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Background: Biodegradable interference screws in anterior cruciate ligament (ACL) reconstruction have gained popularity because of their similar or superior fixation strength in comparison to metallic interference screws and because they do not cause imaging artifacts and do not need to be removed., Case Description: We report the case of a 23-year-old man who presented with slowly progressive firm swelling of 2 months' duration at the site of the tibial tunnel 3 years after ACL reconstruction using a biodegradable interference screw. After curettage and débridement, the material was sent for histopathologic examination, which was reported as a fibroxanthoma., Literature Review: Reported complications are osteolysis around the screw, allergic reaction, sterile abscess formation, ganglion cyst formation, and intraarticular migration. A fibroxanthoma consists of fibroblasts and mononuclear or multinucleated cells with large lipid-filled histiocytes (foam cells). The cells are negative for S-100 and keratin and positive for anti-human macrophage marker HAM-56., Purposes and Clinical Relevance: Use of biodegradable screws is associated with high healing rates and low complication rates; however, awareness of their potential complications may help in early recognition and prevention of associated morbidity.

Angiomatoid fibrous histiocytoma is a neoplasm of uncertain histogenesis, which most commonly arises in the subcutaneous tissue of the extremities of children and young adults. We report the first case of a calcifying sclerosing variant of this entity. This case arose in bone-a site where there has been just 1 previously published case of typical (nonsclerosing/mineralizing) angiomatoid fibrous histiocytoma. The patient presented with the classical paraneoplastic syndrome that can occur with this tumor type and, apart from the described extracellular matrical features, displayed typical histologic features. Due to the rarity of angiomatoid fibrous histiocytoma at this site and the presence of matrical sclerosis/mineralization, this case raised the important differential diagnosis of osteosarcoma, both histologically and radiologically. The diagnosis was confirmed by molecular analysis; fluorescence in situ hybridization for EWSR1 gene disruption, and reverse transcription-polymerase chain reaction using newly designed primers on both frozen and decalcified, paraffin-embedded tissue samples showing an EWSR1-ATF1 translocation. It is important to recognize that this relatively indolent tumor can arise in bone and that it can contain focally mineralized hyalinized sclerotic matrix to avoid making the serious misdiagnosis of high-grade osteosarcoma and administering aggressive systemic chemotherapeutic treatment.

The fibronexus (fibronexus junction) has been thought to be a characteristic ultrastructural feature of myofibroblasts, but it is controversial whether the fibronexus is also a characteristic of various myofibroblastic tumors. We report here a case of pleomorphic bone sarcoma (pleomorphic/storiform malignant fibrous histiocytoma) with fibronexus junctions arising in the head of the left humerus of a 70-year-old woman. By light microscopy the tumor was composed of large spindle or polygonal cells occasionally arranged in fascicles. Foamy giant cells with bizarre nuclei were not uncommon. Immunohistochemically, the tumor cells were positive diffusely for vimentin and focally for muscle actin (HHF35) and alpha-smooth muscle actin but were negative for desmin, high-molecular weight caldesmon, and S-100 protein. Ultrastructurally, the tumor cells had indented nuclei and spindle or polygonal cytoplasm, with little rough endoplasmic reticulum and small vesicles, and rather numerous mitochondria. The tumor cells had myofilaments with focal densities in the periphery, fibronectin fibrils adjacent to intracellular myofilaments, and by definition, therefore, fibronexus junctions. These findings suggest myofibroblastic differentiation, and a diagnosis of pleomorphic myofibrosarcoma is thought to be appropriate. We believe that the fibronexus is a characteristic and useful ultrastructural feature for differentiating myofibroblastic tumors from other pleomorphic myogenic sarcomas.

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq 99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and 99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of 99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33% +/- 9% vs 17% +/- 9%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of 99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.

We recently reported a tumor-rejection antigen, SART1259, possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs). This study investigated the expression of SART1259 antigen in osteosarcoma and other skeletal malignant tumors to explore for a potential molecule for use in specific immunotherapy. The SART1259 antigen was detected in the cytosol fraction of 13 of 21 (62%) osteosarcoma cell lines and 3 of 8 (38%) osteosarcoma tissues, and 3 of 10 (30%) malignant fibrous histiocytoma (MFH) tissues. The HLA-A24+ and SART1259+ osteosarcoma cells were recognized by the HLA-A24 restricted and SART1 specific CTLs. These results raise a possibility that the SART1259 would be an appropriate molecule for use in specific immunotherapy of approximately one-third of HLA-A24+ patients with osteosarcoma and MFH.

Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.

