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C H A P T E R 23
of the Jaws
M. ANTHONY POGREL, BRIAN L. SCHMIDT, CHAD G. ROBERTSON
• The differential diagnosis should be established early and should guide the diagnostic work-up, method of
biopsy, and planned treatment of jaw tumors.
• Overall, odontogenic tumors are rare and form only a small proportion of the lesions found in the jaw. They
are virtually all benign.
• Several tumors exist, which only appear to occur in the jaws. Although they do not normally contain
odontogenic tissue, they are probably odontogenic because of their site of origin.
• Several lesions of the jaws contain giant cells, and their differentiation often presents a problem. The
diagnosis of a lesion of the jaw containing giant cells often depends on a combination of histological
examination, the clinical history, and ancillary laboratory tests. Treatment should be tailored to the biological
behavior of the speciﬁc lesion.
• Obtaining a representative biopsy is of paramount importance. Many lesions are misdiagnosed on inadequate
biopsy material. An adequate biopsy may require general anesthesia.
ODONTOGENIC TUMORS OF THE JAW and the more mature the dental tissues, the less aggres-
sive they are. The vast majority of these tumors are
This rare group of tumors may derive from the tooth- benign or locally aggressive with few malignant variants
forming elements of the jaws. In general, the more being reported. In many cases their relationship to the
primitive the dental structures from which they are teeth is fairly clear-cut, both histologically and radio-
derived, the more aggressive they are thought to be, graphically. In other cases, their relationship to teeth
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PA R T I I ONCOLOGY 491
and teeth-forming structures is less well deﬁned in that
tissues resembling dental tissues are rarely, if ever,
found within them, and the assumption that they are Odontogenic tumors are normally classiﬁed by their
odontogenic in origin derives from the fact that they presumed tissue of origin, being epithelial, mesenchy-
are only found in the jaws and therefore may have a mal, or a mixed lesion (Box 23-1). Studies of odon-
relation to teeth and teeth-bearing tissues. togenic tumors reveal that there are often no clear
Conversely, tumors that are strongly thought to be divisions among many types of tumors, but rather a
odontogenic do have histologically similar lesions occur- transition from one to another, and it is not unusual for
ring in other parts of the body where teeth are not tumors to show areas that resemble different types of
found (e.g., the relationship between the ameloblas- tumors within the lesion. Because of this, there have
toma and the adamantinoma of the tibia and the cranio- been numerous attempts at reclassiﬁcation of these
pharyngioma), and this sometimes causes confusion as lesions, as well as attempts to introduce new variants of
to whether these tumors are truly odontogenic in origin. lesions, which are generally extremely rare with only a
In general, odontogenic tumors only occur in the jaws, handful of cases reported. In general these lesions have
but they have been reported in tooth-bearing tissues in been avoided in this chapter. However, there are numer-
such structures as dermoid cysts and teratomas. ous reports of combined tumors, new tumors, and
Odontogenic and Nonodontogenic Tumors of the Jaws
ODONTOGENIC TUMORS Langerhans cell disease
EPITHELIAL TUMORS Chronic localized
Benign: Chronic disseminated
Ameloblastoma Acute disseminated
Calcifying epithelial odontogenic tumor Lesions containing multinucleated giant cells
Adenomatoid odontogenic tumor Central giant cell granuloma
Squamous odontogenic tumor Giant cell tumor
Malignant ameloblastoma Cherubism
Clear cell odontogenic carcinoma Aneurysmal bone cyst
Odontogenic carcinoma Neurogenic tumors
MESENCHYMAL TUMORS Neurofibroma
Benign: Osteoid osteoma and osteoblastoma
Odontogenic fibroma Osteoma
Odontogenic myxoma Desmoplastic fibroma
Cementifying fibroma Malignant:
Ameloblastic fibrosarcoma Peripheral osteosarcoma
MIXED EPITHELIAL AND MESENCHYMAL Fibrosarcoma of bone
TUMORS (ALL BENIGN) Malignant fibrous histiocytoma
Odontoma Ewing’s sarcoma
Ameloblastic fibroma Burkitt’s lymphoma
Ameloblastic fibro-odontoma Multiple myeloma
Solitary plasmacytoma of bone
NONODONTOGENIC TUMORS OF THE JAWS Malignant peripheral nerve sheath tumor
Benign: Postradiation sarcoma of bone
Fibro-osseous tumors Metastatic carcinoma
Juvenile ossifying fibroma
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492 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
histological variants on established odontogenic tumors,
and new classiﬁcations of these lesions will probably
occur.1-10 However, few of them have any clinical sig- These tumors present with various histological pat-
niﬁcance because the vast majority of these lesions are terns including follicular, plexiform, and granular cell
benign, and true malignant variants are extremely rare. variants. They are thought to be of histological interest
only and do not affect the treatment or prognosis.16 At
one time the granular cell ameloblastoma was believed
BENIGN EPITHELIAL ODONTOGENIC to be a more aggressive variant, but this is no longer
TUMORS OF THE JAW the case. These tumors are benign but locally aggressive
and can occasionally metastasize (see later).17,18 They
most commonly occur in the mandible, particularly
around the angle of the mandible. They are most com-
The ameloblastoma is a benign tumor located exclu- monly found in the third to ﬁfth decades of life. The
sively in the jaws. It has a distinctive histological appear- male-to-female ratio is approximately equal.19
ance, and the diagnostic cells are columnar, basally The exact incidence is unknown, but there do appear
staining cells arranged in a palisaded pattern along the to be geographical variations. In most studies they are
basement membrane (Fig. 23-1). The name of this tumor the second commonest odontogenic lesions after odon-
derives from the fact that these cells closely resemble tomas.20 However, studies from Africa suggest that they
ameloblasts and are felt to be the cells of origin. Studies may represent more than 50% of all tumors of the head
have almost certainly conﬁrmed this hypothesis because and neck, although this may be due to referral patterns
it is now known that these cells are epithelial in origin and late presentation in these areas.21,22 Larsson and
and can express amelogenin, a precursor of enamel.11,12 Almeren23 described an incidence of 0.3 cases per mil-
Histologically similar tumors seen in other parts of the lion people per year in Sweden.
body are now believed to be unrelated. The adaman- Imaging of these lesions is normally initially with
tinoma of the tibia is believed to be a locally malignant plain radiography such as Panorex radiographs, rein-
tumor of bone,13,14 while the craniopharyngioma, which forced by computed tomography (CT) scans, when
appears histologically similar, is felt to be a develop- there is any question of lingual or buccal expansion or
mental anomaly arising from the remnants of Rathke’s perforation (Fig. 23-2).
pouch.15 Ameloblastomas are divided into three fairly Although benign, these tumors are locally aggressive
distinct types: with a high recurrence rate when treated locally.
Enucleation has been traditionally associated with a
• Solid ameloblastomas
recurrence rate of between 60% and 80%,24-27 man-
• Cystic ameloblastomas
dating that more aggressive treatment be performed.
• Peripheral ameloblastomas
Histologically, cells have been shown to be present
several millimeters from the radiographical margin of
the lesion,28 and this has led to a general principle that
surgery should be performed with 1-centimeter bony
margins around the radiographical limits of the lesion
and a single tissue plane clearance in the case of
soft tissue extension (e.g., a supraperiosteal dissection).
Sometimes this can be carried out with a marginal
mandibulectomy, but often a segmental resection is
required. The inferior alveolar nerve is often sacriﬁced
and can be reconstructed with a nerve graft if indicated.
Techniques have been described for segmentally resect-
ing the mandible with nerve preservation, but this does
run the theoretical risk of recurrence around the nerve.29
In the maxilla, wide margins can result in invasion of
the sinus, nasal cavity, orbit, and infratemporal fossa.
Fig. 23-1 The typical histological appearance of a follicular Intermediate techniques such as aggressive local curet-
ameloblastoma showing follicle of deeply staining basophilic tage followed by liquid nitrogen cryotherapy have also
cells in palisaded pattern on a basement membrane (hema- been advocated.30-32 These techniques have been asso-
toxylin and eosin, ×40). ciated with high levels of success and do deserve con-
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PA R T I I ONCOLOGY 493
Fig. 23-2 A large multilocular solid ameloblastoma of the right angle of the mandible and
displacing teeth. A, Panorex. B, Axial computed tomography (CT) scan. C, Coronal CT
scan. D, Resected specimen.
sideration in treatment planning. Algorithms have been and spread through the posterior wall of the maxilla
developed recommending curettage and cryotherapy into the pterygomaxillary space also occurs. Addition-
for intrabony lesions and resection for lesions with an ally, inﬁltration of the greater palatine canal up to the
extraosseous component.33 base of the skull is not unknown. Resection involving
1-cm margins is generally guided by CT or magnetic
Maxillary Ameloblastomas. Maxillary ameloblas- resonance imaging but often involves a maxillectomy,
tomas, although rarer, are often more troublesome than frequently with an incontinuity resection of the ptery-
mandibular lesions. Histologically, they are identical goid plates (Fig. 23-3). Reconstruction of this area is
and behave similarly except that their pathways to normally by means of a skin graft and prosthetic obtu-
inﬁltrate are more numerous. Involvement of the maxil- rator, although in some centers autogenous reconstruc-
lary sinus and nasal cavity tends to occur fairly early, tion of the palate with microvascular free flaps has been
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494 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
Fig. 23-3 An ameloblastoma of the posterior maxilla
extending to the pterygoid plates. A, Panorex (lesion
arrowed). B, Axial computed tomography (CT) scan. C,
Coronal CT scan. D, Weber-Fergusson incision for
surgical access. E, Resected specimen.
used. Ultimately, implants would be placed in any bone was ﬁrst described in 1977 by Robinson and Martinez.34
graft for the ﬁnal prosthetic reconstruction. They reported that the unicystic variant is a less aggres-
sive type of ameloblastoma and suggested simple enu-
cleation as treatment. The unicystic ameloblastoma has
been reported to occur in a younger population (third
This is a difﬁcult diagnosis because many ameloblas- decade) than its solid counterpart (fourth decade). It is
tomas have cystic components within them (Fig. 23-4). most commonly encountered in the posterior mandible,
A particular variant called a unicystic ameloblastoma followed by the parasymphysis region, anterior maxilla,
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PA R T I I ONCOLOGY 495
Fig. 23-4 Panorex radiograph of a multicystic ameloblastoma of the left posterior
and posterior mandible (Fig. 23-5). It has also been bony involvement.40 Apparently, lesions that may
reported that they commonly occur in association with previously have been reported as basal cell carcinoma
an impacted tooth.35-37 In 1988 unicystic ameloblas- of the gingiva may in fact be peripheral ameloblas-
tomas were classiﬁed into three histological subsets,38 tomas.41 The peripheral ameloblastoma is a painless,
depending on whether they had a cystic lining com- sessile, ﬁrm, exophytic growth that is usually relatively
posed of simple odontogenic epithelium or a cystic smooth or granular. It may also have a warty appear-
lesion showing intraluminal plexiform proliferation of ance. They are generally believed to represent between
the epithelial lining or a cystic lesion with epithelial 2% and 10% of all ameloblastomas diagnosed. They
invasion of the supporting connective tissue in either a have been reported in all age-groups between the ages
follicular or plexiform form. At this time it was sug- of 9 and 92, with a mean age of 52.1.
gested that the ﬁrst two groups were nonaggressive and Cases reported in males outnumber those in females
may be treated by enucleation, whereas the third group 1.9 to 1. Seventy percent of peripheral ameloblastomas
would require more aggressive treatment. The problem appear to occur in the mandible, with the body of the
with this philosophy is that in many cases the diagnosis mandible anterior to the mental foramen being most
can only be made retrospectively from the histological frequently associated. Although histologically they appear
material. Clinical ﬁndings indicate that many lesions identical to intraosseous ameloblastomas, palisading in
diagnosed radiographically as unicystic turn out to be the stellate reticulum is seldom conspicuous. Ghost
multicystic on exploration, and it is quite likely that the cell formation is often present, and clear cells may be
prognosis for multicystic ameloblastomas is similar to present. The cells of origin of these lesions are probably
solid ameloblastomas. Studies have also shown clini- not ameloblasts, but they are more likely to arise
cally that simple enucleation of so-called cystic amelo- directly from the surface epithelium or from residues
blastomas is actually associated with a high recurrence from the dental lamina lying outside the bone. Some
rate, which may be as high as 60%.39 Therefore it would authors consider them to be hamartomas rather than
seem that simple enucleation is an inappropriate treat- neoplasms, and they appear to behave in a benign
ment for these lesions, and possibly a more aggressive fashion and do not recur following simple complete
treatment with peripheral ostectomy or liquid nitrogen excision.40
cryotherapy, or both, may be more appropriate.39
CALCIFYING EPITHELIAL ODONTOGENIC
Peripheral Ameloblastoma TUMOR
The peripheral ameloblastoma is also known as the Pindborg ﬁrst described this tumor in 1955.42 Earlier
extraosseous ameloblastoma, or soft tissue ameloblas- cases were probably classiﬁed as variants of ameloblas-
toma. It generally occurs in the gingiva, and there is no toma. This is a rare rumor, and fewer than 200 cases
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496 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
Fig. 23-5 A unicystic ameloblastoma of the posterior right
mandible. In all respects this appears like any other cystic
lesion of the posterior mandible. A, Panorex. B, Axial
C computed tomography scan. C, Enucleated specimen.
have been reported in the literature, so some aspects of deﬁned, mixed radiolucent/radiopaque lesions, though
its pathogenesis and behavior are still in doubt. The radiolucent and radiopaque variants have been described.
lesion has been reported in ages ranging from 13 to They can be unilocular or multilocular43 (Fig. 23-6).
