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Sarcoma, Osteogenic

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Treatment

Histopathologic Classification of Bone Neoplasms:
Based on the putative cell of origin.
Malignant tumors may arise from any cellular constituent present in bone. This includes:
1. Osteogenic (osteosarcoma),
2. Chondrogenic (chondrosarcoma),
3. Hematopoietic (multiple myeloma, lymphoma),
4. Vascular (angiosarcoma, hemangioendothelioma, leiomyosarcoma),
5. Lipogenic (liposarcoma),
6. Neurogenic (neurofibrosarcoma, chordoma),
7. Histiocytic & fibrohistiocytic (MFH, Ewing’s sarcoma).

Histologic subtyping is based on the predominant cellular pattern present within the tumor, degree of anaplasia, & its relationship to the bone (intramedullary vs surface).


CLASSIFICATION OF OSTEOGENIC SARCOMA
CONVENTIONAL (85% of cases)
Osteoblastic
Chondroblastic
Fibroblastic
MORPHOLOGICAL VARIANTS
Intraosseous well-differentiated osteosarcoma
Osteosarcoma resembling osteoblastoma
Telangiectatic osteosarcoma
Small cell osteosarcoma
Dedifferentiated chondrosarcoma
Malignant fibrous histiocytoma
SURFACE VARIANTS
Parosteal osteosarcoma
Dedifferentiated parosteal osteosarcoma

CLINICAL VARIANTS
Osteosarcoma in jaw
Post-radiation osteosarcoma
Paget's osteosarcoma
Multifocal osteosarcoma
Osteosarcoma in other benign conditions


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How to Distinguish PNET & Ewing’s from other small round cell tumors?

The monoclonal antibody, HBA71, recognizes a cell-surface glycoprotein (p30/32MIC2) in human Ewing’s sarcoma & PNET. The strong immunoreactivity of HBA71 in Ewing’s sarcoma & PNET distinguishes these tumors from other small round cell tumors of childhood & adolescence.
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Cytogenetics

Translocation t(11;22) results from fusions of the EWS & FLI1 genes. It is seen in 90% of pts with Ewing’s sarcomas & PNETs.
Different breakpoints, such as the most frequently occurring type I fusion transcript (seen in 65% of patients in one series), seem to be associated with better overall survival.
REF= JCO16: 1248, 1998

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TREATMENT

PRIMARY TREATMENT OF BONE SARCOMAS
Note:
1. Wide tumor excision with limb preservation has supplanted amputation as the principal surgical method for eradicating local disease in patients with primary bone sarcomas (regardless of histology or grade).
2. Randomized clinical trials have established that adjuvant chemotherapy is effective in preventing relapse or recurrence in patients with localized resectable primary tumors. One randomized trial has suggested that there is no difference in DFS between immediate surgery followed by adjuvant chemotherapy & preoperative chemotherapy. REF= JCO 5:21, 1987 ; NEJM 314(25):1600, 1986 ; Proc Annu Meet Am Soc Clin Oncol; 14:A1420 1995


1. Low-grade sarcomas: Surgical excision!
2. High-grade tumors: Multimodality therapy.

For most high-grade bone sarcomas (excluding chondrosarcoma) preoperative multiagent chemotherapy (3 to 4 cycles) is followed by surgical extirpation of the primary tumor. Chemotherapy is reinitiated postoperatively after wound healing has occurred.

EWING's. Radiotherapy +/- surgery (Recent trend is surgery, +/- radiotherapy)!

TREATMENT OF METASTATIC DISEASE:
OPTION 1: Preoperative chemotherapy followed by surgical ablation of the primary tumor & resection of metastatic disease, followed by post-op combination chemotherapy (high-dose methotrexate, doxorubicin, cyclophosphamide, cisplatin, ifosfamide, etoposide, and carboplatin).

OPTION 2: Surgical ablation of the primary tumor & metastases, if possible, followed by combination chemotherapy (ie. high-dose methotrexate, doxorubicin, cyclophosphamide, cisplatin, ifosfamide, etoposide, & carboplatin).
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5-year DFS with osteosarcoma of the extremities treated with either amputation or limb-salvage surgery alone is < 20%

The incorporation of chemotherapy as part of the standard therapy for osteosarcoma has improved both RFS & OS.

PROGNOSTIC FACTORS:
1. Classification
2. Location
distal>prox
extremity>axial
3. Size
<5 , >15 cm
4. Symptom duration
Long 6-12 mo worse than short
5. Age
>20 & <10 do worst
6. Gender
F>M
7. ALK-PHOS & LDH
8. Skip lesions/pathologic fx
9. Mets at presentation
10. Histologic grade
11. LOH, ploidy, her-2-neu
12. Histologic tumor necrosis
pathologic response>90% tumor necrosis= good response!
13. Surgical margins