Takeshi Minamizaki

Long-term follow-up after limb salvage in skeletally immature children with a primary malignant tumor of the distal end of the femur.

BACKGROUND Skeletally immature children with a primary malignant tumor in the distal end of the femur are candidates for limb-salvage surgery; however, functional impairment due to subsequent limb-length discrepancy must be considered. Our aim was to evaluate the long-term clinical outcome of limb salvage in patients with a sarcoma of the distal end of the femur who were eleven years old or less, focusing on limb-length discrepancy and complications. METHODS The cases of forty children were retrospectively reviewed in a multicenter study based on the responses to a questionnaire. Twenty-eight patients had had endoprosthetic reconstruction, and twelve had had biological reconstruction. Functional evaluation was based on the Musculoskeletal Tumor Society scoring system, with numerical values from 0 to 5 points assigned for each of the following six categories: pain, function, emotional acceptance, use of supports, walking ability, and gait. These values were added, and the functional score was presented as a percentage of the maximum possible score. Limb-length discrepancy was measured with orthoroentgenograms. Complications and their treatment were analyzed. Patient survival and the survival of the reconstructions were analyzed with use of the Kaplan-Meier method. RESULTS Seven patients died and thirty-three remained alive, for a survival rate of 82% at ten years postoperatively. For the surviving patients, the mean follow-up periods (and standard deviations) were similar for the twenty-two who had endoprosthetic reconstruction (13.2 +/- 3.9 years) and the eleven who had biological reconstruction (10.4 +/- 4.4 years). All patients had reached skeletal maturity. The mean final functional score was 74% +/- 18% in the endoprosthetic reconstruction group and 68% +/- 17% in the biological reconstruction group (p = 0.37). For the nineteen patients who underwent limb-lengthening, the mean functional score increased significantly from 65% +/- 21% before the procedure to 81% +/- 11% after the lengthening (p = 0.0016). There were five early and twenty-eight late complications. In the endoprosthetic reconstruction group, the most frequent complications were deep infection and aseptic loosening. In the biological reconstruction group, the most frequent complications were implant breakage and nonunion. Revision surgeries were required in seventeen patients, including five who had an amputation. The rate of survival of the endoprosthetic reconstructions was 77% at five years and 51% at ten years postoperatively, whereas the rate of survival of the biological reconstructions was 46% at both five and ten years postoperatively. CONCLUSIONS Endoprosthetic or biological reconstructions as limb salvage provided good functional outcome in skeletally immature children with a malignant bone tumor of the distal aspect of the femur despite a high rate of revisions and limb-lengthening procedures.

Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J

BackgroundOsteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out.MethodsTo evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multiinstitutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible.ResultsThe 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy.ConclusionsWe analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.

Ossifying fibromyxoid tumor of soft parts.

A histologically uncommon soft‐tissue tumor of the extremities and neck of a 54‐year old male is reported. The solid, bony‐hard tumors occurred at the inner region of the right thigh at 44 years of age with additional tumor formation at the posterior region of the same thigh, at the inner region of the right upper arm and at the neck during the following 10 years. All tumors were located in the deep muscle layer. The neck tumor directly invaded the fifth cervical vertebra and later the upper mediastinum. Histologically, all three tumors of the extremities contained mixed lobular growths of round to fusiform cells with myxoid matrix and an extensive bone formation. The tumor cells showed a small round nucleus and eosinophilic cytoplasm lacking cytoplasmic glycogen. The myxoid matrix was stained significantly by alcian blue and colloidal iron and was digested completely by pretreatment with hyaluronidase. Another major component was mature bone trabeculae showing a dense meshwork throughout the entire tumor with active bone formation toward the periphery. Positive immunostaining was obtained against anti‐vimentin and S‐100 protein antibodies. We suggest that this uncommon tumor can be tentatively distinguished as an ossifying fibromyxoid tumor of soft parts, (an entity defined by Enzinger et al.), differing from other previously described soft‐tissue tumors. Acta Pathol Jpn 41: 480–486, 1991.

