Osteosarcoma pathophysiology: Difference between revisions
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Revision as of 20:29, 29 September 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
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Osteosarcoma Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Osteosarcoma pathophysiology On the Web |
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American Roentgen Ray Society Images of Osteosarcoma pathophysiology |
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Risk calculators and risk factors for Osteosarcoma pathophysiology |
Overview
The osteosarcomas may be localized at the end of the long bones (commonly in the metaphysis). Most often it affects the upper end of tibia or humerus, or lower end of femur. On gross pathology, areas of bone formation, hemorrhage, fibrosis, and cystic degeneration on cut surface are characteristic findings of osteosarcoma. On microscopic histopathological analysis, presence of osteoid within the tumor, pleomorphic cells, anaplastic cells, and atypical mitoses are characteristic findings of osteosarcoma.
Pathophysiology
The osteosarcomas may be localized at the end of the long bones (commonly in the metaphysis). Most often it affects the upper end of tibia or humerus, or lower end of femur. Osteosarcomas tend to occur at the sites of bone growth, presumably because proliferation makes osteoblastic cells in this region prone to acquire mutations that could lead to transformation of cells (the RB gene and p53 gene are commonly involved).
Gross Pathology
- Macroscopically osteosarcomas are solid, hard, bulky tumors.
- Heterogeneous cut surface demonstrates areas of hemorrhage, fibrosis and cystic degeneration.
- Areas of bone formation are characteristic of osteosarcomas, with the degree of bone formation varying widely.
- The tumor is irregular ("fir-tree" or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating in right angles. These right angles form what is known as Codman's triangle, which is characteristic but not diagnostic of osteosarcoma. Surrounding tissues are infiltrated.
| [[file:osteosarcoma (2).jpg|thumb|350px|[1]] |
Microscopic Pathology
- The characteric feature of osteosarcoma is presence of osteoid (bone formation) within the tumor.
- Tumor cells are very pleomorphic, anaplastic, some are giant, and numerous atypical mitoses.
- These cells produce osteoid describing irregular trabeculae (amorphous, eosinophilic/pink) with or without central calcification (hematoxylinophilic/blue, granular) - tumor bone.
- Tumor cells are included in the osteoid matrix. Depending on the features of the tumor cells present (whether they resemble bone cells, cartilage cells or fibroblast cells), the tumour can be subclassified. Presence of immature blood vessels (sarcomatous vessels lacking endothelial cells) favors the bloodstream metastasizing.
Telanagiectatic osteosarcomas
- Most osteosarcomas have a small telangiectatic component but in order to classify as a telangiectatic osteosarcoma the telangiectatic component should comprise more than 90%.
- Most of the tumor comprises of large blood filled spaces separated by thin bony septations.
- Microscopically, the tumor consist of vascular sinusoids surrounded by thin septae, osteoid matrix and cells with significant pleomorphism and high mitotic rate.
Low grade osteosarcoma
- Histologically it is a low grade tumor which occurs in medullary canal of long bones.
- It contains osseous matrix with blend fibrous stroma and there is variable amount of bone production.
- Histologic pattern is similar to fibrous dysplasia and low grade parosteal osteosarcoma.
Periosteal osteosarcoma
- Periosteal osteosarcoma arise from the inner germinative layer of periosteum.
- Cytologic grade of this tumor is higher than parosteal osteosarcoma and lower than conventional osteosarcomas, so it is considered as intermediate grade osteosarcoma (grade 2).
- It predominantly contains chondroid matrix.
Intracortical osteosarcoma
- Intracortical osteosarcoma is a low grade tumor of cortical bones and it typically does not extend into medullary canal and surrounding soft tissue until late stage of the disease.
- Histologically characterazied as a sclerosing variant of the osteosarcoma contains osteoid matrix with few fibroblastic foci within and mild degree of cellular atypia.
Parosteal osteosarcoma
- They are composed of a dense osteoid component attached to the outer cortex over a narrow zone.
- Parosteal osteosarcoma originates from the outer fibrous layer of periosteum.
- It exhibits extensive bone matrix and minimal fibroblastic cellular atypia, and as such is considered to be a low grade tumor.
Extraskeletal osteosarcoma
- Grossly, it is a well defined lesion with haemorrhagic and necrotic areas within.
- Microscopically, it is typically a high grade spindle cell malignancy with osteoid and chondroid matrix.
- The histologic appearance of extraskeletal osteoosarcoma resembles malignant fibrous histiocytoma, osteoblastic osteosarcoma and chondroblastic osteosarcoma.
Genetics
Hereditary syndromes of osteosarcoma have been identified:[2]
- Rothmund-Thomson Syndrome
- RECQL4 gene mutations
- RB1 gene mutations (also implicated in retinoblastoma)
- Li-Fraumeni syndrome
These syndromes are extremely rare within the Osteosarcoma diagnosis, and probably represent less than 0.5% of those diagnosed.
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This high-power photomicrograph demonstrates the cellular growth pattern. Note that the cells are fusiform and they grow in sheets. -
This high-power photomicrograph demonstrates the growth pattern and the cell morphology. -
This is a high-power photomicrograph of the tumor cell morphology and the periosteum (arrow). -
This high-power photomicrograph of the tumor demonstrates the fusiform morphology of the cells. Note the marked variability in size and staining intensity of the nuclei. -
This is a high-power photomicrograph of the tumor demonstrating the anaplastic cell morphology. -
This is a high-power photomicrograph of the tumor demonstrating the anaplastic cell morphology. -
This is a high-power photomicrograph of the tumor demonstrating the anaplastic cell morphology and multiple mitotic figures (arrows).
References
- ↑ Image courtesy of Dr Frank Gaillard. Radiopaedia (original file [1]). Creative Commons BY-SA-NC]
- ↑ Wang LL. Biology of osteogenic sarcoma. Cancer J 11:294-305, 2005.