Practical Approach to Radiopaque Jaw Lesions PDF

This copy is for personal use only. To order printed copies, contact [email protected] 1164 NEURORADIOLOGY Practical Approach to Radiopaque Jaw Lesions Kenneth R. Holmes, MSc R. Davis Holmes, M...

This copy is for personal use only. To order printed copies, contact [email protected] 1164 NEURORADIOLOGY Practical Approach to Radiopaque Jaw Lesions Kenneth R. Holmes, MSc R. Davis Holmes, MD, MASc Radiopaque lesions of the jaw are myriad in type and occasionally Montgomery Martin, MD protean in appearance. In turn, the radiologic analysis of these le- Nicolas Murray, MD sions requires a systematic approach and a broad consideration of clinical and imaging characteristics to enable reliable radiologic Abbreviations: CEOT = calcifying epithelial diagnosis. Initially categorizing lesions by attenuation pattern pro- odontogenic tumor, COD = cemento-osseous vides a practical framework for organizing radiopaque jaw lesions dysplasia, COF = cemento-ossifying fibroma, MRONJ = medication-related osteonecrosis of that also reflects important tissue characteristics. Specifically, the the jaw, OSJ = osteosarcoma of the jaw, PCO = appearance of radiopaque lesions can be described as (a) densely primary chronic osteomyelitis, PDB = Paget dis- sclerotic, (b) ground glass, or (c) mixed lytic-sclerotic, with each ease of bone category representing a distinct although occasionally overlapping RadioGraphics 2021; 41:1164–1185 differential diagnosis. After characterizing attenuation pattern, the https://doi.org/10.1148/rg.2021200187 appreciation of other radiologic features, such as margin character- Content Codes: istics or relationship to teeth, as well as clinical features including From the Departments of Medicine (K.R.H.) demographics and symptoms, can aid in further narrowing the dif- and Radiology (R.D.H.), University of British ferential diagnosis and lend confidence to clinical decision making. Columbia, 2775 Laurel St, 11th Floor, Vancou- The authors review the potential causes of a radiopaque jaw lesion, ver, BC, Canada V5Z 1M9; BC Cancer Agency, Vancouver, British Columbia, Canada (M.M.); including pertinent clinical and radiologic features, and outline and Vancouver General Hospital, Vancouver, a simplified approach to its radiologic diagnosis, with a focus on British Columbia, Canada (N.M.). Presented as an education exhibit at the 2019 RSNA An- cross-sectional CT. nual Meeting. Received July 29, 2020; revision requested September 24 and received November An invited commentary by Buch is available online. 13; accepted December 14. For this journal- © based SA-CME activity, the authors, editor, and RSNA, 2021 radiographics.rsna.org reviewers have disclosed no relevant relation- ships. Address correspondence to R.D.H. (e- mail: [email protected]). © RSNA, 2021 Introduction The differential diagnosis of radiopaque jaw lesions remains broad SA-CME LEARNING OBJECTIVES and presents a significant challenge to practicing radiologists (Table). After completing this journal-based SA-CME As discussed by Curé et al (1), the radiologic analysis of these lesions activity, participants will be able to: is informed by numerous factors, including attenuation pattern, „ Classify radiopaque jaw lesions as margin characteristics, and relationship to the teeth. First categoriz- densely sclerotic, ground glass, or mixed lytic-sclerotic. ing lesions by attenuation pattern provides a practical framework to organize radiopaque lesions that also reflects important tissue char- „ Identify distinct imaging features of radiopaque jaw lesions. acteristics. Dense radiopacities mainly result from unerupted teeth, „ Describe clinical associations of radi- aberrant production of odontogenic hard tissues, or local osteoscle- opaque jaw lesions that allow a narrower rosis and cortical thickening. The relationship of densely sclerotic differential diagnosis. lesions to adjacent teeth and cortical bone, as well as assessment of See rsna.org/learning-center-rg. lesion margins, often allows one to arrive at a single diagnosis. For example, a densely sclerotic lesion, which is pericoronal relative to an unerupted tooth, is an odontoma. A lesion with a ground-glass appearance typically arises from disorganized calcification, either related to abnormal bone remodeling or as a result of a neoplastic process. These lesions can occur in the setting of systemic disorders such as renal osteodystrophy. Therefore, a final diagnosis can often be made at assessment of extragnathic bone findings. A mixed lytic- sclerotic appearance indicates the presence of multiple tissues with RG Volume 41 Number 4 Holmes et al 1165 ment of 32 permanent teeth. The permanent teeth TEACHING POINTS are commonly divided into six regions, termed „ At imaging, odontomas appear as nonaggressive densely sextants, with the mandible and maxillae each con- sclerotic masses surrounded by a radiolucent rim, reflecting a fibrous capsule. Odontomas are pericoronal when associated sisting of an anterior and two symmetric posterior with unerupted teeth and periapical relative to erupted teeth. sextants, delineated by the border of the canine „ Appreciation of a clear attachment to the root is nearly and first premolar teeth. pathognomonic of cementoblastoma and key in distinguish- Projecting from the gingiva, each tooth pos- ing it from osteoblastoma, as well as from other sclerotic peri- sesses a visible crown covered in enamel, which apical lesions such as COD. is produced by ameloblasts present only dur- „ Unlike extragnathic fibrous dysplasia, lesions of the jaw are ing the embryonic development of the tooth; poorly defined, which is key in distinguishing fibrous dysplasia thus enamel has no regenerative capacity. Below of the jaw from cemento-ossifying fibroma. Displacement of teeth or the mandibular canal is common, although root re- the gingiva, each tooth also forms a gomphosis sorption is characteristically rare. (peg-and-socket joint) with either the maxilla or „ Metastatic dissemination to the jaw is rare, representing about mandible, extending one or more roots into the 1% of jaw malignancies and typically indicating widespread alveolar bone. These roots are covered by cemen- disease. However, the diagnosis of a metastatic jaw bone tu- tum, a unique mineralized tissue produced by mor is still frequently the first indication of an occult malig- embedded cementoblasts, which supports tooth nancy. anchorage within the alveolar socket. The crown „ Features of stage 3 MRONJ are most important to recognize, and root meet at the neck of the tooth to form as sequestrectomy and segmental mandible resection have a primary role in treatment in addition to antimicrobials. the cementoenamel junction at approximately the level of the gingiva. Deep to the enamel and cementum lies a layer of calcified connective tissue called dentin, different radiopacities, usually reflecting both continually produced by odontoblasts throughout bone resorption with adjacent apposition of new one’s life. Dentin serves mainly to support overly- bone or heterogeneous maturation of lesional ing enamel and prevent fracturing during load- tissues. Distinguishing mixed lytic-sclerotic le- ing. At the center of each tooth lies a pulp cavity sions on the basis of the presence of aggressive consisting of specialized cells including odonto- features is important. Unfortunately, aggressive blasts and fibroblasts, as well as blood vessels, lesions significantly overlap in appearance, often nerves, and a complex matrix. Local fibroblasts precluding a definitive imaging diagnosis. How- produce a periodontal ligament that spans the ever, recent literature suggests a role for advanced periodontal ligament space to connect the root imaging techniques, which may obviate the need surface to adjacent compact alveolar bone termed for biopsy. the lamina dura. Together, this forms the primary An algorithmic approach to the initial as- mechanism to stabilize the tooth. sessment of sclerotic lesions of the jaw bones is outlined in Figure 1. Importantly, this serves Densely Sclerotic Lesions as a general guide to the diagnostic process, as All densely sclerotic lesions are benign and have many lesions demonstrate considerable radiologic a relatively homogeneous attenuation similar to variability. As such, a broader consideration of that of cortical bone or tooth constituents (eg, clinical and imaging characteristics is imperative dentin or cementum), without significant lucent in the comprehensive evaluation of these lesions. components. The prototypical densely sclerotic lesion is the bone island or enostosis. While not Anatomy of the Jaw applicable to all densely sclerotic lesions, mean A knowledge of the anatomy and development of attenuation greater than 885 HU is highly sensi- the jaw is helpful in understanding the origin of tive and specific for enostosis (2). many odontogenic lesions, which do not occur elsewhere in the body. Arising largely from the first Odontogenic Lesions branchial arch, the mandible and maxillae begin to form by intramembranous ossification during the Odontoma and Supernumerary Teeth.