Osteogenic sarcoma develops from cells of the mesenchymal series, which form neoplastic osteoid and osseous tissue either directly or indirectly by rapid growth of development.
The classic osteogenic sarcoma develops in the interior of a bone. Juxta-cortical osteogenic sarcoma develops in relation to the periosteum and immediate parosteal connective tissue. It is less common, but has a much better prognosis. Endosteal osteo-sarcoma is a variant of parosteal osteosarcoma that arises within bone from the endosteum, a low-grade malignant tumor that grows slowly and metastasizes late.
Telangiectatic osteosarcoma is a high-grade malignant lesion that shows
- Minimal ossification
- Cystic and necrotic changes
- Rapid growth
- Weakened by the rapid destructive osteolytic process often resulting in fractures
Generally, the tumor occurs in the age group of 10 to 25 years, though it can occur in as young as 5 years and as old as 50 years. In an older person, the possibility of malignant transformation of a pre-existing benign bone disease such as Paget’s disease of bone or fibrous dysplasia should be considered.
The tumour occurs equally in males and females.
The tumor occurs in metaphyseal region of a long bone but on occasion may be diaphyseal in its site. The most common sites are the lower end of the femur and the upper end of the tibia. The upper ends of the humerus and the femur are next in frequency of localization. On a rare occasion, it may be encountered in the fibula, pelvic bones, or in encountered in the fibula, pelvic bones, or in the vertebral column. Occurrence in the distal part of a limb (hand or foot) is extremely rare.
The tumor has been described in every bone in the body. Multiple or multicentric osteogenic sarcoma.
The tumor ordinarily begins in the medullary cavity of a long bone near the metaphysis. By the time it is recognized, it has already penetrated and extended through the cortex raising the periosteum. In advanced cases, the periosteal barrier may be broken, and one may find a soft-tissue tumor mass invading the contiguous muscle tissue.
Central portion of the neoplasm displays greater ossification than do the peripheral areas. The ossified portions are of a gritty and yellowish. The boundaries of the epiphyseal end of the tumor are not clearly distinguishable.
The physis remains unbroken until later in the course of the disease. Also the articular cartilage serves to block the extension of the neoplasm into the joint. Skip extension may occasionally occur.
Microscopic examination shows the presence of a frankly sarcomatous stroma and direct formation of neiplastic osteoid and bone.
The microscopic picture is of four types.
- Osteoid production is the predominant findings
- Osteoid and cartilage are formed
- Neither osteoid nor cartilage is produced, but collagen is formed
- There is little or no indication of the presence of these intercellular substances.
There is no correlation between clinical performance of osteogenic sarcoma and microscopic type.
- Local pain in the affected part.
- Initially, the pain is intermittent, but within a matter of weeks, becomes severe and constant.
- There may be a history of trauma that has precipitated discomfort from the tumor.
- Anntalgic limp in case of lower limb.
- Local swelling that is hard and fixed
- Increased local heat and sensitivity to pressure.
- Firmness of the swelling varies, depending on the extent of ossification.
Limitation of joint motion and disuse atrophy of the muscles are other findings.
A pathologic fracture through the lesion may be the presenting condition.
The general heatlh of the child is usually fair except for in the cases where pulmonary metastases have already occurred in the early stages.
Osteogenic sarcoma presents a typical radiographic picture of destructive and osteoblastic changes.
The neoplasm usually begins eccentrically in the metaphyseal region of a long bone.
Bone destruction manifests itself as a loss of normal trabecular pattern and the appearance of irregular ill-defined, poorly marginated, ragged radiolucent defects.
New bone formation may be neoplastic or reactive and appears in the form of areas of increased radiopacity.
The cortex is seen to be invaded by the growing tumor, as evidenced by destruction of the cortical wall and raising of the periosteum.
The “sunburst” appearance is produced by the formation of spicules of new bone laid down perpendicularly to the shaft along the vessels passing from the periosteum to the cortex.
Codman’s triangle has its base perpendicular to the shaft and is created by the subperiosteal reactive new bone but is not characteristic of osteogenic sarcoma, as it is also seen in osteomyelitis and Ewing’s sarcoma.
A soft-tissue mass will be discernible in the radiograms as the tumor advances further, transgressing the cortex. Pathologic fracture may occur.
Linear tomography and computed tomography are of great value in depicting the details of bone destruction and tumor bone production within the lesion.
The neoplastic bone is amorphous and not stress oriented. The areas of cortical erosion by the tumor tissue are well delineated. The degree of soft-tissue extension and the relationship of the extra-compartmental tumor to fascialo planes is clearly demonstrated by the CT scan.
Occult skip metastases of 2 mm. or more in diameter are identified by CT scan.
Conventional radiograph of the chest (dual inspiration and expiration views) will detect metastatic nodules 10 mm. or greater in diameter; ordinary tomography will demonstrate metastatic lesions between 5 and 10 mm.
Bone scan with technetium-99m will show marked increase in the uptake of the radionuclide due to active formation of new tumor bone. The vascularity of the lesion augments the intensity of the uptake.
Angiography is of great value in delineating the extent of soft-tissue extension and its relationship to adjacent neurovascular structures. The early arterial phase demonstrates the reactive neovasculature awhereas the late venous phase shows the intrinsic vascularity.
Angiography is of particular value when limb salvage is being combined with radical ablation of osteogenic sarcoma.
The serum alkaline phosphatase level is elevated in osteosarcoma which varies with the activity of the neoplastic osteoblasts within the lesion and the size of the tumor.
An immunologic findings in osteogenic sarcoma is the presence of antisarcoma antibody in the serum.