Enhanced hepatocyte growth factor (HGF) receptor (Met) signaling has been suggested to play an important role in the development and progression of various epithelial and nonepithelial tumors. N-terminally truncated forms of the HGF receptor have been shown to be constitutively activated and tumorigenic in animal experiments. In the present study, 102 benign and malignant human musculoskeletal tumors were examined for expression of the HGF receptor by Western blotting and/or immunohistochemistry. A clear predominance of HGF receptor expression was seen in malignant as compared to benign tumors (Western blotting, P < 0.001; immunohistochemistry, P < 0.02). For the first time we show HGF receptor expression in the following four tumor types: dermatofibrosarcoma protuberans, clear cell sarcoma of tendons, malignant primitive neuroectodermal tumor, and benign fibrous histiocytoma. In three cases of sarcoma with high HGF receptor expression by Western blotting, we found indications of a short 85-kd N-terminally truncated HGF receptor that was tyrosine phosphorylated and located in the cytoplasm. Although fragments of this length were seen in 18 of 65 tumors, most were not tyrosine-phosphorylated. Northern blotting revealed only the 7.5-kb full-length HGF receptor transcript, suggesting that the 85-kd fragment is generated by an alternative initiation of translation or by proteolytic cleavage. Southern blotting detected no amplification of the Hgfr/Met gene in the 35 tumors examined, in contrast to our recent report of Hgfr/Met gene amplification in 7, 12-dimethylbenz(a)anthracene (DMBA)-induced rat sarcomas. The present data suggest that the locally aggressive and malignant properties of human mesenchymal tumors maybe related, in part, to high levels of full-length HGF receptors, and in some cases to the occurrence of N-terminally truncated HGF receptors, activated independently of HGF.

A case of a 54-year-old woman is described who developed synchronously two malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous differentiations were not observed in the anaplastic sarcoma cells. The MFH in the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed positivity for M-actin and desmin pointing to myogenous differentiation. DNA-cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53 gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in exon-8 with the transversion from G to T in codon 294 resulting in a substitution of a stop codon for GLU. The mutation was not observed in the MFH. From these immunohistologic, DNA-cytometric and molecular biologic investigations, we consider it probable that the tumor in the lower tibia is a second highly malignant bone tumor and not the metastasis of the dedifferentiated portion of the dedifferentiated chondrosarcoma in the olecranon.

Background: Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identified BMPs in a subset of osteosarcomas. In the present study, the authors extend the analysis of BMP expression to other bone and soft tissue sarcomas., Methods: Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with frozen sections of bone tumors (71 specimens), soft tissue sarcomas (69 specimens), and normal tissues., Results: Among bone tumors, BMP was detected in osteosarcomas (17 of 29 samples), malignant fibrous histiocytomas (MFHs) (6 of 6), and the spindle cell sarcomatous components of spindle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in conventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). Histologic subtypes of osteosarcoma differed for BMP expression, with 8 of 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immunostaining was localized in the cytoplasm of primitive mesenchymal cells, with little or no staining in tumor matrix and more mature osteoblastic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwannomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcomas (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) were BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity., Conclusions: Bone morphogenetic protein is expressed in a subset of osteosarcomas, a high proportion of MFHs of bone and soft tissue, and in spindle cell chondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no or little BMP is detected in the more differentiated elements of bone and soft tissue sarcomas. Different histologic types of bone and soft tissue sarcomas may mimic discrete stages of mesenchymal differentiation as defined by BMP expression and histologic criteria.

The p53 gene is one of the best studied tumour suppressor genes. Recently we performed mutation analysis on the p53 gene in a large number of bone and soft tissue sarcomas, and found that approximately one-third of the sarcomas have some type of DNA alteration at the p53 locus (Toguchida et al., 1992). However, the expression of the p53 protein resulting from these alterations still remains to be clarified. In this study, p53 expression in the sarcoma tissues was analysed immunohistochemically using antibody PAb421 (Oncogene Science) and its relationship to DNA alterations was examined. Of 113 tumours, 29 (25.7%) showed positive staining for the p53 protein. These included 19 of 67 osteosarcomas, five of 20 chondrosarcomas, four of 11 malignant fibrous histiocytomas (MFHs) and one Ewing's sarcoma. In chondrosarcomas, most of the p53-positive tumours belonged to highly malignant and atypical tumour types (dedifferentiated or mesenchymal type), suggesting a role for p53 mutation in the progression of cartilaginous tumours. All the cases with a missense mutation showed strongly positive staining, while no immunoreactivity was observed in the remaining three-quarters with DNA alterations including gross rearrangement, frame-shift mutation, nonsense mutation or mutation at splicing site except in one case. These results demonstrated the dominance of the p53 mutations with null protein expression in bone and soft tissue sarcomas, showing a unique characteristic of these types of tumours compared with other malignancies such as colon carcinomas.

Methods: The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex., Results: As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed., Conclusion: These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.

The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.