Pediatric maxillary and mandibular tumors offer considerable challenges to otolaryngologists, oral surgeons, pathologists, and radiologists alike. Because of the close proximity to vital structures, appropriate steps toward a definitive diagnosis and treatment plan are of paramount importance. This article reviews the most common causes of pediatric jaw masses and discusses diagnostic and therapeutic considerations and recommendations.
Key points
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Pediatric masses of the jaw can include both benign and malignant processes of both odontogenic and nonodontogenic origin, as well as infectious processes.
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High-resolution imaging with computed tomography and/or MRI can be suggestive, but often a definitive diagnosis requires tissue for histopathology.
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Treatment is usually surgical and must take into account the growth potential of the facial bones, the aggressiveness of the lesion, and the rate of recurrence.
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The clinical presentation of certain benign jaw lesions may suggest an underlying genetic disorder.
| BL | Burkitt lymphoma |
| CGCG | Central giant cell granuloma |
| CT | Computed tomography |
| ES | Ewing sarcoma |
| FD | Fibrous dysplasia |
| LCH | Langerhans cell histiocytosis |
| MRI | Magnetic resonance imaging |
| NBCCS | Nevoid basal cell carcinoma syndrome |
| OKC | Odontogenic keratocyst |
| PCO | Primary chronic osteomyelitis |
| PFD | Polyostotic fibrous dysplasia |
| PTCH | Patched |
| XRT | Radiotherapy |
Introduction
Pediatric maxillary and mandibular tumors encompass a broad range of causes, histopathologies, and clinical behaviors. Although many benign lesions are asymptomatic and are discovered only on a routine dental radiograph, locally aggressive lesions and malignancies can cause pain, facial swelling, and trismus. The work-up is often challenging because many of the tumors have nonspecific radiographic findings; open or excisional biopsy is often necessary for a definitive diagnosis. Treatments range from simple enucleation to a large segmental resection and reconstruction. The clinician must be cognizant of both odontogenic and nonodontogenic processes that can be involved in order to prevent either an unnecessarily aggressive resection with resultant facial deformity or an overly conservative resection that leads to recurrence.
Introduction
Pediatric maxillary and mandibular tumors encompass a broad range of causes, histopathologies, and clinical behaviors. Although many benign lesions are asymptomatic and are discovered only on a routine dental radiograph, locally aggressive lesions and malignancies can cause pain, facial swelling, and trismus. The work-up is often challenging because many of the tumors have nonspecific radiographic findings; open or excisional biopsy is often necessary for a definitive diagnosis. Treatments range from simple enucleation to a large segmental resection and reconstruction. The clinician must be cognizant of both odontogenic and nonodontogenic processes that can be involved in order to prevent either an unnecessarily aggressive resection with resultant facial deformity or an overly conservative resection that leads to recurrence.
Nonodontogenic benign tumors
Osteoma
Osteomas are slow-growing benign osteogenic tumors most commonly discovered in late adolescents and young adults. They are composed of well-differentiated lamellar or compact bone. Although small endosteal (derived from bone marrow) lesions are often asymptomatic, larger lesions can cause a progressive enlargement of the affected area with impingement on adjacent structures. Paranasal sinus osteomas are more common than mandibular osteomas, and most of these arise in the frontal or ethmoid sinuses. Maxillary osteomas are rare, and can remain asymptomatic for long periods of time. Mandibular lesions are commonly found in the posterior body or mandibular condyle, with the latter causing a progressive shift in occlusion. Treatment includes either watchful waiting for smaller or asymptomatic maxillary tumors or conservative surgical excision for symptomatic tumors.
In addition to the differential from more aggressive bone-forming tumors, the discovery of a craniofacial osteoma is significant because of the association with Gardner syndrome, which is a triad consisting of colonic polyps, multiple osteomas, and soft tissue tumors such as epidermoid cysts and desmoid tumors. Gardner syndrome is an autosomal dominant disorder with near 100% penetrance caused by a genetic mutation at chromosome 5. Colonic polyps begin to manifest during puberty and have a high rate of malignant transformation. The onset of multiple osteomas during puberty should alert the clinician to the possibility of Gardner’s syndrome.