80 with no gender predilection. The majority of cases Histologically, the calcifying epithelial odontogenic
occur in the mandible with a ratio of approximately 3:1. tumor (CEOT) is most characterized by sheets of large
The mandibular premolar molar area appears to be the eosinophilic staining epithelial cells. The stroma is a
most common site for these lesions. They are slow hyaline-like homogenous material that has been identi-
growing and asymptomatic until they are either found ﬁed as amyloid (Fig. 23-7). Liesegang rings are promi-
by chance on routine radiography or they become large nent calciﬁcations in concentric shapes that can occur
enough for the patient to be aware of them. Radio- in the amyloid areas and account for the radiopacities
graphically, they are classically described as being well seen radiographically. The lesion is thought to arise
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PA R T I I ONCOLOGY 497
Fig. 23-6 Imaging studies of a calcifying epithelial
odontogenic tumor. A, Panoral radiograph of a lesion of
the posterior right mandible. B, Coronal computed
tomography scan of lesion showing lingual perforation
by the lesion. B
reported following local enucleation. Malignant variants
(odontogenic carcinoma) have been described rarely.45
A prominent clear cell component (seen in 8% of
lesions) may be associated with increased aggressive-
ness and cortical perforation.46 In general the CEOT
appears to be less aggressive than the solid ameloblas-
toma. Treatment is usually recommended as wide local
excision with margins of 5 to 10 mm, which in the
mandible may require a marginal resection or even seg-
mental resection and subsequent reconstruction.
ADENOMATOID ODONTOGENIC TUMOR
Fig. 23-7 Typical histological appearance of a calcifying The adenomatoid odontogenic tumor contains struc-
epithelial odontogenic tumor with sheets of darkly staining tures that resemble enamel formation. It is presumed to
cells in a homogenous amyloid containing matrix (hema-
be of odontogenic origin, as it only occurs in the jaws.
toxylin and eosin, ×40).
Immunohistochemical and ultrastructural ﬁndings have
revealed that the eosinophilic deposits normally seen
from the stratum intermedium tissue of the developing probably represent some form of enamel matrix and are
enamel organ.44 positive for amelogenin in limited areas.47 The adeno-
The behavior of the calcifying epithelial odontogenic matoid odontogenic tumor is more common in females
tumor remains in some doubt, but it is believed to be than males (1.9:1). It represents approximately 3% of
locally aggressive with recurrence rates of 14% to 20% odontogenic tumors and appears between the ages
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498 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
of 5 and 30 years. The most common site is the anterior
SQUAMOUS ODONTOGENIC TUMOR
maxilla, and this tumor is often found in association
with impacted teeth (Fig. 23-8). This rare odontogenic tumor was ﬁrst described in
Intraosseous follicular (70%), extrafollicular (26%), 1975.51 It normally involves the alveolar process and
and peripheral variants (4%) have been described, but appears to originate from the rests of Malassez in the
they are all histologically identical.48 A subvariant of the periodontium. In the past it has been confused with
extrafollicular type of adenomatoid odontogenic tumor other odontogenic entities such as ameloblastomas, carci-
may mimic periapical disease radiographically.49 The nomas, and ﬁbromas.52 The tumor is often asympto-
classic radiographical appearance is of a pear-shaped matic but can present with pain and tooth mobility. It
radiolucency with speckled opaque foci distributed appears to occur in the mandible and maxilla equally,
throughout the lesion, indicating calciﬁcation (Fig. 23-9). though when in the maxilla it seems to favor the
Magnetic resonance imaging ﬁndings correlate with anterior maxilla.53 When in the mandible, it favors the
radiography and histology.50 Divergence of roots is not posterior mandible.
unusual. They are most often discovered as chance Multiple lesions have been described, as have famil-
radiographical ﬁndings. ial lesions. The age range appears to extend from the
Simple enucleation seems to be all that is necessary second to the seventh decade with a mean age of
in the way of treatment (see Fig. 23-8), and although around 40. There is no gender predilection. The char-
recurrences have been reported, they are usually because acteristic radiographical appearance is of a triangular
of incomplete primary excision. Clinically, they behave shape or semilunar radiolucency associated with the
more like a hamartoma than a neoplasm. roots of erupted or erupting teeth.54 Histologically, the
Fig. 23-8 An adenomatoid odontogenic tumor. A, A
firm swelling over the upper left canine and first pre-
molar. B, Radiographical appearance showing a pear-
shaped lesion with speckled opaque foci. C, Clinical
C appearance of enucleated lesion.
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PA R T I I ONCOLOGY 499
Fig. 23-9 An ameloblastoma of the left posterior mandible. A, Presenting radiographical
appearance as a well-developed radiolucency. B, Histological appearance of lesion showing
plexiform appearance with some atypical and hyperchromatism (hematoxylin and eosin,
×20). C, Axial computed tomography scan 3 years after initial resection showing a
metastasis to the posterior orbit (arrow). D, Histological appearance of the metastasis
showing dedifferentiation with hyperchromatism, pleomorphism, and mitotic figures.
Lesion is now an ameloblastic carcinoma (hematoxylin and eosin, ×80).
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tumor is characterized by the formation of variably shown to be effective, but chemotherapy with pacli-
sized nests and cores of uniform benign-appearing taxel and carboplatin and oral cyclophosphamide has
squamous epithelium with occasional vacuolization and been used with some effect.62
keratinization. Treatment is by conservative surgical Malignant variants of ameloblastoma occur in the
excision, which is normally curative, though recur- same sites as the more frequent well-differentiated
rences have been reported. lesion and are therefore more common in the posterior
mandible, although both mandibular and maxillary
cases have been described.
MALIGNANT EPITHELIAL Most ameloblastic carcinomas are believed to arise
ODONTOGENIC TUMORS OF THE JAW de novo, although there are a few reports of apparent
change from a normal well-differentiated ameloblas-
Malignant odontogenic tumors are rare and comprise toma into an ameloblastic carcinoma,63 and there are
only about 4% of all odontogenic tumors.55 also reports of hybrid lesions histologically showing
areas of normal ameloblastoma and areas of ameloblas-
tic carcinoma, suggesting that extensive tissue sampling
MALIGNANT VARIANTS OF
may be required in some cases (see Figs. 23-11 and
23-12). Death has been reported from ameloblastic
Malignancy in the ameloblastoma has been subdivided carcinoma often due to extensive local recurrence
into two distant lesions. A malignant ameloblastoma involving the base of the skull and cranial cavity.
is diagnosed when a seemingly histologically benign
ameloblastoma produces a metastasis resembling the
CLEAR CELL ODONTOGENIC CARCINOMA64-66
original lesion. Both lesions are microscopically well
differentiated with the characteristic histological fea- This rare neoplasm has been described in both the
tures of the ameloblastoma. The second lesion is the mandible and maxilla and is of unknown etiology, but
ameloblastic carcinoma, which is a term reserved for the fact that it has only been described in the jaws and
tumors that demonstrate a malignant morphological has some resemblance to other odontogenic lesions
appearance regardless of whether metastasis is present suggests that it is probably odontogenic in origin. It
at the time of discovery and treatment. appears to occur most commonly in females, often
older than the age of 60. It appears as a locally aggres-
sive lesion and is poorly circumscribed both clinically
and radiographically. Histologically, it consists of clear
As already stated, these cases are diagnosed retro- cells, which are positive for cytokeratin and negative for
spectively when a metastasis is discovered. These vimentin and also negative for mucicarmine, which
metastases generally only arise after many surgical differentiates it from some of the other clear cell tumors
attempts at treatment of the original lesion and are often such as mucoepidermoid carcinoma and renal carci-
isolated pulmonary metastases that can sometimes be noma and CEOT. Metastases to the lungs67 and neck
treated surgically.18,56-58 Lymph node metastases also have been described, necessitating a metastatic work-
occur. In some cases the metastasis may in fact be up on these patients.
caused by aspiration or implantation at the time of
This is a central lesion occurring most often in the
mandible and is felt to arise from remnants of the dental
In this case, either the primary or metastatic lesion lamina or reduced enamel epithelium.70 Histologically,
exhibits less microscopic differentiation showing cyto- it has all the appearances of a squamous cell carcinoma
logic atypia and mitotic ﬁgures. The lesion often has a and usually appears to be well differentiated. Because
spindle cell appearance,58 though immunohistochem- the lesion cannot be differentiated histologically from
istry shows that the spindle cells are epithelial in any other squamous cell carcinoma, its odontogenic
origin, being positive for cytokeratin and negative for origin can only be assumed when there is no connec-
vimentin.59,60 They metastasize locally to the lymph tion to the epithelium or any other site of a squamous
nodes but also have distant metastases in the lungs, cell carcinoma and there is no possibility of this being
bone,61 and myocardium. Treatment of the primary site a metastatic lesion. If it is contiguous with the overlying
is essentially surgical and often includes a lymph node mucosa, the perception is that it almost certainly arose
dissection of the neck. Radiation therapy has not been in the mucosa and only involved the bone secondarily.
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PA R T I I ONCOLOGY 501
Radiographically, it normally appears as a poorly appear to behave similarly. The lesions are normally
deﬁned radiolucency and the diagnosis is often made well demarcated but nonencapsulated. Treatment is
from routine radiographs, although instances have been enucleation and excision. Recurrence is rare, although
described where the presenting feature was involve- more aggressive variants have been described.78
ment of the inferior alveolar nerve or a nonhealing
socket following tooth removal (Fig. 23-10).71
Odontogenic carcinoma is often found in conjunc-
tion with another odontogenic lesion72,73 and may result The cementoblastoma is also known as the true cemen-
from epithelial malignant change within the lesion.74,75 toma and is a rare odontogenic lesion representing less
Treatment is as for squamous cell carcinoma in other than 1% of all odontogenic tumors.79 It is most common
sites and involves a metastatic work-up followed by in the second and third decades of life and typically
primary surgery, which can often involve a neck dissec- affects the lower molar region.80 It is intimately asso-
tion followed by radiation therapy depending on the ciated with the root of a tooth being formed from the
adequacy of the surgical margins, their histological cementum and is commonly associated with a lower
appearance, and the presence or absence of metastatic molar tooth including the third molar. The tooth nor-
spread. mally remains vital, and symptoms include cortical
expansion and a low-grade intermittent pain.
Radiographically, the lesion appears as a radiopaque
BENIGN MESENCHYMAL ODONTOGENIC lesion attached to and surrounding the root of a tooth.
TUMORS Classically, it is surrounded by a radiolucent ring that
represents the periodontal ligament space around the
tumor (Fig. 23-11).
Histologically, cementum and bone are difﬁcult to
The central odontogenic ﬁbroma, a rare lesion that distinguish from each other, and this lesion is the
occurs in both males and females and in all age-groups, cemental equivalent of the osteoblastoma. Radiographi-
is found in both the mandible and maxilla. Fewer than cally, symptomatically, and histologically, they are almost
100 cases have been reported worldwide.76 Radio- identical, and it is difﬁcult to differentiate the two if the
graphically, it appears as a radiolucent lesion that is causative tooth is not present.
often multilocular and can cause cortical expansion. It Radiographically, it must be distinguished from an
thus resembles a number of other odontogenic lesions. odontoma, focal sclerosing osteomyelitis, and hyper-
Histologically, two patterns have been described, one cementosis.
with a mass of mature ﬁbrous tissue containing a few Treatment is normally removal of the lesion and the
epithelial rests and the other a more mature connective associated tooth. Thorough curettage is required, and
tissue with abundant rests and calciﬁc deposits of either recurrence is rare but has been recorded. Peripheral
dentin or cementum.77 Clinically, the two subgroups ostectomy has also been recommended as a treatment
Fig. 23-10 An odontogenic carcinoma involving the roots of the lower right second molar
(arrow). No connection with the overlying mucosa existed at surgery.
