Yao MS, Chang CM, Chen CL, Chan WP
Synovial chondrosarcoma arising from synovial chondromatosis of the knee.
JBR-BTR. 2012 Nov-Dec; 95(6):360-2 [PubMed]

We report the case of a 51-year-old woman who had suffered from right knee pain and stiffness for 40 years. Her symptoms had gradually worsened over the past 5 years. One year previously, when she first visited our clinic, plain radiographs and CT scan images had revealed synovial chondromatosis over the right knee. At the current admission, follow-up MRI showed synovial masses around the knee and worsening of endosteal cortical scalloping in the patella, femoral condyle, and tibial plateau. After diagnosis on the basis of frozen sections, the patient had total excision of the lesions and total knee athroplasty. Histological examination revealed synovial chondromatosis in the joint cavity and grade 1 chondrosarcoma invasion into the adjacent bone. In long-standing synovial chondromatosis, presentation with aggravated symptoms and deterioration on imaging findings should alert clinicians to the potential for malignant change.

Buda I, Hod R, Feinmesser R, Shvero J
Chondrosarcoma of the larynx.
Isr Med Assoc J. 2012; 14(11):681-4 [PubMed]

BACKGROUND: Chondrosarcoma of the larynx is a rare tumor. The most common symptom is hoarseness. Treatment is controversial.
OBJECTIVES: To describe six patients with laryngeal chondrosarcoma from a single center.
METHODS: The medical records of a major tertiary hospital were reviewed for all patients with laryngeal chondrosarcoma diagnosed and treated from 1959 to 2010. Data on background, clinical treatment and outcome were collected.
RESULTS: Six patients, all males with a mean age of 53.3 years, were identified. Partial laryngectomy was performed in three patients, and total laryngectomy, local excision, and partial cricoidectomy in one patient each. Four patients had a permanent tracheostomy after surgery. One patient required postoperative chemotherapy and one radiotherapy. Follow-up time was 12-216 months (mean 102 months). Recurrence developed in two patients 2 and 8 years after initial treatment and was treated by salvage surgery in both patients. One patient died during the follow-up from an unrelated cause. The others are currently alive.
CONCLUSIONS: This study supports earlier reports recommending initial treatment with partial or total laryngectomy for laryngeal chondrosarcoma. Long-term follow-up for recurrence is advised. We recommend preserving the larynx, if possible, even if a permanent tracheostomy is necessary.

Oh YJ, Yang I, Yoon DY, et al.
Extraskeletal myxoid chondrosarcoma of the neck.
Dentomaxillofac Radiol. 2013; 42(1):31808012 [PubMed]

Extraskeletal myxoid chondrosarcoma is a rare malignant soft-tissue tumour that is typically in the deep soft tissues of the lower extremity. The tumour is usually a well-defined, multinodular soft-tissue mass without calcifications. A 62-year-old woman with a history of nasopharyngeal cancer presented with a palpable mass in the anterior neck. Radiologically, the lesion was a well-defined soft-tissue mass with the extensive calcifications on various imaging examinations. Although this lesion was histopathologically diagnosed as extraskeletal myxoid chondrosarcoma, the unusual imaging findings were challenging and very intriguing.

Matanić D, Kukuljan M, Grgurević E, et al.
Central type of chondrosarcoma with a fulminant course--a case report.
Coll Antropol. 2012; 36(3):1037-40 [PubMed]

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.

Abbas S, Vincourt JB, Habib L, et al.
The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.
Toxicol Lett. 2013; 216(2-3):189-99 [PubMed]

Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC(50) values, cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (K(m) 22 μM, V(max) 571 nmol/mg proteins/min). On the other hand, the three cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of V(max)/K(m), the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.

Bloch O, Parsa AT
Skull base chondrosarcoma: evidence-based treatment paradigms.
Neurosurg Clin N Am. 2013; 24(1):89-96 [PubMed]

Chondrosarcomas are indolent but invasive chondroid malignancies that can form in the skull base. Standard management of chondrosarcoma involves surgical resection and adjuvant radiation therapy. This review evaluates evidence from the literature to assess the importance of the surgical approach and extent of resection on outcomes for patients with skull base chondrosarcoma. Also evaluated is the ability of the multiple modalities of radiation therapy, such as conventional fractionated radiotherapy, proton beam, and stereotactic radiosurgery, to control tumor growth. Finally, emerging therapies for the treatment of skull-base chondrosarcoma are discussed.

