Usefulness of PET/CT for diagnosis of periosteal chondrosarcoma of the femur: A case report.

Periosteal chondrosarcoma is an extremely rare low-grade malignant cartilaginous tumor arising from the external bone surface. Diagnosis of periosteal chondrosarcomas may be challenging, since this condition closely resembles periosteal chondromas. It has been reported that positron emission tomography (PET) is useful in distinguishing benign from malignant cartilaginous tumors using a maximum standardized uptake value (SUVmax) cut-off of 2.0 or 2.3. This report presents the case of a 40-year-old female with an 18-month history of a tender mass in the left distal femur. Radiological findings demonstrated periosteal buttressing. Magnetic resonance imaging (MRI) revealed a chondrogenic tumor of 3 cm in size developing from the external bone surface. It was difficult to differentiate periosteal chondrosarcoma from periosteal chondroma on the basis of size and the radiological and MRI findings. PET/computed tomography (CT) revealed abnormal linear uptake with an SUVmax of 2.7, indicating a malignant tumor. A diagnosis of periosteal chondrosarcoma was made, and wide resection was performed. Tumor histology was consistent with grade II chondrosarcoma. PET/CT is thus useful in differentiating periosteal chondrosarcoma from periosteal chondroma.

A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site.

Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5-7 fusions were reported recently, they are classified as type 1-7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion.

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells.

Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MICB by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.

Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death.

We investigated the effects of valproic acid (VPA), a histone deacetylase inhibitor, in combination with hydralazine, a DNA methylation inhibitor, on the expression of cell-surface Fas and MHC-class I-related chain molecules A and B (MICA and B), the ligands of NKG2D which is an activating receptor of NK cells, and on production of their soluble forms in HOS, U-2 OS and SaOS-2 human osteosarcoma cell lines. We also examined the susceptibility of these cells to Fas- and NK cell-mediated cell death. VPA did not increase the expression of Fas on the surface of osteosarcoma cells, while hydralazine did, and the combination of VPA with hydralazine increased the expression of cell-surface Fas. In contrast, the combination of VPA with hydralazine did not increase the production of soluble Fas by osteosarcoma cells. Both VPA and hydralazine increased the expression of cell-surface MICA and B in osteosarcoma cells, and their combination induced a greater increase in their expression. VPA inhibited the production of both soluble MICA and MICB by osteosarcoma cells while hydralazine produced no effect. Both VPA and hydralazine enhanced the susceptibility of osteosarcoma cells to Fas- and NK cell-mediated cell death and the combination of VPA with hydralazine further enhanced the effects. The present results suggest that combined administration of VPA and hydrazine is valuable for enhancing the therapeutic effects of immunotherapy for osteosarcomas.

Small cell osteosarcoma successfully treated by high-dose ifosfamide and methotrexate, combined with carboplatin and pirarubicin.

Small cell osteosarcoma (SCO) is the most rare subtype of osteosarcoma and has a poor prognosis. An 11-year-old boy presented with 2-month history of painful tumefaction in the lower leg. Imaging analysis demonstrated a mixture of osteolytic and osteosclerotic lesions in the proximal tibia and extraskeletal area. Histology of the open biopsy showed small round cells producing mucous matrix. Based on these findings, SCO was suspected. The patient received three cycles of neoadjuvant chemotherapy using high-dose ifosfamide, high-dose methotrexate, pirarubicin and carboplatin. Wide-margin resection was performed followed by tibial lengthening using the Ilizarov method and two cycles of adjuvant chemotherapy with the same drugs as for neoadjuvant chemotherapy. Histology of the resected specimen showed that almost all tumor cells were necrotized. Neither recurrence nor metastasis was found after 4 years. Our experience suggests that neoadjuvant chemotherapy, such as the one used here, would be exceedingly effective for SCO without serious non-hematological toxicities.

Posterior interosseous nerve palsy caused by synovial chondromatosis arising in the annular periradial recesses of the elbow.

