Explore the vast range of titles available.

The grade of chondrosarcoma relates to the likelihood of local recurrence and metastases. Many Grade I chondrosarcomas behave benignly if aggressively, and the question arises regarding whether wide resection is essential to control the disease. We therefore asked whether intralesional surgery also could be extended to Grade I chondrosarcomas without an increase in recurrence. We retrospectively reviewed 31 patients with Grade I chondrosarcomas of the limbs. The minimum followup was 66 months (mean, 157 months; range, 66–296 months). None of the 16 patients treated by resection had recurrences during the followup and two of the 15 patients with intralesional excision had recurrences, both of which resolved with resection of the site involved by the recurrence without progression of the disease. The Musculoskeletal Tumor Society scores averaged 72% in patients treated with wide resection compared with 89% in the 15 patients treated by intralesional surgery. The two recurrences occurred in patients whose radiographs showed thinning of the cortex combined with bone enlargement and marked endosteal scalloping; histologic examination in these two patients also showed a correlation between radiographic aggressiveness and the presence of myxoid areas and hypercellularity. Level of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Myofibroma is a rare benign nodular tumor of soft tissues, bones, or internal organs that can affect both children and adults. The solitary form in adults shows a predilection for the subcutaneous tissue in the head and neck region. Intraosseous lesions are more often found in children. Radiographically, the tumor appears as a well-defined unilocular radiolucent lesion located in the mandible, which may simulate cystic or other odontogenic lesions. A careful differential diagnosis needs to be carried out at the clinical, imaging, and histopathologic levels, because the tumor can have overlapping features with more aggressive spindle cell tumors. The present paper discusses the disease characteristics useful for a correct diagnosis with a particular emphasis on radiological features, describes the complete imaging study of a case of adult myofibroma involving the mandible, and reviews the pertinent literature.

Dedifferentiated peripheral chondrosarcoma is a rare subtype of chondrosarcoma arising superimposed on the cartilage cap of a preexisting osteochondroma. It consists of two clearly defined components, a low-grade malignant, well-differentiated cartilage component and a high-grade non-cartilaginous sarcoma. Signaling pathways having a role in normal cartilage development were analyzed in these tumors, and compared with available data of other cartilaginous tumors. Sixteen well-characterized dedifferentiated peripheral chondrosarcomas were immunohistochemically analyzed for parathyroid hormone-like hormone (PTHLH)-BCL-2, fibroblastic growth factor (FGF), and transforming growth factor- β signaling molecules, as well as matrix molecules and p53, comparing the chondrogenic component of dedifferentiated peripheral chondrosarcomas with the anaplastic component and with previously published data obtained from conventional grade I and II secondary peripheral chondrosarcomas. Results were correlated with clinical outcome. In the anaplastic component, various lines of differentiation could be found (collagen I (6/16), CD31 (1/16), smooth muscle actin (12/16), muscle-specific actin (12/16) and desmin (2/9)). Compared with the anaplastic component, the chondrogenic component of dedifferentiated peripheral chondrosarcomas shows more often expression of cyclin D1 ( P =0.05), p53 ( P =0.008), plasminogen activator inhibitor 1 (PAI-1) ( P =0.005), and CD44 ( P =0.030). Compared with secondary peripheral chondrosarcomas, more samples were positive in the chondrogenic component of dedifferentiated peripheral chondrosarcomas for FGF signaling (FGF receptor 3 P =0.000; bFGF P =0.003) and CD44 ( P =0.000). Lower expression of BCL-2 ( P =0.025) and absence of CD44v3 ( P =0.000), a splice variant of CD44, was observed in the chondrogenic component of dedifferentiated peripheral chondrosarcomas compared with secondary peripheral chondrosarcomas. With regard to clinical data, PAI-1 expression in the chondrogenic component of dedifferentiated peripheral chondrosarcomas correlated with better survival ( P =0.019). In conclusion, in the chondrogenic component of dedifferentiated peripheral chondrosarcomas, FGF signaling pathway is active, whereas PTHLH signaling seems to be low/downregulated. Interestingly, although the chondrogenic component of dedifferentiated peripheral chondrosarcoma is CD44+/CD44v3−, secondary peripheral chondrosarcomas is CD44−/CD44v3+, which suggest different splicing (preference). The prognostic value of PAI-1 in dedifferentiated peripheral chondrosarcomas might also be of interest for the more common dedifferentiated central chondrosarcomas.

