Bone & Soft Tissue Pathology
Case 6 -
Osteosarcoma of Jaw (Maxilla)
Post-radiation Osteosarcoma of Jaw
A. Kevin Raymond
MD Anderson Cancer Center
Click on each slide thumbnail image for an enlarged view
Historically, osteosarcoma was viewed as a single, stereotypic disease with limited treatment options,
and a near universally dismal prognosis. With accrual and study of significant numbers of cases,
together with advances in diagnostic and therapeutic techniques, this viewpoint has been modified. It is
estimated that the incidence of osteosarcoma is 1 per 100,000 in the United States of America. But,
despite its rarity, osteosarcoma represents the most common non-hematological tumor of bone. Those cases
arising in the head and neck region comprises an estimated 6% of osteosarcoma.
Case 6 - Figure 1 - Imaging: CT-scan. There is a largely radio-opaque lesion involving the left maxilla. Tumor appears to arise from the posterior aspect of the maxilla and largely fills the posterior aspect of the maxillary sinus. Tumor invades both the medial and lateral walls, with extension into overlying connective tissues
Case 6 - Figure 2 - Imaging: CT-scan. There is a largely radio-opaque lesion involving the left maxilla. Tumor appears to arise from the posterior aspect of the maxilla and largely fills the posterior aspect of the maxillary sinus. Tumor invades both the medial and lateral walls, with extension into overlying connective tissues
Case 6 - Figure 3 - Imaging: CT-scan. The orbit appears free of tumor
Diagnosis: Osteosarcoma of jaw (maxilla) - Post-radiation Osteosarcoma of jaw
The demographics of jaw osteosarcoma are different than those arising in the appendicular skeleton.
Osteosarcoma is generally thought of as a disease of the young, most frequently affecting patients in the
second decade of life; affecting men more frequently than women (1.5:1 to 2:1 ratio); and showing a
profound proclivity for the distal femur, proximal tibia and proximal humerus. However, when looking at
those cases arising in the jaws, osteosarcoma tends to have a near-equal gender distribution and to occur
in near-equal numbers in a broad age range.
A number of conditions are associated with an increased incidence of osteosarcoma. The most frequent
are Paget's disease of bone (i.e., osteitis deformans) and radiation exposure. Less frequent
associations include retinoblastoma and fibrous dysplasia. Although there may be some variation between
series, these predisposing conditions are associated with less than 5% of appendicular osteosarcoma. In
contrast, as many as 20-30% of jaw osteosarcoma may arise in association with such predisposing factors.
Severe, unrelenting pain, with or without mass, is the hallmark of appendicular osteosarcoma. In
contrast, mass is the most common symptom in jaw osteosarcoma. It may be as much as 2-3 times more
common than pain as a presenting symptom. Less frequently encountered symptoms include anesthesia,
infection and bleeding.
Radographically, these lesions tend to be destructive and in the majority of cases, point towards a
diagnosis of malignancy. However, the imaging features may be somewhat non-specific. Although usually
at least partially mineralized, the degree of intra-lesional calcification and reactive bone formation in
jaw osteosarcoma tends to be significantly less that their appendicular counterparts. Most cases tend to
be mixed lytic/blastic, less frequently purely lytic and much less frequently purely radioopaque. Of
equal importance has been the historical limitation on staging information garnered from traditional
radiographic techniques. The use of CT and MRI have significantly added to our ability to accurately
assess the extramedullary extent of disease in jaw osteosarcoma. Unfortunately, current imaging
techniques are still limited in their ability to accurately define intraosseous tumor extension; of
particular importance in evaluating mandibular lesions and determination of the transmedullary resection
The overall appearance of these lesions is that of a destructive mass that may or may not have
resulted in expansion of the parent bone. More specific gross findings are reflective of the underlying
histology; specifically matrix content. Chondroblastic lesions tend to have an overall lobulated,
firm, slick, gray-blue cut surface. While osteoblastic lesions are granular, rock-hard and tan. Tumors
with a high content of neoplastic cells and minimal matrix (e.g., fibroblastic, small cell types)
typically have the classic tan to white, firm, fish-flesh appearance.
