Induction of sarcomas by mutant IDH2.

More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10T1/2 mesenchymal progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation that could be reversed by treatment with DNA-hypomethylating agents. Introduction of mutant IDH2 also induced loss of contact inhibition and generated undifferentiated sarcomas in vivo. The oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate. Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic in mesenchymal cells.

Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature.

Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS.

Identifying bone sarcoma survivors facing psychosocial challenges. A study of trajectories following treatment.

OBJECTIVE: Bone sarcoma survivors face a number of physical and psychosocial challenges in relation to the late effects they experience following treatment. The present study aimed to identify and explore the different trajectories that bone sarcoma survivors might navigate during follow-up. METHODS: In-depth and semi-structured interviews were conducted, and an inductive thematic analysis was performed. RESULTS: When they were interviewed three to ten years after the primary diagnosis, the eighteen bone cancer survivors were found to be in three different rehabilitation phases that followed fairly distinct trajectories, namely, back to normal, a new normal and still struggling. Only three participants felt that they had returned to a life that was quite similar to the one they had lived prior to having cancer. Fifteen participants considered their lives and their bodies to be significantly altered. CONCLUSION: Sarcoma survivors who undergo life-changing treatment and return to very different lives than they had before should be identified by healthcare professionals and guided through this demanding phase to better cope with their new living conditions. Information on and tailored guidance related to psychosocial challenges may be of particular importance. Active focus on reorientation, as well as possibilities for growth, seems to be important.

Surgical treatment of low-grade chondrosarcoma involving the appendicular skeleton: long-term functional and oncological outcomes.

BACKGROUND: The traditional treatment for chondrosarcoma is wide local excision (WLE), as these tumors are resistant to chemotherapy and radiation treatment. While achieving negative margins has traditionally been the goal of chondrosarcoma resection, multiple studies have demonstrated good short-term results after intralesional procedures for low-grade chondrosarcomas (LGCS) with curettage and adjuvant treatments (phenol application, cauterization or cryotherapy) followed by either cementation or bone grafting. Due to the rarity of this diagnosis and the recent application of this surgical treatment modality to chondrosarcoma, most of the information regarding treatment outcomes is retrospective, with short or intermediate-term follow-up. The aim of this study was to assess the long-term results of patients with LGCS of bone treated with intralesional curettage (IC) treatment versus WLE. This retrospective analysis aims to characterize the oncologic outcomes (local recurrence, metastases) and functional outcomes in these two treatment groups at a single institution. METHODS: Using an institutional musculoskeletal oncologic database, we retrospectively reviewed medical records of all patients with LGCS of the appendicular skeleton that underwent surgical treatment between 1985 and 2007. Thirty-two patients (33 tumors) were identified with LGCS; 17 treated with IC and 15 with WLE. RESULTS: Seventeen patients (18 tumors) with a minimum clinical and radiologic follow-up of 10 years were included. Nine patients were treated with IC (four with no adjuvant, three with additional phenol, one with liquid nitrogen and one with H2O2) with either bone graft or cement augmentation, and nine others were treated with WLE and reconstruction with intercalary/osteoarticular allograft or megaprosthesis. The mean age at surgery was 41 years (range 14-66 years) with no difference (p = 0.51) between treatment cohorts. There was a mean follow-up of 13.5 years in the intralesional cohort (range 10-19 years) and 15.9 years in the WLE cohort (range 10-28 years, p = 0.36). Tumor size varied significantly between groups and was larger in patients treated with WLE (8.2 ± 3.1 cm versus 5.4 ± 1.2 cm, at the greatest dimension, p = 0.021). There were two local recurrences (LR), one in the intralesional group and one in the wide local excision group, occurring at 3.5 months and 2.9 years, respectively, and both required revision. No further LR could be detected with long-term follow-up. The MSTS score at final follow-up was significantly higher for patients managed with intralesional procedures (28.7 ± 1.7 versus 25.7 ± 3.4, p = 0.033). There were less complications requiring reoperation in the intralesional group compared with the wide local excision group, although this difference was not found to be statistically significant (one versus four patients, respectively; p = 0.3). CONCLUSION: This series of low-grade chondrosarcoma, surgically treated with an intralesional procedures, with 10-year follow-up, demonstrates excellent local control (88.9%). Complications were infrequent and minor and MSTS functional scores were excellent. Wide resection of LGCS was associated with lower MSTS score and more complications. In our series, the LR in both groups were detected within the first 3.5 years following the index procedure, and none were detected in the late surveillance period.

