Three Metachronous Osteosarcomas within 22 Years without Pulmonary Metastases: A Case Report and Review of the Literature

Abstract

Introduction. We present the extremely rare case of a patient with three metachronous osteosarcomas within 22 years without evident pulmonary manifestation of disease 30 years after first diagnosis. Case Presentation. In 1983, a high-grade osteosarcoma of the left distal femur was diagnosed in an 18-year-old Caucasian male. He received rotationplasty accompanied by pre- and postoperative chemotherapy. Ten years later, an osteoblastic osteosarcoma occurred in TH12. En bloc resection and pre- and postoperative chemotherapy followed. In 2005, the patient developed another high-grade osteosarcoma in his right distal femur. Treatment included a wide resection and reconstruction with a tumour endoprosthesis as well as (neo)adjuvant chemotherapy. After the third tumour occurrence, cytogenetic and molecular genetic examinations (p53, rb1) were performed, showing a normal genetic pattern. Screening for metastases never showed clinical evidence of extraskeletal tumour manifestation. Discussion. In patients presenting metachronous osteosarcoma, identification of their lesions clonality (second primary tumour or metastases) could lead to a better understanding of tumour development and help to filter patients who need extended long-term followup due to a higher risk of late occurring sarcoma recurrence.

Metachronous Osteosarcoma, A Differential Diagnosis to be Considered in Children With Osteosarcoma: A Review of Literature and a Case From Our Center

“…Currently, there is no exact scientific way to distinguish the MOS and metastasized osteosarcoma scientifically, including no reliable methods to evaluate special molecular features. 8 , 9 , 15 The diagnosis of MOS is more or less an empirical and clinical decision made on the basis of well-known and described routes of metastasation through the blood stream and the lymphatic drainage. 25 , 26 Metastasizing is a very inefficient and complicated process, needing a fine-tuned microenvironment at the destination site of the tumor’s spread.…”

“…However, it is not certain that all reported cases are secondary osteosarcomas. Currently, there is no exact scientific way to distinguish the MOS and metastasized osteosarcoma scientifically, including no reliable methods to evaluate special molecular features 8,9,15. The diagnosis of MOS is more or less an empirical and clinical decision made on the basis of well-known and described routes of metastasation through the blood stream and the lymphatic drainage 25,26.…”

“…4 Approximately 30% of patients develop a recurrence with pulmonary metastasis as a common relapse. [5][6][7] In comparison, the occurrence of skeletal lesions consecutively to the initial primary tumor is rare, 8,9 but there seems to be a small subset of patients who develop 1 or more new nonmetastatic tumors in the skeleton after the successful treatment of the initial osteosarcoma. These lesions, which occur distant from the primary tumor after the initial treatment of primary osteosarcoma are denoted as metachronous osteosarcoma (MOS).…”

Distinct genomic features between osteosarcomas firstly metastasing to bone and to lung

“…According to the series of Cooperative Osteosarcoma Study Group (COSS) trials, metastasis most commonly develops in the lungs (81.4%) and then in bones (7.8%) but rarely in lymph nodes [ 6 , 7 ]. There is a small subset of osteosarcoma patients who first experience relapse with distal skeletal metastasis alone, which has been assumed to be different with regard to clinical and biological features compared to those who experience first relapse involving the lung [ 7 , 8 ]. It is noteworthy that this population is different from those with local recurrences involving disputable suspicion of former surgical margins [ 9 ].…”

Distinct Genomic Features Between Osteosarcomas Firstly Metastasing to Bone and to Lung

“…According to the series of Cooperative Osteosarcoma Study Group (COSS) trials, metastasis most commonly develops in the lungs (81.4%) and then in bones (7.8%) but rarely in lymph nodes, with a median time from diagnosis to relapse of 1.6 years (range, 0.1 to 14.3 years) [6,10]. There is a small subset of OS patients who rst experience relapse with distal skeletal metastasis alone, which has been assumed to be different with regard to clinical and biological features compared to those who experience rst relapse involving the lung [10][11][12]. It is noteworthy that this population is also different from those who present with synchronous regional bone metastases (skip metastases) with an outlook extremely poor [13], as well as those with local recurrences involving disputable suspicion of former surgical margins [14].…”