ORAL LEUKOPLAKIA
DEVELOPMENTS IN ONCOLOGY Volume 8 Previously published in this series: 1. Cleton F. J. and Simons J. W. 1. M (eds): Genetic Origins of Tumor Cells. 1980. ISBN 90-247-2272-1 2. Aisner J. and Chang P. (eds): Cancer Treatment Research. 1980. ISBN 90-247-2358-2 3. Ongerboer de Visser B. W., Bosch D. A. and van Woerkom-Eykenboom W. M. H. (eds): Neuro-Oncology: Clinical and Experimental Aspects. 1980. ISBN 90-247-2421-X 4. Hellmann K., Hilgard P., Eccles S. (eds): Metastasis: Clinical and Experimental Aspects. 1980. ISBN 90-247-2424-4 5. Seigler H. F. (ed): Clinical Management of Melanoma. 1982. ISBN 90-247-2584-4 6. Correa P. (ed): Epidemiology of Cancer of the Digestive Tract. 1982. ISBN 90-247-2601-8 7. Liotta L. A. and Hart I. R. (eds): Tumor Invasion and Metastasis. 1982. ISBN 90-247-2611-5
ORAL LEU KOPLAKIA Jolan Banoczy Clinic of Maxillo-Facial Surgery and DentiBtry SemmelweiB Univer8ity Medical School BudapeBt, Hungary, I. I I ~ Ii': 1982 Martinus Nijhoff Publishers The Hague Boston. London
Translated by I. Koch English translation edited by M. B. Edwards The distribution of this book is handled by the following team of publishers: for the United States and Oanada Kluwer Boston, Inc. 190 Old Derby Street Hingham, MA 02043 USA for all other countries Kluwer Academic Publishers Group Distribution Center P.O. Box 322 3300 AH Dordrecht The Netherlands for Hungary, Albania, Bulgaria, Ohina, Ouba,Ozechoslovakia, German Democratic Republic, Democratic People's Republic of Korea, Mongolia, Poland, Roumania, Soviet Union, Democratic Republic of Vietnam, and Yugoslavia Kultura, Hungarian Foreign Trading Co., H-1389 Budapest 62, P.O. Box 149 Hungary Library of Congress Cataloging in Publication Data Ban6czy, J olano Oral leukoplakia. (Developments in oncology; v. 8) Includes index. 1. Leukoplakia, Oral. I. Title. II. Series. [DNLM: 1. Leukoplakia, Oral. WI DE998N V. 8/ WU 280 B2190] RC815.B34 616.3'1 82-3467 ISBN-13: 978-94-009-7566-8 AACR2 ISBN-13: 978-94-009-7566-8 c-isbn-13: 978-94-009-7564-4 DOl: 10.1007/978-94-009-7564-4 Akademiai Kiad:>, Budapest 1982 Softcover reprint of the hardcover 1st edition 1982 All rights reserved. No part of this publication may be reproduced,.tored iu a retrieval system, or trans mitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Joint edition published by MARTINUS NIJHOFF PUBLISHERS P.O.B. 566, 2501 CN the Hague, The Netherlands.and AKADEMIAI KIADO. 1054 Alkotmany u. 21, Budapest, Hungary
CONTENTS Preface 9 Introduction The definition, nature and frequency of oral leukoplakia. Objectives 11 Chapter I. Results of clinical follow-up studies in oral leukoplakia 15 Malignant trasformation rate 20 Age and sex distribution 20 Site ofleukoplakia and carcinoma 22 Correlation between the clinical type and malignant transformation of oral leukoplakia 24 Latency period 25 Chapter II. The role of etiological factors 28 The etiological importance of smoking habits 29 Cytological investigations 29 Histological examinations 33 The etiological importance of mechanical factors 37 The etiological importance of differences in electrical potential 39 The role of inflammatory and atrophic changes of the oral mucous membrane in the pathogenesis ofleukoplakia 42 Migratory glossitis 43 Lesions of the tongue in association with anaemia 52 Median rhomboid glossitis 53 Chapter III. Transformations in the clinical type of leukoplakia during longitudinal studies 60 Chapter IV. Comparative study of the clinical types and histological characteristics of oral leukoplakia 64 Epithelial changes 65 Connective tissue changes 72 Comparative analysis of non-dysplastic cases 72 Incidence of epithelial dysplasia and longitudinal study of leukoplakias with dysplasia 75 5
Chapter V. Cytological studies in oral leukoplakia 87 Studies of the keratinization pattern in oral leukoplakia 88 The value of cytodiagnostics in the detection of cancer development from oral leukoplakia 92 Chapter VI. Electron microscopic studies of oral leukoplakias 98 Transmission electron microscopic (TEM) studies 102 Simple leukoplakia 103 Verrucous leukoplakia 110 Erosive leukoplakia 117 Morphometric (stereological) investigations 123 General morphometric features ofleukoplakic and normal epithelium 128 Composition of the epithelial tissue 129 Structural density gradients of cytoplasmic organelles 133 Scanning electron microscopic (SEM) examinations 138 Chapter VII. Oral "white lesions" other than leukoplakia 146 Clinical (longitudinal) studies on patients with oral lichen planus 146 Simultaneous occurrence ofleukoplakia and oral lichen 155 Investigations of white sponge naevus (leukoedema exfoliativum mucosae oris) 163 Clinical examinations 164 Histological observations 165 Cytological observations 166 Electron microscopic observations 167 Morsicatio buccarum et labiorum: a clinicopathological examination 177 Chapter VIII. The therapy of oral leukoplakia 182 Chapter IX. Summary References 195 Colour photos 219 Subject index 229 6
This monograph is dedicated to Dr. L. Sugar, my tutor in scientific research, in grateful appreciation of the selfless support received from him in my studies of precancerosis which I had the privilege to start as his assistant. I also owe a tribute to the memory of the late Professor K. Balogh, my beloved first master, who opened my eyes to the pleasures of scientific work and gave me invaluable help and advice for two decades. The Author
PREFACE Clinical and pathological observations have unequivocally indicated an increase in the incidence of malignant neoplasia during the last two decades. Despite important advances in surgery, radiotherapy and chemotherapy, mortality from tumours still tends to increase. Cancer research has therefore concentrated not only on early diagnosis and therapy but also, in line with recent trends in medical science, on the prevention of oncogenesis. One efficient prophylactic approach is the treatment of preblastomatoses, which include the preneoplastic lesions of the mouth. The most frequent oral precancerosis, leukoplakia, has been studied extensively during the last 20 years with regard to its pathogenesis,clinical course,and response to therapy. In Hungary, studies of oral leukoplakia have a century-long tradition. The term leukoplakia was coined by the Hungarian dermatologist Ern/) Schwimmer who recognized the precancerous nature of the condition and its relationship to tobacco smoking exactly 100 years ago. In the middle of this century another Hungarian scientist, Karoly Balogh established that most leukoplakias have two stages, - reversible and irreversible - and that early lesions may heal spontaneously after the elimination of irritational factors. The incidence of leukoplakia in random population groups was determined for the first time in the world by the Hungarian investigator Pal Bruszt, and reported to be 3.6 %. Subsequent studies in other countries confirmed a range of 0.2-8.1 %, depending on geographical and environmental conditions, way of life, and relevant habits. The definition of leukoplakia has been much disputed because white patches of the oral mucosa may arise in many different pathological states. The conflicting opinions have been reconciled by the W. H. O. Collaborating Centre for Oral Precancerous Lesions (of which JoianBan6czy is a member), through the definition of leukoplakia as a white patch on the oral mucosa which cannot be classified as any other entity. It should be noted that the original term leukoplakia has been internationally accepted and used without synonymous substitution in any language. Various aspects of leukoplakia such as frequency and clinical features have often been studied in samples collected from single examinations made at 9
one given time. However, certain aspects, especially the rate and etiology of malignant transformation, can be covered more satisfactorily by longitudinal studies based on annual or bi-annual examination of the patients over long periods. Such studies enable the clinical course to pe followed, and results of treatment to be evaluated. Follow-up studies of this kind were initiated in the Clinic of Maxillo-Facial Surgery and Dentistry, Dental Faculty of Semmelweis University Medical School, Budapest by Jolan Ban6czy and myself. In this collaborative study we established the rate of malignant transformation, and the significance of the site of the lesion. Ban6czy made an independent contribution of important information on various aspects of oral leukoplakia from long-term studies of a very large group of patients. She presented evidence of the transformation of one clinical type into another, assessed the frequency of regressive and progressive changes, and showed that malignant transformation was closely related to the type of keratinization, since cancer most frequently developed from parakeratinized lesions. She also described the ultrastructural characteristics of oral leukoplakia with special reference to clinical type and histological structure. Benign hyperkeratosis of inflammatory origin often cannot be differentiated from early carcinoma in situ by clinical features alone. Closer investigations into the nature of precanceroses are therefore imperative, and it is expected that the information which will emerge from such studies will contribute to a better knowledge of carcinogenesis, and thereby to more efficient therapy and prevention of neoplastic diseases. Laszl6 Sugar 10