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new cases/million people/year.83 Odontogenic myxoma
typically occurs between the second and fourth decades,
is more common in females than males (male-to-female
ratio 1:1.5), and two thirds of cases occur in the mandible
and one third in the maxilla.84 The tumor typically pre-
sents as either a swelling in the affected jaw or as an
asymptomatic radiographical ﬁnding. Radiographically,
more than 50% of these tumors are multilocular and
somewhat less than 50% unilocular with fairly well-
deﬁned borders. Larger lesions are more likely to
be multilocular. They are only rarely associated with
The radiographical appearance of myxoma is similar
A to that of the ameloblastoma, but differences have been
noted on dynamic magnetic resonance imaging scan-
ning85 with the center of the myxoma showing enhance-
ment while the ameloblastoma did not (Fig. 23-12).
Histologically, the lesion contains a loose mesenchy-
mal ﬁbrous tissue that lacks atypia. It has a bland
histological appearance. Odontogenic epithelium is rarely
found within the lesion, and its odontogenic origin is
assumed from the fact that it does not appear to occur
elsewhere in the body (see Fig. 23-17). Although lesions
containing myxomatous tissue have been recorded in
other parts of the body, they normally represent myxo-
matous degeneration in another type of lesion. The
odontogenic myxoma is assumed to derive from primi-
tive dental pulp or primitive dental papilla. In fact, the
dental papilla and the tooth follicle of a mature individ-
ual is histologically similar to the myxoma, and errors
have been made histologically in differentiating a nor-
mal dental follicle from a myxoma, which can result in
overtreating some patients.86
The odontogenic myxoma is a benign but locally
aggressive lesion that is slightly less aggressive than the
solid ameloblastoma. Normally it is treated by either
enucleation and radical curettage or peripheral ostec-
tomy. In larger lesions or lesions perforating the buccal
or lingual plate, segmental resection of the mandible or
B a hemimaxillectomy in the maxilla may be required.
Fig. 23-11 A cementoma associated with the lower left first Physicochemical adjuncts to treatment such as liquid
molar. A, A cementoblastoma associated with the roots of nitrogen cryotherapy or Carnoy’s solution have also
the first molar. Note the radiolucent ring around it been used in addition to enucleation. Recurrence rate is
representing the periodontal ligament. B, Resected and
normally quoted as between 15% and 20%.
for these lesions if recurrence is likely to be a problem
(see Fig. 23-15).81 A cementifying ﬁbroma is the odontogenic equivalent
of the ossifying ﬁbroma; these ﬁbromas are clinically
and histologically similar, if not identical. Lesions in
the areas of the jaws where cementum could be found
This odontogenic tumor may comprise 15% to 20% of and which contain calciﬁed spherules are normally
odontogenic tumors.82 It is the second most common believed to be cementifying ﬁbromas (Fig. 23-13). They
odontogenic tumor with a possible incidence of 0.07 have been described in both the maxilla and mandible
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PA R T I I ONCOLOGY 503
Fig. 23-12 An odontogenic myxoma of the right mandible.
A, Radiograph of an odontogenic myxoma of the right
mandible. The myxoma appears as a moderately well-
defined multilocular radiolucency. B, The mandible grossly
sectioned through the myxoma. Despite its irregular
B borders, it is gelatinous in nature and fairly well defined.
but are more frequent in the mandible, and they are
classiﬁed as benign ﬁbro-osseous lesions. Although
histologically similar, differences have been found on
immunohistochemical staining because ossifying ﬁbromas
show no signiﬁcant immunoreactivity for keratin sulfate
or chondroitin-4-sulfate, while the cementifying ﬁbroma This represents the only well-described odontogenic
has signiﬁcant immunoreactivity for keratin sulfate. mesenchymal malignant tumor. Malignant odontogenic
Chondroitin-4-sulfate is also found to have intense tumors are rare and represent only about 4% of odon-
immunostaining in the premineralized and poorly min- togenic tumors. The ameloblastic ﬁbrosarcoma is one
eralized matrices of cementifying ﬁbromas.87 Maxillary of the rarer variants with fewer than 80 cases in the
lesions have been described in the maxillary antrum,88 literature. Clinically, two thirds arise de novo, while one
ethmoids,89 and sphenoids90 and have even caused third arise in preexisting benign odontogenic lesions.93
proptosis.91 Although cementifying ﬁbromas are gener- Possible malignant transformation from ameloblastic
ally believed to be benign and they respond well to ﬁbroma (normally believed to be benign) has been
enucleation, recurrences have been described necessi- described.94 Histologically, the lesions are composed
tating local resection.92 of a benign-appearing epithelial component consisting of
Unlike the ossifying ﬁbroma, a juvenile aggressive epithelial islands and strands within a cellular mass of
version has not been described. mesenchymal tissue with stellate- and spindle-shaped
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Fig. 23-13 A cementifying fibroma of the right posterior mandible. A, Radiographical
appearance showing the lesion possibly arising from the mesial root of the lower right first
molar. B, Histology of specimen. Note calcified spherules representing cementum
(hematoxylin and eosin, ×20).
ﬁbroblast-like cells with marked pleomorphism. The MIXED EPITHELIAL AND
ﬁbrous stroma is believed to be malignant. Occasional MESENCHYMAL ODONTOGENIC
cementum-like calciﬁcation has been noted.95 Immuno- TUMORS
histochemically, the mesenchymal cells are positive for
Ki 67, PCNA, p53, and vimentin, unlike the negativity of
the ameloblastic ﬁbroma.96 They appear to be most fre-
quently located in the posterior region of the mandible, The odontoma, or odontome, is the most common odon-
and the average age of affected patients is 22.9.93 togenic tumor, representing approximately 22% of all
The lesion is thought to be locally aggressive, and odontogenic tumors, and consists of fully differentiated,
one study noted that 37% of reported cases had at least irregularly arranged, mature dental tissues. Odontomas
one metastasis. The overall prognosis is generally are mixed tumors, as they contain both epithelial and
believed to be good, although one study showed that mesenchymal elements, and they are benign. They are
19.3% of patients died of their disease.93 Nevertheless, developmental abnormalities found in young people and
wide surgical excision remains the standard treatment, are most often found on routine radiographs, although
augmented if necessary by radiation therapy and they can present as a swelling or with an infected
chemotherapy.96,97 lesion, particularly if they erupt. Because they contain
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PA R T I I ONCOLOGY 505
mature dental tissue, they often replace a missing tooth. Odontomes have limited growth potential, although
They can be found throughout the jaws but are most they normally reach a certain size and then cease to
frequent in the mandibular molar region. grow. Enucleation is the curative treatment, and recur-
Two distinct forms have been described, but the rences do not occur.
difference is of radiographical and histological interest
only because the prognosis and treatment are the same
for both. The compound odontome (Fig. 23-14), which
is more commonly found in the anterior part of the This is a true mixed odontogenic lesion containing both
mouth, contains numerous small denticles or tooth-like epithelial and mesenchymal neoplastic components. It
fragments within the lesion, each containing a denticle occurs in young people, often in the second or third
of enamel with dentin and pulp (see Fig. 23-14). In decades of life, and is extremely rare after the age of 40.
the complex odontome, most frequently found in the The ameloblastic ﬁbroma has no gender predilection,
posterior part of the mouth (Fig. 23-15), there is an and although it has been reported in all areas of the
amorphous conglomeration of dental tissues consisting alveolus, it appears to be most frequent in the lower
of enamel, dentin, cementum, pulp, and enamel organ. bicuspid region. This ﬁbroma is often associated with
The compound odontone is twice as common as the an impacted tooth and may appear as a radiolucency
complex odontome.98 The epithelial cells have been either associated with the crown or the root of an
shown to have the ability to keratinize, and keratin can impacted tooth. The associated teeth are vital. The
sometimes be found in these lesions. ameloblastic ﬁbroma may represent approximately 2%
Radiographically, the lesions appear as well-circum- of all odontogenic tumors.99
scribed radiopaque lesions, often surrounded by a Radiographically, the ameloblastic ﬁbroma appears
small, clear margin that may represent a periodontal as a well-deﬁned radiolucency that can be either uniloc-
ligament. In a compound odontome, the small denticles ular or multilocular. Teeth may be displaced but are not
can often be differentiated radiographically, whereas in normally resorbed (Fig. 23-16, A).
the complex odontome radiographs show a more amor- Histologically, the lesion shows islands of odonto-
phous pattern with what looks like a multilobular appear- genic epithelium, often two cells thick in a loose or
ance. The differential diagnosis of similar radiopaque myxomatous connective tissue matrix (Fig. 23-16, B).
lesions of the jaws would include the ossifying ﬁbroma, The lesion is encapsulated, and treatment consists
cementoblastoma, and possibly focal sclerosing osteitis. of enucleation. Recurrences are rarely encountered
A ﬁne dividing line exists between a deformed tooth (Fig. 23-16, C and D). The ameloblastic ﬁbrosarcoma
such as a geminated or dilacerated tooth and an (already described) may represent the malignant coun-
odontome. terpart of the ameloblastic ﬁbroma.
Fig. 23-14 A compound odontome. A, Occlusal radiograph showing discrete and
separate denticles. B, Histology of the specimen showing denticles with enamel, dentin,
and pulp (hematoxylin and eosin, ×10).
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Fig. 23-15 A complex odontome. A, Radiograph of an
amorphous mass of enamel and dentin, a radiolucent
border, and an embedded tooth. B, Enucleated specimen of
cementum-like material, or both. As a result of histo-
This lesion is best thought of as a combination of an logical similarities, ossifying ﬁbroma, ﬁbrous dysplasia,
ameloblastic ﬁbroma with an odontoma,99 which may and cemento-osseous dysplasia are classiﬁed together
be either compound or complex in type. Thus radio- as benign ﬁbro-osseous lesions. The diagnosis of benign
graphically, it appears as a combined radiolucent/ ﬁbro-osseous lesions is based on clinical, radiographi-
radiopaque lesion and must be differentiated from other cal, and histopathological correlation. Chromosomal
similar-appearing lesions such as the ossifying ﬁbroma, abnormalities have been identiﬁed in the ossifying
the calcifying epithelial odontogenic tumor, the calcify- ﬁbroma100-102; however, the molecular mechanisms that
ing odontogenic cyst, an odontoma, and an adenomatoid underlie the development of this tumor remain unknown.
odontogenic tumor. The age and gender predilection is An ossifying ﬁbroma usually presents as a painless,
the same as ameloblastic ﬁbroma, as is treatment, which slow-growing, expansile lesion (Fig. 23-17, A). Although
consists of enucleation. these ﬁbromas occur over a wide age range, most cases
occur in the third and fourth decades of life. Female
predilection is deﬁnite. Ossifying ﬁbromas are believed
BENIGN NONODONTOGENIC TUMORS to be conﬁned to the jaws and craniofacial complex.103
OF THE JAW The mandible, particularly the premolar-molar region, is
affected more commonly than the maxilla. Rare multi-
FIBRO-OSSEOUS TUMORS centric or familial ossifying ﬁbromas, or both, have
Ossifying Fibroma (Cemento-Ossifying Fibroma)
The radiographical appearance is typically a well-
The ossifying ﬁbroma is a benign neoplasm charac- deﬁned radiolucency with a variable degree of internal
terized by the replacement of normal bone by ﬁbrous calciﬁcation (Fig. 23-17, B). The borders may be
tissue and varying amounts of newly formed bone or sclerotic. Larger mandibular lesions characteristically
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PA R T I I ONCOLOGY 507
Fig. 23-16 An ameloblastic fibroma in a 26-year-old female. A, Presenting on a panoral
radiograph, as a well-defined radiolucency displacing teeth. B, Histological appearance.
Note islands of odontogenic epithelium in a loose myxomatous matrix. C, After it has been
de-roofed but before enucleation. D, As a cream-colored, lobulated specimen following
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Fig. 23-17 Ossifying fibroma. A, Frontal view of a 21-year-old female demonstrating
expansion of the right side of the mandible. B, Mixed radiolucent-radiopaque lesion of the
mandible extending from the first molar region on the right to the first premolar region on
the left, producing a bowing of the inferior border. C, Submental three-dimensional
reconstructed computed tomography demonstrating the expansion of the mandible.
produce bowing of the inferior border (Fig. 23-17, C). margins than the 1 cm typically required for an amelo-
Root displacement and, less commonly, root resorption blastoma, odontogenic myxoma, or a calcifying epithe-
may be seen. Histologically, these ﬁbromas are lial odontogenic tumor. Involved teeth with evidence of
composed of a ﬁbrous stroma with bony trabeculae or resorption should be removed with the lesion.
cementum-like spherules, or both, evenly distributed
throughout the stroma. The microscopical appearance
Juvenile Ossifying Fibroma (Juvenile Aggressive
may be indistinguishable from ﬁbrous dysplasia.
