title: Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16.
abstract: BACKGROUND
  Mesothelioma patients often present with serosal effusions, which are ideal for cytopathological diagnoses. However, the morphological overlap between malignant and benign mesothelial proliferation can make a conclusive cytological diagnosis of mesothelioma elusive because immunohistochemical staining does not discriminate definitively between the two in this setting. p16 is deleted in up to 80% of pleural mesotheliomas. The aim of this study was to establish the correlation between the p16 deletion status of the cell block with that of its corresponding tumor using fluorescence in situ hybridization (FISH) analysis for individual patient tumors.
  
  
  METHODS
  Twenty-two biopsies and 24 corresponding cell blocks, containing serosal effusions with atypical mesothelial cells from 22 patients with histologically confirmed pleural mesotheliomas, were analyzed with p16 FISH. Seventeen cell blocks consisting of serosal effusions with reactive mesothelial cells from nonmesothelioma cases were also analyzed. Combined immunofluorescence and FISH were also performed.
  
  
  RESULTS
  Seventeen of the 22 mesothelioma patients (77.3%) showed homozygous deletions of p16 in the tumor tissue and in the atypical mesothelial cells from the cell blocks. p16 FISH followed by immunofluorescence with EMA was helpful towards identifying the mesothelioma cells in the cell blocks.
  
  
  CONCLUSIONS
  We confirmed that the p16 FISH results obtained from the cell blocks are as reliable as those from the tissue sections. Cell block analysis is recommended for patients with serosal effusions of unknown origins with the following methods: immunohistochemistry should be performed to validate the mesothelial origin, and p16 FISH should be performed to confirm malignancy. Diagn. Cytopathol. 2016;44:591-598. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Respirology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Mizue
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Thoracic Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Eitetsu
authors.initials: E
authors.lastname: Koh
authors.affiliation: Department of Thoracic Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Department of Pathology, Chiba Rosai Hospital, Ichihara, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ozaki
authors.affiliation: Department of Thoracic Surgery, Chiba Rosai Hospital, Ichihara, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yusa
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Walts
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marchevsky
authors.affiliation: Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Surgery, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003937:Diagnosis, Differential; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins
keywords: cell block; cytology; fluorescence in situ hybridization (FISH); immunofluorescence; mesothelioma; p16