The less common

types include ACTHoma, CRHoma, Serotoninoma, Calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone-related peptide tumor. Nonfunctioning PETs are either an incidental finding or are associated with an expanding mass rather than a hormonal syndrome. Quizartinib nonfunctional tumors tend to present at later clinical stages with symptoms attributable to mass effect or metastases. Although nonfunctional tumors do not produce specific clinical syndromes, they Inhibitors,research,lifescience,medical may secrete inactive amine and peptide products such as neurotensin, alpha-subunit of human chorionic gonadotropin (alpha-hCG), neuron-specific enolase, pancreatic polypeptide (PP) and chromogranin A. Histopathology findings PETs may be either well circumscribed or infiltrative. The cut surface appears red to tan, reflecting the abundant microvasculature, or sometimes yellow because of high lipid content. Morphologically, well-differentiated PETs have characteristic “organoid” arrangements Inhibitors,research,lifescience,medical of the tumor cells, with solid, nested, trabecular, or ribbon-like/gyriform, tubuloacinar/psuedoglandular and mixed patterns. The cells are relatively uniform, with round to oval nuclei, Inhibitors,research,lifescience,medical coarsely granular and stippled (imparting the classical “salt-and-pepper” appearance) chromatin, and variable from pale to moderately eosinophilic cytoplasm. The cells produce abundant neurosecretory granules, as

reflected in the strong and diffuse immunohistochemical expression of neuroendocrine markers Inhibitors,research,lifescience,medical such as synaptophysin and chromogranin. Electron microscopy can identify secretory granules. There is usually minimal pleomorphism but less commonly there can be anaplasia, mitotic activity, and necrosis (1). Generally, the histologic features of the tumor do not correlate with anatomic location or hormone production, but there are exceptions:

amyloid deposition (insulin-associated peptide) Inhibitors,research,lifescience,medical often indicates an insulin-secreting PET, and glandular architecture with abundant psammoma body formation is usually seen in periampullary somatostatin-secreting PETs (1). The morphologic spectrum of these tumors can be variable, and the pathologic differential diagnosis includes chronic pancreatitis with neuroendocrine hyperplasia, poorly differentiated ductal adenocarcinoma, solid pseudopapillary tumor, acinar cell carcinoma, and pancreatoblastoma (6). However, serologic or immunohistochemical Tolmetin evidence for elevated hormones may be identified for PETs. PETs show tissue immunoreactivity for markers of neuroendocrine differentiation (chromogranins, synaptophysin, neuron-specific enolase, PGP9.5 and CD56) and may secrete various peptides and hormones. Expression of peptides such as insulin, glucagon, PP, somatastain, gastrin or VIP is common, and most functional PETs can be shown to produce the appropriate peptide by immunohistochemistry. In addition, minor cell populations producing a variety of other peptides are commonly detectable.