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Malignant Neoplasms of the Gnathic Bones
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Osteosarcoma
Osteosarcoma (OS) is defined as a group of malignant tumors whose neoplastic cells produce bone. It is the most common primary malignant bone tumor. Aggressive behavior is usually associated with high-grade morphology of the atypical osteoid-producing osteoblasts. Tumors of the jaw are the fourth most common site of OSs, accounting for approximately 6% of all OSs. Other sites are paranasal sinuses and skull base.
Clinical Features
Osteosarcoma—Disease Fact Sheet
Definition
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Bone-producing sarcoma, frequently high grade
Incidence and Location
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Most common primary malignant bone tumor
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6% develop in the jaws
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Mandible > maxilla
Sex, Race, and Age Distribution
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Equal sex distribution
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Tend to be younger than appendicular skeleton, mean 35 years
Clinical Features
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Swelling and pain
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Possibly tooth displacement and overlying ulceration
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Radiation and Paget disease of bone may predispose
Radiographic Features
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Poorly defined, mixed radiodense and radiolucent
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Symmetrical widening of the periodontal ligament space in tooth bearing areas
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Sunburst periosteal reaction
Prognosis and Treatment
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Mortality is usually due to local disease, with distant metastases, usually in high-grade tumors
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Oncologic resection
Affected patients are one to two decades older than patients with peripheral OS, with an average age of 33 to 36 years, without a sex predilection. Most patients present with swelling and pain; tooth displacement and overlying ulceration are possible. Previous radiation or Paget disease of bone are predisposing factors to tumor development in a small subset of patients. There are more tumors in the mandible than maxilla.
Low-grade OSs (central and parosteal, Table 16.1 ) are genetically characterized by MDM2 amplification, whereas high-grade OSs show complex genetic changes.
TABLE 16.1
Osteosarcoma classification scheme
| Type | Variants | Grade |
|---|---|---|
| Central (intramedullary) | Conventional: | High |
| Osteoblastic | ||
| Chondroblastic | ||
| Fibroblastic | ||
| Rare variants: | High | |
| Teleangiectatic | ||
| Small cell | ||
| Epithelioid | ||
| Giant cell-rich | ||
| Osteoblastoma-like | ||
| Chondroblastoma-like | ||
| Low-grade central | Low | |
| Surface (juxtacortical) | Parosteal | Low |
| Periosteal | Intermediate | |
| High-grade surface | High |
Radiographic Features
Radiographs show a poorly defined mixed radiodense and radiolucent lesion, usually with soft tissue extension ( Fig. 16.1 ). Symmetrical widening of the periodontal ligament space in tooth bearing areas and sunburst periosteal reaction are radiologic hallmarks.
Pathologic Features
Osteosarcoma—Pathologic Features
Gross Findings
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(Multi)nodular tan-gray-white gritty and hard mass showing destruction of bone and infiltration into soft tissue
Microscopic Findings
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Histology is variable
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By definition, neoplastic bone must be identified
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Bone may be focal, immature, lace-like, sclerotic, or heavily mineralized
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Many subtypes are recognized, but in the jaws chondroblastic is most common
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Extension into soft tissue helps to diagnose low-grade tumors
Pathologic Differential Diagnosis
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Chondrosarcoma, benign fibro-osseous lesions (ossifying fibroma)
Gross Findings
OSs are (multi)nodular, tan-gray-white, gritty masses. Some tumors are very hard due to heavy mineralization. There is destruction of preexisting bone and often extension into soft tissue. Cartilaginous differentiation shows a gray, glistening cut surface like chondroid tumors. Sometimes there is a mucoid matrix, cystic degeneration, or hemorrhage.
Microscopic Findings
The histologic pattern can vary. Essential is the identification of neoplastic bone, which may be focal, immature to lace-like, and in other cases very sclerotic and heavily mineralized. Tumor cells in high-grade lesions are pleomorphic showing hyperchromatic nuclei ( Fig. 16.2 ). Low-grade lesions are well differentiated with slight pleomorphism and often obvious osteoblastic differentiation ( Fig. 16.3 ). Mitoses are often scarce, especially in low-grade tumors. Subtypes are listed in Table 16.1 , but in general the dominant matrix defines the variant: chondroblastic, osteoblastic, and fibroblastic subtypes. Chondroblastic OS is more common in the jaw bones and must be separated from chondrosarcoma (CS), which is quite rare in this site.
