title: Pulmonary neuroendocrine tumors with nuclear inclusion.
abstract: Nuclear inclusion or pseudoinclusion is a peculiar cytological feature, and its recognition in appropriate clinicopathological settings can aid in the diagnosis of several disease entities. To the best of our knowledge, only 1 case of pulmonary neuroendocrine tumor (NET) with nuclear pseudoinclusion has been reported. A review of 227 patients who had undergone surgical resection for pulmonary NETs revealed 2 tumors with different mechanisms of nuclear inclusion. To explore the cause of nuclear inclusion, NET with nuclear inclusion was characterized immunohistochemically and ultrastructurally. Nuclear inclusions were observed in 2 of the 227 (0.9%) patients with pulmonary NETs. The first patient was a 46-year-old woman with small cell carcinoma. Tumor cells with nuclear inclusions were distributed focally. Ultrastructural analysis showed that these inclusions were pseudoinclusions. The second patient was a 62-year-old man with large-cell neuroendocrine carcinoma. Nuclear inclusions were observed in the focal area of the tumor. Immunohistochemical analysis revealed that the intra-nuclear materials consisted of biotin and aberrant cytoplasmic and nuclear accumulation of β-catenin. Mutational analysis revealed a CTNNB1 gene mutation. Although very rare, diagnostic errors may be observed in cases of pulmonary NETs with nuclear inclusions. The mechanisms of nuclear inclusion differed, with one due to herniation of the cytoplasm into the nucleus (pseudoinclusion) and the other due to accumulation of biotin resulting from a CTNNB1 gene mutation.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Naoshi
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shibuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D045586:Intranuclear Inclusion Bodies / Q000235:genetics / Q000648:ultrastructure*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics
chemical_list: D051176:beta Catenin
keywords: Nuclear inclusion; Pulmonary neuroendocrine tumor; β-Catenin mutation