Oral Cytology

Ravi Mehrotra Editor

Oral Cytology

A Concise Guide

Editor Ravi Mehrotra, MD, PhD, MIAC, FRCPath Institute of Cytology and Preventive Oncology (ICPO) Noida - 201301, Uttar Pradesh, India

ISBN 978-1-4614-5220-1 ISBN 978-1-4614-5221-8 (eBook) DOI 10.1007/978-1-4614-5221-8 Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012951676

© Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

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v

Foreword

Oral cancer is a major public health problem all over the world but particularly in the Indian subcontinent. With well-known risk factors—tobacco and alcohol—and the potential for screening, effective measures for prevention and control are warranted.

Cytological examination is a well-established and effective method of screening for cervical cancer, and signi fi cant gains have been made in the control of this form of cancer by the routine use of exfoliative cytology. Application of cytology in the oral cavity is not common but it could be used for screening of patients with suspi-cious premalignant and malignant conditions of the oral cavity. Hence this mono-graph, designed to provide a state-of-the-art review of the major issues speci fi c to the fi eld of oral cytology, is very timely . This book provides a comprehensive review of all aspects of oral cytology including sample collection, manual/automated anal-ysis, pitfalls, gray zones, and controversies in diagnosis. Ancillary techniques such as DNA ploidy, molecular biology, and biomarkers are also discussed. The book is extensively illustrated with excellent cytological images.

This book will fi ll a critical need for reliable knowledge on oral cytology and will be useful for pathologists currently in training as well as pathologists and clinicians dealing with the diagnosis of oral lesions. The editors and authors are to be com-mended for this effort, since it fi lls an important gap in our current knowledge.

Chicago , IL , USA Vinay Kumar Donald N. Pritzker

Professor and ChairmanDepartment of Pathology,

Biologic Sciences Division and the Pritzker School of Medicine

University of Chicago

vii

Acknowledgements

The goal of this book is to form a blend between new and existing information about oral cytopathology. It will hopefully serve as a bench-side companion to the general cytopathologist, oral pathologist, specialist in oral medicine, and head and neck experts.

This compendium is a combined effort from authors of different specialties including cytopathologists, oral pathologists, and basic scientists—all of whom have in common an interest in the diagnosis of oral cancer. Experts from four differ-ent continents viz. Asia, Africa, Europe, and the Americas have contributed their vast knowledge and experiences in this fi eld.

Acknowledgments are due to my source of inspiration my beloved; my wife, Deepa Mehrotra, my children, Aditi, Shayak and Vinayak; and my well-wishers, especially my teachers/mentors, Drs. Mamta Singh and Premala A. Singh, Allahabad. They are also due to my colleagues, Drs. Vatsala Misra, Kachnar Verma, Vishal Dhingra, Pallavi Singh, and Anshul Singh of the Department of Pathology, Moti Lal Nehru Medical College, Allahabad; Dr. R. Khanna, Allahabad; Drs. V.L. Lahiri and Atul Gupta, Agra; Drs. Raj Mehrotra and M.M. Goel, Lucknow; Col. S.K.P. Matwanakar, Pune; Dr. Maqsood Siddiqi, Kolkatta; Dr. Bernard Fitzharris, Christchurch; Dr. Raj K. Gupta, Wellington, New Zealand; Dr. Svante Orell, Adelaide, Australia; Dr. Bernard Fox, Portland; Dr. Raj Puri, Bethesda; Dr. Vinod B. Shidham, Detroit; Dr. Prabodh Gupta, Philadelphia; Dr. Carlos Bedrossian, Chicago; Dr. Kamlesh Asotra, California; Dr. Rajesh Sharan, Shillong; my numer-ous MD and Ph.D students around the world including Madhu, Neeta, Anurag, Mayank, Sanjay, Smita, Santosh, Shruti, Ajay, and Rahela; and, of course, the great-est teacher any doctor can possibly have—my patients.

viii

I have special word of thanks to Prof. Vinay Kumar, Chicago Editor-in Chief, Robbins Pathologic Basis of Disease (which provided my fi rst introduction to this fascinating fi eld and help motivate me to embark on this journey) for kindly agree-ing to write the preface.

This book is dedicated to my respected mother, Raj Rani Mehrotra and to the fond memory of my father Prof. T.N. Mehrotra, MD, Ph.D. Founder Professor of Pathology and Principal, Moti Lal Nehru Medical College, Allahabad, without whose inspiration and constant guidance, this book would never have seen the light of the day. Finally, grateful thanks are due to the ever-helpful and dynamic team at Springer, especially Richard Hruska, Senior Editor, Clinical Medicine, William Loob, Development Editor, Andy Kwan, Assistant Editor and Maria Luz Calibo, Project Offi cer without whose support, this monograph would never have seen the light of the day.