Jahangiri A, Jian B, Miller L, et al.
Skull base chordomas: clinical features, prognostic factors, and therapeutics.
Neurosurg Clin N Am. 2013; 24(1):79-88 [PubMed]

Chordomas of the skull base are one of the rarest intracranial malignancies that arise from ectopic remnants of embryonal notochod. The proximity of many chordomas to neurovascular structures makes gross total resection difficult, and the tendency for recurrence leads to the routine use of adjuvant postoperative radiation. Several surgical approaches are used ranging from extensive craniotomies to minimally invasive endonasal endoscopic approaches. In this review, the histopathology and epidemiology, imaging characteristics, surgical approaches, adjuvant therapies, prognostic factors, and molecular biology of chordomas are described.

Forest F, David A, Arrufat S, et al.
Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the spectrum of tumors associated with SMARCB1 germline mutations.
Am J Surg Pathol. 2012; 36(12):1892-6 [PubMed]

SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less aggressive tumors with a later onset have also been reported in a context of SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No other tumor type has formally been observed in such a context thus far. We report on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age who subsequently developed a mandibular conventional chondrosarcoma at 13 years of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1 (exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion encompassing SMARCB1 was found in the germline. This context was a strong incentive to investigate SMARCB1 alterations in the second tumor. As expected, the chondrosarcoma showed the large 22q11.2 deletion but also an additional c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report relates for the first time a pediatric conventional chondrosarcoma to the wide family of SMARCB1-deficient tumors. Moreover, we report here the first case of conventional chondrosarcoma arising in a context of constitutional SMARCB1 deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.

Carozzo S, Schardt D, Narici L, et al.
Electrophysiological monitoring in patients with tumors of the skull base treated by carbon-12 radiation therapy.
Int J Radiat Oncol Biol Phys. 2013; 85(4):978-83 [PubMed]

PURPOSE: To report the results of short-term electrophysiologic monitoring of patients undergoing (12)C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery.
METHODS AND MATERIALS: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision.
RESULTS: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline.
CONCLUSIONS: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may help predict, possible late toxicity.

Niini T, Scheinin I, Lahti L, et al.
Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study.
Cancer Genet. 2012; 205(11):588-93 [PubMed]

Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.

Gurung U, Joy L, Thapa NM, Pradhan B
Chondrosarcoma of posterior nasal septum.
Kathmandu Univ Med J (KUMJ). 2012 Apr-Jun; 10(38):89-91 [PubMed]

Chondrosarcoma is a rare non-epithelial tumor comprising of 10-20% of primary bone tumor. The nasal septum is a rare site for its occurrence. We present one such case of chondrosarcoma of the nasal septum who was treated with endoscopic removal followed by post operative radiotherapy and discuss the relevant clinical presentation, diagnosis and treatment and review the literature also.

Maughan E, Pankhania M, Shah K, Gurr P
Managing chondrosarcoma of the epiglottis: a case report.
Ann R Coll Surg Engl. 2012; 94(8):e240-2 [PubMed]

Laryngeal chondrosarcomas are a very rare malignancy with less than 150 cases reported in the literature. Of these, the epiglottis is the most unusual primary neoplastic subsite. Uncertainties arise owing to the extremely rare nature of the condition with regard to treatment and investigation for metastases in overtly low grade cases. We present the case of a 62-year-old woman with a low grade chondrosarcoma, arising from the tip of the epiglottis, presenting with dysphagia but no other symptoms.

Naumov VA, Generozov EV, Solovyov YN, et al.
Association of FGFR3 and MDM2 gene nucleotide polymorphisms with bone tumors.
Bull Exp Biol Med. 2012; 153(6):869-73 [PubMed]

Association study of 6 candidate single-nucleotide polymorphisms (rs7921, rs7956547, rs3761243, rs11737764, rs6599400, rs1690916) was carried out in a group of patients with bone tumors of different histological structure (n=68) and control group of normal subjects (n=96). Significant associations of rs6599400 and rs1690916 polymorphisms with disease risk were detected (odds ratio 2.15 [1.06-4.24] and 0.39 [0.19-0.78], respectively). These polymorphisms were located in untranslated genome regions: polymorphism rs6599400 in the 5' region of fibroblast growth factor-3 receptor gene (FGFR3), rs1690916 in the 3' region of mouse MDM2 p53-binding protein homolog (MDM2). These data indicated a possible role of hereditary genetic factors in the formation of predisposition to bone sarcomas and confirmed previous findings according to which these genes should be regarded among the most probable factors involved in tumor development, including tumors of the bone and cartilage tissues.

