Tadaki Matsumura

MRI and histological evaluation of the infiltrative growth pattern of myxofibrosarcoma.

ObjectiveMyxofibrosarcoma often shows abnormal signal infiltration along the fascial plane on magnetic resonance imaging (MRI). The objective was to describe this MRI characteristic of myxofibrosarcoma with pathologic findings for comparison.Materials and methodsClinical, histological, and imaging data for 21 patients with myxofibrosarcoma were reviewed retrospectively.ResultsSeventeen tumors showed a diffuse infiltrative pattern on MRI. All tumors with diffuse infiltrative growth pattern showed borderless extension of atypical cells with moderate nuclear atypia to the muscle fascia. Notably, the remaining four patients with focal growth pattern on MRI also demonstrated infiltrative growth pattern histologically suggesting that myxofibrosarcoma shows an infiltrative growth property even in the lack of infiltrative growth pattern on MRI.ConclusionMost myxofibrosarcoma show an infiltrative growth pattern histologically. Orthopedic oncologist should pay careful attention to accurately assess tumor extension. It seems prudent to resect the entire area of abnormal signal extension seen on MRI whenever possible to obtain an adequate surgical margin of myxofibrosarcoma.

The level of vascular endothelial growth factor as a predictor of a poor prognosis in osteosarcoma

We undertook a prospective study to evaluate the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma. The levels were measured by an enzyme-linked immunosorbent assay in 15 patients with osteosarcoma before commencing treatment. The patients were divided into two groups, with a high or a low serum VEGF level, and the incidence of metastases and overall survival rate were compared. No significant relationship was observed between the serum VEGF levels and gender, age, the size of the tumour or the response to pre-operative chemotherapy. Patients with a serum VEGF > 1000 pg/ml had significantly worse survival than those with a level < 1000 pg/ml (p = 0.002). The serum VEGF level may be useful in predicting the prognosis for survival in patients with osteosarcoma.

Angiomatoid fibrous histiocytoma including cases with pleomorphic features analysed by fluorescence in situ hybridisation

Background Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue tumour of uncertain differentiation and low metastatic potential. Cytogenetics and/or molecular genetics have revealed that most have a rearrangement of the EWSR1 gene, whereas a FUS gene rearrangement is present in a minority of cases. Although some cases of AFH display striking pleomorphism and mitotic activity, there are no known clinical, morphological or genetic factors that predict metastasis. The authors present clinicopathological features of AFH, including cases showing a pleomorphic histological appearance, and results of fluorescence in situ hybridisation analysis of EWSR1 and FUS rearrangements. Methods Tumour samples from 10 patients were subjected to clinicopathological and immunohistochemical analysis and dual-colour fluorescence in situ hybridisation for EWSR1 and FUS with split-signal probes. Results All cases showed clinical features (sites: extremities followed by trunk; age: adolescent to young adult), morphology (multinodular proliferation of spindle cells, lymphoid cuffs and pseudovascular spaces) and immunohistochemical results (more than half were positive for CD68, CD99, desmin and epithelial membrane antigen) typical of AFH. There were two local recurrences in each of two patients. Two patients developed distant metastases and died from the disease; tumours of these two patients showed focal proliferation of large pleomorphic cells with hyperchromatic nuclei and high proliferative activity (>10/10 high-power field and Ki-67 labelling index >10%). There were no clinical, histological or immunohistochemical differences between the nine cases with EWSR1 rearrangement and one case with FUS rearrangement. Conclusions Wide surgical excision and careful follow-up are necessary for patients with AFH in view of its risk of local recurrence and metastasis leading to a fatal outcome.

Advantage of FISH analysis using FKHR probes for an adjunct to diagnosis of rhabdomyosarcomas

Translocations can be detected using fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissues. Recently, a commercially available FKHR (13q14) dual-color, break-apart rearrangement probe has been developed. However, the advantages of using this probe have not been reported. This study demonstrated the usefulness of this probe for the clinical diagnosis of rhabdomyosarcomas (RMS). We studied 33 RMS (19 embryonal rhabdomyosarcomas [ERMS], including three sclerosing-type RMS, and 14 alveloar rhabdomyosarcomas [ARMS]). Fluorescence signals were detected for 18 of the 19 (94.7%) ERMS and 13 of the 14 (92.8%) ARMS. A split-signal pattern was detected in 12 of 13 (92.3%) ARMS but was not detected in any of the ERMS, including the three sclerosing-type RMS. Amplification and polyploidy were present in both the ERMS and the ARMS. Our FISH study highlighted the excellent performance of the presently reported commercial break-apart probe for the detection of FKHR gene rearrangements in RMS. Because amplification and polyploidy were detected in both the ERMS and the ARMS, sufficient care should be taken when counting the nuclear signals. No rearrangements of the FKHR gene were found in any of the three sclerosing-type RMS when examined using a FISH assay, supporting the hypothesis that sclerosing RMS can be included as an ERMS.

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma

Aims: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. Methods: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. Results: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. Conclusion: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Acid-sensing ion channel 3 or P2X2/3 is involved in the pain-like behavior under a high bone turnover state in ovariectomized mice.

We have recently demonstrated that pathological changes leading to increased bone resorption by osteoclast activation are related to the induction of pain‐like behavior in ovariectomized (OVX) mice. In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid‐sensing nociceptor, improved the threshold value of pain‐like behaviors accompanying an improvement in the acidic environment in the bone tissue based on osteoclast inactivation. The aim of this study was to evaluate the effect of (i) an inhibitor of vacuolar H+‐ATPase, known as an proton pump, (ii) an antagonist of acid‐sensing ion channel (ASIC) 3, as another acid‐sensing nociceptor, and (iii) the P2X2/3 receptor, as an ATP‐ligand nociceptor, on pain‐like behavior in OVX mice. This inhibitor and antagonists were found to improve the threshold value of pain‐like behavior in OVX mice. These results indicated that the skeletal pain accompanying osteoporosis is possibly associated with the acidic microenvironment and increased ATP level caused by osteoclast activation under a high bone turnover state.

Impaired cutaneous wound healing in mice lacking tetranectin

Tetranectin was originally purified from human serum on the basis of plasminogen kringle 4‐binding properties. Tetranectin enhances plasminogen activation by a tissue‐type plasminogen activator so that it has been suggested to play a role in tissue remodeling. We have generated mice with a targeted disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin‐null mice compared with wild‐type mice. A single full‐thickness incision was made in the dorsal skin. By 14 days after the incision, the wounds fully healed in all wild‐type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild‐type mice showed complete reepithelialization and healed by 14 days after the incision. However, those of tetranectin‐null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process.

Periosteal chondrosarcoma with microscopic cortical invasion.

The periosteal chondrosarcoma is an uncommon juxtacortical malignant bone tumor. Most are low-grade (grade 1), and their relatively good prognosis is emphasized even if treatment is local resection. Once periosteal chondrosarcomas recur, however, the grade of malignancy may become higher and it may be diffi cult to excise the tumor completely. Therefore, it is important to demonstrate the extent of the tumor accurately. We report a case of grade 2 periosteal chondrosarcoma of the femur and focus on tumor invasion into the underlying cortex.