Clinical Pathology Odontogenic and Nonodontogenic Tumors of the Jaws

Document Sample
Clinical Pathology Odontogenic and Nonodontogenic Tumors of the Jaws Powered By Docstoc
					Ch23-F10053.qxd   5/15/06   6:00 PM   Page 490

           C H A P T E R                         23
           Clinical Pathology:
           Odontogenic and
           Nonodontogenic Tumors
           of the Jaws


           KEY POINTS
           • 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
Ch23-F10053.qxd   5/15/06    6:00 PM    Page 491

          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

             BOX 23-1
             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:                                                       Hyperparathyroidism
                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
                Cementoblastoma                                           Chondroma
                Odontogenic myxoma                                        Desmoplastic fibroma
                Cementifying fibroma                                    Malignant:
             Malignant:                                                   Osteosarcoma
                Ameloblastic fibrosarcoma                                 Peripheral osteosarcoma
                                                                          Mesenchymal chondrosarcoma
             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
                   Ossifying fibroma
                   Juvenile ossifying fibroma
Ch23-F10053.qxd   5/15/06   6:00 PM    Page 492

          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,
                                                                                     Solid Ameloblastomas
          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-
Ch23-F10053.qxd       5/15/06   6:00 PM   Page 493

          PA R T I I      ONCOLOGY                                                                                                  493



                      C                                                     D
                                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
Ch23-F10053.qxd   5/15/06       6:00 PM   Page 494

          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
          Cystic Ameloblastomas
                                                                                        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,
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 495

          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
Ch23-F10053.qxd     5/15/06   6:00 PM   Page 496

          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

                A                                                                 B

                                                                                      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
Ch23-F10053.qxd   5/15/06   6:00 PM    Page 497

          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
Ch23-F10053.qxd   5/15/06   6:00 PM    Page 498

          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

                  A                                                               B

                                                                                      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.
Ch23-F10053.qxd       5/15/06   6:00 PM   Page 499

          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).
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 500

          500                  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

          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
                                                                                    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
          Malignant Ameloblastoma
                                                                                    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
                                                                                    ODONTOGENIC CARCINOMA68,69
                                                                                    This is a central lesion occurring most often in the
          Ameloblastic Carcinoma
                                                                                    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.
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 501

          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.
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 502

          502                  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

                                                                                    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
                                                                                    unerupted teeth.
                                                                                        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%.
          sutured specimen.

                                                                                    CEMENTIFYING FIBROMA
          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
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 503

          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
                                                                      MALIGNANT MESENCHYMAL
          classified as benign fibro-osseous lesions. Although
                                                                      ODONTOGENIC TUMORS
          histologically similar, differences have been found on
          immunohistochemical staining because ossifying fibromas
                                                                      AMELOBLASTIC FIBROSARCOMA
          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
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 504

          504                  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. 23-13 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
Ch23-F10053.qxd       5/15/06   6:00 PM   Page 505

          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
                                                                               AMELOBLASTIC FIBROMA
          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.

                  A                                                        B
                                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).
Ch23-F10053.qxd   5/15/06   6:00 PM   Page 506

          506                  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. 23-15 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
                                                                                    been reported.104,105
          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
Ch23-F10053.qxd       5/15/06   6:01 PM   Page 507

          PA R T I I     ONCOLOGY                                                                                           507



                  D                                                         C
                                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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 508

          508                  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. 23-17 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
Ch23-F10053.qxd   5/15/06     6:01 PM     Page 509

          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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 510

          510                  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. 23-19 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
                                                                                    GIANT CELLS
          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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 511

          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
                                                                         (Fig. 23-20).
          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.
Ch23-F10053.qxd   5/15/06   6:01 PM    Page 512

          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.
Ch23-F10053.qxd   5/15/06   6:01 PM    Page 513

          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.

          A                                                B
                       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
                       mandibular condyles.
Ch23-F10053.qxd   5/15/06   6:01 PM    Page 514

          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,


                  B                                                                C
                            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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 515

          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-
          Schwannoma (Neurilemmoma)
                                                                       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
                                                                            following findings:
          Neurofibroma                                                      Schwannoma
             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
Ch23-F10053.qxd   5/15/06   6:01 PM    Page 516

          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
                                                                                     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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 517

          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
                                                                      DESMOPLASTIC FIBROMA
          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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 518

          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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 519

          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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 520

          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
Ch23-F10053.qxd       5/15/06   6:01 PM   Page 521

          PA R T I I     ONCOLOGY                                                                                                 521



                  C                                                     D
                           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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 522

          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
Ch23-F10053.qxd   5/15/06   6:01 PM     Page 523

          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
                                                                           EWING’S SARCOMA
          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,
                                                                           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
Ch23-F10053.qxd     5/15/06   6:01 PM   Page 524

          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

                A                                                                     B

                                                                                    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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 525

          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
                                                                       MULTIPLE MYELOMA
          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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 526

          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-
                                                                                    TUMOR (NEUROFIBROSARCOMA,
          cial in preventing pathological vertebral fractures,
                                                                                    MALIGNANT SCHWANNOMA)
          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.
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 527

          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.
                                                                       METASTATIC CARCINOMA
          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
                                                                          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
Ch23-F10053.qxd   5/15/06   6:01 PM   Page 528

          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.