We present a rare case report of a patient who presented with posterior interosseous nerve palsy caused by synovial chondromatosis. Synovial chondromatosis arising in the annular periradial recesses of the elbow joint was detected, and the mass developed two major portions constricted with the annular ligament. After surgical resection, posterior interosseous nerve palsy fully recovered and there was no recurrence of the lesion of synovial chondromatosis.

Sodium valproate, a histone deacetylase inhibitor, augments the expression of cell-surface NKG2D ligands, MICA/B, without increasing their soluble forms to enhance susceptibility of human osteosarcoma cells to NK cell-mediated cytotoxicity.

MHC class I-related chain molecules A and B (MICA and B) expressed on the cell-surface of tumor cells are ligands for an activating receptor, NKG2D, expressed on natural killer (NK) cells and stimulate the NK cell-mediated cytotoxicity. On the other hand, the soluble form of MICA and B produced by proteolytic cleavage of cell-surface MIC interferes with NK cell-mediated cytotoxicity. We investigated effect of sodium valproate (VPA), a histone deacetylase inhibitor, on the production of cell-surface and soluble MICA and B and NK cell-mediated cytotoxicity in four human osteosarcoma cells. VPA at 0.5 and 1.0 mM induced acetylation of histones bound to MICA and B gene promoters, increased cell-surface but not soluble MICA and B, and augmented the susceptibility of osteosarcoma cells to NK cell-mediated cytotoxicity. The present results indicate that VPA sensitizes human osteosarcoma cells to cytotoxicity of NK cells.

Enhanced suppression of pulmonary metastasis of malignant melanoma cells by combined administration of alpha-galactosylceramide and interleukin-18.

alpha-Galactosylceramide (alpha-GalCer) shows antitumor effects by activating natural killer (NK) cells indirectly through stimulation of the secretion of cytokines by NKT cells, whereas interleukin (IL)-18 shows antitumor effects by activating NK cells directly. In the present study, we examined the antitumor effect of the combined administration of alpha-GalCer and IL-18. An injection of NK cell-sensitive mouse B16 melanoma cells into a mouse tail vein produced pulmonary metastasis. The daily administration of alpha-GalCer or IL-18 alone for 4 days starting 1 day after the injection of B16 melanoma cells markedly suppressed the number of pulmonary metastatic foci, and their combined administration enhanced the antitumor effect compared with single administration. The antitumor effect of their combined administration was completely abolished by treatment of mice with anti-asialo GM1 serum, which depletes NK cells but not NKT cells. Combined administration of alpha-GalCer and IL-18 enhanced the cytotoxicity of NK cells and increased the number of NK cells in the lung. Analysis of NKT cell-dependent and NK cell-independent secretion of cytokines, to which NK cells can respond, showed that the administration of alpha-GalCer increased the secretion of IL-2, IL-4, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IL-10, and the combined administration of alpha-GalCer and IL-18 enhanced the secretion of IL-2, IL-4, interferon-gamma, and granulocyte-macrophage colony-stimulating factor further but only slightly. These results show that IL-18 in combination with alpha-GalCer exerts an antitumor effect on NK cell-sensitive tumors primarily by the direct stimulation of NK cells by IL-18 and the indirect stimulation of NK cells by alpha-GalCer through its activation of NKT cells.

Giant cell tumor of the sternum: a case report and review of the literature.

Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor. The sternum is a rare location. To date, only four cases have been reported with detailed information. Here, we present a case with sternal GCT and discuss the clinical manifestation and treatment, in addition to reviewing the literature. A 53-year-old female noted pain in the sternum after a trauma. Radiographic findings revealed an expanding osteolytic lesion in the body of the sternum. Extended curettage of the tumor was performed followed by polymethylmethacrylate (PMMA) filing. No recurrence was found over a 7-year follow-up period. In conclusion, even though sternal benign tumors are rare, GCT should be considered as one of the differential diagnoses in a patient presenting with a sternal lesion in the 5th or 6th decade of life. The initial treatment should be extended curettage followed by filling with PMMA.