—Odon- fourth week of embryonic development and to- tomas are hamartomas of mixed hard and soft gether comprise the anatomic jaw. Both the upper dental tissues. These lesions are the most com- and lower jaw bones possess an alveolar process monly diagnosed odontogenic tumor, with most that gives rise to teeth, delineated in the mandible manifesting before the age of 20 years, without a from the basal bone by the mandibular canal (Fig significant gender predilection (3). Odontomas 2). Extending from the 6th week in utero to early can be categorized as compound or complex. adult life, odontogenesis involves the development Compound odontomas are well-defined col- of 20 deciduous teeth, followed by the develop- lections of small structures with a toothlike 1166 July-August 2021 radiographics.rsna.org Differential Diagnosis of Radiopaque Jaw Lesions according to Attenuation Pattern Lesion Type Densely Sclerotic Ground-Glass Mixed Lytic-Sclerotic Odontogenic Odontoma COF Developing odontoma Condensing osteitis CEOT COD Cementoblastoma Nonodontogenic Osteoma Fibrous dysplasia Osteosarcoma Exotoses and tori PDB Metastases Renal osteodystrophy Chronic osteomyelitis Osteonecrosis Note.—CEOT = calcifying epithelial odontogenic tumor, COD = cemento-osseous dysplasia, COF = cemento- ossifying fibroma, PDB = Paget disease of bone. resemblance, termed denticles. Complex odon- Early in development, odontomas appear as tomas exhibit a lower degree of differentiation, jaw lucencies owing to bone resorption, which reflecting poorly organized enamel, cementum, then proceeds to calcify. The lesions previously and dentin (3). Supernumerary teeth, which are termed ameloblastic fibro-odontoma or fibrodenti- morphologically normal erupted or unerupted noma have been recently reclassified as developing teeth in addition to the full permanent tooth odontomas (10). The bulk of cases are reported set, share the same pathogenesis as odontomas, in the posterior jaw, most commonly the posterior namely focal hyperactivity or failed resorption mandible, with most identified while investigating of the dental lamina, a tissue involved in tooth an unerupted tooth or following reports of painless development (4). swelling (11). These lesions manifest as well- Anatomically, compound odontomas show defined unilocular masses, with an attenuation a predilection for the anterior maxilla, typically pattern ranging from mixed lytic-sclerotic (Fig 4a, involving the anterior sextant, while complex 4b) to densely sclerotic (Fig 4c) as they mature. odontomas are mostly found in the posterior Displacement of nearby teeth is also common, but mandible (5). Clinically, over half of patients with root resorption is infrequently observed (12). odontomas present with unerupted teeth and are The treatment of choice for odontomas is otherwise asymptomatic. However, swelling is enucleation, which yields an excellent prognosis reported in approximately one-fourth of cases, and with minimal recurrence (5,12). rarely pain or infectious symptoms are reported (6,7). The presence of multiple odontomas should Cemento-osseous Dysplasia.— Cemento-osseous raise suspicion for Gardner syndrome, a subtype dysplasia (COD) describes a spectrum of idio- of familial adenomatous polyposis (autosomal pathic odontogenic fibro-osseous lesions in which dominant mutation in APC) that is associated with normal bone is replaced by an admixture of multiple extracolonic growths, including osteomas cementum, bone, and fibrous connective tissue. and desmoids, as well as dental abnormalities such COD can be divided into subtypes on the basis of as dentigerous cysts (8). the affected region and extent of involvement: At imaging, odontomas appear as nonag- (a) periapical, (b) focal, or (c) florid. Periapical gressive densely sclerotic masses surrounded by COD is the predominate subtype, which typically a radiolucent rim, reflecting a fibrous capsule. arises adjacent to the roots of vital teeth in the Odontomas are pericoronal when associated with anterior sextant of the mandible. While solitary le- unerupted teeth and periapical relative to erupted sions can occur, multifocal presentations affecting teeth. Supernumerary teeth have the appearance multiple teeth are also commonly seen. Lesions of morphologically normal teeth (Fig 3a). How- are termed focal COD when they occur away ever, a count of the teeth will reveal hyperdontia. from the periapical region, typically arising in the Compound odontomas appear as a collection of posterior jaw. Florid COD is a more diffuse vari- small rudimentary teeth that together approxi- ant characterized by multifocal lesions affecting mate the size of a normal tooth for that site (Fig multiple regions of the mouth (13). 3b). Conversely, a complex odontoma appears COD has a strong female predilection (80%– as a more ill-defined solitary sclerotic mass (Fig 90% of cases) and a predisposition for women 3c). Odontomas are often associated with an of African and East Asian descent (13). The unerupted tooth and are occasionally associated majority of cases are identified incidentally in with a calcifying odontogenic cyst (9). the 4th and 5th decades of life (13). Only about RG Volume 41 Number 4 Holmes et al 1167 Figure 1. Flowcharts show the diagnostic approach to radiopaque lesions of the jaw according to attenu- ation pattern: densely sclerotic lesions (a), ground-glass lesions (b), and mixed lytic-sclerotic lesions (c). Many bony lesions show considerable radiologic variability. As such, a broader consideration of clinical and imaging characteristics is imperative. CKD = chronic kidney disease. *A minority of large (>3 cm) CEOTs have aggressive features. **Cherubism is a hereditary variant of fibrous dysplasia, with diffuse involvement of the mandible and/or maxilla. 1168 July-August 2021 radiographics.rsna.org Figure 2. Overview of odonto- genic anatomy. Figure 3. Three cases of incidentally identified supernumerary teeth and odontomas at CT. (a) Sagittal CT image of supernumerary teeth shows a morphologically normal unerupted tooth (arrow) with a thin well-defined lucent rim and thin bony capsule. Tooth count confirmed that this is a supernumerary tooth. (b) Sagittal CT image of a compound odontoma shows multiple abnormal- appearing unerupted teeth (arrowhead) encapsulated by a thin lucent and bony rim. (c) Sagittal CT image of a complex odontoma shows an amorphous densely sclerotic pericoronal lesion with a well-defined rim of sclerosis (arrowhead). Mineralized lesion matrix contains components that are isoattenuating relative to the enamel and dentin in the adjacent tooth. one-fourth of cases are symptomatic, typically tumors) analogous to osteoblastoma elsewhere in with pain or swelling, although higher rates are the body (18). It is characterized by cementum- reported in florid COD (13–15). forming tissue in connection with a tooth root, At imaging, periapical COD appears as a single usually arising during the 2nd or 3rd decade of or multiple densely sclerotic masses, with well- life (18,19). There is no definitive gender prefer- circumscribed sclerotic margins abutting but not ence in the disease, despite numerous reports continuous with the roots of one or more teeth (Fig (20). Cementoblastomas have a predilection for 5a). A narrow radiolucent halo distinguishes COD the mandibular first molar, while incisor involve- from condensing osteitis and idiopathic osteoscle- ment is exceedingly rare (19). Cementoblastomas rosis. However, imaging characteristics can deviate can be locally destructive, invading the root canal according to the evolution of the lesion, and COD and pulp space. They occasionally may also be can be mistaken for a periapical inflammatory le- associated with primary or unerupted teeth. Most sion at early stages (16). COD is also occasionally patients are symptomatic, presenting with pain or associated with simple bone cysts or osteomyelitis swelling owing to bony expansion of the alveolar in the setting of a secondary infection (17). After ridge. Patients typically report awareness of the diagnosis, treatment is rarely needed as these lesion for greater than 1 year before diagnosis (19). masses are nonaggressive. Surgical intervention is Cementoblastoma classically appears as a well- typically reserved for patients who remain sig- circumscribed radiopaque periapical mass fused to nificantly symptomatic with pain or deformity, at the root of the affected tooth, with a thin radiolu- which point enucleation is the definitive treatment. cent halo surrounding the remainder of the lesion (19). Appreciation of a clear attachment to the Cementoblastoma.—Cementoblastoma is a root is nearly pathognomonic of cementoblastoma rare benign neoplasm (about 1% of odontogenic and key in distinguishing it from osteoblastoma, as RG Volume 41 Number 4 Holmes et al 1169 Figure 4. Two cases of developing odontoma. (a, b) Sagittal CT bone reconstructions through the mandible show a pericoronal lesion (arrow in a) with nonaggressive sclerotic margins in the posterior mandible. The lesion is predominantly lytic, with a small mineralized matrix component (arrowhead in b). (c) Sagittal CT bone reconstruction in the posterior maxilla shows a densely sclerotic lesion (white arrowhead) with a pericoronal relationship to an unerupted tooth (arrow). The lesion is encapsulated by a well-defined lucent rim (black arrowhead), an appearance indistinguishable from complex odontoma. Figure 5. Periapical COD versus cement- oblastoma. (a) Sagittal CT image shows a homogeneous densely sclerotic periapical lesion with nonaggressive thinly sclerotic margins and an inner lucent rim (arrow). There is an absence of aggressive changes to the adjacent tooth root (arrowhead), and, importantly, the lesion is not in con- tinuity with adjacent roots, supporting the diagnosis of COD. (b) Coronal CT im- age with bone reconstruction shows a ho- mogeneous densely sclerotic nonaggres- sive periapical lesion that is in continuity with an adjacent tooth root, findings in keeping with a cementoblastoma. well as from other sclerotic periapical lesions such Idiopathic Osteosclerosis.