title: Multiple endocrine neoplasia type 1-associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas.
abstract: A novel combination of tumors was found in a 68 year-old female with Multiple Endocrine Neoplasia type-1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense-cored neurosecretory granules, larger zymogen-like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.
authors.affiliation: Department of Pathology, Japan National Hospital Organization, Hakodate Hospital, Hakodate, Japan. kimura-path@hnh.hosp.go.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Kimura
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Komuro
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchino
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
authors.forename: Takuzo
authors.initials: T
authors.lastname: Ishidate
authors.forename: Masanori
authors.initials: M
authors.lastname: Ishizaka
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002784:Cholesterol; D005260:Female; D015745:Granuloma, Foreign-Body / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D002784:Cholesterol