Sarcoma survivors' perspectives on their body image and functional quality of life post-resection/limb salvage surgery.

Sarcomas often occur in patients' extremities and treatment typically involves bone resection/limb salvage surgery. Such treatments leave survivors with physical disfigurements, functional disabilities, and/or emotional traumas. Our post-surgery psychological intervention investigated how these experiences impinge on sarcoma survivors' lives. Twenty-three survivors aged 19-60 years (M = 36 years) participated in a tri-disciplinary (rehabilitative exercise, plastic surgery and psychological) intervention. Of these, 17 participated in psychodynamic counselling, 10 completed a mental-health questionnaire and seven kept a reflective journal. An exemplar case study research design was employed and data were subjected to interpretative phenomenological analysis. The findings reveal that survivors typically experience a number of body image issues and mobility difficulties, which they are reluctant to share with their oncologist in case they are viewed as being ungrateful or vain. In instances where such issues remain unaddressed, then sarcoma survivors have a tendency to adopt avoidant coping strategies and social isolation practices. These practices negatively impact on their mental health and functional quality of life. Hence, it is suggested that a short three part (body image, mobility, and coping strategy) screen be devised and used at all sarcoma 2-year follow-up assessment consults to identify which survivors are in need of psychological assistance.

Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term?

BACKGROUND: In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized. QUESTIONS/PURPOSES: The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX(®)) score reflect fracture likelihood? METHODS: All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 ± 12 years; mean followup, 12 ± 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients´ BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors. RESULTS: Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the study cohort were lower than reference values for the femur neck (mean difference, 0.64; 95% CI, 0.27-1.01; p < 0.0015), but not for the spine (mean difference, 0.39; 95% CI, -0.06 to 0.84; p = 0.09). Thirteen patients (45%) reported a history of fractures not distinguishing between low and high impact. The incidence of fractures was 2.8 greater than expected from a comparison with a published microcensus survey of the Austrian population. No effect of the FRAX(®) score on fracture risk could be identified (p = 0.057). CONCLUSIONS: Long-term survivors of chondrosarcoma appear to be at greater risk for having low BMD develop than the healthy population. Although these results are preliminary and based on a very small sampling of patients, if they can be confirmed in larger studies, BMD assessment by dual-energy x-ray absorptiometry might be considered as these patients are followed posttreatment by sarcoma care units. The reasons for low BMD still must be elucidated. LEVEL OF EVIDENCE: Level IV, prognostic study.

Interleukin-1ß and cyclic AMP mediate the invasion of sheared chondrosarcoma cells via a matrix metalloproteinase-1-dependent mechanism.

Matrix metalloproteinase-1 (MMP-1) is a potential biomarker for chondrosarcoma that is overexpressed at the invading edges of articular cartilage, and its expression correlates with poor survival rates. However, the molecular mechanisms of MMP-1 regulation and its potential contribution to chondrosarcoma cell invasion have yet to be elucidated, especially in shear-activated cells. Using molecular biology tools and an in vitro fluid shear model, we report that shear stress upregulates cyclic AMP (cAMP) and interleukin-1ß (IL-1ß) release, which in turn promotes the invasion of chondrosarcoma cells via the induction of MMP-1 in a phosphoinositide 3-kinase (PI3-K)- and ERK1/2-dependent manner. Activated PI3-K and ERK1/2 signaling pathways phosphorylate c-Jun, which in turn transactivates MMP-1 in human chondrosarcoma cells. Collectively, fluid shear stress upregulates matrix MMP-1 expression, which is responsible for the enhanced invasion of human chondrosarcoma cells.

Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research.