          and provide little clue as to the site of the primary                       1. Wakoh M, Harada T, Inoue T: Follicular/desmoplastic
          lesion. In such cases, immunohistochemistry can aid                            hybrid ameloblastoma with radiographic features of
          in determining the site of the primary carcinoma.                              concomitant fibro-osseous and solitary cystic lesions,
          Immunoperoxidase stain for cytokeratin will verify the                         Oral Surg Oral Med Oral Pathol Oral Radiol Endod
          presence of cells of epithelial origin in all carcinomas,                      94(6):774-780, 2002.
          and tissue-specific markers may be used to further                           2. Ide F, Sakashita H, Kusama K: Ameloblastomatoid,
          characterize the tumor. However, the final diagnosis                            central odontogenic fibroma: an epithelium-rich variant,
          depends on a complete medical history, physical exami-                         J Oral Pathol Med 31(10):612-614, 2002.
                                                                                      3. Garcia-Pola Vallejo M, Gonzalez Garcia M, Lopez-Arranz
          nation, and appropriate investigations.
                                                                                         JS et al: Adenomatoid odontogenic tumor arising in a
              Management of metastatic carcinoma to the jaws                             dental cyst: report of unusual case, J Clin Pediatr Dent
          begins with identification of the primary site and deter-                       23(1):55-58, 1998.
          mining the extent of metastatic involvement. Jaw metas-                     4. Hisatomi M, Asaumi J, Konouchi H et al: A case of
          tases are usually evidence of widely disseminated                              glandular odontogenic cyst associated with ameloblas-
          disease, and palliative treatment should be aimed at                           toma: correlation of diagnostic imaging with histopatho-
          eliminating pain and preserving function. Depending                            logical features, Dentomaxillofac Radiol 29(4):249-253,
          on the type of carcinoma, its responsiveness to treat-                         2000.
          ment, and the overall health status of the patient,                         5. Braunshtein E, Vered M, Taicher S et al: Clear cell
          palliation may involve surgical excision of the metasta-                       odontogenic carcinoma and clear cell ameloblastoma: a
          tic deposit, radiation therapy, chemotherapy, or chemo-                        single clinicopathologic entity? A new case and com-
                                                                                         parative analysis of the literature, J Oral Maxillofac Surg
          radiotherapy. If the metastatic lesion of the jaw
                                                                                         61(9):1004-1010, 2003.
          represents the only site of metastasis, adequate surgical                   6. Hirshberg A, Kaplan I, Buchner A: Calcifying odonto-
          treatment or chemoradiotherapy may improve the                                 genic cyst associated with odontoma: a possible separate
          prognosis. Overall, the prognosis of metastatic carci-                         entity (odontocalcifying odontogenic cyst), J Oral
          noma of the jaws is poor, with a mean survival of 6 to                         Maxillofac Surg 52(6):555-558, 1994.
          7 months.213,216                                                            7. Aithal D, Reddy BS, Mahajan S et al: Ameloblastomatous
                                                                                         calcifying odontogenic cyst: a rare histologic variant,
           PITFALLS                                                                      J Oral Pathol Med 32(6):376-378, 2003.
                                                                                      8. Mosqueda-Taylor A, Carlos-Bregni R, Ramirez-Amador V
           • The oral and maxillofacial pathologist should also                          et al: Odontoameloblastoma. Clinico-pathologic study of
             be given a representative and large enough biopsy                           three cases and critical review of the literature, Oral
             specimen. Diagnosis is often made by pattern                                Oncol 38(8):800-805, 2002.
             recognition of the lesion, and the margins may not                       9. Zeitoun IM, Dhanrajani PJ, Mosadomi HA: Adenomatoid
             be important for diagnosis.                                                 odontogenic tumor arising in a calcifying odontogenic
           • For a lesion of the jaws, there may be debate                               cyst, J Oral Maxillofac Surg 54(5):634-637, 1996.
             regarding the order of investigations as to whether                     10. Piattelli A, Scarano A, Piattelli M: Calcifying odontogenic
                                                                                         cyst associated with compound odontoma: a study on
Ch23-F10053.qxd     5/15/06    6:01 PM     Page 529

          PA R T I I    ONCOLOGY                                                                                                        529

