermore, the expression of the inflammation related receptors CD14, CD45 and toll like receptor 4 (TLR4) were also confirmed ( Figure 2G ).