—Idiopathic osteoscle- as COD (Fig 5b). Other distinguishing features rosis (Fig 6), or dense bone island, refers to a focal include invasion of the root canal with root resorp- increase in bone density of unclear origin but may tion and involvement or displacement of adjacent represent a developmental variant (22). Patients teeth (18,19). Management of cementoblastomas are asymptomatic, with idiopathic osteosclerosis requires complete removal of the mass and affected typically identified incidentally at imaging for tooth. Otherwise the rate of recurrence remains other reasons. While idiopathic osteosclerosis high, with 66% recurring in one case series (18). manifests as a similar-appearing sclerotic focus to that of condensing osteitis, idiopathic osteosclero- Condensing Osteitis.—Condensing osteitis (also sis can be distinguished by well-defined margins termed sclerosing osteitis or sclerosing osteomyelitis) re- lacking a radiolucent rim. Idiopathic osteosclerosis fers to local reactive sclerosis resulting from chronic is also less frequently associated with the roots of odontogenic inflammation, typically related to teeth, and if adjacent to a root, pulp vitality testing periodontal or endodontal disease. In turn, patients should be normal, in contrast to that of condens- with condensing osteitis are usually symptomatic. ing osteitis (22). Condensing osteitis manifests as focal ill-defined sclerosis (Fig 5), often abutting the root of a tooth Nonodontogenic Lesions with periodontal disease such as periapical abscess or granuloma, or with periodontal ligament space Osteoma.—Osteomas are benign osteogenic widening (21,22). While any tooth can be affected, neoplasms of unclear cause, consisting pre- these changes are most commonly seen with nonvi- dominantly of lamellar bone, either cortical or tal mandibular premolars and molars. cancellous in structure. These lesions are largely 1170 July-August 2021 radiographics.rsna.org Figure 6. Two cases of idiopathic osteo- sclerosis. (a) Sagittal CT image shows a densely sclerotic periapical lesion (arrow) without a lucent rim. The lesion is adjacent to a noncarious tooth, and its appearance is in keeping with that of periapical idio- pathic osteosclerosis. (b) Axial CT image shows a densely sclerotic lesion without a lucent rim (arrowhead) abutting the root of the left third mandibular molar (non- carious), an appearance in keeping with that of idiopathic osteosclerosis. restricted to the craniofacial skeleton and can de- velop from either endosteal or periosteal surfaces, giving rise to central or peripheral osteomas, respectively. Reports vary, but peripheral osteo- mas are estimated to comprise between 49% and 93% of cases (23,24). The mandible is also more frequently affected than the maxilla, especially the posteromedial aspect. In fact, the mandibu- lar condyle is the most commonly affected site outside the paranasal sinuses, although osteomas that significantly affect the temporomandibular joint remain rare (24). Osteomas can occur at any age. However, peak incidence is spread across the 3rd–6th decades of Figure 7. Mandible osteoma. Axial CT image life (23,24). There is a slight male predominance with bone reconstruction shows a homogeneous among cases, although this remains disputed in densely sclerotic expansile lesion (arrow) with the literature (24). Osteomas of the jaw are typi- nonaggressive margins, centered in the lingual cally slow-growing painless masses that are often cortex of the right hemimandible. identified incidentally on radiographs or following reports of painless swelling in the case of periph- eral osteomas. These tumors typically range in is rarely seen in the jaw (26). Given their benign size from several millimeters to a few centimeters nature and indolent course, the decision to treat but in rare cases can grow much larger, causing osteomas is made clinically on the basis of func- marked disfigurement (25). Sporadic cases usually tion, cosmesis, and rarely, symptoms. If indicated, manifest as solitary masses of the jaw. However, surgical resection is preferred, with recurrence similar to odontomas, the presence of multiple os- reported to be extremely rare (27). teomas of the jaw should raise suspicion for Gard- ner syndrome. Interestingly, osteoma development Oral Exostosis and Tori.—Exostoses refer to in Gardner syndrome often precedes any intestinal benign nodular protuberances arising from non- polyposis, which may facilitate earlier diagnosis of neoplastic overgrowth of mature bone. The term the condition (8). torus is used to refer to a site-specific exostosis. At imaging, osteomas are homogeneously While predominantly cortical bone, exostoses can sclerotic pedunculated or sessile lesions aris- contain limited marrow and are covered by a thin ing from the cortical or endosteal surface, with poorly vascularized mucosa, with sizes ranging well-circumscribed margins (Fig 7) (25). Root from a few millimeters to multiple centimeters resorption may be seen if the lesion is located in a (28). Intraoral exostoses are extremely com- tooth-bearing area. The lack of a radiolucent halo mon, with an estimated prevalence of over 20% is helpful in differentiating osteomas from similar in American populations, although some reports radiopaque lesions, such as cementoblastoma or have been significantly higher (28,29). The vast complex odontoma. Of note, the classic intra- majority of these lesions are clinically silent, cortical osteoid osteoma found in the appen- although in rare circumstances tori can ulcerate dicular skeleton manifesting with a radiolucent and may also interfere with the fitting of dental nidus, surrounding sclerosis, and pain relieved by prosthetics in edentulous patients, necessitating nonsteroidal anti-inflammatory drugs (NSAIDs) surgical resection (30). If imaged, these lesions RG Volume 41 Number 4 Holmes et al 1171 Figure 8. Tori and exostoses. (a) Coronal CT image with bone reconstruction shows a torus palatinus, a midline bony protrusion arising from the hard palate (white arrowhead). Note the torus maxillaris, bony protrusions with medullary continuity arising from the lingular cortex of the alveolar process of the maxillae (black arrowheads). (b) Axial CT image with bone reconstruction shows a torus mandibularis, bilateral cortical bone protrusions (arrows) from the lingular cortex adjacent to the first molar and second premolar. (c) Axial CT image with bone reconstruction shows buccal exostosis, bilateral thick cortical protrusions arising from the buccal cortex of the alveolar process of the maxillae (arrows). appear as protrusions of normal-appearing dense ground-glass lesions can have a heterogeneous cortical bone and can often be distinguished at appearance owing to focal areas of superimposed imaging by the presence of marrow or by their lucency, in which case they are best described as bilaterality and nonpedunculated morphology. mixed lytic-sclerotic. With that, classic ground- Further, exostoses also typically manifest in a glass entities should also be considered in the characteristic distribution, which carries an as- assessment of mixed lytic-sclerotic lesions. sociated name. Torus palatinus is the most common intraoral Odontogenic Lesions exostosis occurring at the midline of the hard palate, usually projecting outward in a symmetric Cemento-ossifying Fibroma.—Now classified as a fashion, sparing the greater palatine foramen (Fig benign mesenchymal odontogenic tumor (32), a 8a). These masses can assume several morpholo- COF describes a thinly encapsulated benign neo- gies: flat, lobular, nodular, or spindle-shaped. Tori plasm consisting of dense fibrocellular tissue, with mandibularis are found on the lingual surface varying amounts of irregular bony trabeculae or of the mandible, superior to the mylohyoid line, cementum-like material. These lesions most com- typically adjacent to the canine or premolar teeth monly affect the posterior mandible (33), where and most often manifest bilaterally (Fig 8b). they are thought to originate from the periodontal Torus maxillaris refers to exostoses arising from ligament (10,33). Previously grouped with COF, the cortex of the maxillary alveolar process (Fig the latest World Health Organization classification 8a), while an overlapping term, buccal exostosis, now recognizes ossifying fibroma to be a distinct describes bony nodules along the external cortex entity of nonodontogenic origin (32), which is of the maxillary or mandibular alveolar processes. commonly reported in other facial bones and the These masses also typically manifest bilaterally, anterior cranial fossa (33). Ossifying fibroma also organized in a symmetric row (Fig 8c) (30). includes a rare juvenile variant, termed juvenile os- sifying fibroma, which typically manifests in middle Ground-Glass Lesions childhood to adolescence and behaves more Ground-glass lesions of the jaw have a differen- aggressively, with a greater tendency to recur tial diagnosis of four entities: fibrous dysplasia, (34). These tumors can rarely occur in hyperpara- cemento-ossifying fibroma (COF), Paget dis- thyroidism–jaw tumor syndrome, an autosomal ease of bone (PDB), and renal osteodystrophy. dominant disorder resulting from a germline mu- Ground-glass lesions are so named because of tation of tumor suppressor gene CDC73, charac- their hazy homogeneous intermediate attenu- terized by parathyroid tumors as well as lesions of ation between lucency and/or absence of bone the uterus and kidneys (35). and dense sclerosis. They are characterized by COF manifests with a peak incidence in the 3rd mineralization of fibrous matrix, which obscures and 4th decades of life and has a predilection for or destroys trabeculae (31). Fibrous dysplasia is females (71% of cases), while males are slightly the prototypical ground-glass bone lesion. Large preferred