Well Differentiated Pancreatic Neuroendocrine Tumor / Islet Cell Tumor
Definition
- Neoplasm of pancreas resembling normal islet cells with an organoid growth pattern, measuring at least 0.5 cm in greatest dimension
Alternate/Historical Names
- Islet cell tumor
- Pancreatic endocrine tumor
- Well-differentiated endocrine carcinoma
- Various names based on functional status or secreted product (see Clinical)
Diagnostic Criteria
- Tumor composed of neuroendocrine cells resembling normal islet cells
- Chromogranin, synaptophysin, and/or CD56 positive
- Round regular nuclei
- Stippled “salt and pepper” chromatin
- Nucleoli may be seen in some cases
- Granular eosinophilic cytoplasm in most cases
- If abundant, may be termed oncocytic
- Generally grossly circumscribed
- May infiltrate surrounding tissues and organs
- Perineural and vascular invasion may be seen
- May entrap normal ducts
- Has been termed ductuloinsular tumor
- Misnomer as the ducts are not neoplastic
- Has been termed ductuloinsular tumor
- May rarely be predominantly cystic
- Multilocular or unilocular
- At least 0.5 cm in maximum dimension
- Non-functioning tumors <0.5 cm are designated neuroendocrine microadenomas
- Mitotic figures no more than 20/10 HPF (100/50 HPF) and Ki67 index <20%
- Varying architectural patterns
- Most common: rounded organoid nests of tumor
- Set within a dense hyalinized stroma
- Trabecular, gyriform, and rosette-like patterns also seen
- Admixtures of patterns are often found within the same tumor
- Most common: rounded organoid nests of tumor
- Amyloid deposition may be seen
- Typically in insulin-producing tumors
- Calcification, rarely psammomatous, may be seen
- Rare Morphologic Variants
- Clear cell variant
- Abundant clear foamy cytoplasm
- Predominantly seen in patients with von Hippel Lindau syndrome
- Pleomorphic variant
- Extensive nuclear pleomorphism, enlargement and hyperchromasia
- No increased mitotic activity or necrosis
- No prognostic significance
- Lipid-rich variant
- Numerous cytoplasmic vacuoles within the tumor cell cytoplasm
- Thought to represent a degenerative phenomenon
- Pigmented, black variant
- Due to lipofuscin accumulation
- Melanoma markers negative
- Rhabdoid variant
- Prominent dense cytoplasmic inclusion
- Inclusion is keratin positive, desmin negative
- Displaces nucleus
- May displace neuroendocrine marker staining to adjacent cytoplasm
- No clear clinical significance
- Prominent dense cytoplasmic inclusion
- Oncocytic
- Hormonally inactive
- Most are aggressive
- Spindle cell
- Hepatoid
carcinomas considered by some to be related
- HepPar1 positive with bile and canaliculi
- Some have an endocrine component
- Aggressive
- Clear cell variant
- Sporadic cases usually solitary
- Syndromic cases frequently multiple
- MEN1
- Pancreatic tumors in 60%
- von Hippel Lindau
- May be conventional or clear cell
- Neurofibromatosis type 1
- Intra-pancreatic tumors rare
- More common is ampullary psammomatous somatostatinoma
- Tuberous sclerosis - rare
- MEN1
Reetesh Pai MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/updates : 2/1/08, 3/18/09, 6/18/10, 12/30/11, 1/1/13, 1/16/13
