Synchronous lung and multiple soft tissue metastases developed from osteosarcoma of tibia: a rare case report and genetic profile analysis

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.

Automated summary

This article reports a case of a young patient initially diagnosed with osteosarcoma of the right tibia and treated with standard chemotherapy and surgical resection. However, pulmonary metastases and multiple soft tissue masses in the skeletal muscle developed four years after the surgery. Genetic analysis revealed several novel variants in genes such as ALK, BLM, and PTCH1, expanding the mutational spectrum of osteosarcoma. These findings are important for understanding the clinical course and genetic characteristics of osteosarcoma patients with metastasis.