Schleger S, Weingartner JS, Costi M, Eichinger WB
A primary pulmonary artery chondrosarcoma manifesting as acute pulmonary embolism.
Ann Thorac Surg. 2012; 94(5):1731-3 [PubMed]

Primary cardiac malignancies are rare, and the majority are benign. Malignant tumors are often found to be sarcomas arising from structural cells such as muscle, connective tissue, and blood vessels. We report a case of a 62-year-old woman who presented with pulmonary embolism secondary to a primary pulmonary artery chondrosarcoma. Radical resection with curative intent was impossible, but partial resection and reconstruction of the pulmonary main stem was performed. The remaining tumor was treated with adjuvant chemotherapy. A positron emission tomography-computed tomography scan 6 months postoperatively showed a nearly complete remission.

Combs SE, Kessel KA, Herfarth K, et al.
Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data.
Radiat Oncol. 2012; 7:170 [PubMed] Free Access to Full Article

BACKGROUND: To report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center.
MATERIALS AND METHODS: We treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology.
RESULTS: Treatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients.
CONCLUSION: Clinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents.

Sánchez-Rodríguez V, Medina-Romero F, Gómez Rodríguez-Bethencourt MÁ, et al.
Value of the bone scintigraphy in multiple osteochrondromatosis with sarcomatous degeneration.
Rev Esp Med Nucl Imagen Mol. 2012; 31(5):270-4 [PubMed]

Multiple osteochondromatosis can become malignant in 20% of the cases, this being more common when the lesion is multiple than when it is solitary. A male patient with multiple osteochondromatosis who had several local recurrences of secondary chondrosarcoma and who is still under follow-up by the Nuclear Medicine Department is presented. The bone scintigraphy findings were compared with the histopathologic results, and the importance of the patient's symptoms was verified when a sarcomatous transformation is suspected. The bone scintigraphy has the potential to detect malignization of the benign bone lesions. It also makes it possible to obtain whole-body images in a single examination, this being very useful to detect the presence of new bone lesions.

Bernstein-Molho R, Kollender Y, Issakov J, et al.
Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas.
Cancer Chemother Pharmacol. 2012; 70(6):855-60 [PubMed]

OBJECTIVE: Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX).
PATIENTS AND METHODS: Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression-free survival (PFS), adverse events, and other relevant clinical data were analyzed.
RESULTS: The median patients' age was 49 (range 28-68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3-30.3). No significant adverse events were observed.
CONCLUSIONS: Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.

Douis H, Saifuddin A
The imaging of cartilaginous bone tumours. II. Chondrosarcoma.
Skeletal Radiol. 2013; 42(5):611-26 [PubMed]

Chondrosarcoma is the third most common primary malignant bone tumour. There are various histological subtypes of chondrosarcomas, of which conventional intramedullary chondrosarcoma is by far the most common. Rarer sub-types include clear cell chondrosarcoma, myxoid chondrosarcoma, mesenchymal chondrosarcoma and dedifferentiated chondrosarcoma. Chondrosarcoma is also classified into central, peripheral and periosteal, dependent upon the lesion site, and into primary chondrosarcoma if the lesion arises de novo and secondary chondrosarcoma if the tumour arises in a pre-existing lesion. The various subtypes of chondrosarcoma have characteristic imaging features that may aid diagnosis and may guide biopsy, therefore potentially preventing misdiagnosis. The aim of this article is to provide an overview of the pertinent clinical and imaging findings of the different forms of chondrosarcoma.

Koto K, Sakabe T, Horie N, et al.
Chondrosarcoma from the sternum: reconstruction with titanium mesh and a transverse rectus abdominis myocutaneous flap after subtotal sternal excision.
Med Sci Monit. 2012; 18(10):CS77-81 [PubMed] Free Access to Full Article