Ossifying Fibroma; Juvenile Active Ossifying
The recommended treatment of ossifying ﬁbromas is
complete surgical excision. They characteristically shell
out from the surrounding bone with ease. Reported The juvenile ossifying ﬁbroma is considered by many
rates of recurrence have ranged from less than 1% to to be a unique lesion because of its reported tendency
63%.106-114 In light of the potential for recurrence, some to occur in children and adolescents, its more complex
authors advocate more extensive surgery for more histological features, and its tendency for more aggres-
aggressive lesions and lesions involving the craniofacial sive growth. However, there is no general agreement
bones.107,115,116 Ossifying ﬁbromas do not display an among pathologists with respect to the proper terminol-
inﬁltrative pattern into bone and therefore require smaller ogy, histopathological features, or criteria for separating
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PA R T I I ONCOLOGY 509
these lesions from conventional ossifying ﬁbromas.117 Although it is considered more aggressive than the
Adding to the controversy are the facts that these more common ossifying ﬁbroma that generally occurs
lesions have been noted in older patients and they are at a later age, conservative excision is recommended
not always particularly aggressive. for the juvenile ossifying ﬁbroma. However, lesions
Two variants of the juvenile ossifying ﬁbroma have involving the craniofacial bones may require more
been described—the trabecular variant118 and the psam- extensive surgery. Recurrence rates of 20% to 58% have
momatoid variant.119 The trabecular variant has strands been reported.117 Recurrences may be managed by local
of immature cellular osteoid within the lesion and usu- excision, and malignant transformation has not been
ally occurs in childhood with a slight maxillary predilec- reported.
tion. The psammomatoid variant has small spherical
ossicles surrounded by osteoid rims within the lesion. It
LANGERHANS CELL DISEASE
occurs over a wider age range than the trabecular
variant and usually affects the orbit or paranasal sinuses Langerhans cell disease was formerly known as histio-
(Fig. 23-18). cytosis X and before that as three separate diseases:
eosinophilic granuloma, Hand-Schüller-Christian disease,
and Letterer-Siwe disease. The clinical manifestations
of these diseases range from solitary or multiple bone
lesions to disseminated visceral, skin, and bone lesions.
Despite their diverse manner of clinical disease expres-
sion, these three diseases are characterized by prolifer-
ation of Langerhans cells accompanied by varying
numbers of eosinophils, other chronic inflammatory
cells, and multinucleated giant cells. Langerhans cells,
which are derived from the monocytic series, are found
in the epidermis, mucosa, lymph nodes, and bone mar-
row. They are dendritic cells that process and present
antigens to T lymphocytes. The etiology and patho-
genesis of Langerhans cell disease remains unknown.
Evidence suggests a neoplastic process,120 viral etiol-
ogy,121 and an overwhelming allergenic challenge.122
Langerhans cell disease generally affects children
and young adults, although it may affect older adults.
Three forms exist. Chronic localized Langerhans cell
disease, formerly known as eosinophilic granuloma,
A refers to solitary or multiple bone lesions only (Fig.
23-19, A). Chronic disseminated Langerhans cell disease,
formerly known as Hand-Schüller-Christian disease, is
classically associated with a clinical triad of lytic bone
lesions, exophthalmos, and diabetes insipidus (Fig.
23-19, B). Acute disseminated Langerhans cell disease,
formerly known as Letterer-Siwe disease, usually affects
infants and is multisystem in nature, affecting the skin,
bones, and internal organs, especially the lungs and
Bone lesions, either solitary or multiple, are the most
common clinical presentation. Lesions most frequently
involve the skull, mandible, ribs, and vertebrae, although
almost any bone may be involved. Jaw lesions may pro-
duce pain and tenderness, tooth mobility, and expan-
B sion. Radiographically, jaw lesions usually appear as
Fig. 23-18 Juvenile ossifying fibroma. A, Axial computed well-deﬁned, punched-out radiolucencies, although they
tomography of a 6-year-old male with an expansile mass of may be ill deﬁned. Lesions often involve the alveolar
the right maxilla. B, Spherical ossicles in a cellular fibroblastic bone, producing the classic appearance of “floating
stroma. teeth.” The involved teeth remain vital; however, they
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Fig. 23-19 Langerhans cell disease. A, Chronic localized form of the disease producing a
punched-out radiolucency seen at the mandibular alveolar crest in the region of the first
premolar. B, Chronic disseminated form of the disease producing multiple mandibular
often do not have adequate support and should not or visceral involvement and to follow them for recur-
prevent biopsy of the tissue deep in the jaws that will rence or disease progression. Individual lesions of
be required for diagnosis. chronic disseminated Langerhans cell disease may be
The diagnosis of Langerhans cells disease may be con- treated as they are with the chronic localized form, but
ﬁrmed using immunohistochemical studies. Langerhans with widespread or visceral involvement, chemotherapy
cells stain positive for S-100 protein and CD1a antigen. is often used. Acute disseminated Langerhans cell dis-
In addition, Langerhans cells contain unique, rod-shaped ease follows a rapidly progressive course and is treated
cytoplasmic structures known as Birbeck granules, which with chemotherapy. The acute disseminated form is
are seen on electron microscopy. frequently fatal.
Accessible bone lesions of chronic localized Langer-
hans cell disease are usually treated with aggressive
LESIONS CONTAINING MULTINUCLEATED
local curettage or resection with 5-mm margins where
possible. Less accessible lesions may be treated with
low-dose radiation therapy. Intralesional steroids have A number of lesions occur within the jaws, with
also been employed with some success,122 and cases of multinucleated giant cells as a prominent histological
spontaneous regression have also been reported.123 It is feature; however, their relationship to one another is ill
necessary to evaluate these patients for additional bone deﬁned. The lesions in this group are similar, if not
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PA R T I I ONCOLOGY 511
identical, histologically, and they usually cannot be quently than the maxilla, and the lesion may be seen
distinguished from one another solely on the basis of to cross the midline. It most often produces painless
light microscopy. Clinical history, physical and radio- expansion of the affected jaw; however, it may infre-
graphical examination, and serum biochemistry may be quently produce pain. Radiographically, central giant
used to differentiate these lesions. cell granulomas may present as a unilocular or multi-
locular radiolucency that is usually well delineated
Central Giant Cell Granuloma
On the basis of clinical and radiographical features,
The central giant cell granuloma is a benign prolif- there appear to be two types of central giant cell
eration of ﬁbroblasts and multinucleated giant cells. granulomas. The ﬁrst is the more common, nonaggres-
This lesion was initially thought to represent a repar- sive lesion, which is asymptomatic, grows slowly, and
ative process—thus it was termed a giant cell reparative does not produce cortical perforation or root resorp-
granuloma.124,125 It is no longer considered to be repar- tion. The second is an aggressive lesion, which presents
ative, and if left untreated the lesion will progress. The with pain, rapid growth, cortical perforation, and root
precise nature of the central giant cell granuloma resorption. The aggressive type may have a higher
remains speculative. It has been suggested that it may recurrence rate. Presently, no histopathological methods
be an inflammatory lesion, a reactive lesion, a neo- of differentiating the aggressive from the nonaggressive
plasm, or an endocrine lesion. type exist.
The proliferating cell in this lesion is the ﬁbroblast, Histologically, the central giant cell granuloma con-
which is thought to produce cytokines, resulting in the tains few to many multinucleated giant cells in a back-
recruitment of monocytes, which subsequently trans- ground of ﬁbroblasts with varying amounts of collagen.
form into multinucleated giant cells. Immunohistochem- The multinucleated giant cells are often focally aggre-
istry has shown the giant cells to be osteoclasts.126 gated; however, they may be evenly distributed.
Whether the central giant cell granuloma is unique to Hemosiderin-laden macrophages and extravasated
the jaws or whether it represents a continuum of the erythrocytes are commonly seen. Foci of osteoid may
same disease process as giant cell tumors affecting the be seen, particularly at the periphery of the lesion.
long bones is debatable and is discussed later. These histopathological features are similar, if not iden-
Central giant cell granulomas of the jaws are most tical, to those seen in the brown tumor of hyper-
often found in children and young adults, with up to parathyroidism and cherubism.
75% of cases occurring before 30 years of age. Females For years surgical curettage has been the treatment
are affected twice as frequently as males. The lesion of choice. Surgical treatment has generally been asso-
most often occurs anterior to the ﬁrst permanent molar ciated with a recurrence rate of 15% to 20%, although
teeth. The mandible is affected three times more fre- recurrence rates as high as 50% have been reported.
Fig. 23-20 Central giant cell granuloma. Radiolucency of the anterior mandible seen to
cross the midline in a 17-year-old male.
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512 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
Recurrence risk and the fact that with large lesions even However, in any particular case it may be difﬁcult to
conservative curettage may be associated with the loss make a distinction. The recurrence rate of giant cell
of teeth, damage to the inferior alveolar nerve, and tumors in long bones following curettage is higher than
sinus and nasal implications has led to the development for central giant cell granulomas of the jaws, leading
of several nonsurgical treatments. The ﬁrst nonsurgical some authorities to advocate resection.
treatment proposed was intralesional corticosteroid
injections.127 Weekly injections of triamcinolone for 6
weeks have been shown to induce partial and in some
cases complete resolution of the lesions.127-130 The Hyperparathyroidism is characterized by the over-
mode of action of this treatment remains unknown. production of parathyroid hormone (PTH). Primary
Subcutaneous calcitonin injections have also been used hyperparathyroidism is the uncontrolled production of
with some success.131-134 The injections are given daily PTH as the result of a parathyroid adenoma, hyper-
for approximately 18 months. The mode of action of plasia, or rarely an adenocarcinoma. Secondary hyper-
calcitonin remains speculative; however, some of the parathyroidism occurs in response to hypocalcemia,
giant cells in these lesions have been shown to have most often as a result of chronic renal failure. In both
calcitonin receptors.133 Thus the therapeutic effect of forms of hyperparathyroidism, excess PTH levels stimu-
calcitonin may be mediated through inhibition of osteo- late osteoclast-mediated bone resorption, which may
clastogenesis. Alpha-interferon given by subcutaneous produce a focal bone lesion known as a brown tumor
injection has also been advocated.135,136 The rationale of hyperparathyroidism. The lesion derives its name
for this therapy is that the antiangiogenic action of the from the color of the tissue as seen on surgical explo-
alpha-interferon will suppress the angiogenic compo- ration, which is a result of the erythrocyte extravasation
nent of the lesion, resulting in resolution. In most cases and hemosiderin deposition within the lesion. Like the
surgery is still required after the alpha-interferon treat- central giant cell granuloma, this lesion appears radio-
ment; however, it may be less radical and there may be graphically as a well-deﬁned unilocular or multilocular
a reduced recurrence rate. radiolucency, and it commonly occurs in the jaws
(Fig. 23-21). These lesions may be solitary or multiple.
They are histologically identical to central giant cell
Giant Cell Tumor
The giant cell tumor normally found in long bones is Patients with primary hyperparathyroidism are hyper-
an aggressive lesion that some people believe is a calcemic, with associated signs and symptoms. In con-
variant of low-grade osteosarcoma. This tumor is gener- trast, those with secondary hyperparathyroidism are
ally believed to be an entity that is separate from the hypocalcemic and those with central giant cell granu-
central giant cell granuloma of the jaws, although some lomas have normal serum calcium levels. Elevated serum
authorities report it rarely occurs in the jaws. Histo- PTH levels are associated with both forms of hyper-
logically, it is similar to the central giant cell granuloma, parathyroidism. Additionally, laboratory studies in sec-
although the giant cells are larger with more nuclei, the ondary hyperparathyroidism demonstrate impaired
giant cells are more evenly distributed, the stroma is renal function. A 24-hour urinary calcium level can
more cellular, and there may be areas of necrosis. be measured to rule out benign familial hypocalciuric
Fig. 23-21 Brown tumor of hyperparathyroidism. Multiple radiolucencies seen in the
mandible of this patient with hyperparathyroidism.
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PA R T I I ONCOLOGY 513
hypercalcemia, which is a hereditary condition that The lesions of cherubism commonly begin to mani-
leads to hyperparathyroidism secondary to low renal fest as painless, bilateral, symmetric expansion of the
sensitivity to parathyroid hormone. Normal PTH levels jaws between 2 and 5 years of age (Fig. 23-22, A),
are found in association with central giant cell granu- although milder forms may not be detected until a later
lomas. Therefore it is prudent to obtain serum calcium age. The lesions are conﬁned to the mandible and
and PTH levels in patients with giant cell lesions in maxilla. The regions most often affected are the mandibu-
order to exclude hyperparathyroidism. If a diagnosis of lar angle, ascending ramus, retromolar region, and
hyperparathyroidism is conﬁrmed, treatment must be maxillary tuberosity; however, in severe cases the entire
aimed at the cause and the lesions will usually resolve mandible and maxilla may become involved. The
without any further treatment. mandibular condyles are always spared. With involve-
ment of the maxillary contribution to the orbital floor,
the globes may be displaced upward, resulting in scleral
show. With eyes that appear to be turned upward and
Cherubism is a rare hereditary condition charac- a round face, children with a severe form of this con-
terized by painless, bilateral, symmetrical expansion of dition appear like cherubs depicted in Renaissance
the jaws. It was ﬁrst described in 1933, when it was paintings.
named familial multilocular cystic disease of the jaws.137 Radiographically, the involved bones show multi-
It follows an autosomal dominant pattern of inheritance locular radiolucencies with thin and expanded cortices
with 100% penetrance in males, 50% to 75% penetrance (Fig. 23-22, B). There may be premature exfoliation of
in females, and variable expressivity. A 2:1 male predom- primary teeth, as well as unerupted and displaced
inance exists. Sporadic cases have also been reported; permanent teeth. Histologically, the lesions resemble
these presumably represent spontaneous mutations. the central giant cell granuloma. However, some lesions
The genetic defect has been mapped to chromosome exhibit eosinophilic perivascular cufﬁng of collagen
4p16.3,138,139 which encodes the binding protein SH3 surrounding small capillaries throughout the lesion,
BP2.140-142 allowing for differentiation between the two lesions.