Osteogenic sarcoma is treated by radical excision and adjuvant chemotherapy. Before one proceeds for treatment, the clinical and radiographic diagnosis should always be confirmed by histologic examination of adequate tissue obtained by open biopsy.
Exuberant callus of a stress fracture, subacute osteomyelitis, active myositis ossificans, aneurysmal bone cyst, and eosinophilic granuloma are some of the benign conditions that can easily be mistaken for osteogenic sarcoma. Ewing’s sarcoma, fibrosarcoma, and metatastic carcinoma are some of the malignant lesions that must be considered in the differential diagnosis.
Staging of the lesion should precede open biopsy.
The objectives of staging are
- To establish the final tissue diagnosis
- To define the local extent of the tumor
- Discover any distant metastasis.
Both staging and open biopsy should be carried out by the surgeon who will perform the definitive operation.
In preoperative staging of osteogenic sarcoma the following diagnostic tests are performed:
- Complete history and physical examination
- Complete blood count with differential, erythrocyte sedimentation rate, and serum levels of calcium, phosphates, and alkaline phosphatase.
- Conventional radiograph of the part and the chest
- Scintigraphy with technetium-99m and in selected cases also with gallium-67 citrate
- Linear tomography to assess longitudinal intraosseous extent.
- Computed tomography of the part involved by the primary tumor and of the chest (to rule out metastases).
- Nuclear magnetic resonance imaging and
- Biplanar peripheral angiography in selected cases, especially if limb salvage is contemplated.
If the staging, open biopsy, and histologic examination of frozen sections indicate the tumor is osteogenic sarcoma, the pediatric oncologist (who is also a hematologist) should perform a bone marrow examination when the patient is under general anesthesia.
It is crucial to verify the site of biopsy by radiograph in the operating room. To ascertain that you have taken the diagnostic tissue, you must obtain frozen sections.Moreover cultures of the tissue specimen should be taken.
Dangers of Biopsy
There is always danger of the tumor spreading as a result of open biopsy. To prevent spilling neoplastic cells into vascular channels it is advisable to use a coagulation diathermy knife at biopsy. Proponents of immediate ablation argue that biopsy delays radical therapy.
An experienced pathologist might make a correct diagnosis on the basis of a frozen section but it is always best to rely on permanent sections for final diagnosis.
First approach to treatment of osteogenic sarcoma is making a definitive diagnosis. After diagnosis has been established, patient should be put on preoperative adjuvant chemotherapy.
This should continue for four to six weeks. Advantgages of preoperative adjuvant chemotherapy are
- It reduces edema and decreases the size of the primary tumor thus making limb salvage surgery feasible
- It helps to determine the response of the primary tumor to a specific chemotherapeutic agents.
Early administration of chemotherapeutic agents,will destroy occult micrometastases and occult microextensions and will improve the overall prognosis.
After preoperative adjuvant chemotherapy, the next step is is definitive surgery followed by additional adjuvant chemotherapy for 12 months.
Tumor cell destruction as shown by histologic examination of the resected primary tumor helps in deciding chemotherapeutic agents.
There are four grades of tumour cell destruction.
- Grade I– Minimal or no effect
- Grade II- Partial response with 50 to 90 percent tumor necrosis.
- Grade III-Greater than 90 percent tumor necrosis, but definite foci of viable tumor are seen in some histologic sections.
- Grade IV– No viable tumor cells noted in any of the histologic sectioin.
In Grade I and II responses the chemotherapeutic agents are changed.
Parosteal osteogenic sarcoma and endosteal ostegenic sarcoma are low grade (Grade I) with less than 10 percent metastatic potential.
Classic osteosarcoma, radiation osteogenic sarcoma, and osteogenic sarcoma developing in Paget’s disease are high grade (Grade II), having a greater than 10 percent metastatic potential.
The part involved by osteogenic sarcoma should be ablated. However, whether the operative local control of the malignant tissue should be by wide local resection or by amputation of the limb-wide resection by transmedullary ablation or radical resection by disarticulation is controversial.
Before surgical ablation of the primary tumor it is essential to rule out the presence of metastases.
Osteogenic sarcoma spreads to the lungs early. In addition to conventional radiography, linear tomographic and computed tomographic studies of the chest and scintigraphic studies should be performed.
Limb Salvage Therapy
This course of action is based on the principle that a part of a limb that can be used should be preserved, provided it does not adversely affect survival.
Surgical adjuvant chemotherapy has made limb salvage feasible when diagnosis is made early, the tumor is intracompartmental, and neurovascular structures are not involved.
The objective of limb salvage is to preserve and to provide maximal function.
The drawbacks of limb salvage are-
- The preserved limb may be disfigured.
- Increased risk of local recurrence.
- Skip lesions may be missed.
The level of amputation is determined by close scrutiny of
- The conventional radiographs
- Bone imaging with technetium-99m and gallium-67 citrate
- Linear and computed tomography
- Nuclear magnetic resonance imaging.
These surgical staging studies should be performed immediately prior to definitive surgery.
The patient and the parents need psychologic support. Initially there will be emotional resistance to ablation of a limb.
It is vital that these patients see other children with amputations and prostheses during the four to six weeks of preoperative adjuvant chemotherapy.
If pulmonary metastasis has already taken place at the time of initial diagnosis, the decision whether to amputate depends on amount of disability of the affected limb caused by local pain and tremendous size of the tumor, which may be so large and painful that the only means of controlling the misery is amputation. Other factors in making the decision are the general condition of the patient and his immediate prognosis.
If pulmonary metatases develop after amputation while adjuvant chemotherapy is in progress, the drugs may have to be changed. When a metatastic lesion is solitary, and sometimes when a maximum of only two or three foci of metastasis are present and remain stationary, a thoracotomy and wide excision are performed.
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