PMID- 23450849 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20130814 IS - 1934-6638 (Electronic) IS - 1934-662X (Linking) VI - 121 IP - 8 DP - 2013 Aug TI - Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology. PG - 415-22 LID - 10.1002/cncy.21269 [doi] AB - BACKGROUND: In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH). METHODS: For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics. RESULTS: Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell-in-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs. CONCLUSIONS: These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. CI - Copyright (c) 2013 American Cancer Society. FAU - Matsumoto, Shinji AU - Matsumoto S AD - Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan. FAU - Nabeshima, Kazuki AU - Nabeshima K FAU - Kamei, Toshiaki AU - Kamei T FAU - Hiroshima, Kenzo AU - Hiroshima K FAU - Kawahara, Kunimitsu AU - Kawahara K FAU - Hata, Sakae AU - Hata S FAU - Marukawa, Katsuji AU - Marukawa K FAU - Matsuno, Yoshihiro AU - Matsuno Y FAU - Taguchi, Kenichi AU - Taguchi K FAU - Tsujimura, Tohru AU - Tsujimura T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130228 PL - United States TA - Cancer Cytopathol JT - Cancer cytopathology JID - 101499453 SB - IM MH - Aged MH - Aged, 80 and over MH - Chromosome Deletion MH - *Chromosomes, Human, Pair 9/genetics MH - Cytodiagnosis/*methods MH - Female MH - Genes, p16 MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Male MH - Mesothelioma/genetics/*pathology MH - Middle Aged MH - Pleural Effusion, Malignant/genetics/*pathology MH - Pleural Neoplasms/genetics/*pathology MH - *User-Computer Interface OTO - NOTNLM OT - 9p21 homozygous deletion OT - cytology OT - fluorescence in situ hybridization OT - p16 OT - pleural mesothelioma EDAT- 2013/03/02 06:00 MHDA- 2013/10/22 06:00 CRDT- 2013/03/02 06:00 PHST- 2012/10/11 00:00 [received] PHST- 2012/11/04 00:00 [revised] PHST- 2012/11/19 00:00 [accepted] PHST- 2013/03/02 06:00 [entrez] PHST- 2013/03/02 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] AID - 10.1002/cncy.21269 [doi] PST - ppublish SO - Cancer Cytopathol. 2013 Aug;121(8):415-22. doi: 10.1002/cncy.21269. Epub 2013 Feb 28.