Morphologic Patterns of Residual Viable Osteosarcoma in Neoadjuvant-Chemotherapy Treated Patients: A Clinico-Pathologic Study of 101 Cases at a Single Institution
MJ Cascio, RJ O'Donnell, AE Horvai. UCSF, San Francisco
Background: Standard treatment for osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection. In treated tumors, > 90% tumor necrosis predicts favorable prognosis, necessitating accurate quantitation by the pathologist. Although criteria for residual viable osteosarcoma have been proposed, treated osteosarcomas display a variety of morphologic patterns making assessment difficult in some cases. The significance of residual cellular tumor cartilage and widely dispersed atypical cells in fibrous stroma is unknown. The purpose of this study was to address these morphologic patterns in relationship to clinical outcome.
Design: We retrospectively reviewed 101 consecutive high-grade osteosarcomas treated at our institution. The osteosarcomas subtype, chemotherapy regimen, type of resection and follow-up information were recorded. Full cross sections of the post-chemotherapy resection specimens were evaluated histologically for the presence and pattern of viable tumor cells. To calculate percent necrosis, two methods were compared: “stringent” and “inclusive.” First, we counted as viable only dense areas of mitotically-active atypical cells in a peripheral, nodular or diffuse pattern (“stringent”). Second, we also included as viable rare, atypical cells in fibrous stroma and tumor cartilage (“inclusive”). Treatment response was judged as good (>90% necrosis) or poor (<90% necrosis) and correlated with recurrence-free survival using the Kaplan-Meier method.
Results: One hundred one patients (63 males, 38 females, average age 18 years (range 5- 58), average clinical follow-up 31 months (range 0 – 106)) were studied. Fifty-seven treated osteosarcomas (57%) contained nodules, peripheral rims or diffuse infiltrates of a dense population of atypical, mitotically-active, cells. Twenty-six (26 %) cases showed only widely dispersed atypical cells (n=19, 19%) in fibrosis or tumor cartilage (n=7, 7%). The remaining 18 (18%) had no evidence of residual tumor cells or cartilage. Recurrence-free survival correlated with good response in the “stringent” group (p=0.0012) but not the “inclusive” group (p=0.1855).
Conclusions: In this study, we describe the patterns of residual viable tumor commonly seen in neoadjuvant resection specimens. These data support that the percent tumor necrosis after chemotherapy is an important prognostic indicator but that areas of tumor cartilage or widely distributed, mitotically inactive, atypical cells should not be scored as residual viable tumor in the calculation.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 9, Tuesday Morning