Osteoblastoma
Osteoblastomas are benign neoplasms of osteoblasts. In the pediatric population they are usually discovered during adolescence. Osteoblastomas often present with pain and swelling that is not relieved with nonsteroidal antiinflammatory drugs. Craniofacial osteoblastomas most commonly involve the medullary bone of the posterior mandible, appearing as radiopaque or radiolucent lesions with patchy areas of mineralization. Most cases are treated successfully by local excision or curettage; however, an aggressive variant of osteoblastoma with irregular histologic features has been described with a recurrence rate of up to 50%.
Fibrous Dysplasia
Fibrous dysplasia (FD) is a nonneoplastic disease caused by the replacement of normal bony architecture by fibrous connective tissue in a loose, whorled pattern intermixed with irregular areas of bony trabeculae. It is caused by a sporadic mutation in the GNAS1 gene on chromosome 20, resulting in abnormal osteoblast differentiation and irregular bone formation. The clinical presentation is that of painless, slowly progressive swelling of the involved bones. FD can be divided into monostotic or polyostotic disease.
Monostotic FD accounts for approximately 80% of patients and usually presents during the second decade of life at periods of significant bone growth. Between 10% and 25% of cases involve the head and neck, and the maxilla is involved twice as often as the mandible. Maxillary lesions are often not monostotic and can involve multiple contiguous facial bones; hence the term craniofacial FD. Lesions classically appear as ground-glass calcifications on radiographs and computed tomography (CT) resulting from disorganized bony trabeculae and are often poorly demarcated, blending into surrounding normal bone ( Fig. 1 ).
Polyostotic FD (PFD) involves 2 or more bones; about 25% of patients have involvement of more than half of the skeleton. PFD can be seen in patients with multiple café-au-lait spots, termed Jaffe-Lichtenstein syndrome. PFD can also be seen in McCune-Albright syndrome, a combination of PFD, café-au-lait spots, and one of various endocrinopathies. PFD in McCune-Albright syndrome often affects the craniofacial skeleton first, with 90% of lesions present by 3 to 4 years of age. Irregular, jagged café-au-lait spots (compared with the smooth, regular spots seen in neurofibromatosis) are often present at or shortly after birth. Endocrinopathies that may be present include precocious puberty (most common), hyperthyroidism, phosphate wasting, and growth hormone and prolactin excess.
Treatment of FD depends on the severity of symptoms, the sites of involvement, and the skeletal maturity of the patient. In many cases the disease stabilizes after the child reaches skeletal maturity, thus small lesions without significant functional or aesthetic deformity can be treated with watchful waiting. Medical treatment with bisphosphonates, especially in children with McCune-Albright syndrome, has been shown to improve bone pain associated with FD, although it may not affect the natural progress of the disease. Surgical removal of maxillary and mandibular disease can entail radical resection and reconstruction with bone graft or free osteocutaneous flap, or can be delayed by managing malocclusion with orthodontic treatment until facial skeletal maturity is reached with subsequent orthognathic procedures. Radiation is not a recommended treatment of FD.
Juvenile Ossifying Fibroma
Juvenile ossifying fibromas are fibro-osseous lesions seen most commonly in the craniofacial skeleton in children aged 5 to 15 years. There are 2 histopathologic subtypes:
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Trabecular, occurring in younger children, with a predilection for the maxilla
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Psammomatoid, which are more common and often seen in the orbitofrontal bones or paranasal sinuses, although mandibular involvement of both subtypes has been seen
They present as either gradual or rapid painless expansions of the regions involved, with the potential to impinge on vital structures. Unlike the lesions of FD, they are typically well-circumscribed radiolucencies on radiograph and CT with expansion and possible perforation of overlying cortical bone. Like FD, lesions can contain central calcifications, giving both a ground-glass appearance. Although treatment of slower-growing lesions may include conservative excision and/or curettage, a wide resection may be necessary for rapidly growing tumors, especially because they can present similarly to a malignancy. There is also a much higher rate of recurrence than osteomas or FD, ranging from 30% to 60%.