BACKGROUND: Chondrosarcoma arising from the sternum is extremely rare and is often untreatable. Removal of the sternum for malignant tumor results in large defects in bone and soft tissue, causing deformity and paradoxical movement of the chest wall and making subsequent repair of the thorax very important. We report a very rare patient with a chondrosarcoma of the sternum who underwent case chest wall resection, followed by reconstruction using a titanium mesh covered with a transverse rectus abdominis myocutaneous (TRAM) flap.
CASE REPORT: A 63-year-old man was referred to our hospital with progressively enlarged swelling of his anterior chest wall. Physical examination showed a 2.5×2.0 cm mass fixed to the sternum, which was diagnosed as a chondrosarcoma based on clinical findings, imaging characteristics and incision biopsy results. The patient underwent a subtotal sternal and chest wall resection to remove the tumor, followed by reconstruction with a titanium mesh and a TRAM flap. There were no complications associated with surgery.
CONCLUSIONS: We report an extremely rare case of a patient who underwent subtotal sternal resection, followed by reconstruction, for a large chondrosarcoma. The elasticity and rigidity provided by the titanium mesh and the complete coverage of the surgical wound by a TRAM flap suggest that these procedures may be useful in reconstructing large defects in the chest wall.

Xu H, Shao M, Sun H, Li S
Primary mesenchymal chondrosarcoma of the kidney with synchronous implant and infiltrating urothelial carcinoma of the ureter.
Diagn Pathol. 2012; 7:125 [PubMed] Free Access to Full Article

Primary mesenchymal chondrosarcoma of the kidney is rare, and it shows distinct undifferentiated tumor cells and well differentiated cartilagenous components. Also assident infiltrating urothelial carcinoma of the ureter is an extremely rare cancer. We report a case of primary mesenchymal chondrosarcoma occurring in the left kidney with an ipsilateral and distinct distal ureteric implant, and a coexisting infiltrating urothelial carcinoma of the ureter in a 64-year-old man. Histopathological examination and immunohistochemical studuies showed the classic features of mesenchymal chondrosarcoma in kidney, as well as a few infiltrating urothelial in ureter. Multitarget fluorescence in situ hybridization (FISH) suggested that the development of the urothelial carcinoma in the ureter may be triggered or induced by the chondrosarcoma component. The patient died 2 month after left nephro-ureterectomy. This is the first reported case of a primary mesenchymal chondrosarcoma of the kidney with coexisting infiltrating urothelial carcinoma of the ureter. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1522835667751019.

Koizumi M, Tanjung NG, Chen A, et al.
Administration of salubrinal enhances radiation-induced cell death of SW1353 chondrosarcoma cells.
Anticancer Res. 2012; 32(9):3667-73 [PubMed]

BACKGROUND: Chondrosarcoma is a common soft tissue malignancy. Although radiation induces DNA damage and integrated stress response (ISR), the sensitivity to ionizing radiation differs among tissues, and traditional radiotherapy for chondrosarcoma is not deemed effective. We examined whether administration of an ISR-inducing agent enhances radiosensitivity of chondrosarcoma.
MATERIALS AND METHODS: SW1353 chondrosarcoma cells and C28/I2 chondrocytes were irradiated with 1-10 Gy of X-rays and cultured with 1-20 μM salubrinal, which is known to induce ISR through inhibiting dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α).
RESULTS: The numbers of cells were reduced after irradiation, and salubrinal further reduced them as well as their clonogenic survival. The levels of phosphorylated eIF2α were elevated by irradiation and administration of salubrinal. SW1353 cells treated with salubrinal after irradiation were more sensitive to radiation than those treated with salubrinal prior to irradiation.
CONCLUSION: Salubrinal may serve as a potential chemotherapeutic agent for enhancing radiosensitivity, and its efficacy may depend upon the dose used and the timing of its administration.

Power PF, Mak IW, Singh S, et al.
ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma.
J Orthop Res. 2013; 31(3):493-501 [PubMed]

Chondrosarcoma is a unique type of bone cancer in that it does not respond to chemotherapy or radiation therapy, and therefore many affected patients die from metastatic disease. Metastasis has been correlated with the upregulation of the matrix metalloproteinase (MMP) family of proteases, which can degrade extracellular components. ETV5 is a transcription factor which has shown to be overexpressed in various types of invasive tumors. We hypothesized that ETV5 regulates MMP2 in human chondrosarcoma with the protease acting as a downstream effector. Gene knock-down of ETV5 in human chondrosarcoma cells reduces MMP2 mRNA expression as well as decreased protein production and significantly decreased MMP2 activity. With plasmid transfected ETV5 upregulation, MMP2 expression is similarly upregulated at the gene expression and protein levels. Data from our bone resorption studies revealed that when a matrix metalloproteinase-2 inhibitor is added to the growth media of chondrosarcoma cells, collagen released from bone chips incubated with the cells decreased by 27%. This data suggests that ETV5 has a significant role in regulating MMP2 expression and therefore matrix resorption in human chondrosarcoma, and thus may be a targetable upstream effector of the metastatic cascade in this cancer.