                 undemineralized material, Bull Group Int Rech Sci             30. Pogrel MA: The use of liquid nitrogen in the manage-
                 Stomatol Odontol 38(3-4):105-109, 1995.                           ment of locally aggressive bone lesions, J Oral Maxillofac
           11.   Snead ML, Luo W, Hsu DD et al: Human ameloblastoma                Surg 51:269, 1993.
                 tumors express the amelogenin gene, Oral Surg Oral            31. Pogrel MA: The management of lesions of the jaws with
                 Med Oral Pathol 74(1):64-72, 1992.                                liquid nitrogen cryotherapy, J Calif Dent Assoc 23(12):54-
           12.   Kumamoto H, Yoshida M, Ooya K: Immunohistochemi-                  57, 1995.
                 cal detection of amelogenin and cytokeratin 19 in epithe-     32. Salmassy DA, Pogrel MA: Liquid nitrogen cryosurgery
                 lial odontogenic tumors, Oral Dis 7(3):171-176, 2001.             and immediate bone grafting in the management of
           13.   Hazelbag HM, Laforga JB, Roels HJ et al: Dedifferentiated         aggressive primary jaw lesions, J Oral Maxillofac Surg
                 adamantinoma with revertant mesenchymal phenotype,                53(7):784-790, 1995.
                 Am J Surg Pathol 27(12):1530-1537, 2003.                      33. Sampson DE, Pogrel MA: Management of mandibular
           14.   Qureshi AA, Shott S, Mallin BA et al: Current trends in the       ameloblastoma: the clinical basis for a treatment
                 management of adamantinoma of long bones. An interna-             algorithm, J Oral Maxillofac Surg 57(9):1074-1077;
                 tional study, J Bone Joint Surg Am 82-A(8):1122-1131, 2000.       discussion 1078-1079, 1999.
           15.   Van Effenterre R, Boch AL: Craniopharyngioma in adults        34. Robinson L, Martinez MG: Unicystic ameloblastoma: a
                 and children: a study of 122 surgical cases, J Neurosurg          prognostically distinct entity, Cancer 40(5):2278-2285,
                 97(1):3-11, 2002.                                                 1977.
           16.   Regezi J, Sceulba JJ, Jordon RCK: Clinical pathologic         35. Philipsen HP, Reichart PA: Unicystic ameloblastoma. A
                 correlations, ed 4, Philadelphia, 2003, Saunders.                 review of 193 cases from the literature, Oral Oncol
           17.   Henderson JM, Sonnet JR, Schlesinger C et al: Pulmonary           34(5):317-325, 1998.
                 metastasis of ameloblastoma: case report and review of        36. Eversole LR, Leider AS, Strub D: Radiographic charac-
                 the literature, Oral Surg Oral Med Oral Pathol Oral               teristics of cystogenic ameloblastoma, Oral Surg Oral
                 Radiol Endod 88(2):170-176, 1999.                                 Med Oral Pathol 57(5):572-577, 1984.
           18.   Campbell D, Jeffrey RR, Wallis F et al: Metastatic pul-       37. Junquera L, Ascani G, Vicente JC et al: Ameloblastoma
                 monary ameloblastoma. An unusual case, Br J Oral                  revisited, Ann Otol Rhinol Laryngol 112(12):1034-1039,
                 Maxillofac Surg 41(3):194-196, 2003.                              2003.
           19.   Reichart PA, Philipsen HP, Sonner S: Ameloblastoma:           38. Ackermann GL, Altini M, Shear M: The unicystic
                 biological profile of 3677 cases, Eur J Cancer B Oral              ameloblastoma: a clinicopathological study of 57 cases,
                 Oncol 31B(2):86-99, 1995.                                         J Oral Pathol 17(9-10):541-546, 1988.
           20.   Daley TD, Wysocki GP, Pringle GA: Relative incidence of       39. Rosenstein T, Pogrel MA, Smith RA et al: Cystic
                 odontogenic tumors and oral and jaw cysts in a Canadian           ameloblastoma—behavior and treatment of 21 cases,
                 population, Oral Surg Oral Med Oral Pathol 77(3):276-             J Oral Maxillofac Surg 59(11):1311-1316; discussion
                 280, 1994.                                                        1316-1318, 2001.
           21.   Arotiba JT, Ogunbiyi JO, Obiechina AE: Odontogenic            40. Philipsen HP, Reichart PA, Nikai H et al: Peripheral
                 tumours: a 15-year review from Ibadan, Nigeria, Br J              ameloblastoma: biological profile based on 160 cases
                 Oral Maxillofac Surg 35(5):363-367, 1997.                         from the literature, Oral Oncol 37(1):17-27, 2001.
           22.   Fregnani ER, Fillipi RZ, Oliveira CR et al: Odontomas and     41. Gardner DG: Peripheral ameloblastoma: a study of 21
                 ameloblastomas: variable prevalences around the world?            cases, including 5 reported as basal cell carcinoma of the
                 Oral Oncol 38(8):807-808, 2002.                                   gingiva, Cancer 39(4):1625-1633, 1977.
           23.   Larsson A, Almeren H: Ameloblastoma of the jaws. An           42. Pindborg J: Calcifying epithelial odontogenic tumor, Acta
                 analysis of a consecutive series of all cases reported to         Pathol Microbiol Scand [suppl] 111:71, 1955.
                 the Swedish Cancer Registry during 1958-1971, Acta            43. Kaplan I, Buchner A, Calderon S et al: Radiological
                 Pathol Microbiol Scand [A] 86A(5):337-349, 1978.                  and clinical features of calcifying epithelial odonto-
           24.   Sehdev MK, Huvos AG, Strong EW et al: Proceedings:                genic tumour, Dentomaxillofac Radiol 30(1):22-28,
                 ameloblastoma of maxilla and mandible, Cancer                     2001.
                 33(2):324-333, 1974.                                          44. Aviel-Ronen S, Liokumovich P, Rahima D et al: The
           25.   Shatkin S, Hoffmeister FS: Ameloblastoma: a rational              amyloid deposit in calcifying epithelial odontogenic
                 approach to therapy, Oral Surg Oral Med Oral Pathol               tumor is immunoreactive for cytokeratins, Arch Pathol
                 20(4):421-435, 1965.                                              Lab Med 124(6):872-876, 2000.
           26.   Waldron CA: Ameloblastoma in perspective, J Oral Surg         45. Veness MJ, Morgan G, Collins AP et al: Calcifying
                 24(4):331-333, 1966.                                              epithelial odontogenic (Pindborg) tumor with malignant
           27.   Mehlisch DR, Dahlin DC, Masson JK: Ameloblastoma: a               transformation and metastatic spread, Head Neck
                 clinicopathologic report, J Oral Surg 30(1):9-22, 1972.           23(8):692-696, 2001.
           28.   Gardner DG, Pecak AM: The treatment of ameloblastoma          46. Anavi Y, Kaplan I, Citir M et al: Clear-cell variant of
                 based on pathologic and anatomic principles, Cancer               calcifying epithelial odontogenic tumor: clinical and
                 46(11):2514-2519, 1980.                                           radiographic characteristics, Oral Surg Oral Med Oral
           29.   Kuriakose MA, Lee JJ, DeLacure MD: Inferior alveolar              Pathol Oral Radiol Endod 95(3):332-339, 2003.
                 nerve-preserving mandibulectomy for nonmalignant              47. Abiko Y, Murata M, Ito Y et al: Immunohistochemical
                 lesions, Laryngoscope 113(7):1269-1273, 2003.                     localization of amelogenin in human odontogenic
Ch23-F10053.qxd     5/15/06    6:01 PM     Page 530