Central Giant Cell Granuloma
Central giant cell granulomas (CGCGs), formerly referred to as reparative granulomas, are benign tumors found in children, adolescents, and young adults. About 70% of CGCGs occur in the mandible, with a predilection for anterior portions of bone with possible expansion to the contralateral side. Lesions are mostly asymptomatic, although more aggressive variants can present with localized swelling and pain. Radiographic findings are nonspecific because lesions may be unilocular or multilocular and can be confused with periapical cysts, ameloblastomas, and others ( Fig. 2 ). Histopathologic examination is crucial for diagnosis, showing multinucleated giant cells in a background of loose cellular stroma containing spindle-shaped mesenchymal cells. CGCGs are histologically similar to brown tumors, thus hyperparathyroidism should be ruled out once discovered in children. CGCGs have been classified clinically into nonaggressive and aggressive lesions, with the rare aggressive subtype resulting in more rapid growth, pain, paresthesias, and a tendency to recur after surgical curettage.
The treatment of CGCGs has classically been thorough surgical curettage; however, a recurrence rate of 11% to 49% has been reported, with higher recurrence rates in aggressive subtypes and in younger patients. Radical resection is an option but can be disfiguring. Alternatives to surgery that have been investigated include calcitonin injections, intralesional steroid injection, and interferon alfa-2a. Intradermal and intranasal salmon calcitonin have been used with moderate success in younger patients when trying to avoid a large resection and in aggressive lesions as an adjunct to curettage. Intralesional steroid injections have had a success rate of about 65% in limited cases, although there are few if any randomized controlled trials studying injections. Interferon alfa-2a has recently been used in aggressive lesions to curtail rapid growth and possibly diminish the size of the tumors; however, preliminary evidence suggests that total remission may not be possible without additional surgery.
Cherubism
Cherubism refers to a rare skeletal dysplasia caused by an autosomal dominant mutation in the SH3BP2 gene on chromosome 4. It presents clinically as bilateral cheek swelling caused by symmetric fibro-osseous lesions involving the posterior mandible. The disease usually becomes clinically evident between the ages of 2 and 7 years. Lesions can expand to involve the orbital floor, causing characteristic upturned eyes with exposure of the inferior sclera. On radiography the lesions appear as multilocular, expansile radiolucencies that are usually bilateral and symmetric. Most cases of cherubism stabilize by puberty and regress thereafter, thus less severely affected children can be followed with watchful waiting. Lesions causing severe cosmetic deformity or functional compromise can be treated surgically, preferably after puberty during the quiescent phase.
Nonodontogenic cysts
Nonodontogenic cysts of the maxilla and mandible in children are uncommon compared with their odontogenic counterparts. These lesions are often clinically similar to odontogenic cysts, with the diagnosis only established by histopathologic examination at the time of surgery.
Simple bone cysts, also known as traumatic bone cysts or hemorrhagic bone cysts, are made of cavities within bone without a true epithelial lining. They are generally encountered during adolescence and are rare in children less than 5 years of age. Nearly all cases in the head and neck involve the mandible. They are thought to arise out of trauma that causes intraosseous hemorrhage and resultant pseudocyst formation after reorganization. Surgical exploration for large or symptomatic lesions is warranted. The walls of the cavity are thin and shiny with minimal tissue obtained because of the lack of an epithelial structure. Curettage of the surrounding bone is often necessary to obtain a definitive diagnosis and to rule out more aggressive lesions. Recurrences are uncommon.
Aneurysmal bone cysts are rare benign lesions consisting of intraosseous blood-filled spaces separated by fibrous connective tissue septae. The cause is unknown, although trauma may be an inciting event. About 60% of lesions occur during the first 2 decades of life, and 3% of cases involve the head and neck, with most cases involving the mandible. The usual presentation is rapid onset of pain and jaw swelling that may be mistaken for acute osteomyelitis. MRI is helpful for diagnosis, showing characteristic trabeculations separating spaces filled with blood ( Fig. 3 ). Treatment of the lesion is surgical. Curettage may be difficult because of the vascularity of the cyst, thus enucleation or en bloc resection may be necessary for larger lesions.
Langerhans cell histiocytosis
Langerhans cell histiocytosis (LCH) refers to a spectrum of diseases characterized by the proliferation of antigen-presenting dendritic histiocytes, or Langerhans cells. More than 60% of cases are diagnosed in children less than 16 years old, with up to 70% of cases involving the head and neck. In children, the skull is the most common site involved, with the frontal bone being the most common bone affected. Only about 10% of cases involve the jaw, which differs from adults in whom the mandible is the most common bone affected.