among cases of juvenile ossifying fibroma 1172 July-August 2021 radiographics.rsna.org Figure 9. Two cases of COFs. (a) Coronal CT image shows a focal periapical lesion (arrow- head) in the right hemimandible. The lesion is mildly expansile, scalloping the buccal cortex (arrow), although it preserves the tooth root. The lesion is predominantly lytic, but its internal matrix produces a subtle ground-glass appearance. (b) Coronal CT image shows a focal ex- pansile maxillary lesion, with ground-glass matrix mineralization (arrowhead). The surround- ing cortical bone is severely thinned or difficult to visualize. The evidence of remodeling (ar- row) and lack of periosteal reaction are findings in keeping with a nonaggressive lesion. (33,36). Most patients present with a painless connective tissue with islands of disorganized wo- swelling or the COFs are discovered incidentally, ven bone. This results from a postzygotic mutation although 16% of patients do present with pain of the GNAS1 gene, which affects proliferation (33). and differentiation of preosteoblasts downstream At imaging, COFs appear as solitary well- (39). Fibrous dysplasia can manifest in monostotic circumscribed expansile lesions surrounded by (85%) or polyostotic (15%) forms (40). normal-appearing bone, often in a periapical The polyostotic form can be seen with Mc- region. Lesions undergo progressive calcification, Cune-Albright syndrome, accompanied by café initially appearing as radiolucencies that gradu- au lait spots and hyperfunctional endocrinopa- ally opacify and range in appearance from a clas- thies such as precocious puberty, hyperthyroid- sic ground-glass pattern to densely sclerotic, with ism, and acromegaly (41). Rarely, fibrous dyspla- a thin rim of radiolucent soft-tissue capsule (Fig sia may also manifest as Mazabraud syndrome, 9). Case series suggest that 58% of lesions are referring to the constellation of fibrous dysplasia ground-glass, 26% are radiolucent, and 16% are and intramuscular myxoma (42). Polyostotic purely sclerotic (33). The appreciation of well-de- manifestations involve the craniofacial region fined borders is key in differentiating COF from in 90% of cases (43). Most cases are unilat- fibrous dysplasia, which appears to blend with eral, in contrast to the similar-appearing PDB. surrounding bone (37). Lower mandible border Cherubism is a rare hereditary variant of fibrous erosion is commonly seen, and adjacent teeth dysplasia, although molecularly distinct (44), that may show signs of displacement or resorption can result in diffuse and/or bilateral mandible in- (34). Lesions of the maxilla may also significantly volvement. It is distinguished from Paget disease displace the maxillary sinus (37). clinically by childhood age of onset and frequent Conservative surgical resection or curettage is maxillary involvement (60%) (45), which is the treatment of choice, with resection reserved absent in Paget disease. Both sexes are affected for aggressive or recurrent lesions (38). COF equally, and the mean age at diagnosis is ap- was traditionally thought not to recur following proximately 24 years. However, polyostotic cases treatment. However, a systematic review reported mainly manifest prepubertally, with an estimated a 12% recurrence rate despite treatment, high- 60% of cases of polyostotic fibrous dysplasia lighting the need for long-term follow-up in these manifesting before age 10 years (40,46). patients (33). The vast majority of patients present with painless swelling or asymmetry, although bone Nonodontogenic Lesions pain and pathologic fractures can occur (40). Cosmesis can also be of particular concern, as Fibrous Dysplasia.—Fibrous dysplasia is a disor- well as compromise of nearby structures (eg, vi- der of benign fibro-osseous lesions characterized sual and auditory systems). These lesions ‘“burn by the replacement of normal bone by fibrous out” as the patient approaches skeletal maturity. RG Volume 41 Number 4 Holmes et al 1173 Figure 10. Three cases of fibrous dysplasia on sagittal CT images that demonstrate its variable appearance. (a) Image shows a pre- dominantly lytic-appearing lesion with peripheral nonaggressive sclerotic margins (arrow), apparent cortical thickening at the angle of the mandible, and absence of periosteal reaction. A faintly visible internal ground-glass attenuation matrix is depicted. (b) Image shows fusiform expansile sclerosis of the hemimandible, with ground-glass attenuation. There is conspicuous preservation of tooth roots (ar- rowheads). (c) Image shows diffuse expansion of the entire hemimandible and replacement with ground-glass attenuation. A similar appearance of the other imaged facial bones and skull is visible and asymmetric with the contralateral side (not shown). Conspicuous preservation of the mandibular canal (arrowhead) indicates that the bony changes are nonaggressive. However, a minority of cases will reactivate in Paget Disease of Bone.—PDB is a chronic disease adulthood, often in response to pregnancy (40). characterized by accelerated remodeling of bone Fibrous dysplasia carries a lifetime risk of malig- owing to dysregulated osteoclast and osteoblast ac- nant transformation of 1%–4%, with radiation tivity. This results in focal areas of excessive bone exposure and McCune-Albright syndrome repre- resorption or accumulation of structurally abnor- senting important risk factors (47). mal bone with marrow fibrosis. There are three Imaging features vary depending on the con- phases to PDB that progress temporally: (a) lytic, tent of bone and fibrous tissue within the lesion. (b) mixed lytic and blastic, and (c) blastic. Classically, fibrous dysplasia appears as fusiform While PDB preferentially targets the axial bony expansion, with a ground-glass appearance skeleton and skull, involvement of the jaw is reflecting a predominant histologic finding of bony considerably rarer. Incidence increases with age, trabeculae with scant fibrous tissue (Fig 10). In with onset typically occurring between 55 and 75 this pattern, cortical bone is usually maintained, years of age and scarcely seen in patients under although a loss of lamina dura and narrowing of 40 (49–51). PDB predominately affects individu- the periodontal ligament space can be observed als of northwestern European descent, with a (48). Unlike extragnathic fibrous dysplasia, le- reported prevalence of up to 3% among Ameri- sions of the jaw are poorly defined, which is key cans and 5% among Britons over the age of 55 in distinguishing fibrous dysplasia of the jaw from years (52). More recent surveys suggest that the cemento-ossifying fibroma. Displacement of teeth prevalence has been decreasing in recent decades or the mandibular canal is common, although root (53). Men are also more affected than women, resorption is characteristically rare (40). Fibrous comprising about 60% of cases (54). dysplasia can also manifest as unilocular or multi- Most cases are discovered incidentally at imag- locular well-demarcated radiolucencies, with few ing or routine bloodwork that shows elevated interspersed bony trabeculae, especially in early alkaline phosphatase levels. Among those with lesions (43). In a systematic review, all cases of symptoms to report at the time of diagnosis, the fibrous dysplasia affecting the jaw bones displayed most common is bone pain. Pertinent complica- buccolingual expansion, while all mandibular cases tions include cosmesis and sarcomatous degener- exhibited downward displacement of the lower ation, which remains rare, occurring in less than border of the mandible, and most maxillary cases 0.5% of all PDB cases (51). However, osteosar- involved the maxillary antrum (40). coma arising from PDB in the jaw carries a 21% In fibrous dysplasia affecting the jaw, surgery 5-year survival rate, far worse than that reported is mostly limited to cosmetic debulking and for primary osteosarcoma of the jaw (OSJ) (55). decompression of affected soft-tissue structures. Radiographically, lesions of the jaw can have Analgesics and bisphosphonates may also be used a variable appearance, reflecting the disease in the setting of persistent bone pain. Otherwise, phase. Multiple phases can occur simultane- management focuses on monitoring for malig- ously in different sections of bone. Early lesions nant transformation (43). can appear as punched-out radiolucencies, while 1174 July-August 2021 radiographics.rsna.org Figure 11. PDB affecting the jaw. Anterior delayed phase (4-hour) bone scintigraphic image shows marked methylene diphospho- nate radiotracer uptake throughout the entire mandible (black arrowhead), producing the Lincoln sign. The uptake within the calvarium (white arrowhead) and lack of uptake in the sphenoid and paranasal sinuses are also char- acteristic of Paget disease. affected bone in the mixed phased can give rise ered for lesions of the jaw and must be weighed to a ground-glass attenuation pattern, described against the increased perioperative risk associ- as a “cotton wool” appearance. Late-stage lesions ated with hypervascular bone and abnormal will manifest as more homogeneously sclerotic bone quality. with bony enlargement. Jaw lesions in PDB also frequently demonstrate cortical and trabecular Renal Osteodystrophy.