—  SPECIALTY CONFERENCE  —

Bone & Soft Tissue Pathology

Case 6 - Osteosarcoma of Jaw (Maxilla)
Post-radiation Osteosarcoma of Jaw

A. Kevin Raymond
MD Anderson Cancer Center
Houston, TX


Click on each slide thumbnail image for an enlarged view
Clinical History
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



Case 6 - Figure 4 - Histology, one part of tumor (H&E). 40x
Case 6 - Figure 5 - Histology, one part of tumor (H&E). 250x
Case 6 - Figure 6 - Histology, one part of tumor (H&E). 250x



Case 6 - Figure 7 - Histology, interface between parts of the tumor (H&E). 40x
Case 6 - Figure 8 - Histology, interface between parts of the tumor (H&E). 100x
Case 6 - Figure 9 - Histology, another part of the tumor (H&E). 40x



Case 6 - Figure 10 - Histology, another part of the tumor (H&E). 250x
Case 6 - Figure 11 - Histology, another part of the tumor (H&E). 250x

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 margin.

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 therapeutic intervention.

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 defined.

References

  1. Bertoni, F., Dallera, P., Bacchini, P., Marchetti, C., Campobassi, A. The Istituto Rizzoli-Beretta experience with osteosarcoma of the jaw.; Cancer 68:1555-1563, 1991.
  2. Clark, J.L., Unni, K.K., Dahlin, D.C., Devine, K.D. Osteosarcoma of the Jaw. . Cancer 51:2311-2316, 1983.
  3. Chan, C.W., Kung, T.M., Ma, L. Telangiectatic Osteosarcoma of the Mandible. Cancer 58:2110-2115, 1986.
  4. Dahlin, D.C., Unni, K.K. Osteosarcoma of Bone and Its Important Recognizable Varieties. Amer J. Surg Pathol 1:61-72, 1977.
  5. Garrington, G.E., Scofiels, H.H., Cornyn, J., Hooker, S.P. Osteosarcoma of the Jaw. Analysis of 56 Cases. Cancer 29:377-391, 1967.
  6. Goepfert, H., Raymond, A.K., Spires, J.R., Chawla, S.P., Wolf, P.F., Lee, Y-Y, Batsakis, J.G. Osteosarcoma of the Head and Neck. ; Cancer Bulletin 42:341-354, 1990.
  7. Nora, F.E., Unni, K.K., Pritchard, D.J., Dahlin, D.C. Osteosarcoma of Extragnathic Craniofacial Bones. Mayo Clin Proc 58:268-272, 1983.
  8. Raymond, A.K., Chawla, S.P., Carrasco, C.H., et al. Osteosarcoma Chemotherapy Effect: A Prognostic Factor. Seminars Diag Pathol 4:212-236, 1987.
  9. Present, D, Bertoni, F., Enneking, W.F.. Osteosarcoma of the Mandible Arising in Fibrous Dysplasia. A Case Report. Clinical Orthopaedics 204:568-244, 1986
  10. Roca AN, Smith LJ, Jin BS. Osteosarcoma and Parosteal Osteogenic Sarcoma of the Maxilla and Mandible: Study of 20 Cases. Amer J Clin Path 54:625-636, 1970.
  11. van Es, R.J.J., Keus R.B., va der Waal, I., Koole, R., Vermey, A. Osteosarcoma of the Jaw Bones – Long-Term Follow up of 48 Cases. Int J Oral Maxillofac Surg, 20:191-197, 1997.
  12. Unni, K.K. Dahlin's Bone Tumors. General Aspects and Data on 11,087 Cases. fifth edition. Lippincott - Raven Publishers. Philadelphia. 1996.