Abstract
BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor with a highly metastatic propensity in children and young adolescents. The majority of metastases develope in the lung, while metastases to the extrapulmonary locations have rarely been discussed, especially in skeletal muscle. CASE PRESENTATION: We reported a young patient with pathologically diagnosed osteosarcoma of the right tibia who was initially treated with standard chemotherapy and complete surgical resection. However, pulmonary metastases and multiple soft tissue masses in skeletal muscle developed four years after the index surgical resection. Subsequently, a targeted next-generation sequencing assay based on an 806 oncogenes and tumor suppressor genes panel was performed to analyze genetic alterations in this patient with rare metastatic pattern. The genetic analysis revealed canonical somatic mutations of RB1 and germline variants of ALK (c.862 T > C), BLM (c.1021C > T), PTCH1 (c.152_154del), MSH2 (c.14C > A), RAD51C (c.635G > A). Using silico prediction programs, the germline variants of the MSH2 and RAD51C were predicted as "Possibly Damaging" by Polymorphism Phenotyping v2 (PolyPhen-2) and "Tolerated" by Sorting Intolerant from Tolerant (SIFT); BLM was classified as "Tolerated", while the germline variant of ALK was predicted to be pathogenic by both PolyPhen-2 and SIFT. CONCLUSIONS: Osteosarcoma with extrapulmonary metastases is rare, especially located in the skeletal muscle, which predicts a worse clinical outcome compared with lung-only metastases. The several novel variants of ALK, BLM, PTCH1 in this patient might expand the mutational spectrums of the osteosarcoma. All the results may contribute to a better understanding of the clinical course and genetic characteristics of osteosarcoma patients with metastasis.