Abstract An interdisciplinary and international group of clinicians and scientists gathered in Philadelphia, PA, to attend the fourth International Research Conference on Multiple Hereditary Exostoses (MHE), a rare and severe skeletal disorder. MHE is largely caused by autosomal dominant mutations in EXT1 or EXT2, genes encoding Golgi-associated glycosyltransferases responsible for heparan sulfate (HS) synthesis. HS chains are key constituents of cell surface- and extracellular matrix-associated proteoglycans, which are known regulators of skeletal development. MHE affected individuals are HS-deficient, can display skeletal growth retardation and deformities, and consistently develop benign, cartilage-capped bony outgrowths (termed exostoses or osteochondromas) near the growth plates of many skeletal elements. Nearly 2% of patients will have their exostoses progress to malignancy, becoming peripheral chondrosarcomas. Current treatments are limited to the surgical removal of symptomatic exostoses. No definitive treatments have been established to inhibit further formation and growth of exostoses, prevent transition to malignancy, or address other medical problems experienced by MHE patients, including chronic pain. Thus, the goals of the Conference were to assess our current understanding of MHE pathogenesis, identify key gaps in information, envision future therapeutic strategies and discuss ways to test and implement them. This report provides an assessment of the exciting and promising findings in MHE and related fields presented at the Conference and a discussion of the future MHE research directions. The Conference underlined the critical usefulness of gathering experts in several research fields to forge new alliances and identify cross-fertilization areas to benefit both basic and translational biomedical research on the skeleton.

Swarm chondrosarcoma: a continued resource for chondroblastic-like extracellular matrix and chondrosarcoma biology research.

Since its first description over four decades ago, the Swarm chondrosarcoma (Swarm rat chondrosarcoma, SRC) remains a valuable tool for studies of chondroblastic-like extracellular matrix (ECM) biology and as an animal model of human chondrosarcoma of histological grades I-III. Moreover, articular joints and skeletal anomalies such as arthritis as well as cartilage regeneration, skeletal development, tissue engineering, hard tissue tumorigenesis and space flight physiology are advanced through studies in hyaline cartilage-like models. With more than 500 articles published since the first report on the characteristics of mucopolysaccharides (glycosaminoglycans) of the tumor in 1971, several transplantable tumor and cell lines have been developed by multiple laboratories worldwide. This review describes the characterization of SRC tumors and cell lines, including the use of SRC lines as a resource for isolation and characterization of several ECM elements that have become vital for the advancement of our understanding of cartilage biology. Also presented is the importance of pertubation of ECM components and the influence of the tumor microenvironment on disease progression. Therapeutic failure and currently pursued avenues of intervention utilizing the SRC lines in treatment of chondrosarcoma are also discussed.

Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter.

Chondrocytes interact with their neighbours through their cartilaginous extracellular matrix (ECM). Chondrocyte-matrix interactions compensate the lack of cell-cell contact and are modulated by proteoglycans and other molecules. The epiphyseal growth plate is a highly organized tissue responsible for long bone elongation. The growth plate is regulated by gradients of morphogens that are established by proteoglycans. Morphogens diffuse across the ECM, creating short- and long-range signalling that lead to the formation of a polarized tissue. Mutations affecting genes that modulate cell-matrix interactions are linked to several human disorders. Homozygous mutations of EXT1/EXT2 result in reduced synthesis and shortened heparan sulphate chains on both cell surface and matrix proteoglycans. This disrupts the diffusion gradients of morphogens and signal transduction in the epiphyseal growth plate, contributing to loss of cell polarity and osteochondroma formation. Osteochondromas are cartilage-capped bony projections arising from the metaphyses of endochondral bones adjacent to the growth plate. The osteochondroma cap is formed by cells with homozygous mutation of EXT1/EXT2 and committed stem cells/wild-type chondrocytes. Osteochondroma serves as a niche (a permissive environment), which facilitates the committed stem cells/wild-type chondrocytes to acquire secondary genetic changes to form a secondary peripheral chondrosarcoma. In such a scenario, the micro-environment is the site of the initiating processes that ultimately lead to cancer.

Giant chondrosarcoma of chest wall.

Primary chest wall tumours are very rare. Chondrosarcoma is the most common tumour arising from the chest wall. We describe the occurrence of a slow-growing chondrosarcoma arising from the anterior chest wall in a 35-year-old male patient. The tumour was resected successfully and chest wall was reconstucted with prolene mesh and muscle flap. The patient was discharged uneventfully without any respiratory compromise. There was no recurrence after a three-year follow-up. Wide surgical resection with chest wall reconstruction appears to be the preferred treatment option for this rare tumour of the chest wall.

