Mandible / Maxilla
Malignant tumors
Osteosarcoma

Author: Anthony Martinez, M.D. (see Authors page)
Editor: Kelly Magliocca D.D.S., M.P.H.

Revised: 30 January 2017, last major update December 2016

Copyright: (c) 2004-2017, PathologyOutlines.com, Inc.

PubMed search: osteosarcoma mandible[title] OR osteosarcoma maxilla [title] malignant

Cite this page: Osteosarcoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/mandiblemaxillaosteosarcoma.html. Accessed February 23rd, 2017.
Definition / General
  • Osteosarcoma (OS) is a malignant, high grade tumor of bone in which the tumor cells produce osteoid (bone)
Essential Features
  • Craniofacial osteosarcomas represent about 6.5% - 7% of all osteosarcomas
  • Patients with osteosarcomas of the jaw are generally 10 to 20 years older than those with osteosarcomas of long bones
  • Chondroblastic OS may be difficult to distinguish from chondrosarcoma due to sampling bias or OS that have large cartilaginous component
    • The cartilaginous component of a chondroblastic OS is usually high grade
    • Chondroblastic OS should be accompanied by osteoid production from the sarcomatous stromal cells
    • Many chondrosarcomas have IDH1 and IDH2 mutations, whereas chondroblastic OS do not
  • Low grade central osteosarcoma may demonstrate histologic overlap with benign fibro-osseous lesions
  • Complete surgical resection with wide margins has been reported as the most significant prognostic factor
Terminology
  • Osteosarcoma (OS)
  • Osteogenic sarcoma
  • Osteosarcoma of the jawbones
  • Conventional osteosarcoma
  • Chondroblastic osteosarcoma
  • Osteoblastic osteosarcoma
  • Secondary osteosarcoma
Epidemiology
  • Most common nonhematopoietic bone malignancy
  • Second most common bone malignancy after myeloma
  • Conventional OS has a bimodal age distribution
    • Most (~60%) seen in second decade
    • Second peak after 50 years
      • Usually in setting of radiation or other secondary causes such as Paget disease
  • Craniofacial osteosarcomas represent about 6.5% - 7% of all osteosarcomas
    • Conventional osteosarcomas are most common
    • Approximately 25% of craniofacial OS are of the chondroblastic subtype
    • Patients with osteosarcomas of the jaw are generally 10 to 20 years older than those with osteosarcomas of long bones
    • Males are affected more frequently than females
Classification
2013 WHO Classification for osteosarcoma is as follows:
  • Low grade central osteosarcoma
  • Conventional osteosarcoma
    • Osteoblastic
    • Chondroblastic
    • Fibroblastic
    • Secondary
  • Small cell osteosarcoma
  • Telangiectatic osteosarcoma
  • Parosteal osteosarcoma
  • Periosteal osteosarcoma
Sites
  • Mandibular tumors are more frequent in the posterior body and ramus
  • Maxillary lesions are more common along the alveolar ridge, sinus floor and palate than the zygoma or orbital rim
  • For other sites, please see osteosarcoma of long bones
Etiology
Clinical Features
  • Variable but can include pain, swelling, paresthesia and ulceration
Diagnosis
  • Diagnosis dependent on clinical, radiologic and pathologic correlation
Radiology Description
  • Can show radiopaque, radiolucent or mixed appearances on plain radiographs
  • May be destructive with permeative margins
  • May break through cortex and elevate periosteum
    • Sunburst pattern due to new bone formation in soft tissue
Prognostic Factors
  • Complete surgical resection with wide margins has been reported as the most significant prognostic factor
    • 70% overall 5 year survival with surgery alone
      • Better than extragnathic OS
  • ~50% of mandibular osteosarcomas recur locally after resection
    • Recurrence rate is even higher with maxillary and skull lesions (80% and 75%, respectively)
  • Metastases are less frequent than local recurrence and occur in about 1/3 of patients with craniofacial osteosarcomas
    • Typically occur within 2 years of initial treatment
  • Radiotherapy in addition to surgery improves overall survival, disease specific survival and local control in craniofacial osteosarcoma with positive / uncertain resection margins (Cancer 2009;115:3262)
Case Reports
Treatment
  • Radical surgery with adjuvant chemotherapy
  • Radiation can be added if tumor cannot be fully removed surgically
Clinical Images
Images hosted on other servers:

Swelling and extension over left zygomatic region

Swelling in left
premaxillary
region with upper
lip protrusion

Computed tomography axial section

Axial CT scan of maxilla showing expansive infiltrative lesion

Osteosarcoma involving right ramus mandibula

Lytic and destructive
lesion in the left maxillary
tuber and molar tooth
area with root resorption

Micro Description
  • Osteosarcomas are composed of sarcomatous tumor cells that produces malignant bone or osteoid
    • The tumor cells may have densely eosinophilic cytoplasm resembling osteoblasts but often are larger than normal osteoblasts and vary in size with nuclear atypia
    • The osteoid may be thin, lace-like (some say it resembles fungal hyphae) or or it may consist of broad, irregular trabeculae
      • The osteoid may be variable in amount
  • For craniofacial OS, conventional OS are most common so morphology would include:
    • Variably amounts of osteoblastic, fibroblastic (pure spindle cell growth with minimal matrix) or chondroblastic (malignant appearing cartilage with peripheral spindling and osteoid production)
Micro Images

Scroll to see all images.

Images hosted on PathOut server:

Case of the Week #350: chondroblastic osteosarcoma of maxilla





Contributed by Dr. Kelly Magliocca and Dr. Anthony Martinez:

Arrows = inferior
border of
the mandible;
Arrowheads =
osteosarcoma

4× (same as first image, without arrows)

40×

100×

200×

400×



Images hosted on other servers:

Chondroid tissue with areas of osseous differentiation

Chondrocytes with
hyperchromatic
and pleomorphic
nuclei

Photomicrograph showing tumor osteoid areas

a) Large osteosarcoma involv-
ing mandible ramus and body
b) Classic chondroblastic
osteosarcoma of the jaw


Various images

Immunohistochemistry
Molecular / Cytogenetics Description
  • Conventional osteosarcomas have complex karyotype with numerous aberrations
    • Chromothripsis is a genetic mechanism where a single cataclysmic event results in tens to hundreds of genomic rearrangements
  • Rb1 inactivation is common (~35%) of sporadic osteosarcomas
  • TP53 mutations also common
  • Differential Diagnosis
    • Chondrosarcoma
      • Can usually be distinguished from osteosarcoma on clinical, radiologic and pathologic grounds
      • More difficult to distinguish when osteosarcomas have large cartilaginous component such as chondroblastic OS
        • The cartilaginous component of a chondroblastic OS is usually high grade
        • Chondroblastic OS should be accompanied by osteoid production from the sarcomatous stromal cells
        • Many chondrosarcomas have IDH1 and IDH2 mutations
    • Fibrous dysplasia
      • Benign fibro-osseous lesion that may involved one or more bones
      • Curvilinear trabeculae (Chinese letters) of metaplastic woven bone (never matures) in hypocellular, fibroblastic stroma
      • Fibrous dysplasia is caused by mutations in GNAS gene
      • Malignant transformation rarely occurs
        • Can be secondary osteosarcoma
    • Ossifying fibroma
      • Benign fibro-osseous neoplasm that is composed of fibrous tissue that contains a variable amount of bony trabeculae or cementum-like spherules
      • Bony trabeculae may be lined by osteoblasts
      • Osteoblasts should not be atypical like the sarcomatous cells of osteosarcoma that produce osteoid
  • Osteoblastoma
    • Some larger osteoblastomas may show prominent periosteal new bone formation and may mimic osteosarcoma radiographically
      • May also involve the craniofacial bones
    • Similar to osteoid osteoma with a nidus containing an interlacing network of bone trabeculae distributed in a loose fibroblastic stroma with a prominent vasculature
      • Prominent rimming osteoblasts and multinucleated osteoclast-like giant cells can be seen
      • The mitotic rate can be high, but atypical mitoses are not seen