Noida , UP , India Ravi Mehrotra, MD, PhD, MIAC, FRCPath

Acknowledgements

ix

Contents

1 Introduction ............................................................................................. 1Ravi Mehrotra

2 Historical Development of Oral Cytology ............................................. 5Vishal Dhingra and Ravi Mehrotra

3 Oral Cytology Techniques ...................................................................... 11Kachnar Varma, Jos Hille, Amir Afrogheh, and Ravi Mehrotra

4 Diagnosis of Infectious Diseases by Oral Cytology .............................. 27Mamta Singh, Rahela Ibrahim, and Ravi Mehrotra

5 Cytological Diagnosis of Benign Lesions of the Oral Cavity............... 49Deborah J. Carroll

6 The Development of a Novel Oral Cytologic Grading System ........... 73Amir Afrogheh, Jos Hille, and Ravi Mehrotra

7 Liquid-Based Oral Cytology and Microhistology ................................ 91Roberto Navone, Monica Pentenero, and Sergio Gandolfo

8 The Role of Ploidy Analysis in Oral Cytology ...................................... 109Torsten W. Remmerbach

9 Diagnostic Cytometry ............................................................................. 125Alfred Böcking, David Friedrich, Chen Jin, André Bell, Thomas Wür fl inger, Dietrich Meyer-Ebrecht, Yu Zhang, Stefan Biesterfeld, Natalia Pomjanski, Leonid Berynskyy, Richard Yeung, Jörg Handschel, Branko Palcic, and Til Aach

x Contents

10 Pitfalls and Limitations of Oral Cytopathology ................................... 147Anshul Singh, Deborah J. Carroll, and Ravi Mehrotra

11 The Way Ahead: Overview of Present Day Use with Areas for Future Research ............................................................. 157Ravi Mehrotra

Index ................................................................................................................. 171

xi

Contributors

Til Aach Institute of Image Analysis and Computer Vision , RWTH Aachen University , Aachen , Germany

Amir Afrogheh TBH Laboratories, Oral & Maxillofacial Pathology, National Health Laboratory Service, University of the Western Cape, Cape Town, South Africa

André Bell Institute of Image Analysis and Computer Vision , RWTH Aachen University , Aachen , Germany

Leonid Berynskyy Institute of Cytopathology, Heinrich-Heine-University , Düsseldorf , Germany

Stefan Biesterfeld Institute of Cytopathology, Heinrich-Heine-University , Düsseldorf , Germany

Alfred Böcking Institute of Pathology, City-Hospital Düren , Düren , Germany

Deborah J. Carroll Oral CDx Laboratories , Suffern , NY , USA

Vishal Dhingra Department of Pathology , Moti Lal Nehru Medical College , Allahabad , Uttar Pradesh , India

David Friedrich Institute of Image Analysis and Computer Vision , RWTH Aachen University , Aachen , Germany

Sergio Gandolfo Department of Clinical and Biological Sciences , Oral Medicine and Oncology Section, University of Turin , Orbassano , Italy

Jörg Handschel Department of Cranio- and Maxillofacial Surgery , Heinrich-Heine-University , Düsseldorf , Germany

xii Contributors

Jos Hille TBH Laboratories, Oral & Maxillofacial Pathology, National Health Laboratory Service, University of the Western Cape, Cape Town, South Africa

Rahela Ibrahim Department of Pathology , Moti Lal Nehru Medical College , Allahabad , Uttar Pradesh , India

Chen Jin Motic China Company , Xiamen , People’s Republic of China

Ravi Mehrotra Institute of Cytology and Preventive Oncology (ICPO) , Noida , Uttar Pradesh , India

Dietrich Meyer-Ebrecht Institute of Image Analysis and Computer Vision, RWTH Aachen University , Aachen , Germany

Roberto Navone Department of Biomedical Sciences and Human Oncology , Pathology Section, University of Turin , Torino , Italy

Anatomia Patologica, University of Turin, Torino, Italy

Branko Palcic British Columbia Cancer Agency and University of British Columbia, Vancouver, Canada

Monica Pentenero Department of Clinical and Biological Sciences , Oral Medicine and Oral Oncology Section, University of Turin , Orbassano , Italy

Natalia Pomjanski Institute of Cytopathology, Heinrich-Heine-University , Düsseldorf , Germany

Torsten W. Remmerbach Oral Medicine Unit, Department of Oral, Maxillofacial and Facial Plastic Surgery , Leipzig , Germany

Anshul Singh Department of Pathology , Moti Lal Nehru Medical College , Allahabad , Uttar Pradesh , India

Mamta Singh Department of Pathology, Moti Lal Nehru Medical College , Allahabad , Uttar Pradesh , India

Kachnar Varma Department of Pathology , Moti Lal Nehru Medical College , Allahabad , Uttar Pradesh , India

Thomas Wür fl inger Institute of Image Analysis and Computer Vision, RWTH Aachen University , Aachen , Germany

Richard Yeung Motic China Company, Xiamen, People’s Republic of China

Yu Zhang Institute of Image Analysis and Computer Vision, RWTH Aachen University , Aachen , Germany

1R. Mehrotra (ed.), Oral Cytology: A Concise Guide, DOI 10.1007/978-1-4614-5221-8_1, © Springer Science+Business Media New York 2013

In a recent report from the American Cancer Society, it was estimated that 35,000 new cases of oral cavity and pharyngeal malignancies are likely to be diagnosed in the United States during 2012, and 6,800 patients will die of the disease [ 1 ] . Majority of the patients with these lesions are located in developing countries, with the highest prevalence of up to 40% reported in the Indian subcontinent [ 2 ] . In developed countries like the United States, the 5 year survival was 63% the period between 1999 and 2005—an increase from 53% during this time period as compared to 1975 and 1977; this difference was found to be statistically signi fi cant [ 1 ] . The improved survival rates may be partially explained by the increasing use of newer diagnostic modalities that detect the disease in its precursor stage and/or use of newer chemotherapeutic options.