Fig. 23-22 Cherubism. A, Frontal view of a 6-year-old male with bilateral facial expansion.
B, Multilocular radiolucencies seen in the maxilla and mandible bilaterally. Note the sparing of the
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514 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
The lesions of cherubism tend to enlarge until stroma containing multinucleated giant cells. The lesion
puberty, at which time they begin to regress. In the occurs most commonly in the long bones and verte-
majority of cases, abnormal facial growth ceases and brae. Within the craniofacial complex it is most com-
the lesions recalcify by age 30. Therefore treatment is mon in the mandible, followed by the maxilla. The
usually conservative, allowing natural regression to occur. etiology and pathogenesis of the lesion remains
If surgical recontouring of expanded bone is necessary, unknown, although the lesion is generally regarded as
it is best to defer it until after puberty. During childhood reactive. Controversy remains over whether the lesion
and early adolescence treatment should be directed occurs as a primary entity or results from the
toward assisting the eruption of teeth. As a result of development of a dilated vascular bed in a preexisting
the histologic similarity to central giant cell granuloma, intrabony lesion.
calcitonin has been used in an attempt to cause The peak incidence occurs within the second decade
resolution, but unlike the central giant cell granuloma it of life, with most occurring before 30 years of age.
has not met with success, suggesting that cherubism There is a slight female predilection. Mandibular and
lesions and central giant cell granuloma lesions are, in maxillary lesions most frequently occur in the molar
fact, different.143 regions. Patients often present with facial swelling that
may develop fairly rapidly and can be associated with
pain. The lesion usually appears radiographically as a
Aneurysmal Bone Cyst
multilocular radiolucency, although it may be unilocular
The aneurysmal bone cyst is a pseudocyst charac- (Fig. 23-23, A). There may be signiﬁcant cortical expan-
terized by blood-ﬁlled spaces in a connective tissue sion and thinning (Fig. 23-23, B). Microscopically,
Fig. 23-23 Aneurysmal bone cyst. A, A radiolucent lesion seen to produce expansion of
the mandibular left angle in a 13-year-old female. B, Coronal computed tomography
demonstrating cortical expansion and thinning. C, Numerous small sinusoids surrounded
by a connective tissue stroma and scattered multinucleated giant cells.
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PA R T I I ONCOLOGY 515
sinusoidal blood-ﬁlled spaces of varying size are seen. result from spontaneous mutation. Two types of this
These spaces are not lined by endothelium but are genetic disorder exist, neuroﬁbromatosis type 1 (von
surrounded by a ﬁbrous connective tissue stroma with Recklinghausen’s disease of skin) and neuroﬁbromato-
variable numbers of multinucleated giant cells (Fig. sis type 2. Type 1 (Box 23-2) is characterized by mul-
23-23, C). Osteoid and woven bone can often be seen tiple cutaneous neuroﬁbromas and café-au-lait spots in
within the lesion. addition to several other features. Type 2 (Box 23-3) is
Although some authors feel aneurysmal bone cysts characterized by the development of bilateral vestibular
are associated with a relatively high recurrence rate, schwannomas in more than 90% of individuals with the
curettage remains the treatment of choice. At the time condition. Peripheral neuroﬁbromas occur rarely in
of surgery lesional tissue appears like a “blood-soaked neuroﬁbromatosis type 2.
sponge”; however, signiﬁcant hemorrhage is usually not Although most commonly reported in soft tissues,
encountered. neuroﬁbromas do occur in bone and have been reported
in association with the inferior alveolar nerve. Pain
or paresthesia may result from lesions of the inferior
alveolar nerve. Patients may also present with cortical
expansion. Intraosseous lesions may produce a well-
demarcated or poorly deﬁned unilocular or multilocular
The schwannoma is a slowly growing, benign neo-
plasm arising from Schwann cells of the nerve sheath
(neurilemma). As this encapsulated tumor enlarges, it BOX 23-2
pushes the involved nerve aside without enveloping it.
It most commonly occurs in the soft tissues of the head
Neurofibromatosis Type 1
and neck, as well as the flexor surfaces of the upper
A diagnosis is established when two or more of the
and lower extremities. Intraosseous lesions are rare; following findings are present:
however, the mandible is the most common site of
1. Six or more café-au-lait spots greater than 5 mm in
occurrence for central lesions and maxillary lesions diameter in prepubertal patients and greater than 15
have been reported. Lesions may occur over a wide age mm in postpubertal patients
range but are most common in young adults. Bony 2. One plexiform neurofibroma or two or more
lesions may be asymptomatic or produce expansion, neurofibromas of any type
pain, paresthesia, tooth mobility, and tooth displacement. 3. Two or more pigmented iris hamartomas (Lisch nodules)
4. Axillary or inguinal region freckling
The usual radiographical appearance is that of a 5. Optic nerve glioma
well-deﬁned, unilocular radiolucency with a thin, scle- 6. A distinctive osseous lesion such as dysplasia of the
rotic border. Histologically, this is an encapsulated greater wing of the sphenoid or pseudoarthrosis
spindle cell tumor that consists of variable amounts of 7. A first-degree relative with neurofibromatosis type 1
two types of tissue, Antoni A and Antoni B. Antoni A From National Institutes of Health Consensus Development Conference:
tissue consists of spindle cells organized in palisaded Arch Neurol 45:575-578, 1988.
whorls and waves around central acellular, eosinophilic
areas termed Verocay bodies. Antoni B tissue consists
of spindle cells randomly arranged within a loose,
myxomatous stroma. The tumor is strongly S-100 pro- BOX 23-3
tein positive. Neurofibromatosis Type 2
Intraosseous schwannomas can be treated by enucle-
ation and curettage. When the lesion arises from an A diagnosis is established when one or more of the
identiﬁable nerve such as the inferior alveolar nerve, it following findings are present:
can be excised from the nerve while preserving the 1. Bilateral cranial nerve VIII masses
integrity of the nerve. Recurrences are rare. 2. A first-degree relative with neurofibromatosis type 2 and
either a single cranial nerve VIII mass or any of the
Neuroﬁbromas arise from a mixture of cell types Meningioma
including Schwann cells and perineural ﬁbroblasts. Glioma
They may occur as solitary lesions or in association Juvenile posterior subcapsular lens opacity
with neuroﬁbromatosis. Neuroﬁbromatosis is an auto- From Consensus Development Panel: Arch Neurol 51:201-207, 1994.
somal dominant condition in which 50% of cases
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516 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
radiolucency. Adjacent soft tissue neuroﬁbromas may toms. These are benign neoplasms, the etiology of
produce cortical erosion. Solitary neuroﬁbromas and which is unknown. Most cases occur in the second
those found in association with neuroﬁbromatosis decade, with 85% to 90% occurring before 30 years of
share the same microscopic features. The tumor is com- age. A 2:1 male predilection exists.
posed of spindle-shaped cells with fusiform or wavy The osteoid osteoma is less than 2 cm in diameter,
nuclei in a delicate connective tissue matrix. It is not occurring most frequently in the femur, tibia, and pha-
encapsulated and may blend with the adjacent con- langes. Rarely it occurs in the jaws. An osteoid osteoma
nective tissues. Mast cells are characteristically scattered classically presents with nocturnal pain that is alleviated
throughout the lesion. A histological subtype known as by aspirin.
a plexiform neuroﬁbroma is highly characteristic of The osteoblastoma is greater than 2 cm in diameter,
neuroﬁbromatosis. occurring most frequently in the vertebrae and long
The normally recommended treatment of solitary bones of the extremities. The craniofacial skeleton is
lesions following biopsy is localized excision. The the site of involvement in 15% of osteoblastomas. The
lesions are often vascular, and extensive blood loss has mandible is affected more frequently than the maxilla.
been reported from surgical management of mandibular Within the jaws, the posterior tooth-bearing portion is
lesions; thus some authors have advocated mandibular the area most often involved. Clinically, it often devel-
resection. The number of neuroﬁbromas that can occur ops relatively rapidly, producing swelling and pain. In
with neuroﬁbromatosis type 1 makes complete surgical contrast to osteoid osteomas, the pain is not typically
therapy impractical. In these cases surgery is reserved nocturnal and it does not respond as well to aspirin.
for lesions that are large and symptomatic or com- Radiographically, these lesions are usually well
promise function, or both. Malignant transformation to deﬁned with a mixed radiolucent-radiopaque pattern
neurogenic sarcoma occurs in 5% to 15% of neuro- (Fig. 23-24). A thin radiolucency may be noted sur-
ﬁbromas associated with neuroﬁbromatosis. Authorities rounding a variably calciﬁed central tumor mass. A
believe that malignant transformation does not occur zone of reactive sclerosis surrounding the lesion is a
with solitary lesions. characteristic feature of the osteoid osteoma. Histologi-
cally, the osteoid osteoma and osteoblastoma are iden-
tical. Irregular trabeculae of osteoid and immature bone
OSTEOID OSTEOMA AND OSTEOBLASTOMA
are seen within a cellular ﬁbrovascular stroma. The
The osteoid osteoma and osteoblastoma share the exact osteoid trabeculae, which exhibit varying degrees of
same histological features. They are distinguished from calciﬁcation, are surrounded by prominent osteoblasts.
one another primarily by size, although there are also In some cases differentiation between osteoblastoma
differences in sites of occurrence and associated symp- and low-grade osteosarcoma may be difﬁcult.
Fig. 23-24 Osteoblastoma. Well-defined calcified mass with a radiolucent rim in the
posterior left mandible.
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PA R T I I ONCOLOGY 517
Treatment is generally conﬁned to conservative sur- carcinoma. In fact, the malignant transformation rate is
gical excision either with curettage or local excision. 50% by age 30. As a result, patients with an established
Reports have been made of some lesions regressing diagnosis of Gardner syndrome typically undergo a
after incomplete excision or biopsy.144 Recurrences prophylactic colectomy.
are rare but have been reported and may necessitate Osteomas are diagnosed and treated by local exci-
more aggressive treatment such as en bloc resection.145 sion. Recurrences are rare. Small, asymptomatic cases
Rare examples of malignant transformation have been may be followed clinically and radiographically. Patients
reported.146,147 with multiple osteomas should undergo investigation
However, due to the possible difﬁculty in differen- for Gardner syndrome.
tiating some osteoblastomas from osteosarcomas, some
of these may represent an incorrect initial diagnosis.
The chondroma is a benign tumor composed of mature
hyaline cartilage. It most commonly occurs in the bones
Osteomas are benign tumors composed of mature of the hands and feet, with rare occurrences in the
compact or cancellous bone. They are distinguished craniofacial complex. Within the maxillofacial region,
from the common palatal and mandibular tori, as well chondromas most often occur in the nasal septum
as buccal exostoses, despite identical histopathology. and anterior maxilla. They have also been reported in
Tori and buccal exostoses are thought to be of devel- the mandibular condyle, coronoid process, body, and
opmental or reactive origin and not true neoplasms. symphysis.