Differential Diagnosis
When osteoid production is low in the chondroblastic subtype, a CS must be considered. However, the presence of neoplastic bone, in any volume, defines OS. Low-grade OS should be distinguished from benign fibro-osseous lesions, such as ossifying fibroma, by cellular atypia and infiltration of the surrounding soft tissue.
Prognosis and Therapy
High mortality is due to local disease. Hematogenous spread in high-grade OS seems to be much more infrequent (up to 21% of patients) and seems to occur later in the course of disease compared with peripheral OS. The vast majority of patients are managed by complete resection. Multimodality treatment should be critically evaluated because the benefit in jaw tumors is not well documented.
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Chondrosarcoma
CS is a bone tumor that produces cartilage. Tumors of craniofacial bones are rare, accounting for only approximately 4% of all CS. The maxilla is more commonly affected than the mandible, but any site can be involved. In the mandible, the symphysis, coronoid process, and condyle are more often affected, sites corresponding to regions of endochondral ossification.
Clinical Features
Chondrosarcoma—Disease Fact Sheet
Definition
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A bone tumor that produces cartilage
Incidence and Location
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Rare, with jaw tumors representing 4% of chondrosarcoma
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Maxilla > mandible
Sex and Age Distribution
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Males slightly more than females
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The peak age at presentation is the 4th decade
Clinical Features
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Pain, swelling, and nasal obstruction
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Rare association with syndromes (Ollier disease, Maffucci syndrome)
Radiographic Features
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Radiolucent lesions with more or less evenly distributed punctuate or ring-like opacities
Prognosis and Treatment
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Recurrence and uncontrolled local extension is associated with a poor prognosis
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Oncologic resection is the treatment of choice
CS is a tumor of adulthood; however, the child/adolescent population may rarely be affected. The peak age at presentation is the 4th decade, with men affected slightly more often than women. Swelling and nasal obstruction are common complaints. Syndrome (Maffuci syndrom or Ollier disease) association is rare.
Radiographic Features
Cartilage neoplasms are radiolucent lesions with more or less evenly distributed punctuate or ring-like opacities. These discrete calcified opacities are the radiologic hallmark. There is variation from predominant lytic to heavily calcified with consolidated areas of opacity, difficult to distinguish from bone-forming lesions.
Pathologic Features
Chondrosarcoma—Pathologic Features
Gross Findings
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Lobulated architecture composed of translucent hyaline nodules
Microscopic Findings
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Uniformly cartilaginous and lobulated with a partially calcified or myxoid matrix
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Cluster disarray and increased cellularity
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Grading (I–III) depends on cellularity, atypia, and mitoses
Ancillary Studies
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Positive: S100 protein, SOX9, podoplanin
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IDH1/2 hot spot mutations
Pathologic Differential Diagnosis
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Chondroblastic osteosarcoma, chondrometaplasia, pleomorphic adenoma
Gross Findings
Lesions have a lobulated architecture composed of translucent hyaline nodules resembling more or less normal cartilage. Mineralized areas are chalk-like. Myxoid change, hemorrhage, and necrosis may be found, the latter usually a sign of a high-grade tumor.
Microscopic Findings
Tumors should be uniformly cartilaginous and lobulated with a partially calcified or myxoid matrix. Low-grade tumors (grade 1) show cluster disarray, slightly increased cellularity, and occasional nuclei with pleomorphism or binucleation, only slightly different from enchondroma. Grade II CS is characterized by a definite increased cellularity ( Fig. 16.4 ). The atypical chondrocytes are more or less evenly distributed with occurrence of loose clusters. Nuclei are enlarged with open chromatin and often distinct nucleoli. Binucleated cells are frequent and atypical multinucleated cells may be seen. Myxoid changes are frequently present. Myxoid CSs are classified as grade II, even when the cellularity is relatively low ( Fig. 16.5 ). High-grade CSs (grade III) are rare and characterized by high cellularity, prominent nuclear atypia, and the presence of mitotic figures. Importantly, chondroblastic OS is much more common in the jaws than primary CS.
Ancillary Studies
Seldom used, but CS are immunoreactive with S100 protein, SOX9, and podoplanin. Hot spot mutations in IDH1/2 are a genetic feature of CS in general.
Differential Diagnosis
Chondroblastic OS shows bone-forming areas. Reactive nodular proliferation of cartilage in the nasal septum may be misinterpreted as CS, while cartilaginous differentiation may be seen in pleomorphic adenoma.