—Renal osteodystrophy thickening, sclerotic changes to the alveolar bone, reflects a variable combination of metabolic and hypercementosis of the roots of teeth with derangements caused by chronic kidney disease, loss of the lamina dura. predominantly secondary hyperparathyroidism At imaging, PDB can be difficult to distinguish and osteomalacia from 1,25-dihydroxycholecal- from fibrous dysplasia, although these conditions ciferol deficiency. In turn, renal osteodystrophy tend to occur at different ages. Pagetic lesions of has a variable expression, with regions of in- the alveolus can also resemble florid COD but creased osteoclastic activity as well as adynamic instead extend into basal bone. Helpful features regions, creating areas of both lucency and in distinguishing PDB include a predominate sclerosis. bilateral and polyostotic manifestation that is Renal osteodystrophy assumes one of three accompanied by other characteristic lesions, radiographic patterns: (a) osteitis fibrosa cystica, frequently a cotton wool expansion of the outer (b) fibrous dysplasia-like, and (c) uremic leontia- table of the skull and a picture frame appearance sis ossea (60). Osteitis fibrosa cystica manifests of vertebral bodies. In addition, the presence with a constellation of subperiosteal resorption of well-circumscribed lytic lesions of the skull, and trabecular coarsening, with a superimposed known as osteoporosis circumscripta, as well as lytic pattern of multifocal brown tumors. The the “tam-o’-shanter” sign reflecting widening of second pattern is characterized by diffuse ground- the diploic space and platybasia caused by soften- glass replacement of the medullary cavity of the ing of the skull base, are highly specific signs of mandible, similar in appearance to fibrous dyspla- PDB (56). However, it should be mentioned that sia but differentiated by a loss of corticomedullary while rare, cases of monostotic PDB affecting the differentiation along with a typical bilateral mani- jaw have been described (57). Diagnosis of PDB festation. Finally, uremic leontiasis ossea is a rare can also be aided by bone scintigraphy, which manifestation of renal osteodystrophy, named for demonstrates diffuse mandible radiotracer uptake the lionlike appearance assumed by the midface. producing a “black beard” appearance that has This pattern manifests with marked hypertrophy been likened to the appearance of U.S. President of the jaw bones, with serpiginous low-attenuation Abraham Lincoln, hence the term Lincoln sign tunneling through the affected bone. A number of (Fig 11). Diffuse calvarial uptake and absence of classic extraoral findings such as widespread sub- involvement of the paranasal sinuses are also char- periosteal resorption, salt and pepper skull, and acteristic (58). Clinical findings such as elevated rugger jersey spine help further distinguish renal serum alkaline phosphatase and urine hydroxy- osteodystrophy (Fig 12) (61). proline levels also support the diagnosis (59). Treatment of PDB, if indicated, is aimed at Mixed Lytic-Sclerotic Lesions addressing symptoms and preventing complica- Mixed lytic-sclerotic lesions are a heterogeneous tions of excessive bone remodeling. Bisphos- group of entities including both benign and ma- phonates are currently the mainstay for medical lignant neoplasms and aggressive processes such treatment of PDB, suppressing osteoclastic as osteomyelitis and osteonecrosis. Mixed lytic- activity. Surgical management is rarely consid- sclerotic lesions are inherently heterogenous in RG Volume 41 Number 4 Holmes et al 1175 Figure 12. Renal osteodystrophy. (a) Axial CT bone reconstruction through the mandible body shows many of the classic findings of renal osteodystrophy, including diffuse medullary sclerosis with a ground-glass appearance (arrow), loss of corticomedullary dif- ferentiation, and loss of the lamina dura (white arrowhead). A nonaggressive lucent focus representing a brown tumor is visible (black arrowhead). (b) Axial CT bone reconstruction through the calvarium from the same examination shows other features of renal osteo- dystrophy, with medullary sclerosis, innumerable lytic foci creating a salt-and-pepper appearance, larger nonaggressive lytic lesions (brown tumors), and accentuation of the temporal fossae (arrows). (c) Sagittal CT bone reconstruction of the spine shows endplate sclerosis sparing the anterior and posterior margins, findings in keeping with a rugger jersey appearance. Figure 13. Calcifying epithelial odon- togenic tumor. Axial (a) and sagittal (b) CT bone reconstructions show a bubbly mixed lytic and sclerotic expansile lesion (arrow in a) in the body of the mandible. There are multiple nonaggressive features, including preserved roots of teeth (arrow- heads in b) within the lesion and cortical scalloping without frank destruction, soft- tissue mass, or periosteal reaction. appearance owing to the combination of areas of quently manifests as a slow-growing mass, with increased lucency with frank absence of mineral- over half of cases accompanied by unerupted teeth ized tissue adjacent to more highly attenuating and only a small minority of patients reporting lesion components. pain (63). Radiologic descriptions of CEOTs vary, ranging from a pericoronal lucency or mixed lytic- Odontogenic Lesions sclerotic lesion to a densely sclerotic mass (Fig 13). A characteristic “driven snow” appearance is Calcifying Epithelial Odontogenic Tumor.— Cal- also commonly described. However, this is rarely cifying epithelial odontogenic tumor (CEOT), or seen in practice (63). The most common manifes- Pindborg tumor, is a rare epithelial odontogenic tation of CEOT involves an expansile mixed pat- neoplasm characterized by the presence of amy- tern mass, comprising between 65% and 75% of loid material that often calcifies. Representing cases (62,63). The remaining lesions are predomi- about 1% of odontogenic tumors, CEOTs are nantly radiolucent and small. Small lesions appear largely benign, although they occasionally dem- to be well-defined, whereas a minority of lesions onstrate locally aggressive behavior and in select larger than 3 cm have ill-defined borders, perhaps cases can undergo malignant transformation and indicative of a more aggressive phenotype (63). form distant metastases (62,63). The mandible is affected in 75% of cases, with The mean age at presentation is 38 years, with preference for the premolar and molar regions the peak incidence spanning ages 20–50 (62). (62). Most reported cases are centrally located There is no sex predilection. CEOT most fre- within bone (94%) and most are pericoronal to an 1176 July-August 2021 radiographics.rsna.org Figure 14. Osteoblastic OSJ in a region of fibrous dysplasia. (a) Sagittal CT bone reconstruc- tion shows an expanded mandible body posteriorly with internal ground glass, findings in keeping with fibrous dysplasia (arrow). A change in features anteriorly with osteolysis and cortical destruction is concerning for malignant transformation. (b) Axial CT soft-tissue recon- struction shows right parasymphyseal cortical breach (white arrowhead), a large soft-tissue component (black arrowhead), and aggressive lesion margins. Matrix mineralization is fluffy and cloudlike, findings in keeping with osteoid matrix. unerupted tooth (64). Adjacent teeth can be dis- (67). OSJ demonstrates an equal sex distribution. located or displaced but rarely experience resorp- However, women may carry a worse prognosis tion, which may help differentiate these lesions (67,68). The classic presentation involves swelling from ameloblastoma (62). Approximately half of with or without mental paresthesias (69). Oc- central lesions also show cortical perforation. Of casionally, patients may also report symptoms of note, CEOTs have historically been described as pain, loose teeth, or trismus. predominantly multilocular, but more recent data At imaging, OSJ usually appears with a lytic or have refuted this (62). mixed lytic-sclerotic pattern, or as dense sclerosis Conservative resection with tumor-free margins less commonly (70,71). There is a slight mandib- appears to be the treatment of choice, but some ular predilection, in which the body is most com- argue that lesions in the posterior maxilla should monly affected (Fig 15) (66). In the maxilla, the be treated more aggressively (65). Recurrence is alveolar ridge appears to give rise to most lesions reported in 12% of cases, although a higher rate (69,70). OSJ has a wide zone of transition and (43%) is associated with lesions that had previ- commonly demonstrates widening of the peri- ously undergone malignant transformation (62). odontal ligament space, termed the Garrington sign. Periosteal reaction is also observed in about Nonodontogenic Lesions half of cases, most commonly manifesting with a characteristic spiculated “sun ray” appearance, Osteosarcoma of the Jaw.—While osteosarcoma and frequently associated with extension into soft is the most common primary malignant tumor of tissues (69,71). the bone, OSJ is considerably less common, ac- Radical surgery and systemic chemotherapy counting for only about 6% of cases (66). How- are the mainstays of treatment of osteosarcoma. ever, OSJ still remains the most common sarcoma The role of radiation therapy in OSJ remains of the jaw bones. OSJ tends to occur in patients controversial, but it may be considered in high- who are 1 to 2 decades older than patients with grade tumors or tumors with positive margins. appendicular osteosarcoma, with a mean age at Overall, 5-year survival is estimated at 53% (67). presentation of 41 years (67). Sarcomatous de- Importantly, OSJ arising secondary to PDB is generation of PDB or other benign bone lesions is believed to have a significantly worse prognosis, presumed in cases affecting older adults (Fig 14). with an estimated 5-year survival of 21% (55). According to the predominant histologic pattern, lesions are classified as osteoblastic, chondroblas- Metastases.