Objective: The cytological diagnosis of coelomic fluid is essential for examining malignant mesothelioma (MM). However, reactive mesothelium (RM), caused by various factors, is morphologically similar to MM and thus often complicates the differential diagnosis. Here, nuclear luminance and steric alterations were assessed for the discriminant analysis of MM and RM. Study Design: Thirteen epithelial MM and 11 RM cases were included. One hundred alterations in the numbers of nuclear pixels and focus layers and the coefficient of variation of nuclear luminance among layers were determined for each case to conduct discriminant analysis using the Mahalanobis distance. Results: A cutoff value of 0.072 allowed highly accurate discrimination of MM (89.5%) and RM (89.6%). Fifteen cells appeared in 6 agglomerates of indiscriminable MM cases. The 6 agglomerates were individually examined. Malignant cells were dominant in 3 agglomerates (50%), allowing the discrimination of malignant cases. Conclusion: Discrimination using nuclear luminance and steric alterations is useful for morphologically indiscriminable MM cases. Three-dimensional analysis of agglomerates will be further investigated to improve the diagnostic accuracy.

1.
Carlos WM, Bedrossian MD: Diagnostic problems in serous effusions.Diagn Cytopathol 1998;19:131–137.
2.
Selvaggi SM, Migdal S: Cytologic features of atypical mesothelial cells in peritoneal dialysis fluid. Diagn Cytopathol 1990;6:22–26.
3.
Fernandez de Castro M, Selgas R, Jimenez C, Auxiliadora Bajo M, Martinez V, Romero JR, de Alvaro F, Vara F: Cell populations present in the nocturnal peritoneal effluent of patients on continuous ambulatory peritoneal dialysis and their relationship with peritoneal function and incidence of peritonitis. Perit Dial Int 1994;14:265–270.
4.
Izumotani T, Ishimura E, Yamamoto T, Otoshi T, Okuno S, Inaba M, Kim M, Nishizawa Y: Correlation between peritoneal mesothelial cell cytology and peritoneal histopathology with respect to prognosis in patients on continuous ambulatory peritoneal dialysis. Nephron 2001;89:43–49.
5.
Churg A, Colby TV, Cagle P, Corson J, Gibbs AR, Gilks B, Grimes M, Hammar S, Roggli V, Travis WD: The separation of benign and malignant mesothelial proliferations. Am J Surg Pathol 2001;25:548–549.
6.
Fentanes de Torres E, Guevara E: Pleuritis by radiation: reports of two cases. Acta Cytol 1981;25:427–429.
7.
Cakir E, Demirag F, Aydin M, Unsal E: Cytopathologic differential diagnosis of malignant mesothelioma, adenocarcinoma and reactive mesothelial cells: a logistic regression analysis. Diagn Cytopathol 2009;37:4–10.
8.
Cagle PT, Churg A: Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies. Arch Pathol Lab Med 2005;129:1421–1427.
9.
Lee A, Baloch ZW, Yu G, Gupta PK: Mesothelial hyperplasia with reactive atypia: diagnostic pitfalls and role of immunohistochemical studies – a case report. Diagn Cytopathol 2000;22:113–116.
10.
Esteban JM, Yokota S, Husain S, Battifora H: Immunocytochemical profile of benign and carcinomatous effusions: a practical approach to difficult diagnosis. Am J Clin Pathol 1990;94:698–705.
11.
Monte SA, Ehya H, Lang WR: Positive effusion cytology as the initial presentation of malignancy. Acta Cytol 1987;31:448–452.
12.
Sears D, Hajdu SL: The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol 1987;31:85–97.
13.
Husain AN, Colby TV, Ordóñez NG, Krausz T, Borczuk A, Cagle PT, Chirieac LR, Churg A, Galateau-Salle F, Gibbs AR, Gown AM, Hammar SP, Litzky LA, Roggli VL, Travis WD, Wick MR: Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med 2009;133:1317–1331.
14.
Sandeck HP, Røe OD, Kjærheim K, Willén H, Larsson E: Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry. Diagn Pathol 2010;6:47.
15.