Al-Rawi M, Harper T, Bafakih F
Chondrosarcoma of the tongue: a case report and a review of the literature.
Laryngoscope. 2013; 123(2):418-21 [PubMed]

Chondrosarcoma of the head and neck is uncommon and reported to constitute between 1% to 12% of all chondrosarcoma cases.1, 2, 3 Extraskeletal chondrosarcoma of the tongue is an extremely rare type of neoplasm with only three previously reported cases. The underlying origin of chondrosarcoma arising in the tongue is controversial. We describe a case of a low-grade chondrosarcoma arising in the base of the tongue of a 54-year-old woman with a central area of dedifferentiation. The patient was treated with complete surgical resection with no evidence of recurrence at 1 year follow-up.

Wong KC, Kumta SM
Joint-preserving tumor resection and reconstruction using image-guided computer navigation.
Clin Orthop Relat Res. 2013; 471(3):762-73 [PubMed] Article available free on PMC after 01/03/2014

BACKGROUND: Joint-preserving surgery is performed in select patients with bone sarcomas of extremities and allows patients to retain the native joint with better joint function. However, recurrences may relate to achieving adequate margins and there is frequently little room for error in tumors close to the joint surface. Further, the tumor margin on preoperative CT and/or MR images is difficult to transpose to the actual extent of tumor in the bone in the operating room.
QUESTIONS/PURPOSES: We therefore determined whether joint-preserving tumor surgery could be performed accurately under image-guided computer navigation and determined local recurrences, function, and complications.
METHODS: We retrospectively studied eight patients with bone sarcoma of extremities treated surgically by navigation with fused CT-MR images. We assessed the accuracy of resection in six patients by comparing the cross sections at the resection plane with complementary prosthesis templates. Mean age was 17 years (range, 6-46 years). Minimum followup was 25 months (mean, 41 months; range, 25-60 months).
RESULTS: The achieved resection was accurate, with a difference of 2 mm or less in any dimension compared to that planned in patients with custom prostheses. We noted no local recurrence at latest followup. The mean Musculoskeletal Tumor Society score was 29 (range, 28-30). There were no complications related to navigation planning and procedures. There was no failure of fixation at the remaining epiphysis.
CONCLUSIONS: In selected patients, the computer-assisted approach facilitates precise planning and execution of joint-preserving tumor resection and reconstruction. Further followup assessment in a larger study population is required in these patients.
LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Matsuura S, Ishii T, Endo M, et al.
Epithelial and cartilaginous differentiation in clear cell chondrosarcoma.
Hum Pathol. 2013; 44(2):237-43 [PubMed]

Clear cell chondrosarcoma is a rare cartilaginous bone tumor, and little is known about its pathology. We investigated the immunohistochemical expression profiles of cytokeratins (CAM5.2, AE1/AE3, CK7, CK8, CK18, and CK20), epithelial membrane antigen, SRY (sex-determining region Y)-box 9, type II collagen, runt-related transcription factor 2, and osteocalcin in clear cell chondrosarcoma and compared them with those in chondroblastoma, conventional chondrosarcoma, and osteosarcoma. Of 5 cases of clear cell chondrosarcoma, 3 demonstrated positive staining for AE1/AE3 and some form of cytokeratin in the clear cell component. Of the 5 cases, 4 strongly expressed SRY (sex-determining region Y)-box 9 in the clear cell component but weakly expressed it in the cartilaginous component. Of the 5 cases of clear cell chondrosarcoma, 3 expressed runt-related transcription factor 2 in both the clear cell and cartilaginous components, but no expression of osteocalcin was detected. In chondroblastoma, 8 of 13 cases expressed AE1/AE3, and other cytokeratins, such as CK7 (4/13), CK8 (6/13), CK18 (8/13), and CK20 (3/13), demonstrated a similar staining extensity pattern between the cellular and cartilaginous components. Clear cell chondrosarcoma and chondroblastoma have similar immunohistochemical features in that they both express epithelial and chondrogenetic markers. On the other hand, tumor cells of clear cell chondrosarcoma have no osteoblastic immunohistochemical expression in comparison with chondroblastoma.