—Metastatic dissemination to the jaw tic, or fibroblastic. OSJ has a higher proportion of is rare, representing about 1% of jaw malignancies chondroblastic lesions compared with osteosar- and typically indicating widespread disease (72). coma affecting the long bones, which is thought However, the diagnosis of a metastatic jaw bone to confer a better prognosis and may explain the tumor is still frequently the first indication of an superior outcomes in patients with primary OSJ occult malignancy (73). Most cases occur in the RG Volume 41 Number 4 Holmes et al 1177 Figure 15. Chondroblastic OSJ. Axial CT soft-tissue (a) and bone (b) reconstructions show a predomi- nantly lytic mass centered in the right hemimandible body, with internal matrix mineralization (ar- row) and multiple aggressive fea- tures, including cortical destruc- tion and an extraosseous soft-tis- sue component (arrowhead in a). Figure 16. Two cases of sclerotic prostate metastases. (a) Coronal CT bone reconstruction shows mul- tifocal circumscribed densely sclerotic foci (arrows) within the mandible. No aggressive features are de- picted. (b) Coronal CT image shows permeative mixed lytic and sclerotic right hemimandible bone destruction, with periosteal reaction and extraosseous extension (arrowhead). 5th to 7th decade of life (73,74). Among men, the monly exhibit a wide zone of transition and most common primary sites in descending order marked periosteal reaction. The mandible is are the lung, kidney, liver, and prostate, while also more frequently affected than the maxilla, in women the most common primary site is the comprising about 80% of cases, with the molar breast, with other sites (genital, renal, colorectal, area being the most common site of involvement thyroid, and lung) variably reported (73,74). Scle- (73,74). When metastatic disease is suspected, a rotic metastases classically result from prostatic systematic survey for the primary lesion and other carcinoma but may also arise from malignancies sites of involvement should be performed, guided of the breast, kidney, and thyroid (72). Of note, by the clinical presentation and histologic findings. treated lytic metastases can also have a sclerotic Oral metastases carry a grim prognosis, with an appearance. average survival of 7 months (72). Pain, swelling, and mental paresthesia are the most common symptoms of jaw metastases (72,74). Chronic Osteomyelitis.—Osteomyelitis of the jaw Metastatic lesions frequently extend into surround- most commonly results from contiguous spread ing soft tissue, and pathologic fractures may occur. of odontogenic infection or following trauma, Dysphagia, intermittent bleeding, trismus, and in- although it may also occur secondary to surgery fection are also regularly reported, especially among or hematogenous spread (75,76). Numerous lesions affecting oral soft tissues (72). systemic factors further increase one’s risk, in- Up to 17% of jaw metastases can appear as cluding diabetes mellitus, malignancies, immune purely sclerotic (Fig 16a) or mixed lytic-sclerotic suppression, malnutrition, anemia, and diseases at imaging (Fig 16b) (73). Metastatic foci com- altering bone vasculature (76). Tobacco, alcohol, 1178 July-August 2021 radiographics.rsna.org Figure 17. Chronic osteomyelitis. Axial contrast-enhanced CT bone (a) and soft-tissue (b) reconstruc- tions show an aggressive mixed lytic-sclerotic lesion in the left hemimandible body. A central sclerotic component (arrow in a) represents a bony sequestrum, while a lytic component results in cortical destruc- tion and periosteal reaction (white arrowhead in a). Reactive ill-defined sclerosis and cortical thickening are visible in the surrounding bone (black arrowhead in a). The expansion and increased enhancement of the masseter (arrow in b) and medial pterygoid, the subcutaneous fat stranding, and the skin thickening support the inflammatory nature of this lesion. and intravenous drug use, as well as radiation persons under 20 years of age (76,80). Chronic therapy, chemotherapy, and antiresorptive agents, osteomyelitis of the jaw commonly manifests have also been specifically linked to osteomyelitis with sustained pain, swelling, and formation of a of the jaw (75,77). draining fistula (75,76). Altered local sensation Osteomyelitis can be subdivided into acute and purulence are also frequently reported. (days to 1–2 weeks), subacute (2–6 weeks), and Osteomyelitis of the jaw has a diverse mi- chronic forms (months to years), informing both crobiology, which is often polymicrobial and radiologic presentation and treatment. Acute influenced by the origin of infection (77). Cases osteomyelitis is an acute suppurative infection with resulting from the spread of odontogenic infec- systemic features (eg, fever and leukocytosis) caus- tion are generally caused by streptococci and an- ing destruction of bone trabeculae and obliteration aerobes (eg, Peptostreptococcus); chronic cases are of vascular channels due to raised intramedullary more commonly caused by polymicrobial anaero- pressure. Nonresolution over weeks gives rise to bic infections (eg, Fusobacterium, Porphyromonas, subacute osteomyelitis, which is a low-grade infec- and Prevotella). Staphylococci and enteric rods tion usually lacking significant systemic manifesta- predominate in cases with a hematogenous ori- tions. Chronic osteomyelitis refers to persistent gin, while fungal osteomyelitis, primarily Aspergil- or recurrent low-grade infection evolving over lus and Candida species, is seen in patients who months to years despite treatment and is com- are immunocompromised or have diabetes. monly associated with a bony sequestrum, a nidus Imaging characteristics of osteomyelitis evolve for chronic infection owing to inaccessibility by with disease chronicity. Acute osteomyelitis mani- the immune system or antimicrobial therapy (78). fests as ill-defined radiolucencies or focal osteope- It is generally chronic osteomyelitis that manifests nia, while chronic osteomyelitis of the jaw typically with sclerotic features at imaging. Primary chronic has mixed lytic-sclerotic features characterized by osteomyelitis (PCO) is a separate entity that refers irregular bony erosions with surrounding sclerosis to a rare nonsuppurative inflammatory process of and areas of cortical thickening (76). A smooth cortical and cancellous bone without clear cause. ossifying periosteal reaction with modest enhance- Some cases have been associated with dental infec- ment of adjacent soft tissues is also characteristic of tion, but up to 38% have no identifiable cause subacute and chronic osteomyelitis but is not seen (79). This condition has also been referred to as in the acute phase (Fig 17) (81). The mandible is diffuse sclerosing osteomyelitis, Garré osteomyeli- much more frequently affected by osteomyelitis tis, and juvenile mandibular chronic osteomyelitis than the maxilla, particularly tooth-bearing areas, (80). Occasionally, patients will also present with which is thought to be related to poor vascular- PCO as part of SAPHO syndrome (synovitis, ity and dense cortical plates (77). Complications acne, pustulosis, hyperostosis, and osteitis). include sequestra formation, cortical disruption, Peak incidence of chronic osteomyelitis of sinus tract formation, and pathologic fractures. the jaw occurs during the 5th and 6th decades The presence of a sequestrum or involucrum of life, with a slight male predilection, while are the most reliable imaging findings to differen- PCO demonstrates an early peak in incidence in tiate chronic osteomyelitis from similar-appearing RG Volume 41 Number 4 Holmes et al 1179 lesions such as osteosarcoma and fibrous dys- opment range from 8 to 19 months (91–93), with plasia (82). Distinguishing chronic osteomyelitis 90% of cases usually occurring within 3 years (94). from osteonecrosis is frequently not possible at Osteoradionecrosis is likely the result of conventional imaging and, in many cases, both radiation-induced microvascular dysfunction conditions will coexist. Bone SPECT/CT demon- leading to tissue hypoxia, hypovascularity, and strates significantly higher maximum standardized hypocellularity, which result in a chronic nonheal- uptake (SUVmax) value in chronic osteomyelitis, ing wound (87). The mandible is more commonly which may be useful for differentiation from med- affected compared with the maxilla, as it is more ication-related osteonecrosis of the jaw (MRONJ) frequently contained within the irradiated field or osteoradionecrosis, although this remains to be and has a more susceptible blood supply (95). replicated (83). To the authors’ knowledge, radio- Risk factors for osteoradionecrosis include treat- labeled white blood cell scintigraphy is sensitive ment factors such as total radiation dose (typi- for mandibular osteomyelitis (84). However, its cally greater than 60 Gy), size and proximity of specificity in patients with MRONJ or osteoradio- therapeutic field, and concomitant chemotherapy, necrosis has not been demonstrated. as well as patient factors including poor dentition, PCO typically differs from suppurative cases smoking, alcohol abuse, and malnutrition (87). radiologically by manifesting with widespread Clinically, patients typically present with sclerosis of the jaw, with only minor osteolytic neuropathic pain, swelling, sensory changes, or areas (85). Periosteal reaction in PCO is often the development of an orocutaneous fistula (87). multilamellated or “onion skin” in appearance. These features may also be accompanied by other However, with increased disease duration, appo- long-term complications of radiation therapy, sitional subperiosteal new bone produces an ap- including xerostomia, trismus, dysphagia, and pearance of cortical thickening similar to that of dental caries (96). Caffey disease (79), hence the alternative name At CT, osteoradionecrosis exhibits a