Currently, the most effective way to control oral cancer is to combine early diag-nosis and timely as well as appropriate treatment. Because more than 90% of all oral cancers are squamous cell carcinomas, the vast majority of oral cancers will be diagnosed from lesions on the mucosal surfaces.

It is well known that the majority of malignancies, if not all, develop in precan-cerous fi elds characterized by speci fi c genetic alterations. Transepithelial “ fi eld mapping biopsies” within widespread lesions are even more essential for cytologi-cal evaluation and further investigation [ 3 ] . Precancerous and cancerous oral lesions may mimic number of benign oral lesions appearing as a white or red lesion (leuko-plakia, erythroplakia, and erythro/leukoplakia) [ 4 ] . The malignant potential of these lesions is generally assessed by histopathology based on the presence and the degree of dysplasia in biopsy material, graded as mild, moderate, and severe [ 5 ] .

Until now, tissue harvesting by scalpel biopsy and subsequent histological exam-ination have been the gold standard for diagnosing premalignant and malignant oral diseases. Oral biopsy is invasive and involves both psychological implications for the patient and technical dif fi culties for the health practitioner. When lesions are

R. Mehrotra (*) Institute of Cytology and Preventive Oncology (ICPO), I-7, Sector - 39, Noida - 201301, Uttar Pradesh, India e-mail: rm8509@gmail.com

Chapter 1 Introduction

Ravi Mehrotra

2 R. Mehrotra

extensive, the most representative areas must be selected to avoid diagnostic errors. A high inter- and intra-observer variability of histological diagnoses for dysplasia is well documented and has been described by several authors [ 6, 7 ] . As highlighted in a study of 200 patients with oral leukoplakia, when two scalpel biopsies are per-formed at different times by different examiners, the agreement rate between them is only 56% [ 8 ] . The morphology of low grade dysplasia is signi fi cantly variable and a reproducible diagnosis is dif fi cult. For high-grade dysplastic lesions, inci-sional biopsies of suspicious lesions, which have a limited reproducibility within the whole lesion, may result in a more or less aggressive surgical and/or radio- chemotherapeutic approach [ 9 ] .

Identifying additional diagnostic tools would be welcome to improve analysis of any suspicious lesion. The oral cytology technique is simple, nonaggressive, rela-tively painless, and tolerated well by patients [ 10 ] . It can also be used for diagnosis and identi fi cation of recurrent potentially malignant and malignant lesions [ 11 ] .

The basic requirements for a useful diagnostic technique include the following: ease to use, minimal patient discomfort, and collection of suf fi cient cells. Ideally, a diagnostic procedure should be neither time-consuming nor complicated and, in addition to high sensitivity, should have the potential for automation. Cytology meets all of these requirements, particularly when it is supplemented by a variety of novel adjunctive aids.

This book is an attempt to concisely bring to the reader a state of the art update on this, rather exotic, but increasingly important diagnostic modality.

References

1. American Cancer Society. Cancer facts & fi gures 2012. 2012. http://www.cancer.org/Cancer/OralCavityandOropharyngealCancer/DetailedGuide/oral-cavity-and-oropharyngeal-cancer-key-statistics . Accessed 1 Mar 2012.

2. Mehrotra R, Pandya S, Chaudhary AK, Kumar M, Singh M. Prevalence of oral premalignant and malignant lesions at a tertiary level hospital in Allahabad, India. Asian Pac J Cancer Prev. 2008;9:263–6.

3. Thomson PJ, Hamadah O. Cancerisation within the oral cavity: the use of ‘ fi eld mapping biopsies’ in clinical management. Oral Oncol. 2007;43:20–6.

4. Johnson NW. Orofacial neoplasms: global epidemiology, risk factors and recommendations for research. Int Dent J. 1991;41:365–75.

5. Pindborg JJ, Reichart PA, Smith CJ, Van Der Waal I. Histological typing of cancer and precan-cer of the oral mucosa. World Health Organisation. Berlin: Springer-Verlag; 1997. p. 21–314.

6. Warnakulasuriya S, Reibel J, Bouquot D, Dabelsteen E. Oral epithelial dysplasia classi fi cation systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37:127–33.

7. Kujan O, Khattab A, Oliver RJ, Roberts SA, Thakker N, Sloan P. Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol. 2007;43:224–31.

8. Lee JJ, Hung HC, Cheng SJ, et al. Factors associated with underdiagnosis from incisional biopsy of oral leukoplakic lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:217–25.