Table Of ContentOral 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
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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