Tischoff I, Neid M, Neumann V, Tannapfel A: Pathohistological diagnosis and differential diagnosis. Recent Results Cancer Res 2011;189:57–78.
16.
Addis B, Roche H: Problems in mesothelioma diagnosis. Histopathology 2009;54:55–68.
17.
Ordonez NG: The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol 2003;27:1031–1051.
18.
Lozano MD, Panizo A, Toledo GR, Sola JJ, Pardo-Mindan J: Immunocytochemistry in the differential diagnosis of serous effusions: a comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears. Cancer 2001;93:68–72.
19.
Bussolati G: Technical pitfalls potentially affecting diagnoses in immunohistochemistry. J Clin Pathol 2008;61:1184–1192.
20.
Osterheld MC, Liette C, Anca M: Image cytometry: an aid for cytological diagnosis of pleural effusions. Diagn Cytopathol 2005;32:173–176.
21.
Friedman MT, Gentile P, Tarectecan A, Fuchs A: Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions. Arch Pathol Lab Med 1996;120:959–966.
22.
Isobe H, Sridhar KS, Doria R, Cohen F, Raub WA, Saldana M, Krishan A: Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma. Cytometry 1995;19:86–91.
23.
Emri S, Akbulut H, Zorlu F, Dinçol D, Akay H, Güngen Y, Içli F: Prognostic significance of flow cytometric DNA analysis in patients with malignant pleural mesothelioma. Lung Cancer 2001;33:109–114.
24.
Washiya K, Konno T, Ishii A, Tokairin T, Ono I: Evaluation of the urine cytodiagnosis using simple method of measuring nucleus brightness histogram. J Jpn Soc Clin Cytol 2008;28:154–155.
25.
Washiya K, Kanno T, Tone K, Kojima K, Kijima H, Watanabe J: Three-dimensional nuclear luminance analysis in well-differentiated adenocarcinoma of the lung. Acta Cytol 2011;55:350–356.
26.
Sato T, Miura T, Nakano K, Nozaka H, Sato T, Ishikawa T, Chiba M, Kanagawa Y, Kizawa C, Hasegawa S, Yasujima M: Reliable differential diagnosis between osteosarcoma and regenerative bone cells in rat through simultaneous analysis of nuclear DNA content and size. Anal Quant Cytol Histol 2000;22:327–332.
27.
Grontoft O, Hellquist H, Olofsson J, Nordstrom G: The DNA content and nuclear size in normal, dysplastic and carcinomatous laryngeal epithelium. A spectrophotometric study. Acta Otolaryngol 1978;86:473–479.
28.
Ranek L: Cytophotometric studies of the DNA, nucleic acid and protein content of human liver cell nuclei. Acta Cytol 1976;20:151–157.
29.
Fossa SD, Kaalhus O: Nuclear size and chromatin concentration in transitional cell carcinoma of the human urinary bladder. Beitr Pathol 1976;157:109–125.
30.
Murata S, Mochizuki K, Nakazawa T, Kondo T, Nakamura N, Yamashita H, Urata Y, Ashihara T, Katoh R: Detection of underlying characteristics of nuclear chromatin patterns of thyroid tumor cells using texture and factor analyses. Cytometry 2002;49:91–95.
31.
Zaidi SK, Young DW, Javed A, Pratap J, Montecino M, Wijnen A, Lian JB, Stein JL, Stein GS: Nuclear microenvironments in biological control and cancer. Nat Rev Cancer 2007;7:454–463.
32.
Kimura F, Kawamura J, Watanabe J, Kamoshida S, Kawai K, Okayasu I, Kuwao S: Significance of cell proliferation markers (minichromosome maintenance protein 7, topoisomerase IIα and Ki-67) in cavital fluid cytology: can we differentiate reactive mesothelial cells from malignant cells. Diagn Cytopathol 2010;38:161–167.
33.
Sato A, Torii I, Okamura Y, Yamamoto T, Nishigami T, Kataoka TR, Song M, Hasegawa S, Nakano T, Kamei T, Tsujimura T: Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium. Mod Pathol 2010;23:1458–1466.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.