The CCN3(NOV) protein belongs to the CCN [cysteine-rich CYR61, connective tissue growth factor (CTGF), nephroblastoma overexpressed gene (Nov)] family of growth regulators, sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Although previous studies have revealed an expression of CCN3 protein in several normal tissues, including kidney, nervous system, lung, muscle, and cartilage, less is known about its expression in tumors. In this study, we analyzed the expression of CCN3 in musculoskeletal tumors, using a panel of human cell lines and tissue samples. An association between CCN3 expression and tumor differentiation was observed in rhabdomyosarcoma and cartilage tumors, whereas, in Ewing's sarcoma, the expression of this protein seemed to be associated with a higher risk to develop metastases. CCN3 expression was found in 15 of 45 Ewing's sarcoma tissue samples. In particular, we did not observe any expression of CCN3 in the 15 primary tumors that did not develop metastases. In contrast, 15 of the 30 primary tumors that developed lung and/or bone metachronous metastases showed a high expression of the protein ( P < 0.001, Fisher's test). Our studies indicate that CCN3 is generally expressed in the cells of the musculoskeletal system. This protein may play a role both in normal and pathological conditions. However, the regulation of CCN3 expression varies in the different neoplasms and depends on the type of cells. Thus, as reported for other CCN genes, the biological properties and regulation of expression of CCN3 are dependent on the cellular context and the nature of the cells in which it is produced. Further studies will help to clarify the biological role of this protein in musculoskeletal neoplasms.

The resistance of tumors to multiple drugs is a major problem in cancer chemotherapy. P-glycoprotein, a transmembrane ATP-dependent efflux pump encoded by the mdr1 gene, 1 has a central role in multidrug resistance in vitro, 2 and its clinical relevance is under investigation. 3 , 4 Increased amounts of P-glycoprotein may confer multidrug resistance on cells by preventing the intracellular accumulation of a variety of cytotoxic drugs, 5 including doxorubicin, the most effective agent for the treatment of osteosarcomas. Drug resistance may represent an important prognostic factor in osteosarcoma, the most frequent primary malignant bone tumor. Although the outcome of osteosarcoma has improved considerably since . . .

Multicentric osteosarcoma (M-OGS) is characterized by multicentricity of osseous osteosarcomas, either synchronous or metachronous, without visceral involvement. The study’s purpose was to clinicopathologically and radiographically analyze 56 cases of M-OGS (22 synchronous and 34 metachronous). The distal femur was the most common site. Histologically, all tumors were high grade. Of 22 patients with synchronous M-OGS, 16 had 3 or more simultaneous tumors; the axial skeleton was involved in 14 (64%) of 22 cases. In metachronous M-OGS, the second malignancy occurred after a median of 22 months. Treatment was surgery, chemotherapy, radiotherapy, or a combination of these. Patients with metachronous osteosarcoma had a median survival longer than did patients with synchronous tumors. Overall, 8 long-term survivors were treated by aggressive surgery with wide margins (plus chemotherapy and/or radiotherapy). M-OGS combines multiple skeletal locations of high-grade conventional osteosarcomas and has a poor prognosis. Aggressive surgery may result in improved long-term survival, particularly in patients with metachronous disease.

Low-grade central osteosarcoma is an uncommon form that is characterized by a long premorbid history, and is compatible with prolonged survival after treatment. However, molecular abnormalities are rare in low-grade central osteosarcomas, whereas p53 mutations occur in approximately 20% of conventional high-grade osteosarcomas. In this study, 21 cases of low-grade central osteosarcoma were analyzed for mutations of the p53 gene, amplification of the MDM2 gene, and mutations of the H-ras gene using formalin-fixed, paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferation activities using the monoclonal antibody MIB-1. One case (4.7%) showed strong p53 immunoreactivity, whereas p53 gene mutations were not detected at all. Seven cases (33.3%) showed immunoreactivity for MDM2 protein. As for gene alterations, MDM2 amplification was found in four cases (19.0%). p21WAF1 expression was detected in 12 cases (57.1%). MIB-1-LI showed very low levels in all the cases and no significant correlation with p53 or MDM2 immuno-reactivity. None of the tumors showed H-ras mutations. In conclusion, the number of p53 gene alterations in low-grade central osteosarcomas is lower than that in conventional high-grade osteosarcomas. MDM2 alterations and p21WAF1 expression might be involved in the tumorigenesis of low-grade central osteosarcomas.