          530                      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

                 tumors, using a polyclonal antibody against bovine                       66. Benton DC, Eisenberg E: Clear cell odontogenic carci-
                 amelogenin, Med Electron Microsc 34(3):185-189, 2001.                        noma: report of a case, J Oral Maxillofac Surg 59(1):83-
           48.   Philipsen HP, Reichart PA: Adenomatoid odontogenic                           88, 2001.
                 tumour: facts and figures, Oral Oncol 35(2):125-131,                      67. Brinck U, Gunawan B, Schulten HJ et al: Clear-cell
                 1999.                                                                        odontogenic carcinoma with pulmonary metastases
           49.   Philipsen HP, Srisuwan T, Reichart PA: Adenomatoid                           resembling pulmonary meningothelial-like nodules,
                 odontogenic tumor mimicking a periapical (radicular)                         Virchows Arch 438(4):412-417, 2001.
                 cyst: a case report, Oral Surg Oral Med Oral Pathol Oral                 68. Thomas G, Pandey M, Mathew A et al: Primary
                 Radiol Endod 94(2):246-248, 2002.                                            intraosseous carcinoma of the jaw: pooled analysis of
           50.   Konouchi H, Asaumi J, Yanagi Y et al: Adenomatoid                            world literature and report of two new cases, Int J Oral
                 odontogenic tumor: correlation of MRI with histopatho-                       Maxillofac Surg 30(4):349-355, 2001.
                 logical findings, Eur J Radiol 44(1):19-23, 2002.                         69. Thomas G, Sreelatha KT, Balan A et al: Primary
           51.   Pullon PA, Shafer WG, Elzay RP et al: Squamous odon-                         intraosseous carcinoma of the mandible—a case report
                 togenic tumor. Report of six cases of a previously                           and review of the literature, Eur J Surg Oncol 26(1):82-
                 undescribed lesion, Oral Surg Oral Med Oral Pathol                           86, 2000.
                 40(5):616-630, 1975.                                                     70. Ide F, Shimoyama T, Horie N et al: Primary intraosseous
           52.   Haghighat K, Kalmar JR, Mariotti AJ: Squamous                                carcinoma of the mandible with probable origin from
                 odontogenic tumor: diagnosis and management,                                 reduced enamel epithelium, J Oral Pathol Med 28(9):420-
                 J Periodontol 73(6):653-656, 2002.                                           422, 1999.
           53.   Kusama K, Kawashima A, Nagai H et al: Squamous                           71. Shimoyama T, Ide F, Horie N et al: Primary intraosseous
                 odontogenic tumor of the maxilla: report of a case,                          carcinoma associated with impacted third molar of the
                 J Oral Sci 40(3):119-122, 1998.                                              mandible: review of the literature and report of a new
           54.   Barrios TJ, Sudol JC, Cleveland DB: Squamous odonto-                         case, J Oral Sci 43(4):287-292, 2001.
                 genic tumor associated with an erupting maxillary                        72. Ide F, Shimoyama T, Horie N et al: Intraosseous
                 canine: case report, J Oral Maxillofac Surg 62(6):742-744,                   squamous cell carcinoma arising in association with a
                 2004.                                                                        squamous odontogenic tumour of the mandible, Oral
           55.   Eversole LR: Malignant epithelial odontogenic tumors,                        Oncol 35(4):431-434, 1999.
                 Semin Diagn Pathol 16(4):317-324, 1999.                                  73. Hamakawa H, Kayahara H, Sumida T et al: Mandibular
           56.   Zwahlen RA, Vogt P, Fischer FS et al: Case report:                           intraosseous carcinoma coexisting with ameloblastoma,
                 myocardial metastasis of a maxillary malignant amelo-                        J Oral Maxillofac Surg 58(4):430-433, 2000.
                 blastoma, J Oral Maxillofac Surg 61(6):731-744, 2003.                    74. Murillo-Cortes J, Etayo-Perez A, Sebastian-Lopez C et al:
           57.   Ciment LM, Ciment AJ: Malignant ameloblastoma                                Primary intraosseous carcinoma arising in a mandibular
                 metastatic to the lungs 29 years after primary resection: a                  cyst, Med Oral 7(5):370-374, 2002.
                 case report, Chest 121(4):1359-1361, 2002.                               75. Scheer M, Koch AM, Drebber U et al: Primary
           58.   Zarbo RJ, Marunick MT, Johns R: Malignant ameloblas-                         intraosseous carcinoma of the jaws arising from an
                 toma, spindle cell variant, Arch Pathol Lab Med                              odontogenic cyst—a case report, J Craniomaxillofac
                 127(3):352-355, 2003.                                                        Surg 32(3):166-169, 2004.
           59.   Avon SL, McComb J, Clokie C: Ameloblastic carcinoma:                     76. Ramer M, Buonocore P, Krost B: Central odontogenic
                 case report and literature review, J Can Dent Assoc                          fibroma—report of a case and review of the literature,
                 69(9):573-576, 2003.                                                         Periodontal Clin Investig 24(1):27-30, 2002.
           60.   Dhir K, Sciubba J, Tufano RP: Ameloblastic carcinoma of                  77. Gardner DG: Central odontogenic fibroma current
                 the maxilla, Oral Oncol 39(7):736-741, 2003.                                 concepts, J Oral Pathol Med 25(10):556-561, 1996.
           61.   Datta R, Winston JS, Diaz-Reyes G et al: Ameloblastic                    78. Drebber U, Scheer M, Zoller JE et al: [The central
                 carcinoma: report of an aggressive case with multiple                        odontogenic fibroma. A rare tumor]. Pathologe 24(2):136-
                 bony metastases, Am J Otolaryngol 24(1):64-69, 2003.                         140, 2003.
           62.   Grunwald V, Le Blanc S, Karstens JH et al: Metastatic                    79. Piattelli A, Di Alberti L, Scarano A et al: Benign
                 malignant ameloblastoma responding to chemotherapy                           cementoblastoma associated with an unerupted third
                 with paclitaxel and carboplatin, Ann Oncol 12(10):1489-                      molar, Oral Oncol 34(3):229-231, 1998.
                 1491, 2001.                                                              80. El-Mofty SK: Cemento-ossifying fibroma and benign
           63.   Cox DP, Muller S, Carlson GW et al: Ameloblastic                             cementoblastoma, Semin Diagn Pathol 16(4):302-307,
                 carcinoma ex ameloblastoma of the mandible with                              1999.
                 malignancy-associated hypercalcemia, Oral Surg Oral                      81. Brannon RB, Fowler CB, Carpenter WM et al: Cemento-
                 Med Oral Pathol Oral Radiol Endod 90(6):716-722, 2000.                       blastoma: an innocuous neoplasm? A clinicopathologic
           64.   Kumar A, Loughran T, Alsina M et al: Management of                           study of 44 cases and review of the literature with special
                 multiple myeloma: a systematic review and critical                           emphasis on recurrence, Oral Surg Oral Med Oral Pathol
                 appraisal of published studies, Lancet Oncol 4(5):293-                       Oral Radiol Endod 93(3):311-320, 2002.
                 304, 2003.                                                               82. Mosqueda-Taylor A, Ledesma-Montes C, Caballero-
           65.   Iezzi G, Rubini C, Fioroni M et al: Clear cell odontogenic                   Sandoval S et al: Odontogenic tumors in Mexico: a
                 carcinoma, Oral Oncol 38(2):209-213, 2002.                                   collaborative retrospective study of 349 cases, Oral Surg
Ch23-F10053.qxd     5/15/06    6:01 PM    Page 531

          PA R T I I    ONCOLOGY                                                                                                           531

