Akira Ogose

Chondrosarcoma of small bones of the hands and feet

Cartilaginous tumors of the hands and feet are not uncommon. Most are enchondromas, but they tend to show high cellularity, enlargement of nuclei, and many double‐nucleated cells. Hence, differentiation between a benign lesion and chondrosarcoma may be difficult.

Tumors of peripheral nerves : correlation of symptoms, clinical signs, imaging features, and histologic diagnosis

Abstract Objective. To distinguish between benign and malignant tumors in the peripheral nerves. Design and patients. The clinical, imaging and histologic findings of 99 benign and 16 malignant tumors in the peripheral nerves were reviewed retrospectively. Results. Preoperative motor weakness was observed in only six of 99 benign tumors and was mild, while slight to severe motor weakness was present in 15 of 16 malignant lesions. Pain at rest was present in five of 99 benign tumors and in 15 of 16 malignant tumors. All benign lesions showed a smooth tumoral margin, while half the malignant lesions showed an invasive margin on CT or MRI. Thirteen of 28 benign lesions on CT and nine of 23 on MRI showed round to geographic central enhancement, but this pattern was not seen in malignant lesions. Conclusion. Absence of severe motor weakness and a central enhancement pattern strongly suggest a benign nature, while severe rest pain and invasive tumor margin suggest malignant lesions in peripheral nerve tumors.

Alveolar Soft Part Sarcoma in Japan: Multi-Institutional Study of 57 Patients from the Japanese Musculoskeletal Oncology Group

Objective: The clinical features and the management of alveolar soft part sarcoma (ASPS) are not well known. The efficacy of chemotherapy for soft tissue sarcoma, including high-dose ifosfamide and cisplatin, has not been established yet. Some reports suggest ASPS may occur primarily in bone. Methods: We report on a series of 57 patients with ASPS over 20 years. Their ages ranged from 7 to 75 years (mean 25). Results: There were 37 females and 20 males. Thirteen lesions (23%) showed bone involvement at the primary site, and 6 of them were diagnosed as bone tumors at presentation. Thirty-seven patients had distant metastases at presentation. Tumor size, bone involvement at the primary site and the presence of metastases at presentation were prognostic indicators (p < 0.05). Marginal excision with radiotherapy or wide excision without radiotherapy achieved good local control. Chemotherapy was performed in 47 patients with different regimens. Two patients treated with intra-arterial chemotherapy regimens responded partially, but intravenous chemotherapy with high-dose ifosfamide or cisplatin failed. Conclusions: ASPS can present primarily as a bone tumor. No advantage of chemotherapy with high-dose ifosfamide or cisplatin could be demonstrated.

Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia.

Abstract Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or rickets. The tumor typically follows a benign clinical course. Even in the rare malignant cases, local recurrence and distant metastasis are uncommon. We report on an example of a malignant phosphaturic mesenchymal tumor which recurred several times over 16 years concurrently causing hypophosphatemia, bone pain, and osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The patient died of disease 17 years after the first surgery. Histologically, the initial tumor was composed of small spindle cells with clusters of giant cells, prominent blood vessels, poorly formed cartilaginous areas, and crystalline material. Cytological atypia was minimal. Following multiple recurrences, the tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism, numerous mitotic figures, and p53 overexpression. This case illustrates the potential lethality of incompletely removed phosphaturic mesenchymal tumors.

A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells: Coordinated activation of bone formation and resorption

In ongoing clinical research into the use of cultured autogenous periosteal cells (CAPCs) in alveolar bone regeneration, CAPCs were grafted into 33 sites (15 for alveolar ridge augmentation and 18 for maxillary sinus lift) in 25 cases. CAPCs were cultured for 6weeks, mixed with particulate autogenous bone and platelet-rich plasma, and then grafted into the sites. Clinical outcomes were determined from high-resolution three-dimensional computed tomography (3D-CT) images and histological findings. No serious adverse events were attributable to the use of grafted CAPCs. Bone regeneration was satisfactory even in cases of advanced atrophy of the alveolar process. Bone biopsy after bone grafting with CAPCs revealed prominent recruitment of osteoblasts and osteoclasts accompanied by angiogenesis around the regenerated bone. 3D-CT imaging suggested that remodeling of the grafted autogenous cortical bone particles was faster in bone grafting with CAPCs than in conventional bone grafting. The use of CAPCs offers cell-based bone regeneration therapy, affording complex bone regeneration across a wide area, and thus expanding the indications for dental implants. Also, it enables the content of particulate autogenous bone in the graft material to be reduced to as low as 40%, making the procedure less invasive, or enabling larger amounts of graft materials to be prepared. It may also be possible to dispense with the use of autogenous bone altogether in the future. The results suggest that CAPC grafting induces bone remodeling, thereby enhancing osseointegration and consequently reducing postoperative waiting time after dental implant placement.