Chromosomal rearrangement t(11;22) in extraskeletal Ewing's sarcoma and primitive neuroectodermal tumour analysed by fluorescence in situ hybridization using paraffin-embedded tissue.

The clonal chromosomal rearrangement t(11;22) has been reported by karyotypic analysis to be specific for Ewings sarcoma of bone and soft tissue origin as well as primitive neuroectodermal tumour. In this report, immunohistological analysis of MIC 2 expression and fluorescence in situ hybridization (FISH) were performed using paraffin‐embedded tissues. We examined t(11;22) in the nuclei isolated from two Ewings sarcomas, four primitive neuroectodermal tumours, and three neuroblastomas, which served as negative controls by FISH with an α‐satellite DNA probe for chromosome 11, a chromosome 22 marker probe, and whole chromosome painting probes for both chromosomes 11 and 22. Both cases of Ewings sarcoma and the four primitive neuroectodermal tumour specimens were immunoreactive for MIC 2. Both Ewings sarcomas and three of the four primitive neuroectodermal tumours contained the tumour‐specific t(11;22), but the three neuroblastomas did not show this translocation. Based on the cytogenetic results and on the immunohistological investigation of MIC 2 expression, Ewings sarcoma is suggested to be related closely to primitive neuroectodermal tumour. FISH is a useful aid in determining the tumour type of Ewings sarcoma and putative related tumours.

Development of the attachment zones in the rat anterior cruciate ligament: changes in the distributions of proliferating cells and fibrillar collagens during postnatal growth.

The development of the attachment zones of the anterior cruciate ligament (ACL) is an important consideration when examining the structural properties. The aim of this study was to elucidate the morphological changes and the distribution of proliferating cells and collagen types I, II and III at the attachment zones of the rat ACL during postnatal growth.

Sacral cyst managed with cyst-subarachnoid shunt : A technical case report

Study Design This report describes the cyst–subarachnoid shunt, a novel surgical treatment, for sacral cysts. Objective To introduce a new surgical technique for sacral cysts. Summary of Background Data There is no consensus on the appropriate treatment for symptomatic sacral cysts. The hydrostatic and pulsatile forces of cerebrospinal fluid are attributed to the growth of the cyst and their becoming symptomatic. Methods The clinical and radiologic features of a 41-year-old man with a symptomatic sacral cyst are detailed. A cyst–subarachnoid shunt was set to equalize the cerebrospinal fluid pressure between the cephalad thecal sac and the cyst. Results Immediately after surgery, the patient had no pain in his left leg and was free of pain at 2 years. Magnetic resonance imaging 1 year after surgery showed a decrease in the size of the cyst. Conclusion Although this is a preliminary study, a cyst–subarachnoid shunt can be a useful alternative for symptomatic sacral cysts.

Osteosarcoma with Prominent Epithelioid Features

Osteosarcoma in the metaphysis to epiphysis of the left femur of a 17 year old male is reported. The lesion appeared osteolytic with sclerotic foci on roentgenographs, accompanied by an extensive tumor shadow in the surrounding soft tissue. While 60% of the tumor was necrotic, histological examination of the remaining viable tissue revealed that it consisted almost entirely of a sheet of epithelioid cells, separated by thin, fibrovascular septa with an alveolar‐like pattern, suggestive of metastatic carcinoma. Only a few areas were characterized by malignant osteoid tissue intermingled with the above cells, showing significant positivity for bone‐specific alkaline phosphatase and 5 nucleotidase, thus permitting a diagnosis of osteosarcoma. Autopsy findings revealed that the metastatic foci were histologically similar to those of the primary tumor. Electron microscopy revealed poor development of cytoplasmic organelles, supporting possible derivation from an osteoblastic cell lineage at an early stage. Acta Pathol Jpn 39: 439 445, 1989.