mixed periostitis ossificans. Cortical disruption and lytic-sclerotic pattern manifesting as cortical fistulous tracts are characteristically absent (86), erosions and loss of adjacent trabeculae, with while mandibular canal enlargement is a recently interspersed bony sequestra (Fig 18) (87,96). recognized distinct imaging feature of PCO. Typi- Widening of the periodontal ligament space of cal MRI features of marrow edema, mandibular nearby teeth and thickening of surrounding soft nerve enhancement, and mild surrounding soft- tissues are also commonly visualized. Severe tissue (eg, masseter) edema are found in PCO cases often exhibit bicortical involvement and can (86), although, given a strong propensity for lead to pathologic fracture. Lesions are typically sclerosis, diffuse T1 and T2 hypointensity are also unilateral and characteristically affect the body of common (85). the mandible, sparing the parasymphyseal regions Treating chronic osteomyelitis of the jaw in- owing to enhanced blood supply (Fig 19). volves surgical débridement followed by culture- MRI signal intensity patterns of osteoradione- directed antimicrobial therapy (77). The extent of crosis are similar to those of drug-related osteo- surgical intervention can range from sequestrec- necrosis. Focal marrow signal with T1 hypoin- tomy to resection and reconstruction dependent tensity and variable T2-weighted fat-suppressed on the scope of infection, with imaging playing an short inversion time inversion-recovery (STIR) important role in preoperative planning. signal, ranging from hypointense to markedly hyperintense, can be visualized (97,98). Cortical Osteoradionecrosis.—Osteoradionecrosis oc- changes including erosions, fragmentation, and curs in 5%–7% of patients as a complication sequestra formation can also be visualized but after radiotherapy (87). It is defined as an area of are better assessed at CT. Surrounding soft-tissue exposed irradiated bone that persists as a nonheal- edema and enhancement involving the masticator ing osteonecrotic region for greater than 3 months, space are well-delineated at MRI (99). without evidence of persistent or recurrent tumor The radiologic appearance of osteoradio- (88). Importantly, similar bony changes can also necrosis can be nonspecific and challenging to be demonstrated with diagnostic imaging in the differentiate from a recurrent malignancy. With absence of mucosal disruption (87). Early stud- that, lesions located distant and contralateral to ies of osteoradionecrosis found the highest risk of the primary tumor support a diagnosis of osteo- disease occurring during the initial 6–12 months radionecrosis. The presence of bony sclerosis or following external beam radiation therapy without a well-defined solid or cystic mass is the most intensity modulation (89,90). Recent literature useful CT feature to suggest osteoradionecrosis based on intensity-modulated radiation therapy over recurrent tumor (100). While an uncom- now suggests that earlier onset may be correlated mon finding, intraosseous gas has been found with higher doses, although median times to devel- to be specific for osteoradionecrosis rather than 1180 July-August 2021 radiographics.rsna.org Figure 18. Osteoradionecrosis in a patient 3 years after chemotherapy and radiation therapy for tonsil- lar squamous cell carcinoma. (a) Sagittal CT image through the mandible shows a mixed lytic-sclerotic region in the mandible body, with an associated pathologic fracture (arrow). The lesion is centered around a site of prior tooth extraction. (b) Coronal contrast-enhanced CT image shows surrounding inflammatory changes (arrowhead) in the soft tissues. Figure 19. Osteoradionecrosis in a patient 8 years after chemotherapy and radiation therapy for base- of-tongue squamous cell carcinoma. Axial CT images show early mixed lytic and sclerotic changes in the right hemimandible (arrow in a). Comparison of the submandibular glands (arrowheads in b) shows atrophy of the right gland, findings in keeping with soft-tissue postradiation therapy changes. recurrence (100). Osteoradionecrosis appears to metabolically active cells, such as technetium to demonstrate restricted diffusion at MRI, and 99m (99mTc) sestamibi and thallium 201 (201Tl), therefore this feature is unlikely to be useful as a have been shown to demonstrate relative photo- dichotomous imaging finding (101). Quantitative penia in osteoradionecrosis (105,106), present- differences in apparent diffusion coefficients may ing a possible noninvasive option to differentiate be a differentiating feature between recurrence osteoradionecrosis from recurrent cancer. and posttreatment changes (102). However, this A conservative approach to management of remains to be demonstrated in osteoradionecrosis osteoradionecrosis involves débridement, antibi- specifically. otic therapy, wound care, and oral hygiene, which Functional imaging may present the most is sufficient for mild cases. More extensive or useful means of differentiating osteoradionecro- refractory lesions necessitate resection and recon- sis and recurrent tumor. Unfortunately, fluorine struction (107). Hyperbaric oxygen therapy may 18 fluorodeoxyglucose (FDG) PET has been also be used as an adjunct in early-stage disease. shown to be unreliable in differentiating osteora- However, evidence for its use remains controver- dionecrosis from recurrent tumor. At FDG PET, sial when surgical intervention is employed (108). recurrent tumor has a higher SUVmax and mean standardized uptake value compared with osteo- Medication-related Osteonecrosis of the Jaw.— radionecrosis, but significant overlap prevents MRONJ is a similar entity to osteoradionecrosis distinguishing these entities in individual patients and describes patients with exposed maxil- (100,103,104). Conversely, radiotracers that lofacial bone persisting longer than 8 weeks demonstrate avid uptake in most tumors related following treatment with an antiresorptive or RG Volume 41 Number 4 Holmes et al 1181 Figure 20. Two cases of MRONJ owing to bisphos- phonates. (a, b) Axial (a) and sagittal (b) mandible CT images in a patient receiving alendronate show a focal region of osteolysis in the left hemimandible body, as well as sclerosis evidenced by cortical thick- ening (arrow in a) and a bony sequestrum (white arrowhead in b). There is a pathologic fracture in keeping with stage 3 MRONJ, with healing perios- teal reaction (black arrowhead in b). There was no evidence of infection in the débridement specimen. (c) Coronal contrast-enhanced CT image shows an edentulous mandible with a lytic channel through the inferior margin of the mandible, which opens into a fistulous tract to the skin surface (arrow). These findings are in keeping with stage 3 MRONJ. concurrent Actinomyces infection have also been implicated (109). Clinically, patients commonly antiangiogenic agent (109). Again, this definition present reporting pain, loose teeth, or altered sen- overlooks cases with demonstrable radiographic sation but may also present with an asymptomatic changes without the presence of exposed bone, fistula or disruption in the oral mucosa. which are estimated to comprise one-third of Radiologic features of MRONJ include both patients (95). MRONJ was initially described in lytic and sclerotic changes (87). Initially, lesions patients receiving bisphosphonates, particularly predominately appear radiolucent, manifesting as intravenous zoledronate and pamidronate, but cortical erosions and reduced trabecular density. numerous other medications have since been Persistence of the tooth socket following extrac- implicated in MRONJ, including denosumab tion is also commonly observed. This is later and antiangiogenic agents such as bevacizumab accompanied by periosteal thickening transition- and sorafenib (109). Development of MRONJ ing to regular sclerotic foci, forming new bone is also much more prevalent in the setting of in parallel with existing cortex. Sclerotic changes malignancy, with risk of MRONJ among cancer also commonly cause narrowing of the periodon- patients approximately 100-fold higher than in tal ligament space and as the lesion matures, those treated with the same agents for osteo- areas of devitalized bone coalesce to give rise to porosis (109). Other factors that predispose to bony sequestra (Fig 20a, 20b). As expected, CT MRONJ include duration of treatment, with has a significant advantage over orthopantograms a sharp increase in prevalence after 4 years of in the detection of bony sequestra, which strongly antiresorptive therapy, as well as poor denti- alters surgical planning (110). MRONJ predomi- tion, bony exostoses, and dental procedures. In nately affects the mandible, frequently involving addition, MRONJ shares a number of systemic bony prominences with thin overlying mucosa risk factors with osteoradionecrosis, including such as exostoses and the mylohyoid ridge (111). diabetes, immunosuppression, smoking, and The radiographic appearance of MRONJ over- alcohol use (95). laps substantially with that of osteoradionecrosis. Given the classes of medications associated However, the former typically appears with more with the condition, leading theories on the patho- pronounced sclerotic changes, both cortical and genesis involve inhibition of bone remodeling and trabecular, owing to the suppression of osteoclas- angiogenesis, although immune dysregulation and tic activity. Periosteal reaction is more common 1182 July-August 2021 radiographics.rsna.org in MRONJ compared with in osteoradionecrosis as sequestrectomy and segmental mandible resec- (101,112) but is only frequently found in higher tion have a primary role in treatment in addition stages (113). It is also