Prognosis and Therapy
Resection is the treatment of choice. Wide oncologic margins are associated with a low recurrence rate. Recurrence and uncontrolled local extension is associated with a poor prognosis. Distant metastases are rare.
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Mesenchymal Chondrosarcoma
Mesenchymal chondrosarcoma (MCS) is a distinct and translocation-associated malignancy defined by a biphasic appearance of small blue round cells with focal cartilaginous differentiation. MCS is an extremely rare sarcoma and has a predilection for the facial skeleton, particularly the jaws, which are involved in approximately 25% of the cases.
Clinical Features
Mesenchymal Chondrosarcoma—Disease Fact Sheet
Definition
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Distinct and translocation-associated, small, blue round cell tumor with focal cartilaginous differentiation
Incidence and Location
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Extremely rare
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Predilection for the facial skeleton
Sex, Race, and Age Distribution
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Equal sex distribution
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Blacks and Latinos more commonly affected
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Age range is broad but mainly children and young adults
Clinical Features
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Swelling, mass, pain
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Site-dependent symptoms may be seen
Radiographic Features
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Destructive growth pattern
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Radiolucent lesion with varying degrees of stippled calcification
Prognosis and Treatment
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Aggressive behavior with early and very late metastases
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Surgery is treatment of choice
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Protracted and relentless clinical course, requiring long-term follow-up
MCS tends to affect children and young adults, although the age range is broad, without a sex predilection. Blacks and Latinas are more commonly affected. Swelling or mass and pain are the main symptoms. Additional site-dependent symptoms include loosening teeth, sinusitis, nasal obstruction, visual change, headaches, epistaxis, or signs of nerve dysfunction.
Radiographic Features
Radiographic features nearly always suggest malignancy with a destructive growth pattern. It appears as a radiolucent lesion with varying degrees of stippled calcification.
Pathologic Features
Mesenchymal Chondrosarcoma—Pathologic Features
Gross Findings
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Well-demarcated, lobulated, gray to pink tumor with foci of cartilage with or without calcification
Microscopic Findings
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Biphasic tumor with undifferentiated small blue round cells and a hyaline cartilaginous component
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Cartilage is often extremely limited requiring many tumor sections and/or deepers/levels
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Prominent staghorn-like vasculature
Ancillary Studies
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Positive: CD99, SOX9 in small cells; S100 protein in cartilaginous component
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Consistent fusion gene HEY1-NCOA2
Pathologic Differential Diagnosis
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Ewing sarcoma/primitive neuroectodermal tumor, synovial sarcoma, alveolar rhabdomyosarcoma, lymphoma, melanoma, undifferentiated carcinoma
Gross Findings
The tumor is usually well-demarcated from the surrounding bone and soft tissue, when involved, and may have a lobulated architecture. The tissue is gray to pink with foci of cartilage with or without calcification.
Microscopic Findings
MCS is a small blue round cell tumor with a distinct biphasic appearance, characterized by undifferentiated round to spindled cells and a hyaline cartilaginous component, which is the hallmark ( Fig. 16.6 ). However, the amount of cartilage may be very limited, frequently requiring many tumor sections and/or levels/deepers to reveal the cartilaginous foci. A staghorn-like vasculature is often present and prominent. The chondroid matrix may calcify and/or ossify.
Ancillary Studies
Immunohistochemically, CD99 and SOX9 are expressed in the small cells, whereas S100 protein highlights the cartilaginous component. The HEY1-NCOA2 fusion appears to be a helpful genetic marker. However, there is some genetic heterogeneity with alternate fusion partners. IDH1/2 mutations are absent.
Differential Diagnosis
Other small blue round cell tumors, such as Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma, undifferentiated carcinoma, melanoma, and lymphoma lack the chondroid component.
Prognosis and Therapy
MSCs are generally aggressive with early and very late metastases. Metastases can occur everywhere in the body. Surgery is the mainstay of treatment. The role of chemotherapy and radiation is uncertain. The clinical course is frequently protracted and relentless, making long-term follow-up mandatory. Some studies suggest the prognosis is more favorable for lesions arising in the jaws compared with other sites.
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Ameloblastic Carcinoma
Ameloblastic carcinoma (AC) is a very rare odontogenic malignancy that combines the histologic features of ameloblastoma and cellular pleomorphism, considered the malignant counterpart of ameloblastoma. They arise de novo or rarely from a preexisting ameloblastoma.
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