Ewing’s sarcoma (ES)/peripheral neuroectodermal tumor (PNET) are malignant neoplasms affecting children and young adults. We performed a study to typify the histological diversity and evaluate antibodies that may offer diagnostic/prognostic support. In total, 415 cases of genetically confirmed paraffin-embedded ES/PNET were analyzed on whole sections and in tissue microarrays. This study confirms the structural heterogeneity of ES/PNET, distinguishing three major subtypes: conventional ES (280 cases); PNET (53 cases); and atypical ES/PNET (80), including large cells, vascular-like patterns, spindle pattern, and adamantinoma-like configuration. All cases presented positivity for at least three of the four tested antibodies (CD99, FLI1, HNK1, and CAV1). CAV1 appeared as a diagnostic immunomarker of ES/PNET being positive in CD99-negative cases. Hence, the immunohistochemical analysis confirmed the diagnostic value of all four antibodies, which together cover more than 99% of the tumors, independently of the histological variety. The univariate analysis for survival revealed atypical ES as the only histological parameter apparently associated with less favorable clinical outcome, particularly in the subgroup of patients treated with surgery. In conclusion, the diagnosis of atypical ES is a challenge for the pathologist and needs support from molecular techniques to perform an optimal differential diagnosis with other small round cell tumors.

Angiosarcomas constitute a heterogeneous group of highly malignant vascular tumors. Angiosarcoma of bone is rare and poorly characterized. For angiosarcoma of soft tissue, some pathways seem to be involved in tumor development. Our aim was to evaluate the role of these pathways in angiosarcoma of bone. We collected 37 primary angiosarcomas of bone and used 20 angiosarcomas of soft tissue for comparison. Immunohistochemistry was performed on constructed tissue microarrays to evaluate expression of CDKN2A, TP53, PTEN, BCL2, CDK4, MDM2, cyclin D1, [beta]-catenin, transforming growth factor-[beta] (TGF-[beta]), CD105, phospho-Smad1, phospho-Smad2, hypoxia-inducible factor-1α, plasminogen activator inhibitor type 1 (PAI-1), VEGF, CD117 and glucose transporter--1. PIK3CA was screened for hotspot mutations in 19 angiosarcomas. In nearly 55% of the angiosarcoma of bone, the retinoblastoma (Rb) pathway was affected. Loss of CDKN2A expression was associated with a significantly worse prognosis. No overexpression of TP53 or MDM2 was found, suggesting that the TP53 pathway is not important in angiosarcoma of bone. Angiosarcoma of bone showed highly active TGF-[beta] signaling with immunoreactivity for phospho-Smad2 and PAI-1. Although the phosphatidylinositol 3-kinase (PI3K)/Akt pathway seems to be active in both tumor groups, different mechanisms were involved: 41% of angiosarcoma of bone showed a decrease in expression of PTEN, whereas in angiosarcoma of soft tissue overexpression of KIT was found (90%). PIK3CA hotspot mutations were absent. In conclusion, the Rb pathway is involved in tumorigenesis of angiosarcoma of bone. The PI3K/Akt pathway is activated in both angiosarcoma of bone and soft tissue, however, with a different cause; PTEN expression is decreased in angiosarcoma of bone, whereas angiosarcomas of soft tissue show overexpression of KIT. Our findings support that angiosarcomas are a heterogeneous group of vascular malignancies. Both angiosarcoma of bone and soft tissue may benefit from therapeutic strategies targeting the PI3K/Akt pathway. However, interference with TGF-[beta] signaling may be specifically relevant in angiosarcoma of bone.