title: Radiation-associated small cell neuroendocrine carcinoma of the thyroid: a case report with molecular analyses.
abstract: BACKGROUND
  Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60 Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin.
  
  
  METHODS
  The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis.
  
  
  CONCLUSIONS
  This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.
authors.affiliation: 1 Department of Tumor and Diagnostic Pathology, Nagasaki University , Nagasaki, Japan .
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Mussazhanova
authors.forename: Shiro
authors.initials: S
authors.lastname: Miura
authors.forename: Boban
authors.initials: B
authors.lastname: Stanojevic
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rougounovitch
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.forename: Toshio
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kurashige
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shichijo
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D014408:Biomarkers, Tumor; D018288:Carcinoma, Small Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011989:Receptors, Thyrotropin; C504003:TTF1 protein, human; D014157:Transcription Factors