                 Oral Med Oral Pathol Oral Radiol Endod 84(6):672-675,               in differential diagnosis, Pediatr Dev Pathol 7(2):148-158,
                 1997.                                                               2004.
           83.   Simon EN, Merkx MA, Vuhahula E et al: Odontogenic            101.   Dal Cin P, Sciot R, Fossion E et al: Chromosome abnor-
                 myxoma: a clinicopathological study of 33 cases, Int J              malities in cementifying fibroma, Cancer Genet Cytogenet
                 Oral Maxillofac Surg 33(4):333-337, 2004.                           71(2):170-172, 1993.
           84.   Kaffe I, Naor H, Buchner A: Clinical and radiological        102.   Gollin SM, Storto PD, Malone PS et al: Cytogenetic
                 features of odontogenic myxoma of the jaws, Dento-                  abnormalities in an ossifying fibroma from a patient with
                 maxillofac Radiol 26(5):299-303, 1997.                              bilateral retinoblastoma, Genes Chromosomes Cancer
           85.   Asaumi J, Matsuzaki H, Hisatomi M et al: Application of             4(2):146-152, 1992.
                 dynamic MRI to differentiating odontogenic myxomas           103.   Fletcher CDM, Unni KK, Mertens F: World Health
                 from ameloblastomas, Eur J Radiol 43(1):37-41, 2002.                Organization classification of tumors: pathology and
           86.   Barker BF: Odontogenic myxoma, Semin Diagn Pathol                   genetics of soft tissue and bone, Lyon, France, 2002, IARC
                 16(4):297-301, 1999.                                                Press.
           87.   Endo Y, Uzawa K, Mochida Y et al: Differential distri-       104.   Yih WY, Pederson GT, Bartley MH Jr: Multiple familial
                 bution of glycosaminoglycans in human cementifying                  ossifying fibromas: relationship to other osseous lesions
                 fibroma and fibro-osseous lesions, Oral Dis 9(2):73-76,               of the jaws, Oral Surg Oral Med Oral Pathol 68(6):754-
                 2003.                                                               758, 1989.
           88.   Santos LD, Arianayagam S: Cementifying fibroma of the         105.   Canger EM, Celenk P, Kayipmaz S et al: Familial ossifying
                 maxillary antrum, Pathology 26(4):499-500, 1994.                    fibromas: report of two cases, J Oral Sci 46(1):61-64,
           89.   Akao I, Ohashi T, Imokawa H et al: Cementifying                     2004.
                 fibroma in the ethmoidal sinus extending to the anterior      106.   Sciubba JJ, Younai F: Ossifying fibroma of the mandible
                 cranial base in an 11-year-old girl: a case report, Auris           and maxilla: review of 18 cases, J Oral Pathol Med
                 Nasus Larynx 30 (suppl):S123-126, 2003.                             18(6):315-321, 1989.
           90.   Molinari SP, Di Rocco A, Merchant C et al: An unusual        107.   Eversole LR, Leider AS, Nelson K: Ossifying fibroma: a
                 sphenoid ridge tumor: cementifying fibroma, J Neurol                 clinicopathologic study of sixty-four cases, Oral Surg
                 243(1):103-104, 1996.                                               Oral Med Oral Pathol 60(5):505-511, 1985.
           91.   Sigler SC, Wobig JL, Dierks EJ et al: Cementifying fibroma    108.   Zachariades N, Vairaktaris E, Papanicolaou S et al:
                 presenting as proptosis, Ophthal Plast Reconstr Surg                Ossifying fibroma of the jaws. Review of the literature
                 13(4):277-280, 1997.                                                and report of 16 cases, Int J Oral Surg 13(1):1-6, 1984.
           92.   Kreutziger KL, Weiss LS: Cementifying fibroma: resection      109.   Sweet RM, Bryarly RC, Kornblut AD et al: Recurrent
                 of recurrent mandibular lesion with microsurgical                   cementifying fibroma of the jaws, Laryngoscope
                 preservation of inferior alveolar nerve and immediate               91(7):1137-1144, 1981.
                 reconstruction, South Med J 87(6):653-658, 1994.             110.   Boysen ME, Olving JH, Vatne K et al: Fibro-osseous
           93.   Bregni RC, Taylor AM, Garcia AM: Ameloblastic fibro-                 lesions of the cranio-facial bones, J Laryngol Otol
                 sarcoma of the mandible: report of two cases and review             93(8):793-807, 1979.
                 of the literature, J Oral Pathol Med 30(5):316-320, 2001.    111.   Dehner LP: Tumors of the mandible and maxilla in
           94.   Nogueira Tde O, Carvalho YR, Rosa LE et al: Possible                children. I. Clinicopathologic study of 46 histologically
                 malignant transformation of an ameloblastic fibroma to               benign lesions, Cancer 31(2):364-384, 1973.
                 ameloblastic fibrosarcoma: a case report, J Oral              112.   Waldron CA, Giansanti JS: Benign fibro-osseous lesions
                 Maxillofac Surg 55(2):180-182, 1997.                                of the jaws: a clinical-radiologic-histologic review of
           95.   Tajima Y, Utsumi N, Suzuki S et al: Ameloblastic fibro-              sixty-five cases. II. Benign fibro-osseous lesions of peri-
                 sarcoma arising de novo in the maxilla, Pathol Int                  odontal ligament origin, Oral Surg Oral Med Oral Pathol
                 47(8):564-568, 1997.                                                35(3):340-350, 1973.
           96.   Huguet P, Castellvi J, Avila M et al: Ameloblastic fibro-     113.   Hamner JE III, Scofield HH, Cornyn J: Benign fibro-
                 sarcoma: report of a case. Immunohistochemical study                osseous jaw lesions of periodontal membrane origin. An
                 and review of the literature, Med Oral 6(3):173-179, 2001.          analysis of 249 cases, Cancer 22(4):861-878, 1968.
           97.   Stambaugh MD, DeNittis AS: Out of radiation field             114.   Smith AG, Zavaleta A: Osteoma, ossifying fibroma, and
                 recurrence of an ameloblastic sarcoma of the maxilla, J             fibrous dysplasia of facial and cranial bones, AMA Arch
                 Oral Maxillofac Surg 56(11):1364, 1998.                             Pathol 54(6):507-527, 1952.
           98.   Amado Cuesta S, Gargallo Albiol J, Berini Aytes L et al:     115.   Said-al-Naief NA, Surwillo E: Florid osseous dysplasia of
                 Review of 61 cases of odontoma. Presentation of an                  the mandible: report of a case. Compend Contin Educ
                 erupted complex odontoma, Med Oral 8(5):366-373,                    Dent 20(11):1017-1019, 1022-1028 passim; quiz 1032,
                 2003.                                                               1999.
           99.   Martin-Granizo Lopez R, Ortega L, Gonzalez Corchon MA        116.   Commins DJ, Tolley NS, Milford CA: Fibrous dysplasia
                 et al: Ameloblastic fibroma of the mandible. Report of               and ossifying fibroma of the paranasal sinuses,
                 two cases, Med Oral 8(2):150-153, 2003.                             J Laryngol Otol 112(10):964-968, 1998.
          100.   Parham DM, Bridge JA, Lukacs JL et al: Cytogenetic           117.   Brannon RB, Fowler CB: Benign fibro-osseous lesions: a
                 distinction among benign fibro-osseous lesions of bone               review of current concepts, Adv Anat Pathol 8(3):126-
                 in children and adolescents: value of karyotypic findings            143, 2001.
Ch23-F10053.qxd   5/15/06    6:01 PM     Page 532

          532                    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

          118. Kramer IR: The World Health Organization: histological                  136. Kaban LB, Troulis MJ, Ebb D et al: Antiangiogenic therapy
               typing of odontogenic tumours: an introduction to the                        with interferon alpha for giant cell lesions of the jaws, J
               second edition, J Dent Assoc S Afr 47(5):208-210, 1992.                      Oral Maxillofac Surg 60(10):1103-1111; discussion 1111-
          119. Johnson LC, Yousefi M, Vinh TN et al: Juvenile active                         1113, 2002.
               ossifying fibroma. Its nature, dynamics and origin, Acta                 137. Jones WA: Familial multi-locular cystic disease of the
               Otolaryngol Suppl 488:1-40, 1991.                                            jaws, Am J Cancer 17:946-950, 1933.
          120. Willman CL, Busque L, Griffith BB et al: Langerhans’-cell                138. Mangion J, Rahman N, Edkins S et al: The gene for
               histiocytosis (histiocytosis X)—a clonal proliferative                       cherubism maps to chromosome 4p16.3, Am J Hum
               disease, N Engl J Med 331(3):154-160, 1994.                                  Genet 65(1):151-157, 1999.
          121. Kawakubo Y, Kishimoto H, Sato Y et al: Human cyto-                      139. Tiziani V, Reichenberger E, Buzzo CL et al: The gene for
               megalovirus infection in foci of Langerhans cell histio-                     cherubism maps to chromosome 4p16, Am J Hum Genet
               cytosis, Virchows Arch 434(2):109-115, 1999.                                 65(1):158-166, 1999.
          122. Arico M, Danesino C: Langerhans’ cell histiocytosis: is                 140. Ueki Y, Tiziani V, Santanna C et al: Mutations in the gene
               there a role for genetics? Haematologica 86(10):1009-                        encoding c-Abl-binding protein SH3BP2 cause
               1014, 2001.                                                                  cherubism, Nat Genet 28(2):125-126, 2001.
          123. Boutsen Y, Esselinckx W, Delos M et al: Adult onset of                  141. Lo B, Faiyaz-Ul-Haque M, Kennedy S et al: Novel mutation
               multifocal eosinophilic granuloma of bone: a long-term                       in the gene encoding c-Abl-binding protein SH3BP2
               follow-up with evaluation of various treatment options                       causes cherubism, Am J Med Genet 121A(1):37-40, 2003.
               and spontaneous healing, Clin Rheumatol 18(1):69-73,                    142. Imai Y, Kanno K, Moriya T et al: A missense mutation in
               1999.                                                                        the SH3BP2 gene on chromosome 4p16.3 found in a case
          124. Jaffe HL: Giant-cell reparative granuloma, traumatic bone                    of nonfamilial cherubism, Cleft Palate Craniofac J
               cyst, and fibrous (fibro-osseous) dysplasia of the                             40(6):632-638, 2003.
               jawbones, J Oral Surg (Chic) 6(1):159-175, 1953.                        143. Southgate J, Sarma U, Townend JV et al: Study of the cell
          125. Bernier JL, Cahn LR: The peripheral giant cell reparative                    biology and biochemistry of cherubism, J Clin Pathol
               granuloma, J Am Dent Assoc 49(2):141-148, 1954.                              51(11):831-837, 1999.
          126. Flanagan AM, Nui B, Tinkler SM et al: The multinucleate                 144. Eisenbud L, Kahn LB, Friedman E: Benign osteoblastoma
               cells in giant cell granulomas of the jaw are osteoclasts,                   of the mandible: fifteen year follow-up showing sponta-
               Cancer 62(6):1139-1145, 1988.                                                neous regression after biopsy, J Oral Maxillofac Surg
          127. Jacoway J, Howell FV, Terry BC: Central giant cell                           45(1):53-57, 1987.
               granuloma: an alternative to surgical therapy, Oral Surg                145. Colm SJ, Abrams MB, Waldron CA: Recurrent osteo-
               Oral Med Oral Pathol 66:572, 1988.                                           blastoma of the mandible: report of a case, J Oral
          128. Terry BJJ: Management of central giant cell lesions: an                      Maxillofac Surg 46(10):881-885, 1988.
               alternative to surgical therapy, Oral Maxillofac Surg Clin              146. Ohkubo T, Hernandez JC, Ooya K et al: “Aggressive”
               N Am 6:579-600, 1994.                                                        osteoblastoma of the maxilla, Oral Surg Oral Med Oral
          129. Kermer C, Millesi W, Watzke IM: Local injection of corti-                    Pathol 68(1):69-73, 1989.
               costeroids for central giant cell granuloma. A case report,             147. Benoist M: Experience with 220 cases of mandibular
               Int J Oral Maxillofac Surg 23(6 Pt 1):366-368, 1994.                         reconstruction, J Maxillofac Surg 6(1):40-49, 1978.
          130. Carlos R, Sedano HO: Intralesional corticosteroids as an                148. Bodmer WF, Bailey CJ, Bodmer J et al: Localization of the
               alternative treatment for central giant cell granuloma,                      gene for familial adenomatous polyposis on chromo-
               Oral Surg Oral Med Oral Pathol Oral Radiol Endod                             some 5, Nature 328(6131):614-616, 1987.
               93(2):161-166, 2002.                                                    149. Groden J, Thliveris A, Samowitz W et al: Identification
          131. Harris M: Central giant cell granulomas of the jaws                          and characterization of the familial adenomatous
               regress with calcitonin therapy, Br J Oral Maxillofac Surg                   polyposis coli gene, Cell 66(3):589-600, 1991.
               31(2):89-94, 1993.                                                      150. Nishisho I, Nakamura Y, Miyoshi Y et al: Mutations of
          132. O’Regan EM, Gibb DH, Odell EW: Rapid growth of giant                         chromosome 5q21 genes in FAP and colorectal cancer
               cell granuloma in pregnancy treated with calcitonin,                         patients, Science 253(5020):665-669, 1991.
               Oral Surg Oral Med Oral Pathol Oral Radiol Endod                        151. Hackney FL, Aragon SB, Aufdemorte TB et al: Chondrosar-
               92(5):532-538, 2001.                                                         coma of the jaws: clinical findings, histopathology, and treat-
          133. Pogrel MA, Regezi JA, Harris ST et al: Calcitonin treat-                     ment, Oral Surg Oral Med Oral Pathol 71(2):139-143, 1991.
               ment for central giant cell granulomas of the mandible:                 152. Marx RE, Stern D, editors: Oral and maxillofacial
               report of two cases, J Oral Maxillofac Surg 57(7):848-853,                   pathology: a rationale for diagnosis and treatment, Carol
               1999.                                                                        Stream, Ill, 2003, Quintessence Publishing.
          134. Pogrel MA: Calcitonin therapy for central giant cell                    153. Bohm P, Krober S, Greschniok A et al: Desmoplastic
               granuloma, J Oral Maxillofac Surg 61(6):649-653; discus-                     fibroma of the bone. A report of two patients, review of
               sion 53-54, 2003.                                                            the literature, and therapeutic implications, Cancer
          135. Kaban LB, Mulliken JB, Ezekowitz RA et al: Antiangio-                        78(5):1011-1023, 1996.
               genic therapy of a recurrent giant cell tumor of the                    154. Kwon PH, Horswell BB, Gatto DJ: Desmoplastic fibroma
               mandible with interferon alfa-2a, Pediatrics 103(6 Pt                        of the jaws: surgical management and review of the
               1):1145-1149, 1999.                                                          literature, Head Neck 11(1):67-75, 1989.
Ch23-F10053.qxd   5/15/06    6:01 PM     Page 533

          PA R T I I   ONCOLOGY                                                                                                         533

          155. Sanfilippo NJ, Wang GJ, Larner JM: Desmoplastic fibroma:         174. Lichtenstein L, Jaffe HI: Chondrosarcoma of bone, Am J
               a role for radiotherapy? South Med J 88(12):1267-1269, 1995.        Pathol 19:553-589, 1943.
          156. Ayala AG, Ro JY, Goepfert H et al: Desmoid fibromatosis:        175. Evans HL, Ayala AG, Romsdahl MM: Prognostic factors in
               a clinicopathologic study of 25 children, Semin Diagn               chondrosarcoma of bone: a clinicopathologic analysis
               Pathol 3(2):138-150, 1986.                                          with emphasis on histologic grading, Cancer 40(2):818-
          157. Goepfert H, Cangir A, Ayala AG et al: Chemotherapy of               831, 1977.
               locally aggressive head and neck tumors in the pediatric       176. Saito K, Unni KK, Wollan PC et al: Chondrosarcoma of
               age group. Desmoid fibromatosis and nasopharyngeal                   the jaw and facial bones, Cancer 76(9):1550-1558, 1995.
               angiofibroma, Am J Surg 144(4):437-444, 1982.                   177. Harwood AR, Krajbich JI, Fornasier VL: Radiotherapy of
          158. Sandberg AA, Bridge JA: Updates on the cytogenetics                 chondrosarcoma of bone, Cancer 45(11):2769-2777,
               and molecular genetics of bone and soft tissue tumors:              1980.
               osteosarcoma and related tumors, Cancer Genet                  178. Krochak R, Harwood AR, Cummings BJ et al: Results of
               Cytogenet 145(1):1-30, 2003.                                        radical radiation for chondrosarcoma of bone, Radiother
          159. Chan CW, Kung TM, Ma L: Telangiectatic osteosarcoma                 Oncol 1(2):109-115, 1983.
               of the mandible, Cancer 58(9):2110-2115, 1986.                 179. Sinkovics JG, Shirato E, Martin RG et al: Chondro-
          160. Giangaspero F, Stracca V, Visona A et al: Small-cell                sarcoma. I. A brief review of eighty-three patients, J Med
               osteosarcoma of the mandible. Case report, Appl Pathol              1(1):15-25, 1970.
               2(1):28-31, 1984.                                              180. Kim RY, Salter MM, Brascho DJ: High-energy irradiation
          161. Eilber FR, Rosen G: Adjuvant chemotherapy for osteo-                in the management of chondrosarcoma, South Med J
               sarcoma, Semin Oncol 16(4):312-322, 1989.                           76(6):729-731, 735, 1983.
          162. Pratt CB, Champion JE, Fleming ID et al: Adjuvant              181. Garrington GE, Collett WK: Chondrosarcoma. I. A
               chemotherapy for osteosarcoma of the extremity. Long-               selected literature review, J Oral Pathol 17(1):1-11,
               term results of two consecutive prospective protocol                1988.
               studies, Cancer 65(3):439-445, 1990.                           182. Nakashima Y, Unni KK, Shives TC et al: Mesenchymal
          163. Kassir RR, Rassekh CH, Kinsella JB et al: Osteosarcoma              chondrosarcoma of bone and soft tissue. A review of 111
               of the head and neck: meta-analysis of nonrandomized                cases, Cancer 57(12):2444-2453, 1986.
               studies, Laryngoscope 107(1):56-61, 1997.                      183. Huvos AG, Rosen G, Dabska M et al: Mesenchymal
          164. Ha PK, Eisele DW, Frassica FJ et al: Osteosarcoma of the            chondrosarcoma. A clinicopathologic analysis of 35
               head and neck: a review of the Johns Hopkins experi-                patients with emphasis on treatment, Cancer 51(7):1230-
               ence, Laryngoscope 109(6):964-969, 1999.                            1237, 1983.
          165. Mardinger O, Givol N, Talmi YP et al: Osteosarcoma of          184. Vencio EF, Reeve CM, Unni KK et al: Mesenchymal
               the jaw. The Chaim Sheba Medical Center experience,                 chondrosarcoma of the jaw bones: clinicopathologic
               Oral Surg Oral Med Oral Pathol Oral Radiol Endod                    study of 19 cases, Cancer 82(12):2350-2355, 1998.
               91(4):445-451, 2001.                                           185. Takahashi K, Sato K, Kanazawa H et al: Mesenchymal
          166. Patel SG, Meyers P, Huvos AG et al: Improved outcomes               chondrosarcoma of the jaw—report of a case and review
               in patients with osteogenic sarcoma of the head and                 of 41 cases in the literature, Head Neck 15(5):459-464,
               neck, Cancer 95(7):1495-1503, 2002.                                 1993.
          167. Smeele LE, Kostense PJ, van der Waal I et al: Effect of        186. Taconis WK, van Rijssel TG: Fibrosarcoma of the jaws,
               chemotherapy on survival of craniofacial osteosarcoma: a            Skeletal Radiol 15(1):10-13, 1986.
               systematic review of 201 patients, J Clin Oncol 15(1):363-     187. Papagelopoulos PJ, Galanis E, Frassica FJ et al: Primary
               367, 1997.                                                          fibrosarcoma of bone. Outcome after primary surgical
          168. August M, Magennis P, Dewitt D: Osteogenic sarcoma of               treatment, Clin Orthop (373):88-103, 2000.
               the jaws: factors influencing prognosis, Int J Oral            188. Bielack SS, Schroeders A, Fuchs N et al: Malignant
               Maxillofac Surg 26(3):198-204, 1997.                                fibrous histiocytoma of bone: a retrospective EMSOS
          169. Junior AT, de Abreu Alves F, Pinto CA et al: Clinico-               study of 125 cases. European Musculo-Skeletal Oncology
               pathological and immunohistochemical analysis of                    Society, Acta Orthop Scand 70(4):353-360, 1999.
               twenty-five head and neck osteosarcomas, Oral Oncol             189. Bramwell VH, Steward WP, Nooij M et al: Neoadjuvant
               39(5):521-530, 2003.                                                chemotherapy with doxorubicin and cisplatin in malig-
          170. Ryan RF, Eisenstadt S, Shambaugh EM: Osteogenic                     nant fibrous histiocytoma of bone: a European Osteo-
               sarcoma of the mandible: a plea for radical initial surgery,        sarcoma Intergroup study, J Clin Oncol 17(10):3260-3269,
               Plast Reconstr Surg 78(1):41-44, 1986.                              1999.
          171. Russ JE, Jesse RH: Management of osteosarcoma of the           190. Bacci G, Picci P, Mercuri M et al: Neoadjuvant chemo-
               maxilla and mandible, Am J Surg 140(4):572-576, 1980.               therapy for high grade malignant fibrous histiocytoma of
          172. Garrington GE, Scofield HH, Cornyn J, Hooker SP:                     bone, Clin Orthop (346):178-189, 1998.
               Osteosarcoma of the jaws. Analysis of 56 cases, Cancer         191. Cotterill SJ, Ahrens S, Paulussen M et al: Prognostic
               20(3):377-391, 1967.                                                factors in Ewing’s tumor of bone: analysis of 975 patients
          173. Garrington GE, Collett WK: Chondrosarcoma. II.                      from the European Intergroup Cooperative Ewing’s
               Chondrosarcoma of the jaws: analysis of 37 cases, J Oral            Sarcoma Study Group, J Clin Oncol 18(17):3108-3114,
               Pathol 17(1):12-20, 1988.                                           2000.
Ch23-F10053.qxd   5/15/06    6:01 PM     Page 534

          534                    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

          192. Rodriguez-Galindo C, Spunt SL, Pappo AS: Treatment of                   205. Ducatman BS, Scheithauer BW, Piepgras DG et al:
               Ewing sarcoma family of tumors: current status and outlook                   Malignant peripheral nerve sheath tumors. A clinico-
               for the future, Med Pediatr Oncol 40(5):276-287, 2003.                       pathologic study of 120 cases, Cancer 57(10):2006-2021,
          193. Kuttesch JF Jr, Wexler LH, Marcus RB et al: Second                           1986.
               malignancies after Ewing’s sarcoma: radiation dose-                     206. Cahan WG, Woodard HG, Higinbotham NL et al: Sarcoma
               dependency of secondary sarcomas, J Clin Oncol                               arising in irradiated bone: report of 11 cases, Cancer 1:3-
               14(10):2818-2825, 1996.                                                      29, 1948.
          194. Burkitt DP: Sarcoma involving jaws in African children,                 207. Arlen M, Higinbotham NL, Huvos AG et al: Radiation-
               Br J Surg 46:218-223, 1958.                                                  induced sarcoma of bone, Cancer 28(5):1087-1099, 1971.
          195. O’Connor GT: Malignant lymphoma in African Children.                    208. Pitcher ME, Davidson TI, Fisher C et al: Post irradiation
               II. A pathologic entity, Cancer 14:270-283, 1961.                            sarcoma of soft tissue and bone, Eur J Surg Oncol
          196. Lindstrom MS, Wiman KG: Role of genetic and epigenetic                       20(1):53-56, 1994.
               changes in Burkitt lymphoma, Semin Cancer Biol                          209. Lagrange JL, Ramaioli A, Chateau MC et al: Sarcoma after
               12(5):381-387, 2002.                                                         radiation therapy: retrospective multiinstitutional study of
          197. Sariban E, Donahue A, Magrath IT: Jaw involvement in                         80 histologically confirmed cases. Radiation Therapist
               American Burkitt’s Lymphoma, Cancer 53(8):1777-1782,                         and Pathologist Groups of the Federation Nationale des
               1984.                                                                        Centres de Lutte Contre le Cancer, Radiology 216(1):197-
          198. Mead GM, Sydes MR, Walewski J et al: An international                        205, 2000.
               evaluation of CODOX-M and CODOX-M alternating with                      210. Robinson E, Neugut AI, Wylie P: Clinical aspects of
               IVAC in adult Burkitt’s lymphoma: results of United                          postirradiation sarcomas, J Natl Cancer Inst 80(4):233-
               Kingdom Lymphoma Group LY06 study, Ann Oncol                                 240, 1988.
               13(8):1264-1274, 2002.                                                  211. Weatherby RP, Dahlin DC, Ivins JC: Postradiation
          199. Spreafico F, Massimino M, Luksch R et al: Intensive, very                     sarcoma of bone: review of 78 Mayo Clinic cases, Mayo
               short-term chemotherapy for advanced Burkitt’s lym-                          Clin Proc 56(5):294-306, 1981.
               phoma in children, J Clin Oncol 20(12):2783-2788, 2002.                 212. Wiklund TA, Blomqvist CP, Raty J et al: Postirradiation
          200. Attal M, Harousseau JL, Stoppa AM et al: A prospective,                      sarcoma. Analysis of a nationwide cancer registry
               randomized trial of autologous bone marrow trans-                            material, Cancer 68(3):524-531, 1991.
               plantation and chemotherapy in multiple myeloma.                        213. van der Waal RI, Buter J, van der Waal I: Oral metastases:
               Intergroupe Francais du Myelome, N Engl J Med                                report of 24 cases, Br J Oral Maxillofac Surg 41(1):3-6,
               335(2):91-97, 1996.                                                          2003.
          201. Sirohi B, Powles R: Multiple myeloma, Lancet                            214. Hashimoto N, Kurihara K, Yamasaki H et al: Pathological
               363(9412):875-887, 2004.                                                     characteristics of metastatic carcinoma in the human
          202. Bruno B, Rotta M, Giaccone L et al: New drugs for treatment                  mandible, J Oral Pathol 16(7):362-367, 1987.
               of multiple myeloma, Lancet Oncol 5(7):430-442, 2004.                   215. Batson OV: The function of the vertebral veins and their
          203. Ruggiero SL, Mehrotra B, Rosenberg TJ et al: Osteo-                          role in the spread of metastases, Ann Surg 112:138-149,
               necrosis of the jaws associated with the use of bisphos-                     1940.
               phonates: a review of 63 cases, J Oral Maxillofac Surg                  216. Hirshberg A, Leibovich P, Buchner A: Metastatic tumors
               62(5):527-534, 2004.                                                         to the jawbones: analysis of 390 cases, J Oral Pathol Med
          204. Marx RE: Pamidronate (Aredia) and zoledronate (Zometa)                       23(8):337-341, 1994.
               induced avascular necrosis of the jaws: a growing
               epidemic, J Oral Maxillofac Surg 61(9):1115-1117, 2003.