Osteomas may arise from the surface of bone (periosteal Chondromas typically present as painless, slowly
osteoma), or they may be located in the medullary bone progressive swelling. They usually appear before 50
(endosteal osteoma). years of age. There is no sex predilection. Radiographi-
Osteomas may arise in the paranasal sinuses, skull cally, they appear as a unilocular or multilocular radio-
bones, and facial bones including the maxilla and lucency, which may have internal foci of calciﬁcation.
mandible. They most commonly develop in young The lesions are composed of well-deﬁned lobules of
adults. Periosteal osteomas most often present as slow- mature hyaline cartilage containing small chondrocytes
growing, painless, discrete bony masses. Endosteal with regular nuclei. The microscopic distinction between
osteomas are usually asymptomatic and noted on rou- a benign chondroma and low-grade chondrosarcoma is
tine radiographs. As a result of their location, some difﬁcult. Considering the rarity with which chondromas
lesions may cause headaches, sinusitis, or ophthalmo- occur in the craniofacial complex, the difﬁculty in
logical complaints. Radiographically, osteomas appear differentiating between a chondroma and a low-grade
as well-circumscribed, sclerotic masses. Two histolog- chondrosarcoma, and the aggressive nature of chondro-
ical variants exist. One variant consists of normal- sarcomas, one should question the diagnosis of a benign
appearing, dense, compact bone with sparse marrow chondroma in the jaws.
tissue. The other form consists of lamellar trabeculae of To avoid the potential risk of undertreating a malig-
cancellous bone with ﬁbrofatty marrow. Osteoblastic nancy, some authors consider chondromas of the jaws
activity is often prominent. as potentially malignant and manage them accord-
Osteomas are usually solitary, except in cases of ingly.151,152 These authors recommend wide surgical
Gardner syndrome. This syndrome is an autosomal excision with 1-cm margins. If the lesion recurs fol-
dominant condition in which patients have intestinal lowing more conservative surgical treatment, the lesion
polyposis, multiple osteomas, ﬁbromas of the skin, should certainly be considered a low-grade chondro-
epidermal cysts, impacted permanent and supernumer- sarcoma and treated with wide surgical excision.
ary teeth, and odontomas. The genetic defect has been
mapped to 5q21 where the familial adenomatous
polyposis coli (APC) gene resides.148-150 The majority
of patients have an incomplete manifestation of the The desmoplastic ﬁbroma is a benign, locally aggressive
syndrome. Osteomas in association with Gardner syn- tumor of bone that is considered to be the osseous
drome are frequently seen at the mandibular angles, as counterpart of soft tissue ﬁbromatosis. The etiology and
well as other facial bones and long bones. Importantly, pathogenesis of this lesion remain unknown, although
the development of osteomas precedes other manifes- genetic, endocrine, and traumatic factors have been
tations of the syndrome. The most clinically important suggested.
aspect of the syndrome is the high rate of malignant The lesion usually occurs in children and young
transformation of bowel polyps into invasive adeno- adults, with most cases being discovered before 30
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518 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
years of age. It most commonly occurs in the long It is the most common primary sarcoma of bone and
bones but may occasionally affect the jaws. Within the second only to plasma cell neoplasms as the most
jaws, the posterior mandible is the area most frequently common primary tumor of bone. It can develop in
involved. Patients most often present with a painless, previously irradiated bone, as well as preexisting bone
slow-growing, ﬁrm swelling of the affected jaw. abnormalities such as Paget’s disease, ﬁbrous dysplasia,
Radiographically, the lesion produces a radiolu- and giant cell tumors. Osteosarcomas may be classiﬁed
cency, which may be unilocular or multilocular (Fig. into the more common central type, which arises from
23-25). The margins may be well deﬁned or poorly the medullary portion of the bone, and the less com-
deﬁned. Cortical perforation and root resorption may mon peripheral (juxtacortical) type, which originates on
be seen. Microscopically, the lesion is composed of the surface of the bone and initially grows outward. The
interlacing bundles and whorled aggregates of densely molecular mechanisms associated with the pathogen-
collagenous tissue with spindled and elongated ﬁbro- esis of osteosarcoma appear to be related to a variety of
blasts. The degree of cellularity may vary from one area genetic alterations resulting in inactivation of tumor-
of the lesion to another. Cellular atypia and mitotic suppressor genes and overexpression of oncogenes.158
ﬁgures are not seen. This lesion does not produce bone. In addition, cytogenetic studies have found that the
Recurrence rates following conservative surgical treat- majority of osteosarcomas are characterized by complex
ment such as curettage and local excision are high, chromosomal abnormalities, often with pronounced
while lesions treated by resection or wide excision do cell-to-cell variation and heterogeneity.158
not tend to recur.153,154 Thus despite a benign histology, Central osteosarcomas most often involve the distal
the desmoplastic ﬁbroma should be treated aggres- femur and proximal tibia of patients in their second
sively. Radiation155 and chemotherapy156,157 have been decade of life. Lesions involving the jaws account for
recommended for lesions involving vital structures and 5% to 7% of all osteosarcomas and most commonly
those located in areas where resection would be affect patients in their third and fourth decades of life,
debilitating. with a mean age of approximately 35 years. There is a
slight male predilection. The mandible is affected more
frequently than the maxilla. The most common symp-
MALIGNANT NONODONTOGENIC toms of jaw lesions are swelling and pain. Depending
TUMORS OF THE JAWS on the location of the lesion, patients may also experi-
ence paresthesia, loosening of teeth, nasal obstruction,
epistaxis, proptosis, or diplopia. Unfortunately, because
some signs and symptoms may be associated with other
Osteosarcoma is a malignant tumor characterized by the nonmalignant conditions, there is often a delay in the
direct production of osteoid by a sarcomatous stroma. diagnosis of osteosarcoma.
Fig. 23-25 Desmoplastic fibroma. A multilocular radiolucency of the posterior left
mandible in a 12-year-old male.
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PA R T I I ONCOLOGY 519
Depending on the degree of calciﬁcation, the radio- and the chondroblastic type most common in the jaws.
graphical appearance of a central osteosarcoma may The prognosis is not dependent on the histologic
vary from a dense radiopaque area to a mixed radio- subtype; however, patients with high-grade lesions
paque and radiolucent lesion to a radiolucent process have a poorer prognosis in comparison with those with
(Fig. 23-26, A). The margins are usually irregular and a low-grade lesion.
poorly deﬁned. Symmetric widening of the periodontal A telangiectatic subtype of osteosarcoma contains
ligament and extracortical bone producing a “sunburst” numerous large blood-ﬁlled spaces and prominent
appearance are radiographical features classically asso- multinucleated giant cells. In addition, there is a small
ciated with osteosarcoma, although these features are cell variant of osteosarcoma, which resembles Ewing
not unique to this condition. Cortical destruction and sarcoma; however, the small round cells produce
root resorption may also be apparent on radiographical osteoid, which does not occur in Ewing sarcoma. Rare
examination. examples of the telangiectatic and small cell variants
The histological appearance is highly variable, have been reported in the jaws.159,160
although all osteosarcomas have a sarcomatous stroma Wide surgical resection with negative margins is the
that directly produces a variable amount of tumor only treatment that conclusively leads to increased
osteoid (Fig. 23-26, B). Lesions are histologically sub- survival. A bone margin of 3 cm from the radiographical
divided into osteoblastic, chondroblastic, and ﬁbro- margin is recommended. As a result of the limited
blastic subtypes, depending on the relative amounts of numbers of patients in most studies and the lack of
osteoid, cartilage, or collagen produced by the stroma. randomized controlled trials, the role of radiation ther-
The osteoblastic type is most common in the skeleton apy and chemotherapy in osteosarcoma of the jaws
Fig. 23-26 Osteosarcoma. A, Poorly defined radiolucency
of the posterior left mandible in a 28-year-old female
complaining of pain in the area. B, Production of osteoid by
B a sarcomatous stroma.
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520 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
largely remains unproven. The vast majority of studies underlying bone may be thickened, but the medullary
indicate radiation therapy has no beneﬁcial effect on space is not involved.
survival. Although chemotherapy in combination with Histologically, the parosteal osteosarcoma is well
surgery has improved the prognosis of osteosarcoma differentiated with a bland appearance. Irregular tra-
of the long bones,161,162 the beneﬁcial effects in the jaws beculae of woven bone are seen in a spindle cell
are not as well established. Most studies have been stroma with minimal atypia and rare mitotic ﬁgures. In
unable to demonstrate a survival beneﬁt with chemo- contrast, the periosteal osteosarcoma is histopatho-
therapy,163-166 while a couple of authors report some logically a higher grade tumor that microscopically
beneﬁt to chemotherapy in combination with sur- resembles a central chondroblastic osteosarcoma. The
gery.167,168 At present, treatment protocols used in the periosteal osteosarcoma typically does not inﬁltrate
treatment of osteosarcoma of the long bones, which medullary bone, differentiating it from the central chon-
include preoperative and postoperative chemotherapy droblastic osteosarcoma that perforates the cortex and
and wide surgical resection, are commonly used to treat extends into the soft tissue.
osteosarcomas of the jaws. Knowledge of the biological behavior, treatment, and
Most reports state an overall 5-year survival rate for prognosis of peripheral osteosarcomas is limited by the
head and neck osteosarcomas of between 40% and rarity with which they occur in the jaws. On the basis
70%.164,166,169-171 The main cause of death in osteosar- of current knowledge, jaw lesions are best treated by
coma of the jaws is uncontrolled local recurrence. en bloc resection. Peripheral tumors of the long bones
Metastasis occurs in approximately 18% of cases,165 are associated with a considerably better prognosis
although rates as high as 50%172 have been reported. than intramedullary tumors. The periosteal subtype is
The lungs are the most frequent site of metastasis. thought to have both a higher recurrence rate and
Because regional lymph node metastasis is rare, neck greater metastatic potential in comparison with the
dissection is not advocated. Osteosarcomas of the jaws parosteal subtype.
generally metastasize less frequently and have a better
prognosis in comparison with lesions of the extremities.
A chondrosarcoma is a malignant tumor characterized
by the formation of cartilage, but not of bone, by the
tumor cells. It is second to osteosarcoma as the most
In contrast to the central medullary osteosarcoma, common primary sarcoma of bone; however, only 1%
which arises from the medullary surface of the bone, to 2% of chondrosarcomas occur in the head and neck
the peripheral osteosarcoma arises from the periosteal region. The maxilla is more frequently involved than
surface of the bone. The peripheral tumors have distinct the mandible. Maxillary lesions occur most often in the
clinical, histological, and radiographical features, in anterior region, and mandibular lesions occur most
addition to a different biological behavior. Peripheral often in the molar-premolar region.
lesions are further divided into parosteal and periosteal This lesion occurs over a wide age range with a peak
subtypes. Peripheral osteosarcomas are much less incidence in the third decade. There is no signiﬁcant
common than the central medullary type. Reports of gender predilection. The most common presentation is
peripheral lesions affecting the jaws are rare, with the that of a slow-growing, painless mass or swelling (Fig.
parosteal type occurring more frequently than the 23-27, A). A minority of lesions produce pain. Lesions
periosteal type. involving the alveolar bone may result in displaced and
Radiographically, the parosteal osteosarcoma appears mobile teeth. Depending on the location of the tumor,
as a radiodense mass on the cortical surface of bone. patients may also experience nasal symptoms, visual
The tumor arises from a broad pedicle and then grows disturbances, and sensory alterations.
along the cortical surface, outgrowing the base of The radiographical appearance may vary, although
origin. A radiolucent line may be seen between the most lesions demonstrate features consistent with a
tumor and the underlying cortex as a result of this malignant process. The majority of chondrosarcomas
mushroom-like pattern of growth. Daughter masses appear as an osteolytic lesion with poorly deﬁned
may be seen adjacent to the principle mass. In contrast, borders containing scattered and variable amounts of
the periosteal osteosarcoma is not as radiodense or radiopaque foci (Fig. 23-27, B, C, and D). The radiopac-
homogeneous and the periphery is not as well deﬁned ities represent calciﬁcation of the neoplastic cartilage.
as with the parosteal type. It has a spiculated appear- Some lesions develop signiﬁcant calciﬁcation and appear
ance and does not outgrow its base. The cortex of the as a densely calciﬁed mass with irregular margins. Some
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PA R T I I ONCOLOGY 521
Fig. 23-27 Chondrosarcoma. A, Expansion of the maxillary left alveolus with mucosal
ulceration laterally. B, Panoramic radiograph demonstrating a poorly defined mass causing
expansion of the posterior left maxilla. C and D, Axial and coronal magnetic resonance
images demonstrating the extent of the tumor.
tumors grow in a lobular pattern with few or no foci considered to be an osteosarcoma, regardless of the
of calciﬁcation, producing a multilocular radiolucency amount of cartilage produced.174 However, calciﬁcation
that appears more like a benign process. Similar to of the chondroid matrix does occur in chondrosarco-
osteosarcoma, some lesions produce a peripheral sun- mas. Additional histological features of a malignant
burst pattern or symmetric widening of the periodontal tumor of cartilage include hypercellularity, particularly
ligament space around involved teeth. The tumor may an increase in the number of cartilage cells with plump
extend well beyond radiographical margins.173 nuclei, binuclear or multinuclear cartilage cells, nuclear
The histological appearance of chondrosarcoma is hyperchromatism, and both cellular and nuclear pleo-
variable, although all demonstrate the formation of morphism. Mitotic ﬁgures may be scarce or absent.
cartilage, but not osteoid or bone, from a sarcomatous Chondrosarcomas have been classiﬁed into grades I, II,
stroma. If the sarcomatous stroma is seen to produce and III on the basis of mitotic rate, cellularity, and
osteoid or bone in any part of the lesion, the tumor is nuclear size.175 This grading system correlates well with
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522 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
prognosis. In the head and neck region, grade I and II cannot be made. The 5-year and 10-year survival rates
chondrosarcomas predominate. for mesenchymal chondrosarcoma are approximately
Radical ablative surgery is the treatment of choice. 50% and 28%, respectively.182,183 Reports limited to
Radiation therapy has generally not been shown to mesenchymal chondrosarcomas of the jaws suggest the
provide a signiﬁcant survival beneﬁt,173,175,176 although prognosis for jaw tumors may be better than that for
there have been occasional reports of long-term bene- extragnathic sites.184,185 Mesenchymal chondrosarcoma
ﬁts.177-180 Thus radiation therapy may be considered in has a propensity for recurrence and metastasis, with
cases of unresectable, residual, or recurrent tumors. The the lung being the most frequent site of metastasis.