important to differenti- to antimicrobial therapy (109). ate MRONJ from malignant lesions, which The best modality for evaluating the extent commonly exhibit a more aggressive pattern of of MRONJ is controversial. While FDG PET/ periosteal reaction. CT and contrast-enhanced MRI have been Adjunctive imaging may also aid in distin- suggested to be superior even to intraoperative guishing MRONJ, with bone scintigraphy and assessment (118), others find that MRI and CT MRI both found to be highly sensitive in depic- are prone to both over- and underestimation of tion of the disease (111). MRONJ has been involvement (119). relatively well studied at MRI. Focal T1 hypoin- tense marrow signal is the earliest MRI finding Conclusion of MRONJ (114). Similar to osteoradionecrosis, Owing to specialized tissues and anatomy, the MRONJ demonstrates focal well-delineated T1 jaw bones give rise to numerous unique lesions, hypointense marrow in all cases. T2-weighted requiring the consideration of a broadened differ- fat-suppressed STIR signal intensity in MRONJ ential diagnosis when assessing patients radiologi- is variable, as expected, based on its CT ap- cally. Organizing jaw radiopacities by attenuation pearance (115). Marked hyperintensity is found pattern and relationship to teeth allows a prag- in the majority of cases. However, minimal matic and systematic radiologic approach to jaw hyper- to isointensity can be expected in up to lesions. With a robust knowledge of epidemio- 29% of cases (116). Areas of lower T2 signal logic, clinical, and radiographic features, one can intensity demonstrate correspondingly lower confidently arrive at a final diagnosis or a short enhancement in both the presence and absence differential diagnosis in most cases. of bony sequestra (116). Morphologically, areas of exposed necrotic bone have been found to References correlate with low T1- and T2-weighted fat-sup- 1. Curé JK, Vattoth S, Shah R. Radiopaque jaw lesions: an approach to the differential diagnosis. RadioGraphics pressed STIR signal intensity, as well as photo- 2012;32(7):1909–1925. penia at bone scintigraphy/SPECT. Surrounding 2. Ulano A, Bredella MA, Burke P, et al. Distinguishing unexposed bone is often necrotic with regenera- untreated osteoblastic metastases from enostoses using CT attenuation measurements. AJR Am J Roentgenol tive vascularity and/or inflammation, leading 2016;207(2):362–368. to high T2 signal intensity and increased bone 3. Thompson LDR. Odontoma. Ear Nose Throat J radiotracer uptake (117). Common surrounding 2019;145561319890175. 4. Pippi R. Odontomas and supernumerary teeth: is there a soft-tissue findings include mandibular nerve common origin? Int J Med Sci 2014;11(12):1282–1297. thickening as well as pterygoid muscle edema 5. Rajendra Santosh AB, Ogle OE. Odontogenic Tumors. and enhancement (114). Dent Clin North Am 2020;64(1):121–138. 6. Kaugars GE, Miller ME, Abbey LM. Odontomas. Oral Surg The American Association of Oral and Maxillo- Oral Med Oral Pathol 1989;67(2):172–176. facial Surgeons endorses a clinical staging system 7. Budnick SD. Compound and complex odontomas. Oral to stratify patients with MRONJ, which influences Surg Oral Med Oral Pathol 1976;42(4):501–506. 8. Seehra J, Patel S, Bryant C. Gardner’s Syndrome revisited: management (109). Stage 0 refers to the unex- a clinical case and overview of the literature. J Orthod posed bone variant, manifesting with nonspecific 2016;43(1):59–64. symptoms and characteristic radiographic changes. 9. Slootweg PJ. Lesions of the jaws. Histopathology 2009;54(4):401–418. Stage 1 is defined as asymptomatic bony exposure 10. Wright JM, Vered M. Update from the 4th Edition of the lacking clinical evidence of infection, with any ra- World Health Organization Classification of Head and Neck diographic changes limited to alveolar bone. Stage Tumours: Odontogenic and Maxillofacial Bone Tumors. Head Neck Pathol 2017;11(1):68–77. 2 refers to patients with exposed and necrotic 11. Nelson BL, Thompson LDR. Ameloblastic fibro-odontoma. bone who have developed infectious features, with Head Neck Pathol 2014;8(2):168–170. radiographic involvement again limited to alveolar 12. Chrcanovic BR, Gomez RS. Ameloblastic fibrodentinoma and ameloblastic fibro-odontoma: an updated systematic bone. Stage 3 encompasses a range of complicated review of cases reported in the literature. J Oral Maxillofac disease including pathologic fracture, extraoral Surg 2017;75(7):1425–1437. fistulas, oroantral or oronasal communications, 13. Alsufyani NA, Lam EWN. Osseous (cemento-osseous) dysplasia of the jaws: clinical and radiographic analysis. J or bony involvement beyond the alveolar region Can Dent Assoc 2011;77:b70. (Fig 20c). Treatment of MRONJ is influenced by 14. Macdonald-Jankowski DS. Focal cemento-osseous radiologic staging, which highlights the role of the dysplasia: a systematic review. Dentomaxillofac Radiol 2008;37(6):350–360. radiologist. Stages 0 and 1 are managed nonop- 15. MacDonald-Jankowski DS. Florid cemento-osseous eratively, and stage 2 is managed primarily with dysplasia: a systematic review. Dentomaxillofac Radiol oral antimicrobial rinse and oral antibiotics with a 2003;32(3):141–149. 16. Resnick CM, Novelline RA. Cemento-osseous dysplasia, minor role for surgical débridement. Features of a radiological mimic of periapical dental abscess. Emerg stage 3 MRONJ are most important to recognize, Radiol 2008;15(6):367–374. RG Volume 41 Number 4 Holmes et al 1183 17. Chadwick JW, Alsufyani NA, Lam EWN. Clinical and 42. Majoor BCJ, van de Sande MAJ, Appelman-Dijkstra NM, radiographic features of solitary and cemento-osseous et al. Prevalence and clinical features of mazabraud syn- dysplasia-associated simple bone cysts. Dentomaxillofac drome: a multicenter european study. J Bone Joint Surg Radiol 2011;40(4):230–235. Am 2019;101(2):160–168. 18. Brannon RB, Fowler CB, Carpenter WM, Corio RL. Ce- 43. Lee JS, FitzGibbon EJ, Chen YR, et al. Clinical guidelines for mentoblastoma: an innocuous neoplasm? A clinicopathologic the management of craniofacial fibrous dysplasia. Orphanet study of 44 cases and review of the literature with special J Rare Dis 2012;7(Suppl 1):S2. emphasis on recurrence. Oral Surg Oral Med Oral Pathol 44. Mangion J, Edkins S, Goss AN, Stratton MR, Flanagan Oral Radiol Endod 2002;93(3):311–320. AM. Familial craniofacial fibrous dysplasia: absence of link- 19. Chrcanovic BR, Gomez RS. Cementoblastoma: An updated age to GNAS1 and the gene for cherubism. J Med Genet analysis of 258 cases reported in the literature. J Cranio- 2000;37(11):E37. maxillofac Surg 2017;45(10):1759–1766. 45. Beaman FD, Bancroft LW, Peterson JJ, Kransdorf MJ, 20. Huber AR, Folk GS. Cementoblastoma. Head Neck Pathol Murphey MD, Menke DM. Imaging characteristics of 2009;3(2):133–135. cherubism. AJR Am J Roentgenol 2004;182(4):1051–1054. 21. Abrahams JJ, Berger SB. Inflammatory disease of the jaw: 46. Riddle ND, Bui MM. Fibrous dysplasia. Arch Pathol Lab appearance on reformatted CT scans. AJR Am J Roentgenol Med 2013;137(1):134–138. 1998;170(4):1085–1091. 47. Stanton RP. Surgery for fibrous dysplasia. J Bone Miner 22. Sisman Y, Ertas ET, Ertas H, Sekerci AE. The frequency Res 2006;21(Suppl 2):P105–P109. and distribution of idiopathic osteosclerosis of the jaw. Eur 48. MacDonald-Jankowski DS, Yeung R, Li TK, Lee KM. J Dent 2011;5(4):409–414. Computed tomography of fibrous dysplasia. Dentomaxil- 23. Kaplan I, Nicolaou Z, Hatuel D, Calderon S. Solitary lofac Radiol 2004;33(2):114–118. central osteoma of the jaws: a diagnostic dilemma. Oral 49. Altman RD, Bloch DA, Hochberg MC, Murphy WA. Surg Oral Med Oral Pathol Oral Radiol Endod 2008; Prevalence of pelvic Paget’s disease of bone in the United 106(3):e22–e29. States. J Bone Miner Res 2000;15(3):461–465. 24. Larrea-Oyarbide N, Valmaseda-Castellón E, Berini-Aytés 50. Ralston SH. Juvenile Paget’s disease, familial expansile L, Gay-Escoda C. Osteomas of the craniofacial region. osteolysis and other genetic osteolytic disorders. Best Pract Review of 106 cases. J Oral Pathol Med 2008;37(1):38–42. Res Clin Rheumatol 2008;22(1):101–111. 25. Sayan NB, Uçok C, Karasu HA, Günhan O. Peripheral 51. Ralston SH. Clinical practice. Paget’s disease of bone. N osteoma of the oral and maxillofacial region: a study of 35 Engl J Med 2013;368(7):644–650. new cases. J Oral Maxillofac Surg 2002;60(11):1299–1301. 52. Cooper C, Dennison E, Schafheutle K, Kellingray S, Guyer 26. Singh A, Solomon MC. Osteoid osteoma of the mandible: P, Barker D. Epidemiology of Paget’s disease of bone. Bone A case report with review of the literature. J Dent Sci 1999;24(5 Suppl):3S–5S. 2017;12(2):185–189. 53. Cundy T, Reid IR. Reprint: Paget’s disease of bone. Clin 27. Ostrofsky M, Morkel JA, Titinchi F. Osteoma of the man- Biochem 2012;45(12):970–975. dibular condyle: a rare case report and review of the literature. 54. Paul Tuck S, Layfield R, Walker J, Mekkayil B, Francis J Stomatol Oral Maxillofac Surg 2019;120(6):584–587. R. Adult Paget’s disease of bone: a review. Rheumatology 28. Sonnier KE, Horning GM, Cohen ME. Palatal tu- (Oxford) 2017;56(12):2050–2059. bercles, palatal tori, and mandibular tori: prevalence and 55. Cheng YSL, Wright JM, Walstad WR, Finn MD. Osteo- anatomical features in a U.S. population. J Periodontol sarcoma arising in Paget’s disease of the mandible. Oral 1999;70(3):329–336. Oncol 2002;38(8):785–792. 29. Kolas S, Halperin V, Jefferis K, Huddleston S, Robinson 56. Cortis K, Micallef K, Mizzi A. Imaging Paget’s disease of HBG. The occurrence of torus palatinus and torus man- bone--from head to toe. Clin Radiol 2011;66(7):662–672. dibularis in 2,478 dental patients. Oral Surg Oral Med Oral 57. MacDonald-Jankowski DS. Gigantiform