Page 591 - Concise Pathology for Exam Preparation ( PDFDrive )

576 SECTION II Diseases of Organ Systems

and potential for recurrence. Osteoblastoma can be differentiated from an osteoid osteoma
based on the following features:
• It is larger than 2 cm (also called giant osteoid osteoma).
• Affects older patients.
• Does not cause localized night pain and, when pain occurs, is not relieved by NSAIDs.
• Does not present with as intense a bony reaction as osteoid osteoma.
• Preferentially involves posterior elements of vertebrae, spine, femur and bones of the
foot. It is less common in the long bones where it typically involves the metaphysis and
may be intracortical or intramedullary in origin.

Osteogenic Sarcoma (OS)
OS is a malignant mesenchymal tumour in which the neoplastic stromal cells directly lay
down bone matrix or osteoid without an intervening stage of cartilage formation. It is the
most common primary malignant bone tumour after myeloma and lymphoma.
Pathogenesis
1. Genetic contribution:
• Germline mutations in P53 gene (Li–Fraumeni syndrome) increase incidence of OS
• Mutations in RB gene are seen in 70% of sporadic cases of OS. (Patients with he-
reditary retinoblastoma have up to 1000 times’ greater risk of developing OS.)
• INK4A is inactivated in some osteosarcomas, INK4A encodes p16 (negative regulator
of CDKs) and p14 (which enhances the action of p53).
• CDK4 and MDM2 are implicated in low-grade osteosarcomas (these are cell cycle
regulators which inhibit p53 and RB genes).
2. Environmental contribution:
Radiation, thorotrast and therapeutic irradiation are all implicated. Children treated
with alkylating agents have an increased risk of OS.
Classification
1. Based on affected age and presence of preexisting bone pathology:
(a) Primary OS: Arises de novo and occurs between 10 and 25 years.
(b) Secondary OS: Arises secondary to preexisting bone pathology. Occurs in patients
more than 40 years and constitutes about 6–10% of all osteosarcomas. Conditions
predisposing to secondary OS are
• Paget disease
• Exposure to radiation
• Chemotherapy (alkylating agents)
• Bone lesions like fibrous dysplasia, osteochondroma, enchondroma, fractures,
intramedullary prosthesis and bone infarcts.
2. Based on skeletal distribution/anatomical site:
• Intramedullary
• Intracortical
• Surface
3. Based on morphology:
• About 85% of osteosarcomas are of the ‘conventional intramedullary’ type, and the
other 15% consist of several other subtypes, including telangiectatic, low-grade in-
tramedullary and small cell, as well as, the surface subtypes parosteal, periosteal and
high-grade surface osteosarcoma.
• Conventional intramedullary OS is mostly metaphyseal in origin (involves long
bones like lower end of femur, upper end of tibia and upper end of humerus, in that
order). It can be further classified into the following subtypes depending on the
predominant constituent element:
• Osteoblastic (shows a large amount of osteoid and bony trabeculae)
• Chondroblastic (malignant cartilage forms nearly 90% of the tumour)
• Fibroblastic (composed of a large spindle cell/fibroblastic component)
Clinical Features
• Presents as a painful, progressively enlarging mass with a large soft-tissue component,
sometimes associated with a pathological fracture.
• OS has a bimodal age distribution

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