title: Lipid-rich variant of pancreatic endocrine neoplasms.
abstract: Most pancreatic endocrine neoplasms (PENs) show characteristic and well-recognized endocrine morphology; however, a lipid-rich pattern, which can present a diagnostic problem in biopsies, has been reported, mostly as individual cases. Some have been included in descriptions of the rare clear-cell variant associated with von Hippel-Lindau (VHL) syndrome. The histogenesis, clinicopathologic characteristics, and significance of this lipid-rich pattern have not been unraveled. In this study, 11 PENs exhibiting foamy, microvesicular cytoplasm were analyzed. In some cases, the nuclei were distorted by the vesicles, and the usual endocrine chromatin pattern was not evident. The growth pattern was relatively diffuse, with vague compartmentalization of the cells by a delicate vasculature; prominent nesting was noted in only 4 cases. Pathology reports indicated substantial diagnostic challenge in these cases; on biopsies, 1 case was originally diagnosed as adrenal cortical carcinoma, another as renal cell carcinoma, a third as solid-pseudopapillary tumor, and a fourth had a fine needle aspiration cytologic diagnosis of adenocarcinoma. All cases were chromogranin and synaptophysin positive. Electron microscopy in 3 cases confirmed the cytoplasmic vesicles to be lipid vacuoles. Neurosecretory granules were also evident. Clinically, as in conventional PENs, there appeared to be two distinct subsets: Two cases were familial or functional/syndromic (1 with VHL and the other with MEN-1 and glucagonoma syndrome) and occurred in younger adults (ages 41 and 47 years); the majority (n = 9) were nonfunctional/nonsyndromic and nonfamilial. The latter group was mostly represented by elderly males (mean age: 65 vs. 58 years in conventional sporadic PENs). Immunohistochemically, markers implicated in VHL-associated neoplasia, including HIF-1alpha, inhibin, and Melan-A (in clear-cell PENs) and MUC6 (in serous cystadenomas) were mostly negative in lipid-rich PENs (1 of 10, 1 of 10, 0 of 10 and 0 of 10, respectively). In conclusion, the lipid-rich pattern, reminiscent of adrenal cortical cells, represents a distinct subset of PENs. It presents a diagnostic challenge for surgical pathologists, especially in biopsies. EM supports the name lipid-rich for this variant. The findings suggest that the pathogenesis of lipid-rich tumors may be different from the VHL-associated clear-cell variants of PENs.
authors.affiliation: Department of Pathology, Harper Hospital and Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Singh
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.forename: Runjan
authors.initials: R
authors.lastname: Chetty
authors.forename: Sanaa
authors.initials: S
authors.lastname: Hussain
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rosa
authors.forename: Asli
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Jeanette D
authors.initials: JD
authors.lastname: Cheng
authors.forename: N Volkan
authors.initials: NV
authors.lastname: Adsay
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000473:pathology; D003937:Diagnosis, Differential; D004701:Endocrine Gland Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008055:Lipids; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006623:von Hippel-Lindau Disease / Q000150:complications
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids