Oral and Maxillofacial Pathology Oral and Maxillofacial Pathology Fourth Edition Brad W. Neville, DDS Carl M. Allen, DDS, MSD Distinguished University Professor Emeritus Professor Director, Division of Oral and Maxillofacial Pathology Division of Oral and Maxillofacial Pathology and Department of Stomatology Radiology James B. Edwards College of Dental Medicine College of Dentistry Medical University of South Carolina The Ohio State University Charleston, South Carolina Columbus, Ohio Douglas D. Damm, DDS Angela C. Chi, DMD Professor Professor Director, Division of Oral and Maxillofacial Pathology Division of Oral and Maxillofacial Pathology Department of Oral Health Science Department of Stomatology College of Dentistry James B. Edwards College of Dental Medicine University of Kentucky Medical University of South Carolina Lexington, Kentucky Charleston, South Carolina 3251 Riverport Lane St. Louis, Missouri 63043 ORAL AND MAXILLOFACIAL PATHOLOGY, FOURTH EDITION ISBN: 978-1-4557-7052-6 Copyright © 2016 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2009, 2002. International Standard Book Number: 978-1-4557-7052-6 Executive Content Strategist: Kathy Falk Professional Content Development Manager: Jolynn Gower Senior Content Development Specialist: Courtney Sprehe Publishing Services Manager: Julie Eddy Senior Project Manager: Marquita Parker Design Direction: Julia Dummitt Printed in Canada Last digit is the print number: 9 8 7 6 5 4 3 2 1 This book is dedicated to three of our mentors: Charles A. Waldron William G. Shafer Robert J. Gorlin in appreciation for all that they taught us and in recognition of their contributions to the field of oral and maxillofacial pathology. v Contributors Theresa S. Gonzales, DMD Edward E. Herschaft, DDS, MA, FACD, FICD Professor and Director of Orofacial Pain Management Professor Department of Stomatology Department of Biomedical Sciences Division of Oral and Maxillofacial Pathology School of Dental Medicine James B. Edwards College of Dental Medicine University of Nevada Las Vegas, Nevada Medical University of South Carolina Professor Emeritus Charleston, South Carolina Department of Stomatology Division of Oral and Maxillofacial Pathology James B. Edwards College of Dental Medicine Medical University of South Carolina Charleston, South Carolina vi Preface About every seven years now, we receive a (dreaded?) phone photographs with us. We have attempted to be as thorough call from our kindly editor suggesting that the time has as possible in listing credit for these images. However, if arrived for us to write an updated edition of our textbook. someone’s name has been inadvertently omitted, please This generally is followed by a lot of wailing and gnashing accept our apologies. of teeth on the part of the authors—probably akin to the A significant change in authorship has occurred in this sound of children who have been asked to clean up their fourth edition with the retirement of Dr. Jerry Bouquot, bedrooms. Just like children who may not see the necessity whose valuable efforts will be greatly missed. However, we of changing their bed sheets, we often do not immediately are delighted and fortunate to add Dr. Angela Chi as full- appreciate the importance of revising our textbook. fledged author/editor for this fourth edition, following up However, once the task is undertaken, the need becomes on the valuable contributions that she made to the third readily obvious. edition. Our great appreciation goes again to Dr. Edward It has become somewhat of a cliché to comment on how Herschaft, who has updated his excellent chapter on Foren- rapidly the world of dentistry and medicine is changing, but sic Dentistry. We also thank Dr. Theresa Gonzales for her nothing could be closer to the truth. Admittedly, some help with the revision of the chapter on Facial Pain and areas seem to change very little (Fordyce granules will Neuromuscular Diseases. In addition, we must acknowl- always be Fordyce granules). However, the expansion of edge the excellent guidance provided by the staff at Elsevier our knowledge in many areas has been dramatic and, for their hard work and support in making this book a sometimes, even transformative (e.g., the relationship success. Special praise goes to Courtney Sprehe, Marquita between high-risk strains of human papillomavirus and Parker, and Kathy Falk for all of their efforts in the editorial oropharyngeal carcinoma). process. In addition to a complete update of information on Finally, our greatest appreciation goes to our families, who previous topics, we also introduce a variety of new entities again have provided us with their unconditional love and to this fourth edition, such as globodontia, lobodontia, support during the long hours spent working on this latest localized juvenile spongiotic gingival hyperplasia, oral leish- edition. We never could have accomplished it without you. maniasis, oral lesions associated with cosmetic fillers, IgG4-related disease, and mammary analogue secretory Brad W. Neville carcinoma of salivary gland origin. A total of 154 new Douglas D. Damm images have been added, and we are greatly indebted to our Carl M. Allen many colleagues who have shared their excellent teaching Angela C. Chi vii 1  Developmental Defects of the Oral and Maxillofacial Region ◆ OROFACIAL CLEFTS fusion of the palatal shelves begins in the anterior palate and progresses posteriorly; it is completed by the twelfth week. The formation of the face and oral cavity is complex in Defective fusion of the medial nasal process with the nature and involves the development of multiple tissue pro- maxillary process leads to cleft lip (CL). Likewise, failure cesses that must merge and fuse in a highly orchestrated of the palatal shelves to fuse results in cleft palate (CP). fashion. Disturbances in the growth of these tissue processes Frequently, CL and CP occur together. Approximately 45% or their fusion may result in the formation of orofacial of cases are CL + CP with 30% being CP only (CPO) and clefts. 25% being isolated CL. Both isolated CL and CL associated Development of the central face begins around the end with CP are thought to be etiologically related conditions of the fourth week of human development with the appear- and can be considered as a group: CL, with or without CP ance of the nasal (olfactory) placodes on either side of the (i.e., CL ± CP). Isolated CPO appears to represent a sepa- inferior aspect of the frontonasal process. Proliferation of rate entity from CL ± CP. ectomesenchyme on both sides of each placode results in The cause of CL ± CP and CPO is still being debated. the formation of the medial and lateral nasal processes. First of all, distinguishing isolated clefts from cases associ- Between each pair of processes is a depression, or nasal pit, ated with specific syndromes is important. Although many that represents the primitive nostril. facial clefts are isolated anomalies, more than 400 develop- During the sixth and seventh weeks of development, the mental syndromes have been identified that may be associ- upper lip forms when the medial nasal processes merge with ated with CL ± CP or CPO. Studies have suggested that each other and with the maxillary processes of the first up to 30% of patients with CL ± CP and 50% of those branchial arches. Thus the midportion of the upper lip is with CPO have associated anomalies. Some of these cases derived from the medial nasal processes, and the lateral are single-gene syndromes that may follow autosomal domi- portions are derived from the maxillary processes. The nant, autosomal recessive, or X-linked inheritance patterns. lateral nasal processes are not involved in the formation of Other syndromes are the result of chromosome anomalies the upper lip, but they give rise to the alae of the nose. or are idiopathic. The primary palate also is formed by the merger of the The cause of nonsyndromic clefts does not follow any medial nasal processes to form the intermaxillary segment. simple Mendelian pattern of inheritance but appears to be This segment gives rise to the premaxilla, a triangular- heterogeneous. Thus the propensity for cleft development shaped piece of bone that will include the four incisor teeth. may be related to a number of major genes, minor genes, The secondary palate, which makes up 90% of the hard and environmental factors that can combine to surpass a and soft palates, is formed from the maxillary processes of developmental threshold. Numerous candidate clefting the first branchial arches. genes and loci have been identified on different chromo- During the sixth week, bilateral projections emerge from some regions. Maternal alcohol consumption has been asso- the medial aspects of the maxillary processes to form the ciated with an increased risk for both syndromic and palatal shelves. Initially, these shelves are oriented in a verti- nonsyndromic clefts. Maternal cigarette smoking at least cal position on each side of the developing tongue. As the doubles the frequency of cleft development compared with mandible grows, the tongue drops down, allowing the nonsmoking mothers. An increased frequency also has been palatal shelves to rotate to a horizontal position and grow related to anticonvulsant therapy, especially phenytoin, toward one another. By the eighth week, sufficient growth which causes a nearly tenfold greater risk of cleft formation. has occurred to allow the anterior aspects of these shelves Although evidence has been mixed, a number of studies to begin fusion with one another. The palatal shelves also have suggested that folic acid supplementation may play a fuse with the primary palate and the nasal septum. The role in prevention of orofacial clefts. 1 2 CHAPTER 1 Developmental Defects of the Oral and Maxillofacial Region CL ± CP and CPO represent the vast majority of orofa- cial clefts. However, other rare clefts also may occur. The lateral facial cleft is caused by lack of fusion of the maxillary and mandibular processes and represents 0.3% of all facial clefts. This cleft may be unilateral or bilateral, extending from the commissure toward the ear, resulting in macrostomia. The lateral facial cleft may occur as an isolated defect, but more often it is associated with other disorders, such as the following: • Mandibulofacial dysostosis (see page 41) • Oculo-auriculo-vertebral spectrum (hemifacial microsomia) • Nager acrofacial dysostosis • Amniotic rupture sequence • Fig. 1-1 Cleft Lip (CL). Infant with bilateral cleft of the upper lip.  The oblique facial cleft extends from the upper lip to (Courtesy of Dr. William Bruce.) the eye. It is nearly always associated with CP, and severe forms often are incompatible with life. The oblique facial cleft may involve the nostril, as in CL, or it may bypass the nose laterally as it extends to the eye. This cleft is rare, representing only 1 in 1300 facial clefts. Some of these clefts may represent failure of fusion of the lateral nasal process with the maxillary process; amniotic bands may cause others. Median cleft of the upper lip is an extremely rare anomaly that results from failure of fusion of the medial nasal processes. It may be associated with a number of syndromes, including the oral-facial-digital syndromes and Ellis-van Creveld syndrome. Most apparent median clefts of the upper lip actually represent agenesis of the primary palate associated with holoprosencephaly. • Fig. 1-2 Cleft Palate (CP). Palatal defect resulting in communica- Clinical and Radiographic Features tion with the nasal cavity.  Clefting is one of the most common major congenital defects in humans. Considerable racial variation in preva- lence is seen. In whites, CL ± CP occurs in 1 of every 700 nostril, but an incomplete CL does not involve the nose. to 1000 births. The frequency of CL ± CP in Asian popula- Complete clefts involving the alveolus usually occur between tions is about 1.5 times higher than in whites. In contrast, the lateral incisor and cuspid. It is not unusual for teeth, the prevalence of CL ± CP in blacks is much lower, occur- especially the lateral incisor, to be missing in the cleft area. ring in 0.4 of 1000 births. Native Americans appear to have Conversely, supernumerary teeth may be discovered. The the highest frequency, around 3.6 of 1000 births. CPO is bony defect can be observed on radiographs. less common than CL ± CP, with a frequency of 0.4 of 1000 A CP shows considerable range in severity (Fig. 1-2). The births in whites and blacks. defect may involve the hard and soft palates or the soft CL ± CP is more common in males than in females. The palate alone. The minimal manifestation of CP is a cleft or more severe the defect, the greater the male predilection; bifid uvula (Fig. 1-3). The prevalence of cleft uvula is much the male-to-female ratio for isolated CL is 1.5 : 1; the ratio higher than that of CP, with a frequency of 1 in every 80 for CL + CP is 2 : 1. In contrast, CPO is more common in white individuals. The frequency in Asian and Native Amer- females. Likewise, the more severe the cleft, the greater the ican populations is as high as 1 in 10. Cleft uvula is less female predilection. Clefts of both the hard and soft palates common in blacks, occurring in 1 out of every 250 persons. are twice as common in females, but the ratio is nearly equal In some instances a submucous palatal cleft develops. for clefts of the soft palate only. The surface mucosa is intact, but a defect exists in the Approximately 80% of cases of CL will be unilateral with underlying musculature of the soft palate (Fig. 1-4). Fre- 20% bilateral (Fig. 1-1). Approximately 70% of unilateral quently a notch in the bone is present along the posterior CLs occur on the left side. In addition, about 70% of uni- margin of the hard palate. This incomplete cleft occasionally lateral CLs will be associated with CP, whereas the fre- appears as a bluish midline discoloration but is best identi- quency of concomitant CP increases to 85% for patients fied by palpation with a blunt instrument. An associated with bilateral CL. A complete CL extends upward into the cleft uvula also usually is seen. CHAPTER 1 Developmental Defects of the Oral and Maxillofacial Region 3 variety of syndromes or other anomalies. Stickler syndrome and velocardiofacial syndrome are the two most frequently associated genetic disorders. Researchers have theorized that constraint of mandibular growth in utero results in failure of the tongue to descend, thus preventing fusion of the palatal shelves. The retruded mandible results in the following: • Posterior displacement of the tongue • Lack of support of the tongue musculature • Airway obstruction Respiratory difficulty, especially when the child is in a supine position, usually is noted from birth and can cause asphyxiation. The palatal cleft often is U-shaped and wider than isolated CP. • Fig. 1-3 Bifid Uvula.  The patient with a cleft is burdened with a variety of problems, some obvious and some less so. The most obvious problem is the clinical appearance, which may lead to psy- chosocial difficulties. Feeding and speech difficulties are inherent, especially with CP. Malocclusion is caused by col- lapse of the maxillary arch, possibly along with missing teeth, supernumerary teeth, or both. Treatment and Prognosis The management of the patient with an orofacial cleft is challenging. Ideally, treatment should involve a multidisci- plinary approach, including (but not limited to) a pedia- trician, oral and maxillofacial surgeon, otolaryngologist, plastic surgeon, pediatric dentist, orthodontist, prosthodon- tist, speech pathologist, and geneticist. • Fig. 1-4 Submucous Palatal Cleft. A cleft of the midline palatal  Surgical repair often involves multiple primary and sec- bone exists, but the overlying mucosa is intact. A bifid uvula also is  present.  ondary procedures throughout childhood. The specific types of surgical procedures and their timing will vary, depending on the severity of the defect and the philosophy of the treatment team. A detailed discussion of these pro- cedures is beyond the scope of this text. However, primary lip closure usually is accomplished during the first few months of life, followed later by repair of the palate. Pros- thetic and orthopedic appliances often are used to mold or expand the maxillary segments before closure of the palatal defect. Later in childhood, autogenous bone grafts can be placed in the area of the alveolar bone defect. Secondary soft tissue and orthognathic procedures may be used to improve function and cosmetic appearance. Distraction osteogenesis of the maxilla can prove useful in patients in whom palatal scarring limits the amount of advancement possible at the time of osteotomy. • Fig. 1-5 Pierre Robin Sequence. Micrognathic mandible in an  Breathing difficulties in infants with Pierre Robin infant with cleft palate (CP). (Courtesy of Dr. Robert Gorlin.) sequence are managed best with conservative measures, such as side and prone positioning. However, in children with significant airway obstruction, placement of a naso- The Pierre Robin sequence (Pierre Robin anomalad) pharyngeal airway may be warranted. In more severe cases, (Fig. 1-5) is a well-recognized presentation characterized by mandibular distraction osteogenesis may be a preferable CP, mandibular micrognathia, and glossoptosis (airway treatment alternative to tracheostomy. obstruction caused by lower, posterior displacement of the Genetic counseling is important for the patient and tongue). The Pierre Robin sequence may occur as an iso- family. In nonsyndromic cases of orofacial clefting, the risk lated phenomenon, or it may be associated with a wide for cleft development in a sibling or offspring of an affected