Endoscopically assisted resection of a scapular osteochondroma causing snapping scapula syndrome.

BACKGROUND: Osteochondroma is the most common benign bone tumor in the scapula. This condition might lead to snapping scapula syndrome, which is characterized by painful, audible, and/or palpable abnormal scapulothoracic motion. In the present case, this syndrome was successfully treated by use of endoscopically assisted resection of the osteochondroma. CASE PRESENTATION: A 41-year-old man had a tolerable pain in his scapular region over a 10 years' period. The pain developed gradually with shoulder motion, in particular with golf swing since he was aiming a professional golf player career. On physical examination, "clunking" was noted once from 90 degrees of abduction to 180 degrees of shoulder motion. A trans-scapular roentgenogram and computed tomography images revealed an osteochondroma located at the anterior and inferior aspect of the scapula. Removal of the tumor was performed by the use of endoscopically assisted resection. One portal was made at the lateral border of the scapula to introduce a 2.7-mm-diameter, 30 degrees Hopkins telescope. The tumor was resected in a piece-by-piece manner by the use of graspers through the same portal. Immediately after the operation pain relief was obtained, and the "clunking" disappeared. CT images showed complete tumor resection. The patient could start playing golf one week after the surgery. CONCLUSION: Endoscopically assisted resection of osteochondroma of the scapula provides a feasible technique to treat snapping scapula syndrome and obtain early functional recovery with a short hospital stay and cosmetic advantage.

Successful treatment of bilateral calcaneal intraosseous lipomas using endoscopically assisted tumor resection.

BACKGROUND: Intraosseous lipoma is a rare benign bone tumor. Removal is required when there is pain or the lesion is large enough to lead to a pathological fracture. However, conventional surgery requires non-weight-bearing for at least 6 weeks. Here, we present a case with bilateral calcaneal intraosseous lipomas successfully treated by the use of endoscopically assisted curettage. CASE PRESENTATION: A 30-year-old female noted pain in both heels for 1 year. Radiological findings revealed well-defined lytic lesions at the neck of both calcanei. Magnetic resonance (MR) images showed hyper-intense signals on the T1 and T2 sequences. Curettage was performed through small bone fenestrations in the medial and lateral aspects under observation with a 2.7-mm-diameter Hopkins telescope. The bone void was filled with beta-tricalcium phosphate (beta-TCP). Full weight-bearing was permitted the day after the surgery. CONCLUSION: Endoscopically assisted curettage is feasible in patients with benign bone tumors of the calcanei to avoid a long period of non-weightbearing post-operatively.

Experimental study of neural repair of the transected spinal cord using peripheral nerve graft.

It has been reported that transected spinal cord shows signs of axonal regeneration after peripheral nerve (PN) graft. We studied the membrane excitability and ion distribution in axons from transected rat spinal cord 3 weeks after PN graft using the spinal cord evoked potential, electron probe X-ray microanalysis, and the patch-clamp technique. Axonal structures were also observed using conventional electron microscopy. At the Th11 level, laminectomy was performed (=control) and the left thoracic segments of the spinal cord 2 mm in length were excised (=nongrafted group). PN sections from 8-week-old male Wistar rats were grafted into the spinal cord gap (=PN-grafted group). The spinal cord evoked potential in the PN-grafted group partly recovered in contrast to that in the nongrafted group, which showed no recovery. Higher Na, Cl, and Ca peaks and lower K peaks in the PN-grafted group were demonstrated compared with those in the nongrafted group. In the PN-grafted group, a higher current signal appeared in the axonal membrane of the spinal cord, suggesting a greater membrane activity compared with that in the nongrafted group. Unlike the nongrafted group, in which no myelinated axons were found, demyelinated axons that were myelinated by Schwann cells from the grafted peripheral nerve were observed in the PN-grafted group. These findings suggested that Schwann cells from the transplanted PN contributed to the repair of the transected spinal cord.