Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

Image features of two rare mediastinal tumors: schwannoma of intrathoracic phrenic nerve and clear cell chondrosarcoma of the rib

The current report focuses on two patients of the same age who presented similar appearances on initial anteroposterior chest images. Follow-up images showed superoanterior and superoposterior mediastinal lesions. The first patient with noninvasive cystic thymoma was suspected before surgery, while the pathologic diagnosis was intrathoracic phrenic nerve schwannoma. The second patient was with an asymmetric, dumbbell-shaped paravertebral tumor over T3 and T4 on the left side. The preoperative…     

Dedifferentiated chondrosarcoma

We reviewed 74 cases of dedifferentiated central and peripheral chondrosarcoma. Histologically these tumours consist of an underlying cartilaginous component (either benign or malignant) juxtaposed to a highgrade non-cartilaginous component, with a typically abrupt transition between the two tissue types. The noncartilaginous component may constitute a very small or a very large proportion of the tumour, so diagnosis often requires histological evaluation of the entire tumour. The diagnosis is often suspected on the basis of the clinical course and careful evaluation of the radiographie characteristics. Central dedifferentiated chondrosarcoma can be classified radiographically into three types. In type 1 (36 cases in our review) the radiographie features are the same as those of a central chondrosarcoma, with the addition of a region with very aggressive radiographie features. Type 2 lesions (20 cases) resemble the underlying benign enchondroma but also have destructive changes and/or a large soft tissue mass. Type 3 lesions (8 cases) are not distinctive radiographically and present as a very high grade destructive lesion of bone. These cases are diagnosed following biopsy or tumour resection. The prognosis of these tumours is extremely poor, with 13% overall 5-year survival in this series. Improved survival was found in those cases where diagnosis was prompt and surgical treatment with a wide or radical margin was attained. No benefit was found from the use of adjuvant chemotherapy or radiotherapy. Thus, early recognition of the characteristic radiographie features, adequate histological sampling, and wide or radical surgical margins are necessary for satisfactory management of this highly malignant variant of chondrosarcoma.     

Histological Changes and Differential Diagnosis of Mesenchymal Chondrosarcoma

Eight cases of mesenchymal chondrosarcoma either of skeletal(5 cases) or extrasketetalorigin (3 cases) are reported. According to histopathological and diagnostic criteria,mesenchymal chondrosarcoma were classified into two types cartilage isiand cell type andundifierentiated small cell type It is believed that the application of this classification in the study ofmesenchymal chondrosarcoma is helptul the estimation of its malignancy and choice of treatmentas well al in the prediction of its prognosis. Mesenchymal chondrosarcoma is a highly malignant neoplasm with poor prognosis. None ofthe patients in this series survived more than five years after they were diagnosed. The diffentialdiagnosis of malignant lymphoma, chondrosarcoma, hemangiopericytosarcoma, etc. was discussed.My data support the assumption that mesenchymal chondrosarcoma originates from the secondarymesenchyme rather than the primary mesenchyme.     

Chondrosarcoma as a complicating factor in Paget’s disease of bone

 A 65-year-old male patient with an 8-year history of poliostotic Paget’s disease complained of shoulder pain that started 6 months prior to admission. An extensive lytic area was identified in the right proximal humerus along with Paget’s disease. There was cortical destruction and a soft tissue mass. Following an incisional biopsy, a diagnosis of grade 2 chondrosarcoma associated with Paget’s disease was made. The histologic identification of chondrosarcoma associated with Paget’s disease is rare. However, the presence of a calcified matrix in a destructive lesion associated with Paget’s disease should alert the radiologist and the pathologist to the possibility of a chondromatous differentiation taking place in the sarcoma associated with Paget’s disease. The histologic evaluation of the lesion will form the basis for the diagnosis.     

Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis)

Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.     

Extraskeletal Osteosarcoma with Unusual Ultrastructural Features

A case of extraskeletal osteosarcoma was observed in the thigh of a 33-year-old male patient. Ultrastructurally the tumor was characterized by the presence of a particular dense type of cell, the nucleus of which showed a characteristic combination of features: large amounts of condensed mar-ginated chromatin, prominent perichromatin granules, vermicellar bodies, and undulating microtubules. The tumor also contained intermediate-type cells with a more typical osteoblastic appearance, and more blastic cells. All three cell types contained varying amounts of dilated rough endoplasmic reticulum with prominent inclusions of crystalline material showing a hexagonal or banded pattern, indicating that the cells represent different stages of maturation rather than genuinely different types of cells. Dense cells showing the same characteristic combination of nuclear features have been described once before in a case of parosteal osteosarcoma. Our results indicate that these cells are a particular form of osteogenic cell. The presence of undulating microtubules and vermicellar bodies suggest a possible association with the presence of virus and/or increased levels of interferon.     

Chondrosarcomatous differentiation in metastatic deposit of serous papillary cystadenocarcinoma

A rare case of serous papillary cystadenocarcinoma of the ovary showing chondrosarcomatous differentiation in a metastatic deposit late in the clinical course is reported. A 49-year-old female underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node metastasis. After six courses of chemotherapy, she was confirmed to be in complete remission following a second laparotomy. Following additional chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In one of these nodes, approximately 5.0 cm in greatest diameter, the predominant histological features were: chondrosarcoma of the bone and soft tissue, with small foci of serous papillary adenocarcinoma and squamous epithelium. A histological transition between mesenchymal and epithelial areas was identified. Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3), vimentin, epithelial membrane antigen, and S-100 protein was observed in both chondrosarcomatous and epithelial areas. The current evidence may suggest that the chondrosarcomatous differentiation was derived from the metastatic epithelial component.     

Carcinoma of the breast with metaplasia to chondrosarcoma: a light and electron microscopic study

Two carcinomas of the breast containing large areas of sarcomatous tissue were studied by light and electron microscopy. In one of these, the sarcomatous element was frankly cartilaginous and in the other, predominantly myxoid but with small cartilaginous-looking foci. By light microscopy, a highly suggestive metaplastic transition could be traced from cells within the epithelial nests to those within the sarcomatous lobules. Ultrastructurally, cells in the former region showed epithelial characteristics and those in the latter region, mesenchymal and/or cartilaginous features. The carcinomatous cells contained desmosomes and formed intercellular spaces lined by microvilli; a few cells showed prominent profiles of rough endoplasmic reticulum. In the first case, the cells in the immediate vicinity of the epithelial nests and those in the fully developed cartilaginous regions showed a progressive dilatation of their endoplasmic reticulum to form large sac-like structures filled with a finely granular and floccular material. The intercellular matrix was electron lucent and contained scattered dense particles, fibrillo-granular material and collagen fibres. Condensation of this material at some distance from the cell resulted in the formation of lacunae. In the second case, the cells in the myxoid areas also showed prominent dilatation of endoplasmic reticulum.     

Dedifferentiated liposarcoma with chondroblastic osteosarcomatous dedifferentiation

We describe a rare case of dedifferentiated liposarcoma with features resembling chondroblastic osteosarcoma in the dedifferentiated component. The tumor was removed from the left thigh in a 78-year-old male. It consisted of a well-differentiated liposarcoma and an anaplastic component that contained numerous osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma. To our knowledge, only two cases similar to the divergent chondroblastic osteosarcomatous dedifferentiation of this disease have been reported in the literature.