The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD‐L1) were evaluated by immunohistochemistry. Moreover, we investigated PD‐L1 and programmed death ligand 2 (PD‐L2) mRNA expression in 19 of the 36 cases, using real‐time PCR. The Kaplan‐Meier method was used to estimate overall survival and progression‐free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD‐L1 expression was observed using immunohistochemistry. Moreover, although PD‐L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression‐free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD‐L1, and PD‐L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.

Multinucleated cells are frequently seen in association with a malignant neoplasm. Some of these multinucleated cells are considered to be neoplastic. The mechanism of neoplastic multinucleation remains unknown, but is considered to be induced by either cell-cell fusion or acytokinetic cell division. Myxofibrosarcoma consists of spindled and pleomorphic tumor cells and bizarre multinucleated giant cells. Some of these multinucleated cells are considered to be neoplastic. We studied the mitotic activity of the multinucleated cells by Ki-67 immunohistochemistry, and the dynamics and differentiation by live-cell video microscopy in the two myxofibrosarcoma cell lines to determine whether the mechanism of multinucleation is cell-cell fusion or acytokinetic cell division A Ki-67 immunohistochemical analysis revealed a high positive rate of multinucleated cells, as well as mononuclear cells, and mitotic ability was shown in the multinucleated cells. In live-cell video microscopy, most of the multinucleated cells were induced via the process of acytokinetic cell division. The current study indicates that a vulnerability of the cytoskeleton components, such as the contractile ring, causes multinucleation to occur from the telophase to the cytokinesis of the cell cycle.

The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts.

Aims: We analyzed the long-term outcomes of patients observed over ten years after resection en bloc and reconstruction with extracorporeal irradiated autograftsPatients and Methods: This retrospective study included 27 patients who underwent resection en bloc and reimplantation of an extracorporeal irradiated autograft. The mean patient age and follow-up period were 31.7 years (9 to 59) and 16.6 years (10.3 to 24.3), respectively. The most common diagnosis was osteosarcoma (n = 10), followed by chondrosarcoma (n = 6). The femur (n = 13) was the most frequently involved site, followed by the tibia (n = 7). There were inlay grafts in five patients, intercalary grafts in 15 patients, and osteoarticular grafts in seven patients. Functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system.Results: There were no recurrences in the irradiated autograft and the autograft survived in 24 patients (88.9%). Major complications included nonunion (n = 9), subchondral bone collapse (n = 4), and deep infection (n = 4). Although 34 revision procedures were performed, 25 (73.5%) and four (11.8%) of these were performed less than five years and ten years after the initial surgery, respectively. The mean MSTS score at the last follow-up was 84.3% (33% to 100%).Conclusion: Considering long-term outcomes, extracorporeal irradiated autograft is an effective method of reconstruction for malignant musculoskeletal tumours Cite this article: Bone Joint J 2019;101-B:1151–1159