Cytoplasmic maspin expression predicts poor prognosis of patients with soft tissue sarcomas

BackgroundMaspin is a 42 kDa protein known to act as a tumor suppressor. Although its function has not been fully elucidated, numerous reports have investigated the prognostic impact of maspin in patients with several types of cancer. However, there have been no reports on the association between maspin expression and the prognosis of patients with soft tissue sarcomas (STS). The aim of this study was thus to explore the association of maspin expression with the prognosis of patients with STS.MethodsOne-hundred and eight paraffin-embedded STS tissue samples were immunohistochemically analyzed using antibodies for maspin and Ki-67 antigen. The patients were followed up for 1 to 300 months (median: 33 months) and the prognostic value was evaluated by log-rank test and Coxs regression hazard model.ResultsCytoplasmic maspin expression was observed in 48.1% of specimens, and was significantly correlated with a higher FNCLCC grade (P = 0.002) and the presence of distant metastases (P = 0.001), and those with cytoplasmic maspin expression had both shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P <0.001, P = 0.001, respectively). By Coxs multivariate analysis, the presence of distant metastases was the only prognostic factor for DFS and OS.ConclusionsThis is the first report to reveal an association between maspin expression and the prognosis of patients with STS. Although further studies with a larger series of patients and a longer follow-up period will be needed, cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with STS.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_205

Osteosarcoma with features mimicking malignant fibrous histiocytoma

Three osteosarcomas (OS) with features resembling malignant fibrous histiocytoma (MFH) were selected and investigated to identify any clinico-pathological similarities. In all cases there was no significant difference from conventional OS on the radiography and laboratory data. The appearance of MFH-like features within the whole tumour tissue varied from 7% to 55%. It was composed of spindle-shaped cells arranged in short irregular fascicles and a storiform pattern admixed with osteoclast-like giant cells, but devoid of neoplastic osteoid. Such spindle-shaped cells had a poorly developed rough endoplasmic reticulum and expressed a strong alkaline phosphatase activity as well as vimentin. A series of allografts to athymic mice using the MFH-like tissues also showed histologically a proliferation of plump spindle-shaped cells with a storiform pattern lacking osteoclast-like giant cells, and intensely positive for alkaline phosphatase. These findings indicate that the MFH-like features are identified as modulated OS. The constituting cells are most likely to be poorly developed with possible phenotypic alteration in the maturation stage of osteoblastic cell lineage, but different from conventional MFH of bone as regards their distinct histochemical pattern.

Alkaline Phosphatase-Positive and Negative Bone Tumors: Ultrastructural and Immunohistochemical Studies of Fibroblast-Like Tumor Cells*

Bone tumors, which consist largely of fibroblast-like cells, were categorized into ALPase-positive (3 ossifying fibromas and 2 fibroblastic osteosarcomas) and negative (4 non-ossifying fibromas and 5 MFHs) groups. They were investigated as to their ultrastructure and immunophenotype using antibodies of fibroblast markers (collagen I, III, aminopeptidase M, dipeptidylpeptidase IV and factor XIIIa), classical macrophage markers (AACT and AAT) and vimentin. In the case of the ALPase-positive group, fibroblast-like cells showed short, branching rough endoplasmic reticulum with bundles of microfibrils in their cytoplasms. They were often intermingled with osteoblastic cells particularly in proximity to osteoid tissue. Furthermore, these cells expressed fibroblast markers of collagen I, aminopeptidase M, dipeptidylpeptidase IV and factor XIIIa. Fibroblast-like cells of the ALPase-negative group more or less revealed phagosomes in addition to fibroblastic features admixed with histiocyte-like cells. They expressed classical macrophage markers, but rarely fibroblast markers. The above findings indicated that derivation from different precursor cells should be proposed between the two groups and that the tumors in the ALPase-positive group might be intimately related to a certain population of the bone marrow stromal cells.