Chordoma:Clinicopathological Characteristics And Factors Affecting Survival

Objective:To confirm the clinical, histopathological, immunohistochemical characteristics and analysize the prognosis of chordoma.Methods:A total of51cases of chordoma between1998to2011treated in Nanjing Ceneral Hospital of Nanjing Military Command were reviewed retrospectively and compared them with10cases of extraskeletal myxoid chondrosarcoma. Immunohistochemical analysis of Brachyury, Galectin-3, C-Met, CK8/18, PDGFR-β and Ki-67were performed on all cases. Follow-up data was obtained from patient’s clinical database. The results were statistically processed and analyzed.Results:Histopathologically, the typical chordoma (TC) specimens contained a large number of cords, strands, or solid nests of atypical physaliphorous cells within an abundant myxoid matrix, often separated by fibrous septa. Tumor cells are variably sized, with abundant clear, eosinophilic, or multivacuolated cytoplasm (so-called physaliferous cells). Mild cytologic atypia may be present, but mitotic activity is low. Chondroid chordoma (CC) was a histologic variant of chordoma that was defined by the presence of varying amounts of cartilaginous elements admixed with cords and lobules of vacuolated or ’physaliferous’ cells of typical chordoma. Dedifferentiated chordoma (DC) was a rare and aggressive variant of the conventional tumour in which an area underwent transformation to a high-grade lesion, including typical fibrosarcoma, and rarely, osteosarcoma or rhabdomyosarcoma. Microscopically, extraskeletal myxoid chondrosarcoma was relatively well circscribed and divided by thin fibrous septa. The lobules consisted of rich myxoid and chondromyxoid stroma mixed with neoplastic cells. The cells interconnected to form characteristic cords, clusters, cribriform arrays, and spindle-cell patterns. The neoplastic cells possessed a modest amount of eosinophilic, and occasionally vacuolated cytoplasm with uniform round to oval nuclei.Immunohistochemically, Brachyury was positive in91.1%of TC,91.7%of CC,40%of DC, and negative in all EMC. Galectin-3was positive in73.5%of TC,50%of CC,80%of DC, and20%of EMC. CK8/18was mainly expressed in chordoma, positively in40%of DC,60%of CC and88.2%of TC, respectively, however, it was negative in EMC except for2(20%) cases of tumor. Brachyury, Galectin-3and CK8/18expression were significantly higher in chordoma than in EMC(P<0.05). C-Met stained positively in68.6%of chordoma and40%of EMC, respectively. PDGFR-P expression was seen in78.4%of chordoma and70%of EMC, respectively. There were no statistically significant differences between chordoma and EMC about C-Met and PDGFR-β expression (P>0.05). The average of Ki-67proliferation index(PI) was usually less than5%and no cases more than20%. However, the PI more than10%could be found in each case of TC and DC.In survival analysis, log-rank test showed that age, gender, tumor size, radiotherapy, recurrence, Brachyury and CK8/18expression had no significant effect on the patient’s prognosis (P>0.05). However, pathological subtype, resection degree, C-Met, Galectin-3, PDGFR-β and Ki-67expression were unfavorable factors for survival (P<0.05). Cox regression analysis showed that both Galectin-3and Ki-67expression were independent factors that affect on the patient’s survival (P<0.05).Conclusion:(1) Chordoma is a rare disease for which treatment is a challenge due to deep location, pattern of extension, high rate of recurrence. As they are not sensitive to radiotherapy or chemotherapy, complete resection remains the preferred method of treatment. The degree of resection was inversely correlated with recurrence rate.(2) C-Met could act as a marker to help to predict the tumor recurrence and the high expression of C-Met indicates that there is high likelihood of recurrence, suggesting that intensive therapy and frequent follow-up should be performed.(3) In terms of pathology subtype, the chondroid chordoma displayed the most favorable outcome, while the dedifferentiated chordoma displayed the poorest outcome.(4) The study suggested that Brachyury, galectin-3, CK8/18are useful adjunct markers for distinguishing chordoma from extraskeletal myoxid chondrosarcoma.(5) Combination of C-Met, PDGFR-p, Galectin-3and Ki-67can be used for the prognosis analysis about chordoma. Chordoma with higher expression of Galectin-3and elevated Ki-67PI were independent factors for a more aggressively clinical course and poorer survival. These biomarkers may thus be used to improve therapeutic stratification.