vast majority of reports involving chemotherapy show Recurrences and distant metastases may take up to 20
no signiﬁcant therapeutic beneﬁt.173,175,176,181 years to manifest following treatment of the primary
The prognosis for chondrosarcomas of the jaws is tumor; therefore long-term follow-up is required.182
worse than that for extragnathic tumors. The overall
5-year survival rate for chondrosarcomas of the jaws
FIBROSARCOMA OF BONE
ranges from 32%173 to 81%.176 Factors influencing the
prognosis for chondrosarcomas of the jaws include Fibrosarcoma is a soft tissue and bone malignancy that
the site of origin, histological grade, and therapeutic rarely occurs in the head and neck region. Following
modality. Mandibular tumors have a more favorable reﬁnement of the diagnostic criteria for ﬁbrosarcoma,
prognosis than maxillary lesions. Grade III lesions have many tumors formerly classiﬁed as such are now
a higher rate of metastasis and a poorer prognosis than considered to be malignant ﬁbrous histiocytomas or
grade I and II lesions. The lung is the most common site another type of spindle cell neoplasm. Tumors that
of metastasis, while lymph node metastasis is rare; thus originate in the bone may theoretically arise from the
neck dissection is not advocated for chondrosarcomas periosteum, endosteum, or periodontal ligament.
of the jaws. The primary factor influencing the rate of Fibrosarcomas of bone occur over a wide age range
recurrence is the adequacy of the surgical resection. with a relatively uniform incidence over the second to
The most common cause of death for jaw lesions is sixth decades. No gender predilection exists. Bone
uncontrolled local recurrence and extension into adja- lesions most commonly occur in long bones, although
cent vital structures. Recurrences may occur 10 to 20 a small proportion occur in the jaws. Patients with jaw
years following surgery; thus long-term follow-up is lesions most often present with jaw expansion and
required. tooth mobility (Fig. 23-28, A). Some patients may also
experience pain or paresthesia.
Radiographically, tumors involving the jaws usually
appear as an osteolytic process with an ill-deﬁned,
Mesenchymal chondrosarcoma is a rare tumor that is irregular pattern (Fig. 23-28, B). Histopathologically,
clinically and histologically distinct in comparison with ﬁbrosarcomas of soft tissue and bone are deﬁned as
chondrosarcoma. Up to one third of cases arise in soft malignant spindle cell tumors showing a herringbone or
tissue. The maxilla and mandible are two of the more interlacing fascicular pattern and no expression of other
commonly involved bony sites. The tumor most com- connective tissue cell markers. Low-grade tumors
monly occurs between 10 and 30 years of age, with an demonstrate a herringbone pattern with rare mitoses
equal distribution between genders. Patients most often and abundant collagen. Higher-grade tumors show
present with swelling and occasionally pain. increased mitotic activity, less collagen, and loss of the
Radiographically, the lesion appears as a radiolu- herringbone pattern.
cency with well or poorly demarcated borders. Stippled Surgical resection with wide margins is the recom-
calciﬁcations may be seen within the lesion. Histologi- mended treatment for ﬁbrosarcoma of bone. The efﬁ-
cally, the tumor displays a bimorphic pattern composed cacy of neither chemotherapy nor radiation therapy
of islands of well-differentiated malignant cartilage sur- is well established. The tumor has minimal metastatic
rounded by an anaplastic small, round cell malignancy. potential. Recurrences are not uncommon and are
The cartilaginous component distinguishes mesenchy- best managed with salvage surgery. Studies that have
mal chondrosarcoma from Ewing sarcoma and heman- assessed survival for ﬁbrosarcoma of bone generally
giopericytoma, which resemble the undifferentiated include cases diagnosed before the reﬁnement of the
small cell component. diagnostic criteria; as a result, cases of malignant ﬁbrous
Surgical resection with wide margins is required to histiocytoma, which are associated with a poor prog-
obtain local control. Information regarding the use of nosis, are frequently included. Thus valid survival data
both radiation therapy and chemotherapy is limited; for ﬁbrosarcoma of the jaws is difﬁcult to obtain. One
thus meaningful conclusions regarding adjuvant therapy report involving 14 patients with ﬁbrosarcoma of the
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PA R T I I ONCOLOGY 523
nancies. The long bones, particularly the femur, are the
most frequently affected osseous sites. Lesions involv-
ing the jaws occur rarely. They may arise as a primary
tumor of bone (70%) or secondary to a preexisting
bone condition (30%) including previously irradiated
bone, Paget’s disease, or bone infarct.
The tumor occurs over a wide age range, with most
occurring older than 40 years of age. A male predilec-
tion exists. Patients most frequently present with jaw
expansion and tooth mobility. The tumor may occa-
sionally be associated with pain. Radiographically,
the tumor typically appears as an ill-deﬁned, irregular
osteolytic lesion. Irregular root resorption may be seen.
Several histological subtypes have been identiﬁed.
A Common to all subtypes is the proliferation of pleo-
morphic spindle cells, histiocyte-like cells, and varying
numbers of multinucleated giant cells. The most com-
mon subtype is the storiform-pleomorphic type, in
which bundles of spindle cells are arranged in a
storiform or pinwheel pattern. The histological subtype
does not affect the prognosis. Most malignant ﬁbrous
histiocytomas are high-grade malignancies.
This is an aggressive tumor with a propensity for
recurrence and distant metastasis, particularly to the
lungs. Wide surgical resection is recommended for
lesions of the jaws. The limited number of reported
cases of malignant ﬁbrous histiocytoma of the jaws
precludes the formulation of meaningful conclusions
regarding chemotherapy and radiation therapy. In
patients with high-grade lesions of the long bones,
chemotherapeutic regimens similar to those used in
B osteosarcoma, which involve preoperative chemother-
Fig. 23-28 Fibrosarcoma of bone. A, Erythematous apy, appear to provide a survival beneﬁt.188-190 The role
gingival lesion seen in the anterior right maxilla. B, Coronal of radiation therapy is limited to unresectable and
computed tomography image demonstrating the extent of incompletely resected tumors. The disease-free 5-year
the tumor. survival for malignant ﬁbrous histiocytoma of the long
bones with preoperative chemotherapy and surgical
resection is greater than 50%.189,190 The prognosis of
jaws found a 5-year survival rate of 71%.186 This sug- tumors affecting the jaws, however, appears to be
gests ﬁbrosarcomas of the jaws may have a better worse.
prognosis than lesions located elsewhere in the skele-
ton because the estimated overall 5-year survival rate
for ﬁbrosarcoma of bone is between 34% and 45%.187
Factors that negatively influence the prognosis include Ewing’s sarcoma is in a family of tumors including the
high-grade tumors and patients older than 40 years primitive neuroectodermal tumors, deﬁned as round
of age. cell sarcomas that show varying degrees of neuro-
ectodermal origin. These tumors are characterized by a
recurrent t(11;22)(q24;q12) chromosomal translocation,
MALIGNANT FIBROUS HISTIOCYTOMA
which is detectable in approximately 85% of cases. This
The malignant ﬁbrous histiocytoma is a malignant family of tumors accounts for 6% to 8% of primary bone
neoplasm of soft tissue and bone, which is composed malignancies, although it is second to osteosarcoma as
of ﬁbroblasts and pleomorphic cells with a prominent the most common sarcoma in bone and soft tissue in
storiform pattern. It occurs most often in soft tissues children. The bones of the lower extremity and pelvis
and represents 2% to 6% of all primary bone malig- are most commonly affected, with lesions of the jaws
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524 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
accounting for less than 3% of Ewing’s sarcomas. In the particularly to the lungs and other bones. Clinically
jaws, the posterior mandible is most frequently affected, apparent metastases are present in 15% of patients with
while maxillary lesions are rare. nonpelvic tumors at the time of diagnosis.191 Treatment
Ewing’s sarcoma primarily affects children and protocols for Ewing’s sarcoma vary; however, the
young adults, with 80% of cases occurring in patients introduction of multimodal therapy has dramatically
younger than 20 years of age. A male predilection improved the prognosis. Treatment protocols involve
exists, and black individuals are rarely affected. Pain multiagent chemotherapy with either surgical resection
and swelling are the most common presenting symp- or radiation therapy or a combination of surgery and
toms. A soft tissue mass, paresthesia, tooth mobility, radiation therapy. Surgery tends to offer slightly better
and fever may also be present (Fig. 23-29, A). local control compared with radiation therapy alone.192
Radiographically, an irregular osteolytic process In addition, the incidence of secondary sarcomas fol-
with ill-deﬁned borders is seen (Fig. 23-29, B). Tooth lowing radiation therapy in Ewing’s sarcoma patients is
displacement and root resorption may also be seen. approximately 6.5%.193 With multimodal therapy the
Histologically, Ewing’s sarcoma is composed of prolif- 5-year survival for patients presenting without metas-
eration of uniform, closely packed cells that may be tatic disease is now 60%, and for those with metastatic
compartmentalized by ﬁbrous bands. The nuclei are disease the 5-year survival is 30%.191 Patients younger
round to oval with ﬁnely dispersed chromatin (Fig. than 15 years tend to have a better prognosis than
23-29, C). The cytoplasm of the tumor cells frequently those older than 15 years of age.191 Ewing’s sarcoma of
stains with periodic acid–Schiff stain, indicating the the mandible appears to have a prognosis that is more
presence of glycogen. Necrosis is commonly seen with favorable than that for other sites of involvement.
viable cells remaining in a perivascular distribution. Additional research into the role of autologous hemato-
The tumor typically grows rapidly with extensive poietic stem cell transplantation, immunotherapy,
destruction of bone and a propensity for metastasis, and biologic modiﬁers may eventually lead to further
Fig. 23-29 Ewing’s sarcoma. A, A mass visible in the
posterior left mandible of a 4-year-old male complaining
of facial swelling and a loose tooth. B, A poorly defined
osteolytic lesion of the posterior left mandible. C, Densely
C packed cells with round nuclei.
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PA R T I I ONCOLOGY 525
improvement in the long-term survival of patients with system prophylaxis. For advanced-stage disease, sur-
Ewing’s sarcoma.192 vival rates of between 70% and 87% have been
achieved using these regimens.198,199
Burkitt’s lymphoma is a high-grade, non-Hodgkin’s
B-cell lymphoma that occurs in several clinical forms. Multiple myeloma is a monoclonal, malignant, neo-
Dennis Burkitt originally described it in 1958 as a jaw plastic proliferation of plasma cells with multicentric
tumor that occurred frequently in African children.194 bone marrow involvement. Extraskeletal sites may
It was later identiﬁed to be a form of malignant occasionally be involved. It accounts for 1% of all
lymphoma.195 Burkitt’s lymphoma has subsequently malignancies in whites and 2% of those in blacks. It is
been recognized to occur sporadically outside of Africa. the most frequently occurring primary malignancy of
The endemic (African) and sporadic (American) forms bone. The bones most frequently involved are the
of Burkitt’s lymphoma are characterized by the activa- vertebrae, ribs, skull, pelvis, femur, clavicle, and scapu-
tion of the c-myc oncogene through reciprocal chromo- la. The mandible and maxilla may also be involved. The
somal translocations, most commonly t(8:14).196 The median age at diagnosis is 68 years with 90% of cases
endemic form is associated with Epstein-Barr virus occurring in individuals older than 40 years of age. A
(EBV) in more than 95% of cases, whereas the sporadic male predilection exists.
form is mostly EBV negative. A third type of Burkitt’s The signs and symptoms characteristic of multiple
lymphoma is associated with human immunodeﬁciency myeloma result from the uncontrolled proliferation of
virus infection in adults. malignant plasma cells within the bone marrow and the
The endemic form has a peak incidence between 3 uncontrolled manufacture of their protein products.
