The Cinicopathological Features Of Dedifferentiated Chondrosarcoma And Clonality Analysis And IDH1 And IDH2 Mutation Detection

Objective: 1.Through the collection of clinical pathological data of dedifferentiated chondrosarcoma and follow-up survey to summarize the clinicopathological eatures of the tumor.2.Clonal analysis was used to prove the two internal components of a DDCS is originates from the same primitive cells.3.IDH1 and IDH2 mutation detection were also performed to confirm the conclusion f the former and further analyze the diagnostic and therapeutic value of IDH utation in dedifferentiated chondrosarcoma.Methods: 1.42 cases of dedifferentiated chondrosarcoma,including clinical history,imaging data and pathological HE sections,were collected from January 2004 to October 2017 in Department of Pathology,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital.All patients were followed up.Then they were observed,summarized,researched and prognosis analysed.2.Select female patients for cloning analysis,extracting DNA separately from the two components,then the DNA was treated with Hpa II enzyme,PCR amplification,and finally analyzed by capillary electrophoresis.3.Select the DDCS paraffin samples in recent years,the two components separately IDH1 and IDH2 gene mutation detection,using fluorescence PCR Capillary lectrophoresis Sequencing Analysis.Simultaneously,selected common hondrosarcoma,osteosarcoma,fibrosarcoma,malignant fibrous histiocytoma as control.Results: 1.Dedifferentiated chondrosarcoma occur in the elderly,the average age was 50 years old,diseased parts with pots triangle,triangle shoulder more common.The majority of patients showed localized pain,swelling,limited mobility,occasionally accompanied by pathological fractures.The typical imaging findings are "biphasic",both the appearance of chondrosarcoma punctate,ring calcification with invasive features of the soft tissue mass.Highly differentiated chondrosarcoma and dedifferentiated components(including osteosarcoma,malignant fibrous histiocytoma,fibrosarcoma,spindle cell sarcoma,low grade osteosarcoma and giant cell tumor of bone)were found under the microscope,both of which were divided obviously.The diagnostic accuracy of preoperative biopsy was only 27.8%.Survival analysis showed that patients with metastasis had a statistically significant prognosis(P = 0.009).2.Five cases of capillary electrophores were successfully completed in 9 DDCS,in which one case showed a single peak both with and without digestion,indicating that it’s homozygous and can’t be analyzed.In the remaining 4 cases,there were two main peaks in the non enzymatic group,however,a sharp decrease or disappearance in one of the main peaks in the enzyme digestion group compared with the former,which means the chromosome that has not been inactivated by methylation was cleaved by the endonuclease,explained the monoclonal of the sample.In the same case,dedifferentiation and chondrosarcoma components were inactivated by the same X chromosome,demonstrating that dedifferentiated chondrosarcoma is a monoclonal origin 3.Mutations were detected in 18 cases,and 11 cases harboured a IDH1 or IDH2 mutation,the mutation rate was 61.1%.There were IDH mutation in 5/11 common chondrosarcoma;no mutation was detected in 10 cases of osteosarcoma,10 cases of fibrosarcoma and 10 cases of malignant fibrous histiocytoma.Conclusions: 1.The histomorphology of DDCS is complex and diverse.As the proportion of chondrosarcoma components and dedifferentiated components is uncertain,preoperative biopsy is often misdiagnosed by only one component of the puncture.And the diagnosis of imaging is also due to the neglect of the less proportion of components,which leads to diagnostic errors.Its correct diagnosis should be closely combined with clinical symptoms,careful observation of imaging,preoperative multi point puncture,pathological selection of multiple regions,careful identification of the pathologists with rich experience.In addition to surgical excision,the disease has no special effective treatment.Patients with metastases at the time of initial diagnosis had a worse prognosis.2.Clonality analysis by capillary electrophoresis shows that the size of the peak’s allele of the capillary electrophoresis were same in two components,and the same single peak remained after the enzyme digestion illustrates that they were inactivated by the same X chromosome,which proves the monoclonal origin of DDCS.3.The results of IDH1/2 gene mutation showed that the mutational state of the two components of DDCS was consistent,which further supports the conclusion of the clonality analysis.The IDH1/2 mutation rate in dedifferentiated chondrosarcoma was 61.1%,dominated by IDH1 mutation.IDH mutation can be used as a promising target for treatment.IDH mutation can be used in the differential diagnosis of mutant dedifferentiated chondrosarcoma and single component tumors.