LCH is most commonly limited to a single organ system, especially in children between 5 and 16 years of age. Previously termed eosinophilic granulomas, lesions present as monostotic or polyostotic radiolucencies that can give teeth a floating-in-air appearance on radiographs because of the underlying bone loss. Children present with jaw swelling, pain, loose teeth, and gingival recession that can often be misdiagnosed as periodontitis.
Multisystem involvement in LCH is more commonly seen in children less than 3 years old. Nearly any organ system can be involved with the characteristic lesions of LCH, including brain, lung, liver, bone marrow, and skin. Between 10% and 20% of patients with systemic involvement develop diabetes insipidus.
The treatment and prognosis in LCH depends on the extent of disease and sites of involvement. Isolated osseous lesions of the jaw have the best prognosis, with granulomas responding well to curettage or local excision. Intralesional steroid injections have also been shown to be efficacious in some lesions. Children with multisystem involvement require prolonged multiagent chemotherapy.
Osteomyelitis
Osteomyelitis of the craniofacial skeleton most commonly involves the mandible. Most cases are caused by spread of an odontogenic bacterial infection to cortical and cancellous bone. Chronic bacterial osteomyelitis is usually defined as an infection lasting longer than 4 weeks and is characterized by suppuration, sequestration of bone, and/or fistula formation. Imaging often shows sclerosis and periosteal thickening of bone with progressive lucencies over time ( Fig. 4 ). Cases lasting longer than 1 month without a clear odontogenic cause are referred to as primary chronic osteomyelitis (PCO), characterized by insidious onset of pain, swelling, and trismus without purulent drainage or cervical lymphadenopathy. Although PCO is characterized by a high recurrence rate after treatment, the clinical course tends toward eventual spontaneous remission.
The treatment of bacterial osteomyelitis of the jaw often involves long-term parenteral antibiotics in addition to resection of any necrotic bone. Conservative approaches such as decortication can be attempted for milder cases; however, antibiotic-resistant cases with fistula formation may require marginal or segmental resection.
Odontogenic cysts
Odontogenic cysts are common in the pediatric population. Although many odontogenic cysts are asymptomatic and found incidentally on radiographs, they can lead to bone destruction and displacement of teeth. Odontogenic cysts arise from the epithelium associated with tooth development and can occur in both the maxilla and the mandible. Compared with adults, children have a higher proportion of developmental cysts and fewer inflammatory cysts. Although typically benign, malignant transformation of various odontogenic cysts has been reported. A summary of the most common clinically benign odontogenic cysts in children is shown in Table 1 .
| Dentigerous Cyst | Eruption Cyst | Periapical Cyst | |
|---|---|---|---|
| Type of cyst | Developmental | Developmental | Inflammatory |
| Cause | Crown of an unerupted tooth | Separation of dental follicle during eruption | Dental pulp necrosis assoc. with nonvital tooth |
| Typical age (y) | >10 | <10 | All |
| Location | Third molars, maxillary canines | Incisors, first molars | All |
| Treatment | Marsupialization or extraction of tooth/enucleation | None; if tooth does not erupt then simple excision | Root canal or tooth extraction with enucleation/curettage |
Keratocystic Odontogenic Tumors
Although odontogenic keratocysts (OKCs) are still classified as odontogenic cysts, they have been given the name keratocystic odontogenic tumors by the latest World Health Organization classification because of their characteristic histologic features and aggressive clinical behavior. OKC originates from cell rests in the dental lamina of either the maxilla or mandible. They can be found at any age from infancy to adult, but within the pediatric population they most commonly occur during adolescence. The mandible is involved in more than 60% of cases, with a predilection for the posterior body and ascending ramus.
Although small OKCs are usually asymptomatic, they can grow to be extremely large, causing pain, swelling, and drainage ( Fig. 5 ). Unlike dentigerous and periapical cysts they tend not to cause obvious bone expansion within the medullary cavity, which can be helpful in making the diagnosis on radiographs; however, this finding is nonspecific. The definitive diagnosis of OKC is based on histopathologic examination, showing a thin fibrous capsule, an epithelial lining 4 to 8 cell layers in thickness, and a palisaded basal cell layer.