Macrophage migration inhibitory factor increases cell motility and up-regulates αvß3 integrin in human chondrosarcoma cells.

The macrophage migration-inhibitory factor (MIF) is a pro-inflammatory cytokine first known for its effect on macrophage migration and activation. Recent studies have shown that MIP plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of MIF on human chondrosarcoma cells are largely unknown. In the present study, MIF was found to increase the migration and the expression of αvß3 integrin in human chondrosarcoma cells. The phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways were activated by MIF treatment, and the MIF-induced expression of integrin and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF-κB cascades. In addition, migration-prone sublines demonstrated that increased cell migration ability was correlated with increased expression of MIF and αvß3 integrin. Taken together, our results indicate that MIF enhanced the migration of the chondrosarcoma cells by increasing αvß3 integrin expression through the PI3K/Akt/NF-κB signal transduction pathway.

Tumors of the coracoid process: clinical evaluation of twenty-one patients.

OBJECTIVE: We present the incidence and management of bone tumors of the coracoid process and discuss the related clinical and imaging findings and treatment. MATERIALS AND METHODS: We present 21 patients (7 males and 14 females; mean age, 39 years) treated for bone tumors of the coracoid process from 1900 to 2010. Mean follow-up was 44 months (range, 12-132 months). Clinical presentation, imaging, surgical treatment, complications, range of shoulder motion, and Musculoskeletal Tumor Society (MSTS) function were evaluated. RESULTS: Bone tumors were benign in 7 (33%) and malignant in 14 (67%). The most common were chondrosarcomas, osteoblastomas, and chondroblastomas. The most common presentation was pain and palpable mass for a mean duration of 11 months. Limb salvage, with or without megaprosthetic reconstruction, was achieved in 20 patients. One patient required forequarter amputation. One patient with chondroblastoma and 2 with chondrosarcoma had local recurrence. The range of shoulder motion varied according to the type of resection: patients with curettage and limited resections without involvement of the abductor mechanism had better shoulder motion, and patients with scapulectomy and proximal humeral resections had significant limitations of motion. The mean MSTS score was 80% (range, 50%-100%). CONCLUSIONS: Chondrosarcomas, osteoblastomas, and chondroblastomas are the most common bone tumors of the coracoid process. Limited resections are associated with nearly normal range of motion and excellent function; however, limited resections are acceptable in only in a small number of patients. In patients with malignant and recurrent lesions, wide resection is required, which is associated with significant limitations of shoulder function.

Central type of chondrosarcoma with a fulminant course--a case report.

Primary chondrosarcoma is a rare malignant tumor. The five types of chondrosarcomas are: central, peripheral, mesenchymal, differentiated and clear cell. The classic chondrosarcomas are central (arising within a bone) or peripheral (arising from the surface of a bone). We describe a patient with central chondrosarcoma of the humerus who underwent surgery and only two weeks later presented with multiple metastases of the lung and small pulmonary tumor embolisms mimicking bilateral pneumonic infiltrates. Therefore, such a fulminant course of central chondrosarcoma, which is not described so far, must be taken into consideration during the treatment of patients with primary chondrosarcoma.

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro.

BACKGROUND: Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro. METHODS: Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed. RESULTS: Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment. CONCLUSIONS: These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.

Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing's sarcoma.

The most prevalent forms of bone cancer are osteosarcoma, chondrosarcoma, and Ewing's sarcoma. Although chemotherapy and radiotherapy have replaced traditional surgical treatments, survival rates have undergone only marginal improvements. Current knowledge of the molecular pathways involved in each type of cancer has led to better approaches in cancer treatment. A number of cell signaling molecules are involved in tumorigenesis, and specific targets have been identified based on these signal transducers. This review highlights some of the important cellular pathways and potential therapeutic targets, tumor site-specific irradiation techniques, and novel drug delivery systems used to administer these drugs.

Curettage and cryosurgery for low-grade cartilage tumors is associated with low recurrence and high function.

