Histomorphologic Features Predictive of Survival in Osteosarcoma
M Herman Chui, Anthony Griffin, Marcus Wong, Martin E Blackstein, Peter C Ferguson, Jay S Wunder, Rita A Kandel, Brendan C Dickson. Mount Sinai Hospital, Toronto, ON, Canada
Background: Osteosarcoma shows considerable histomorphologic heterogeneity, and traditional grading schemes have not been universally effective in predicting outcome. Following biopsy confirmation, treatment regimens typically consist of neoadjuvant chemotherapy followed by surgical resection; depending on the response to treatment, chemotherapy may be modified accordingly. The purpose of this study is to examine osteosarcoma for histomorphologic features yielding reliable predictors of clinical outcome.
Design: We conducted a retrospective review for osteosarcoma diagnosed on biopsy (needle core, or curettage). Slides were reviewed and histomorphologic tumour attributes recorded, including: histologic subtype, cell shape, cell size, percent necrosis, mitotic rate, nuclear pleomorphism, nucleoli, percent osteoid, extent of mineralization, lymphovascular invasion, chondroid matrix, and multi-nucleated giant cells. Univariate associations with overall survival (OS) were analyzed by Kaplan-Meier survival analysis and the independent effect of predictors assessed by multivariate Cox proportional hazards regression.
Results: 168 patients with a pathologic diagnosis of osteosarcoma, treatment, and follow-up information at our institution were identified. Median OS was 163 months. By univariate analysis, histologic subtype was predictive of OS (p = 0.017), with the chondroblastic and telangectatic variants associated with the worst survival, fibroblastic with the longest OS, and the osteoblastic variant in between. Spindle cell shape (p = 0.04) was also associated with increased OS, whereas there was a negative trend with the presence of chondroid (p = 0.086), reflecting covariance with histologic subtype. Extensive necrosis (>50%) and histologically identifiable nucleoli were poor prognostic features (p < 0.001 and p = 0.022 respectively). The multivariate model retained subtype (p = 0.047), extensive necrosis (p = 0.002, HR 2.56, 95% CI 1.40, 4.67) and histologically identifiable nucleoli (p = 0.023, HR 1.87, 95% CI 1.09, 3.21) as significant independent predictors.
Conclusions: Tumour necrosis and prominent nucleoli appear to be independent predictors of poor OS in osteosarcoma and may merit inclusion in grading schemes. In contrast, mitotic rate and nuclear pleomorphism do not appear to be predictive of outcome. In addition, these preliminary results confirm histologic subtypes of osteosarcoma are distinct with respect to clinical behaviour and underlying biology.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 6, Tuesday Afternoon