title: Biotin-rich intranuclear inclusions in morule-lacking adenocarcinoma of the gallbladder: a new category of "neoplastic/non-morular" lesions.
abstract: Biotin-rich intranuclear inclusions, also called "optically clear nuclei," are observed in various neoplastic and non-neoplastic lesions, including pregnancy-related endometrium and benign and malignant neoplasms with morular structures. A recent study reported that lesions with biotin-rich intranuclear inclusions can be classified as "(non-neoplastic) pregnancy-related endometrial" and as "(neoplastic) morular" category. In the present report, we describe two cases of well-differentiated adenocarcinoma of the gallbladder in which biotin-rich intranuclear inclusions were found without morular structures. Immunohistochemically, as reported previously, the intranuclear inclusions were positive for biotin and two biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). Intranuclear expression of beta-catenin was also observed in neoplastic cells with and without intranuclear inclusion. We also detected a frame shift mutation of APC gene in one case but no mutation of beta-catenin gene in both cases. Although intranuclear expression of beta-catenin by mutation of APC gene might contribute to carcinogenesis in our cases, the relationships among intranuclear expressions of beta-catenin, biotin, biotin-binding enzymes and intranuclear inclusions remain unclear. Our cases are the first neoplastic lesions with biotin-rich intranuclear inclusions that lacked morular structures. We propose a new "neoplastic/non-morular" category for lesions with biotin-rich intranuclear inclusions.
authors.affiliation: Department of Pathology, Faculty of Medicine, Oita University, Hasama-machi, 879-5593, Oita, Japan. kimuray@med.oita-u.ac.jp
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Daa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitano
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kubo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D000368:Aged; D001710:Biotin / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005706:Gallbladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000032:analysis; D055271:Mucin 5AC; D055272:Mucin-6; D009077:Mucins / Q000032:analysis; D011766:Pyruvate Carboxylase / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055272:Mucin-6; D009077:Mucins; D015534:Trans-Activators; D051176:beta Catenin; D001710:Biotin; D011766:Pyruvate Carboxylase; D043586:Methylmalonyl-CoA Decarboxylase