Retrospective Study Of The Transformation Mechanism And Clinical Outcomesof Secondary Bone Malignancies Based On Clinical And Pathological Characteristics

Background: Bone malignancies arerare,accounting for about 0.2% of all mesenchymal malignancies.However,it is one of the most common malignant tumors in adolescents and has a poor prognosis.Primary bone sarcomas form the majority of all bone malignancies.However,it cannot be ignored that there exist a few cases of secondary bone sarcomas,which means primary bone benign or invasive lesions may transform into malignancies,accompanied with the pathological features completely altered,sometimes even performed as a soft tissue tumor-like pathological phenotype.The occurrence,development and proper mechanisms of secondary bone tumors are not well understood,and few related studies have been done.Although the clinical incidence is not high,it still occurs from time to time.We need to know more about the biological behavior,clinical phenotypic characteristics,pathogenesis,prognosis and certain treatment strategies of secondary bone malignancies.Methods: Data for this retrospective study were derived from Ruijin Hospital,which receives patients with secondary bone malignancies from 2004 to 2022.We studied and analyzed clinical features such as phenotype of the primary lesion,malignant tumor phenotype,prognosis,and the change of pathological manifestations retrospectively to infer the pattern of the evolution of tumor pathology.By studying the malignant transformation mode,and combined with the clinical treatment effect on the malignant lesions,the clinical outcome and prognosis of these patients after the occurrence of secondary bone malignant tumors were studied.Also,gene detection and analysis of 4 cases were carried out to detective the evidence of potential mutations in the evolution of these bone malignancies,and to explore the future treatment methods for different bone malignancies.Results: 40 patients with secondary malignant bone sarcomas were included in this study.Among them,22 were male and 18 were female.The primary benign or invasive lesions included 12 cases of giant cell tumor of bone,8 cases of fibrous dysplasia of bone,5 cases of synovial chondroma,8 cases of mutiple osteochondroma,1 case of fibrous histiocytoma,2 cases of non-ossifying fibroma,1 case of myositis ossification,1 case of solitary osteochondroma,1 case of enchondroma,and 1 case of osteoblastoma.The median follow-up time was 3.2 years(0.5 years to 10 years).The mean age of diagnosis of the malignant tumor was 43.68 years(39.84 years to 47.51years),the rate of lung metastasis was 42.5%,and the overall 5-year survival rate was32.5%.The results of the study suggest that age,gender,tumor site,and primary lesion were not significantly associated with prognosis.Since both the primary and secondary tumor cells in this study are derived from mesenchymal cells,according to their cell lineage classification and pathological manifestations,the malignant transformation mechanism of these cases can be summarized into three different modes — primary lesion cells undergo dedifferentiation and transformation to intra-lineage cells,cells dedifferentiate to pleomorphic high-grade undifferentiated changes,and primary lesion cells undergo dedifferentiation followed by trans-lineage differentiation.The emergence of trans-lineage differentiation suggested an increased probability of lung metastasis and poor prognosis.Through genetic testing of certain tumor specimens,we found differences in mutational burden and mutational patterns between secondary and primary osteosarcomas.This may have certain potential value for guiding the selection of therapeutic drugs and treatment methods for secondary bone malignancies in the future.Conclusion: Secondary bone malignant tumors have obvious characteristics of dedifferentiation from primary benign or invasive lesions into malignant cells.After dedifferentiation,tumor cells may transform into malignant cells of the same lineage,or trans-lineage malignant differentiation,or directly evolve into undifferentiated pleomorphic sarcoma.Patients with malignant transformation are treated according to the phenotype of malignant tumor,which is the same as primary bone sarcoma.Their prognosis was related to the mode of transformation.The probability of lung metastasis in patients with trans-lineage is significantly higher,and the clinical prognosis is poor.The molecular mutation pattern of secondary osteosarcoma is significantly different from that of primary osteosarcoma,suggesting that the standard treatment of primary osteosarcoma is not completely suitable for such secondary osteosarcoma,and drugs targeting its molecular mutations may occupy a certain position in the treatment of secondary osteosarcoma in the future,and it isworthy of further research.