PPY-cell hyperplasia accompanying NENs: Immunohistochemical and nuclear medicine analysis.

Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of the neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H and its corresponding clinical and imaging findings still need to be fully elucidated. We present 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN). PPY-H was analyzed with the help of immunohistochemistry and confocal microscopy; preoperative clinical data and imaging studies were evaluated retrospectively. We observed PPY-H emerging from pancreatic ducts, and in some cases, we observed simultaneous NKX6.1 positivity in ducts and PPY-H. Additional clinical-pathological correlations suggests that gastrointestinal symptoms (e.g., epigastric pain and cholestasis) could be more related to PPY-H than to NEN hormonal production. In particular cases, SSTR2 expression was strong in PPY-H and correlated with distinguishable accumulation of activity next to NEN on 99 mTc EDDA/Hynic-TOC SPECT/CT. In another case, 18F-FDG-PET/CT showed increased metabolic activity in the area of PPY-H surrounding NEN. Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of 99 mTc EDDA/Hynic-TOC or 68Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.

PAR2: The Cornerstone of Pancreatic Diseases.

It has been 30 years since the first member of the protease-activated receptor (PAR) family was discovered. This was followed by the discovery of three other receptors, including PAR2. PAR2 is a G protein-coupled receptor activated by trypsin site-specific proteolysis. The process starts with serine proteases acting between arginine and serine, creating an N-terminus that functions as a tethered ligand that binds, after a conformational change, to the second extracellular loop of the receptor, leading to activation of G-proteins. The physiological and pathological functions of this ubiquitous receptor are still elusive. This review focuses on PAR2 activation and its distribution under physiological and pathological conditions, with a particular focus on the pancreas, a significant producer of trypsin, which is the prototype activator of the receptor. The role in acute or chronic pancreatitis, pancreatic cancer, and diabetes mellitus will be highlighted.