The histological features of jaw osteosarcoma reflects the diversity of osteosarcoma in general, while
at the same time providing some unique twists. Osteosarcoma is not a single tumor, but a family of
tumors which have in common the production of osseous matrix; a primary malignant tumor of bone in which
the neoplastic cells produce osteoid and/or bone, even if only in small amounts. Approximately 75% of
osteosarcoma has biological properties that are similar and are therefore comparable; i.e., conventional
osteosarcoma. The remaining 25% comprises "variants" that are biologically different from conventional
osteosarcoma, and each other. These variants are defined by a number of parameters reflecting clinical
setting, morphology or location on the surface of bone. All forms of osteosarcoma that are seen in the
appendicular skeleton (i.e., conventional and variants) may occur in the jaws; however, there appear to
be differences in the relative incidences.
As indicated above, 75% of cases of appendicular osteosarcoma, are "conventional" and their
histological appearance may be divided into three overall groups as a function of matrix production;
osteoblastic (50%), chondroblastic (25%) and fibroblastic (25%) subtypes. In most reported series of jaw
osteosarcoma there appears to be a predominance of one type over others; however, the specific
subtype(s) vary between series. As with Mayo Clinic, the M.D. Anderson Cancer Center series has a
predominance of chondroblastic osteosarcoma (45%). And while hyaline cartilage is the typical matrix of
appendicular chondroblastic osteosarcoma, this does not appear to be true of jaw osteosarcoma. The vast
majority of cases have cartilage matrix that is either myxoid cartilage or mimics the pattern seen in
periosteal osteosarcoma. In the former, the matrix is poorly formed, with infrequent lacunes and
stellate neoplastic cells similar to the appearance of soft tissue (myxoid) chondrosarcoma. While in the
second form, the cartilage has the appearance of zonated hyaline cartilage. It is centrally
hypocellular, while being hypercellular at the periphery, and osteoid is present either in the center
and/or as fine filigree lines running through and from the lobule periphery.
Metastasis, clinical or subclinical, is estimated to occur in >80-95% of appendicular
osteosarcoma. Prior to the advent of contemporary multidisciplinary therapy, these metastases resulted
in the deaths of the overwhelming majority (i.e., 80-95%). of osteosarcoma patients. Within anatomical
considerations and appropriate surgical options, local relapse is infrequent (i.e., 1-5%) in conventional
appendicular osteosarcoma. Although it may impact on ultimate survival, local relapse can usually be
managed surgically, as a site-dependent phenomenon. With the advent of contemporary multidisciplinary
therapy, and more precise definitions of appropriate therapy, the expected survival in appendicular
osteosarcoma is in the range of 55-70%.
In contrast, the incidence of metastasis in jaw osteosarcoma is relatively low and has been reported
as 6 - 21%. However, survival in jaw osteosarcoma has been reported at 30 - 60% and is a function of
both metastases, and to a greater extent, uncontrolled local relapse. Because of the rarity of the tumor
and relatively low incidence of metastases, systemic therapy has not undergone the intensive scrutiny in
jaw osteosarcoma that it has in its appendicular counterpart. Surgery therefore remains the mainstay of
Although different investigators point to a variety of outcome-determining prognostic factors, all
appear to agree on the importance of tumor size in relationship to surgical adequacy and the ability to
achieve complete tumor extirpation. In all series there appears to be a direct relationship between
resection margin status, local relapse and ultimate survival.
In the current case there is an additional prognostic factor: prior radiation therapy for
nasopharyngeal carcinoma. As a single prognostic factor survival in this group of patients is less than
20% at 5 years.
In summary, osteosarcoma of jaw represents a group of tumors with histological, radiographic and
biological properties sufficiently distinct from conventional/classical osteosarcoma that it is
recognized as an osteosarcoma "variant." There are features of anatomy and tumor/anatomical interaction
that provide unique clinical problems that significantly impact the evaluation and treatment of these
patients. At the same time there are histological features that are relatively unique to this group of
tumors that may cause diagnostic difficulties. At the same time, although complete surgical extirpation
of tumor remains the core of successful therapy, the precise role of systemic therapy remains to be
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