Fatty Pancreas: Its Potential as a Risk Factor for Pancreatic Cancer and Clinical Implications

Abstract

With the increasing use of imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging, incidental findings of pancreatic abnormalities, including pancreatic cysts and fatty pancreas (FP), have become more common. FP, also referred to as pancreatic steatosis, intra-pancreatic fat deposition, or fatty pancreas disease, is characterized by the accumulation of fat in the pancreas. Although FP has been associated with metabolic syndromes such as obesity and diabetes, its clinical significance remains unclear. Recent evidence suggests that FP may play a role in pancreatic carcinogenesis. Metabolic disorders, including obesity, insulin resistance, and diabetes, have been implicated in the development of FP. Additionally, FP has been linked to an increased risk of pancreatic ductal adenocarcinoma (PDAC), possibly due to chronic inflammation, lipotoxicity, and an altered pancreatic microenvironment. While early detection of PDAC remains challenging, surveillance strategies for high-risk individuals, such as those with pancreatic cysts, new-onset diabetes, or a genetic predisposition, may be crucial. In this context, FP may be incorporated into this surveillance of high-risk individuals. Some pharmacological interventions, including glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors, have shown potential in reducing pancreatic fat accumulation, although further studies are needed to confirm their efficacy.

Keywords: fatty pancreas; intra-pancreatic fat deposition (IPFD); pancreatic ductal adenocarcinoma (PDAC).

Figure 1

Immunohistochemical staining with anti-perilipin-1 antibody and hematoxylin counterstain demonstrates fatty infiltration in the pancreas. Fatty infiltration in the intralobular location (white arrowheads) and the extralobular location (black arrows) are shown. Immunohistochemical staining was performed using an anti-perilipin-1 antibody to highlight lipid droplets. Scale bar: 1 mm in (a) and 500 μm in (b).

Figure 2

Ultrasonographic images show (a) a non-fatty pancreas with normal echogenicity and (b) a fatty pancreas with increased echogenicity of the pancreatic body.

Figure 3

EUS images show (a) a non-fatty pancreas with normal echogenicity and a clearly delineated main pancreatic duct (MPD) margin, and (b) a fatty pancreas with severe hyperechogenicity, an obscure MPD margin, and increased echogenicity of the pancreas compared to that of the spleen.

Figure 4

Unenhanced transverse CT images showing 1 cm ROIs placed in the nontumorous pancreatic parenchyma and spleen: (a) In a non-fatty pancreas, the pancreatic and splenic CT attenuation values were 56.77 and 56.53 HU, respectively. (b) In a fatty pancreas, the values were 19.84 and 50.91 HU, respectively.

Figure 5

Proposed mechanisms linking intra-pancreatic fat deposition (IPFD) to pancreatic carcinogenesis. IPFD may increase the risk of pancreatic cancer development and progression by promoting the secretion of adipokines that stimulate inflammation, antagonize apoptosis, and enhance cell proliferation and migration. IL-6, including interleukin-6; TNF-α, tumor necrosis factor-α; TGF-β, transforming growth factor-β; α-SMA, α-smooth muscle actin; MCP-1, monocyte chemoattractant protein-1; PanIN, pancreatic intraepithelial neoplasia; PDAC, pancreatic ductal adenocarcinoma.