BACKGROUND: Chondrosarcomas of bone traditionally have been treated by wide or radical excision, procedures that may result in considerable lifelong disability. Grade 1 chondrosarcomas have little or no metastatic potential and are often difficult to distinguish from painful benign enchondromas. Curettage with adjuvant cryosurgery has been proposed as an alternative therapy for Grade 1 chondrosarcomas given the generally better function after the procedure. However, because it is an intralesional procedure, curettage and cryosurgery may be associated with higher rates of recurrence. QUESTIONS/PURPOSES: We asked whether Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery are associated with low recurrence rates and high functional scores. PATIENTS AND METHODS: We retrospectively reviewed the records of 46 patients with Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery. Forty-one patients had tumors of the long bones. Patients were followed a minimum of 18 months (average, 47.2. months; range, 18-134 months) for evidence of recurrence and for assessment of Musculoskeletal Tumor Society (MSTS) functional score. RESULTS: Two of the 46 patients had recurrences in the original tumor site (4.3% recurrence rate), which subsequently were removed by wide excision, and both patients were confirmed to be disease-free 36 and 30 months, respectively, after the second surgery. The mean MSTS score was 27.2 of 30 points (median, 29 points). CONCLUSIONS: Our observations show curettage with cryosurgery is associated with low recurrence of Grade 1 chondrosarcoma and high functional scores. Curettage with cryosurgery is a reasonable alternative to wide or radical excision as the treatment for Grade 1 chondrosarcomas, and allows for more radical surgery in the event of local recurrence. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Indian hedgehog signaling pathway differences between swarm rat chondrosarcoma and native rat chondrocytes.

Indian Hedgehog (Ihh)--Parathyroid related protein (PTHrP) and Fibroblast Growth Factor 3 (FGFR3) signaling pathways are important in regulating endochondral bone formation. In the growth plate, Ihh and PTHrP are involved in a feedback loop to increase proliferation and delay differentiation of chondrocytes. Fibroblast Growth Factor Receptor 3 (FGFR3) conversely decreases proliferation and hastens differentiation with an agonist. Since proliferation is the hallmark of chondrosarcoma cells, we hypothesized that Ihh/PTHrP and FGF3R pathways may be dysfunctional on these cells. Therefore, we sought to investigate the role of these signaling pathways in the Swarm rat chondrosarcoma cells utilizing expression and functional studies. Semiquantitative RT-PCR analysis demonstrated difference in expression between normal growth plate chondrocytes and chondrosarcoma cells (JWS). JWS had an increased mRNA expression of FGF2 and FGFR3 suggesting a mechanism to reverse the proliferative rate of the cells. Immunohistochemical analysis showed increased staining for FGFR3 and patched-1 (Ihh receptor) in JWS compared to the rat tibia growth plate (p = 0.O004 and 0.02 respectively). In vitro functional experiments demonstrated that the use of FGF2, a FGFR3 receptor agonist, dramatically decreased the proliferative rate of Swarm chondrosarcoma cells (LTC). Cyclopamine, a hedgehog inhibitor, did not have a significant effect on their proliferative rate. However, when cyclopamine was used on normal chondrocytes, it effectively decreased the proliferative rate of these cells, suggesting abnormalities in this pathway in the chondrosarcoma cells. In conclusion, our investigation describes dissimilarity in the Indian Hedgehog and FGFR3 signaling pathways between the rat chondrosarcoma cells and native rat chondrocytes. Understanding the underlying mechanisms may provide a target for future therapy for chondrosarcoma.

Primary extraskeletal myxoid chondrosarcoma in cerebellum: A case report with literature review.

RATIONALE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm of which intracranial EMC is the rarest. PATIENT CONCERNS: We present an unusual case report of a 41-year-old woman who was sent to the emergency department for a sudden headache and other symptoms related to increased intracranial pressure. INTERVENTIONS: Emergent CT revealed an occupying lesion in the left cerebellum with surrounding edema. A complete surgical excision of the lesion through a transcortical approach was performed. After the operation, this patient received adjuvant radiotherapy and temozolomide treatment. DIAGNOSES: Pathology diagnosis was an intracranial EMC. OUTCOMES: The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival exceeded 20 months. LESSONS: We have reviewed the literature and here summarize the diagnosis and treatment options for intracranial EMC. Diagnosis and treatment options of this rare disease are discussed.