and 8 years of age. Jaw involvement is common and These signs and symptoms include bone pain, patho-
related to age, with almost 90% of patients younger logical fracture, hypercalcemia, anemia, renal failure,
than 3 years of age and 25% of those older than 15 and recurrent bacterial infections. Because these tumors
years of age having jaw lesions. The maxilla is involved are derived from a single neoplastic clone, they are
more frequently than the mandible, although all four associated with the production of monoclonal immuno-
quadrants may be involved. In contrast, the sporadic globulin components. This is demonstrated on serum
form occurs in a slightly older age-group with a peak protein electrophoresis as an abnormal monoclonal
incidence between 10 and 12 years of age; the jaws are immunoglobulin protein spike, called the M compo-
involved in just 16% of cases at the time of diagnosis; nent. The immunoglobulin is most frequently of the IgG
the lesions are more localized, most commonly involv- or IgA class, with the light chain restricted to either the
ing one quadrant; and the mandible is affected more lambda or kappa type. Monoclonal light chain (Bence-
frequently than the maxilla.197 Jaw lesions of Burkitt’s Jones protein) is found in the urine of approximately
lymphoma can progress rapidly, appearing as a facial 50% of patients. Bence-Jones protein is directly toxic
swelling or exophytic mass. These tumors may be to renal epithelial cells and is a major contributing
associated with mobility of teeth, pain, and paresthesia. factor in the development of renal failure in multiple
Radiographically, an osteolytic process with ragged, myeloma. In up to 25% of patients the light chain
ill-deﬁned margins is seen. Histologically, Burkitt’s lym- protein also accumulates in soft tissues, resulting in the
phoma represents an undifferentiated small, noncleaved development of amyloidosis, which may manifest in the
B-cell lymphoma. The tumor is composed of sheets of maxillofacial region as macroglossia. Approximately 1%
medium-sized B cells with round nuclei and multiple of multiple myeloma patients do not have an identi-
nucleoli. Interspersed throughout the tumor cells are ﬁable M component in the serum or urine. This form of
macrophages that stain less intensely than the hyper- the disease is termed nonsecretory myeloma.
chromatic neoplastic B cells, resulting in a “starry sky” The typical radiographical appearance is that of mul-
appearance. Mitoses are numerous; in fact, this tumor is tiple well-deﬁned, punched-out radiolucencies of bone,
known to have the highest proliferation rate of any which are noncorticated. These may be particularly
neoplasm in humans. evident on views of the skull. Rather than having focal
This aggressive malignancy, if untreated, results in osteolytic lesions of bone, generalized osteoporosis or,
death within 4 to 6 months of diagnosis. Intensive more infrequently, osteosclerotic lesions may be seen
chemotherapy has resulted in a dramatic improvement in some patients. Bone lesions in multiple myeloma
in the prognosis of Burkitt’s lymphoma. Current treat- usually are not evident on a bone scan. Histologically,
ment involves intensive, short-term, multi-agent chemo- the lesional tissue is composed of monotonous sheets
therapy including intrathecal drugs for central nervous of neoplastic, variably differentiated plasma cells. With
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526 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
the use of immunohistochemistry, the monoclonal and treat any dental pathology before initiation of
nature of the intracytoplasmic immunoglobulin light bisphosphonate therapy. With patients on pamidronate
chain can be demonstrated. This may be used to differ- or zoledronate, invasive dental procedures should be
entiate multiple myeloma from reactive plasma cell avoided when possible.
inﬁltrates, which are uniformly polyclonal.
The treatment of multiple myeloma involves systemic
SOLITARY PLASMACYTOMA OF BONE
chemotherapy to control the progression of the disease
and supportive care to prevent serious morbidity from A solitary plasmacytoma is a unifocal, monoclonal,
the complications of the disease. High-dose chemother- neoplastic proliferation of plasma cells that most often
apy with autologous stem cell transplantation has occurs within bone but may occasionally be found in
signiﬁcantly improved complete remission rates, event- soft tissue. To establish the diagnosis, a complete radio-
free survival, and overall survival as compared with logical skeletal survey and a bone marrow biopsy away
conventional chemotherapeutic regimens.200 Improve- from the solitary lesion must demonstrate no evidence
ments in the management of multiple myeloma have of plasmacytosis in other areas. The lesion occurs at
resulted in complete remission rates of 20% to 59% a mean age of 50 years with a male predilection.
and median overall survival of 4.4 to 7.1 years, with Although rarely found in the jaws, the mandible is
a substantial proportion of patients surviving more affected more commonly than the maxilla. Presenting
than 10 years.201 Despite improvements in survival, at signs and symptoms include pain, swelling, and patho-
present there is no cure and patients eventually relapse. logical fracture.
Death is most commonly a result of infection, renal Radiographically, the lesion appears as a well-deﬁned
failure, or progressive myeloma. Recent research has radiolucency without sclerotic borders. The histological
led to the development of biological treatments such appearance is identical to that of multiple myeloma. An
as thalidomide, thalidomide analogs, and proteasome abnormal monoclonal immunoglobulin protein spike
inhibitors, which target the myeloma cell and the bone (M component) may be demonstrated in the serum or
marrow microenvironment.201,202 These agents have urine in up to 25% of cases of solitary plasmacytoma.
shown promise in the management of relapsed or Radiation therapy using 3500 cGy to 4500 cGy is
refractory patients with multiple myeloma by over- the treatment of choice for solitary plasmacytomas.
coming resistance to conventional chemotherapy, yet Unfortunately, approximately 70% of patients with soli-
they do not have the potential to cure. In addition to tary lesions develop multiple myeloma; however, it is
chemotherapy, localized radiation therapy may be used not possible to predict which ones will do so. The
to treat painful bone lesions. overall mean survival of patients diagnosed with a
Bisphosphonates, which inhibit osteoclastic resorp- solitary plasmacytoma is 10 years.
tion of bone and may also have direct antitumor effects,
are routinely used in the management of multiple
MALIGNANT PERIPHERAL NERVE SHEATH
myeloma. Bisphosphonates have proven to be beneﬁ-
cial in preventing pathological vertebral fractures,
hypercalcemia, and ameliorating bone pain.54 A sig-
niﬁcant maxillofacial complication related to bisphos- The malignant peripheral nerve sheath tumor (MPNST)
phonate therapy has recently been recognized. The use is a rare malignancy that may develop within a pre-
of intravenous pamidronate and zoledronate has been existing neuroﬁbroma, de novo, or as a postradiation
associated with the development of osteonecrosis of the sarcoma. Fifty-two percent of cases develop in patients
jaws.203,204 Deﬁnitive management of this complication with neuroﬁbromatosis type 1.205 The Schwann cell
has proven difﬁcult. Débridement cannot be carried and possibly other nerve sheath cells are believed to be
out to viable bleeding bone and may cause further the cell of origin. The lesion occurs most frequently
exposure of bone as a result of the systemic effect of in the soft tissues of the extremities and trunk, with
the bisphosphonate therapy. Furthermore, the effective- intraosseous lesions occurring rarely. The most com-
ness of hyperbaric oxygen therapy has been limited and mon site for intraosseous lesions is the mandible, where
discontinuation of bisphosphonate therapy has not 55% of reported intraosseous lesions have occurred. In
proven beneﬁcial. Palliative treatment limited to inter- contrast to soft tissue MPNSTs, intraosseous lesions are
mittent courses of antibiotics, chlorhexidine mouth rinses, infrequently associated with neuroﬁbromatosis type 1.
wound irrigation, and if necessary minor débridement Intraosseous tumors have been reported in patients
of superﬁcial bony sequestrae is most appropriate. To ranging in age from 4 to 76 years of age with no sex
reduce the risk of developing osteonecrosis, patients predilection. The tumor frequently produces paresthe-
should have a thorough dental evaluation to identify sia or anesthesia in the regional nerve distribution.
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PA R T I I ONCOLOGY 527
Within the jaws it may also produce bony expansion encouraging results.210 If the tissues in the site of the
and tooth mobility. radiation-induced sarcoma have not previously been
Radiographically, tumors of the mandible may pro- treated to tissue tolerance, radiation therapy may be
duce widening of the inferior alveolar canal or the considered, but its role is limited. The 5-year survival
mental foramen or a diffuse, irregular radiolucency. rate is approximately 30%.208,209,211,212
Microscopically, the lesion consists of fascicles of spin-
dle cells that closely resemble the cells of ﬁbrosarcoma.
The nuclei may be wavy or comma shaped, and nuclear
pleomorphism may be prominent. Streaming and pal- Metastatic carcinoma is the most common form of
isading of nuclei are often seen. Less cellular myxoid malignancy affecting bone. Bones with active marrow
areas may also be present. Heterologous elements such such as the vertebrae, ribs, pelvis, and skull are the
as skeletal muscle, cartilage, or bone may be seen. The preferential sites for metastasis. The jaws are relatively
malignant Triton tumor is a highly aggressive variant uncommon sites of metastasis. Approximately 1% of
that shows rhabdomyoblastic differentiation. Deter- all oral malignancies represent malignancies that have
mining that the tumor arises from a nerve trunk or a metastasized from elsewhere in the body.213 However,
neuroﬁbroma aids in the differentiation between the incidence of metastasis to the jaws may be under-
MPNST and ﬁbrosarcoma. In addition, MPNSTs are estimated. A report involving autopsied carcinoma
S-100 protein positive in 50% of cases. cases demonstrated 16% of the mandibles to have
The treatment of choice for intraosseous MPNSTs microscopic deposits of metastatic tumor cells, despite
is surgical resection with wide margins. Due to the the lack of radiographical evidence of metastatic
rarity of intraosseous tumors, the role of radiation and deposits in these mandibles.214 The most common sites
chemotherapy remains undetermined, although neither of the primary carcinoma are the breast and lung,
has been found to provide a survival beneﬁt in soft followed by the kidney, prostate, thyroid, colon, and
tissue tumors.205 Recurrence is common, and metastasis rectum. Metastatic spread of carcinoma to the jaws
occurs via the hematogenous route. Survival data for occurs by the hematogenous route. Emboli of primary
intraosseous tumors is limited; however, the 5-year carcinomas distant from the jaws may enter the venous
survival rate for soft tissue tumors in patients without circulation and bypass the lungs via the valveless
neuroﬁbromatosis is 53%, compared with 16% for those paravertebral venous plexus of Batson to deposit into
with neuroﬁbromatosis.205 the jaws.215 In patients with metastatic lesions in the
jaws, the jaw lesions are the ﬁrst indication of a malig-
nancy in 30% of cases.216
POSTRADIATION SARCOMA OF BONE
The majority of patients with metastatic carcinoma to
Postradiation sarcoma of bone, a sarcoma that develops the jaws are in their ﬁfth to seventh decades, with a
in a bone within a previous irradiated ﬁeld, is a rare mean age of 45 years. Within the jaws, approximately
tumor. Radiation-induced sarcomas occur more fre- 80% of the metastases are to the mandible, 14% to the
quently in soft tissues than in bone. Postradiation maxilla, and 5% to both jaws.216 The molar/premolar
sarcoma of bone is estimated to occur in 0.02% of region is the area within both the mandible and the
irradiated patients. Postradiation sarcomas develop a maxilla most frequently affected. Swelling, pain, and
mean of 14 years following the initial radiation therapy. paresthesia are the most common presenting symp-
Although there are reports of cases developing with less toms. Tooth mobility, trismus, and pathological fracture
than 1-year latency, authors have proposed a minimum may also be clinically evident.
latency period that ranges between 3 and 5 years to Radiographically, a metastatic lesion in the jaws
make a diagnosis of postradiation sarcoma.206,207 The usually appears as an irregular radiolucency (Fig 23-30).
risk of development of postradiation sarcoma is related However, metastatic prostate and breast lesions are
to the dose of radiation received. The most common often characterized by an osteoblastic process, resulting
types of sarcomas that occur in a previously irradiated in either a radiopaque lesion or a mixed radiopaque-
ﬁeld are osteosarcoma, malignant ﬁbrous histiocytoma, radiolucent lesion. The histological appearance of
and ﬁbrosarcoma. These tumors have clinical, radio- metastatic carcinoma is highly variable depending on
graphical, and histological features that are similar to the tumor type and the degree of differentiation. Some
their de novo counterparts. However, postradiation tumors may be sufﬁciently well differentiated and
sarcomas tend to behave more aggressively and are less distinctive enough to provide a strong indication of the
responsive to treatment. primary site. This most frequently occurs with renal cell
Wide surgical resection provides the best chance for carcinomas and thyroid tumors. However, metastatic
cure.208,209 Adjuvant chemotherapy has not provided carcinomas are more frequently poorly differentiated
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528 CHAPTER 23 C L I N I C A L PAT H O L O G Y: O D O N T O G E N I C A N D N O N O D O N T O G E N I C T U M O R S O F T H E J AW S
biopsy should precede three-dimensional imaging
or not. If the biopsy is taken ﬁrst, it may cause
artifact on the three-dimensional imaging. If the
imaging is done ﬁrst, it may prove to have been
unnecessary or inadequate once the diagnosis is
• Treatment of ameloblastoma should not vary on
the basis of histological subtype. The histological
subtype can easily be misdiagnosed because of
sampling. Furthermore, the data regarding clinical
behavior and histologic subtype are equivocal.
• Follow-up for aggressive odontogenic tumors
(including ameloblastoma, odontogenic myxoma,
and calcifying epithelial odontogenic tumor) should
be at least 20 years and possibly for life.
Fig. 23-30 Metastatic breast cancer. An irregular radio-
lucency of the mandibular right body.
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