Multiple schwannomas in the peripheral nerves

Multiple tumours of peripheral nerves are often seen in patients with neurofibromatosis of type 1 or 2. Multiple schwannomas may occur without other manifestations of neurofibromatosis. We have reviewed 12 patients with multiple schwannomas arising from peripheral lesions who did not fulfil the criteria for either type of neurofibromatosis. Four had spinal and one an intracranial lesion in addition to the peripheral tumours. Two patients had one and three café-au-lait spots, respectively, and another had a probable family history. The largest tumours were 45 to 250 mm in size. Three patients had been referred as having von Recklinghausens disease. The large size of tumours, the difficulties of histological diagnosis on biopsy, and the confusion with neurofibromatosis can lead to overtreatment. Malignant change seldom, if ever, occurs in patients with multiple schwannomas.

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: A study from the Japanese Musculoskeletal Oncology Group†

In the present study, we evaluated the safety and effectiveness of SYT‐SSX‐derived peptide vaccines in patients with advanced synovial sarcoma. A 9‐mer peptide spanning the SYT‐SSX fusion region (B peptide) and its HLA‐A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14‐day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freunds adjuvant and then administered subcutaneously six times at 14‐day intervals. In addition, interferon‐α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six‐injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed‐type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Extracorporeal irradiated autogenous osteochondral graft: A HISTOLOGICAL STUDY

We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48) following extracorporeal irradiation and re-implantation to replace bone defects after removal of tumours. The specimens were obtained from six patients (mean age 13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral bone (five), external callus (one) and tendon (one). The tumour cells in the grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage specimens, viable chondrocytes were detected. The survival of chondrocytes was confirmed with S-100 protein staining. Three specimens from the subchondral region and a tendon displayed features of regeneration. Callus was seen at the junction between host and irradiated bone.

Osteosarcomas after the age of 50: a clinicopathologic study of 64 cases--an experience in northern Japan.

Background: The clinicopathologic profile and prognostic factors of osteosarcomas after the age of 50 years have been obscure.Methods: Clinicopathologic features were analyzed in 645 patients with osteosarcoma who were registered at the Tohoku Musculoskeletal Tumor Society and National Cancer Center in Tokyo between 1972 and 2002.Results: Sixty-four patients (9.9%; 34 men and 30 women) were more than 50 years old. The most common location was the distal femur (n = 13), followed by the pelvis (n = 10), proximal femur (n = 9), and proximal fibula (n = 6). Seven (11%) patients had lung metastasis at initial presentation. On radiographs, an osteolytic appearance without periosteal reactions was a common and characteristic feature. Forty-eight tumors (75%) were classified as conventional osteosarcomas. Fourteen cases (22%) were secondary; postradiation osteosarcoma was most common in these patients, but there was no Paget’s sarcoma. At the initial presentation, misdiagnoses without biopsy were made in 15 (23%) of the 64 cases. Preoperative chemotherapy was given to 22 patients, but the effect was poor in 18 cases (82%). Fifty-four patients underwent surgery, whereas the other 10 patients were treated without surgery because of systemic or inoperable local conditions. The overall survival rate at 5 years was 55.5%. Multivariate analysis showed initial pulmonary metastasis, axial tumor location, and larger tumors as significant prognostic factors.Conclusions: In northern Japan, most patients with osteosarcoma after the age of 50 had primary osteosarcoma. Careful radiological examination and biopsy are mandatory for correct diagnosis. Current systemic chemotherapy is not effective for this age group. Alternative treatment strategies should be considered.

Expression of podoplanin in human bone and bone tumors : New marker of osteogenic and chondrogenic bone tumors

Podoplanin is known as a lymphatic marker because its expression is detected in lymphatic but not vascular endothelium. Podoplanin is also expressed in several normal tissues including osteocytes or osteoblasts. A systematic examination of the podoplanin expression was conducted in normal skeletal tissues and some bone tumor cell lines, and the diagnostic value determined in primary bone tumors. Podoplanin mRNA was expressed at a high level in bone marrow tissue and cartilage, and was upregulated with differentiation to osteoblasts in bone marrow cells. Strong podoplanin expression was seen in osteocytes, chondrocytes, and osteoblasts on immunohistochemistry. Podoplanin mRNA was expressed at a high level in several osteosarcoma and chondrosarcoma cell lines, whereas podoplanin was expressed at a low level in a Ewings/primitive neuroectodermal tumor cell line. In the clinical samples, osteosarcomas (22/26) expressed podoplanin at various levels. In small cell osteosarcomas (2/2), podoplanin was expressed strongly, although the tissue samples included few diagnostic osteoids. Chondrosarcomas (10/10) expressed podoplanin strongly, and chondroblastomas (5/5) expressed podoplanin moderately, while podoplanin was absent or expressed at low levels in Ewings sarcomas (0/5), chordomas (0/6) and giant cell tumors of bone (1/7). Therefore, podoplanin may be a sensitive immunohistochemical marker of osteogenic and chondrogenic bone tumors.