title: Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations.
abstract: Because most of malignant pleural mesothelioma (MPM) patients first present with pleural effusion, detection of mesothelioma cells on effusion smears is critical for early diagnosis. Recently, accumulating evidence indicating that the cytological diagnosis of MPM supported by ancillary techniques is as reliable as that based on histopathology has led to new guidelines for the cytopathologic diagnosis of MPM. Based on the guidelines, a combination of cytomorphological criteria and verification by ancillary techniques is required for the cytologic diagnosis of MPM. Detection of p16 homozygous deletion by fluorescence in situ hybridization (FISH) is the most reliable ancillary technique for differentiating MPM from reactive mesothelial cells (RMC) because of its relatively high sensitivity and extremely high specificity. We showed that the p16 deletion status of MPM cells in pleural effusions reflected that of the underlying invasive MPM tissues, indicating the usefulness of p16 FISH in effusion smear cytology for MPM diagnosis. Thus, for differentiating MPM from RMC, we propose to perform p16 FISH as often as possible. A positive p16 homozygous deletion supports the diagnosis of MPM. However, a negative result does not rule out the possibility of MPM. In such cases, a morphological assessment is critical. Therefore, we analyzed the morphological characteristics of p16 deletion-positive mesothelioma cells using a combination of virtual microscopy and p16 FISH, and identified three morphological characteristics useful for the differentiation, including cell-in-cell engulfment with or without hump formation, multinucleate cells, and larger berry-like cell aggregates. Diagn. Cytopathol. 2016;44:774-780. © 2016 Wiley Periodicals, Inc.
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 Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.affiliation: Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Pathology, PCL Japan Fukuoka, Pathology-Cytology Center, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kamei
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, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.affiliation: Department of Pathology, Osaka Prefectural Medical Center for Respiratory and Allergic Disease, Habikino, Japan.
authors.forename: Kunimitsu
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D003937:Diagnosis, Differential; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008654:Mesothelioma / Q000235:genetics / Q000473:pathology*; D010996:Pleural Effusion / Q000235:genetics / Q000473:pathology*; D010997:Pleural Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: ancillary techniques; cytologic diagnosis; fluorescence in situ hybridization; homozygous deletion; malignant pleural mesothelioma; p16 gene