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General Information About Osteosarcoma and Malignant Fibrous Histiocytoma (MFH) of Bone

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Necrosis following induction or neoadjuvant chemotherapy

Most treatment protocols for osteosarcoma use an initial period of systemic chemotherapy prior to definitive resection of the primary tumor (or resection of sites of metastases for patients with metastatic disease). The pathologist assesses necrosis in the resected tumor. Patients with at least 90% necrosis in the primary tumor after induction chemotherapy have a better prognosis than those with less necrosis.[26] Patients with less necrosis (<90%) in the primary tumor following initial chemotherapy have a higher rate of recurrence within the first 2 years compared with patients with a more favorable amount of necrosis (≥90%).[36] Less necrosis should not be interpreted to mean that chemotherapy has been ineffective; cure rates for patients with little or no necrosis following induction chemotherapy are much higher than cure rates for patients who receive no chemotherapy.

Imaging modalities such as dynamic magnetic resonance imaging (MRI) or positron emission tomography (PET) scanning are under investigation as noninvasive methods to assess response.[37,38,39,40,41,42]

Additional prognostic factors

Patients with osteosarcoma as a second malignant neoplasm, including those tumors arising in a radiation field, share the same prognosis as patients with de novo osteosarcoma if they are treated aggressively with complete surgical resection and multiagent chemotherapy.[43,44,45,46] Possible prognostic factors identified for patients with conventional localized high-grade osteosarcoma include the age of the patient, LDH level, alkaline phosphatase level, and histologic subtype.[26,47,48,49,50,51,52] Age older than 18 years at presentation appears to be associated with a poorer outcome.[52] A number of potential prognostic factors have been identified but have not been tested in large numbers of patients. These include the expression of HER2/c-erbB-2 (there are conflicting data concerning the prognostic significance of this human epidermal growth factor);[53,54,55] tumor cell ploidy; specific chromosomal gains or losses;[56] loss of heterozygosity of the RB gene;[57,58] loss of heterozygosity of the p53 locus;[59] and increased expression of p-glycoprotein.[60,61] A prospective analysis of p-glycoprotein expression determined by immunohistochemistry failed to identify prognostic significance for newly diagnosed patients with osteosarcoma, although earlier studies suggested that overexpression of p-glycoprotein predicted for poor outcome.[62] In a large series, a delay of 21 days or more from the time of definitive surgery to the resumption of chemotherapy was an adverse prognostic factor.[63] Pathologic fracture at diagnosis or during preoperative chemotherapy does not have adverse prognostic significance.[64]

Syndromes Associated With Osteosarcoma

Rothmund-Thomson syndrome

Patients with Rothmund-Thomson syndrome have an increased risk of developing osteosarcoma compared with the general population. They also tend to develop osteosarcoma at a younger age.[65] Rothmund-Thomson syndrome, also called poikiloderma congenitale, is a rare autosomal recessive condition attributed to mutations of the RECQL4 helicase gene on 8q24. It is characterized by distinctive skin findings (e.g., atrophy, telangiectasias, pigmentation), sparse hair, cataracts, small stature, skeletal anomalies, and a significantly increased risk for osteosarcoma. There is no adverse prognostic significance for osteosarcoma in conjunction with Rothmund-Thomson syndrome.

Genetic diseases that predispose to osteosarcoma

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