Puri A, Gulia A
The results of total humeral replacement following excision for primary bone tumour.
J Bone Joint Surg Br. 2012; 94(9):1277-81 [PubMed]

Rarely, the extent of a malignant bone tumour may necessitate resection of the complete humerus to achieve adequate oncological clearance. We present our experience with reconstruction in such cases using a total humeral endoprosthesis (THER) in 20 patients (12 male and eight female) with a mean age of 22 years (6 to 59). We assessed the complications, the oncological and functional outcomes and implant survival. Surgery was performed between June 2001 and October 2009. The diagnosis included osteosarcoma in nine, Ewing's sarcoma in eight and chondrosarcoma in three. One patient was lost to follow-up. The mean follow-up was 41 months (10 to 120) for all patients and 56 months (25 to 120) in survivors. There were five local recurrences (26.3%) and 11 patients were alive at time of last follow-up, with overall survival for all patients being 52% (95% confidence interval (CI) 23.8 to 74) at five years. The mean Musculoskeletal Tumor Society score for the survivors was 22 (73%; 16 to 23). The implant survival was 95% (95% CI 69.5 to 99.3) at five years. The use of a THER in the treatment of malignant tumours of bone is oncologically safe; it gives consistent and predictable results with low rates of complication.

Zhou Q, Lu G, Liu A, Kohno T
Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia.
Diagn Pathol. 2012; 7:112 [PubMed] Article available free on PMC after 01/03/2014

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682.

Subbiah V, Brown RE, Buryanek J, et al.
Targeting the apoptotic pathway in chondrosarcoma using recombinant human Apo2L/TRAIL (dulanermin), a dual proapoptotic receptor (DR4/DR5) agonist.
Mol Cancer Ther. 2012; 11(11):2541-6 [PubMed] Article available free on PMC after 01/11/2013

Recombinant human Apo2L/TRAIL (dulanermin) is based on the ligand for death receptors (DR4 and DR5), which promotes apoptosis. We report a patient with refractory chondrosarcoma who showed a prolonged response to dulanermin and explore mechanisms of response and resistance. This heavily pretreated patient had progressive metastatic chondrosarcoma to the lung. On dulanermin (8 mg/kg i.v. on days 1-5 in a 21-day cycle), the patient achieved a sustained partial response with only subcentimeter nodules remaining. After 62 months of dulanermin treatment, progressive disease in the lungs was noted, and the patient underwent a resection that confirmed chondrosarcoma. DR4 was detected (immunohistochemistry) in the patient's tumor, which may have enabled the response. However, upregulation of prosurvival proteins, namely, phosphorylated (p)-NF-κBp65 (Ser 536), p-STAT3 (Tyr 705), p-ERK 1/2 (Thr 202/Tyr 204), p-mTOR (Ser 2448), FASN, and Bcl-2, were also detected, which may have provided the underlying mechanisms for acquired dulanermin resistance. The patient was restarted on dulanermin and has continued on this treatment for an additional 16 months since surgery (78 months since initiation of treatment), with his most recent computed tomography (CT) scans showing no evidence of disease.

Waaijer CJ, de Andrea CE, Hamilton A, et al.
Cartilage tumour progression is characterized by an increased expression of heparan sulphate 6O-sulphation-modifying enzymes.
Virchows Arch. 2012; 461(4):475-81 [PubMed]

Chondrosarcomas are malignant cartilage-forming tumours that can arise centrally (in the medulla) or peripherally (at the surface) of the bone. They are classified into three histological grades which correspond to the clinical severity. Previous studies by our group have shown altered signal transduction of the fibroblast growth factor and Wnt signalling pathways during peripheral chondrosarcoma progression. Heparan sulphate (HS) is a glycosaminoglycan that facilitates receptor binding of multiple growth factors, in which the sulphation of 6O position plays a pivotal role. 6O-Sulphation occurs through three HS 6O-sulphotransferases (HS6ST1-3) and is fine-tuned by two endosulphatases (SULF1-2) that remove 6O-sulphate groups. We have investigated whether the expression of HS6STs and SULFs changes during chondrosarcoma progression and have determined 6O-sulphation levels in two chondrosarcoma cell lines. Immunohistochemistry on tissue microarrays of chondrosarcomas showed that HS6ST3 and SULF1 were highly expressed in most chondrosarcomas, whereas SULF2 expression was absent in most cases. HS6ST1 and HS6ST2 expression are significantly increased during chondrosarcoma progression, which suggest that 6O-sulphation is increased during progression. This was confirmed in one grade III chondrosarcoma cell line, which showed a dramatically increased 6O-sulphation compared to an articular chondrocyte cell line by HPLC; another cell line showed an increased expression of one 6O-sulphated HS disaccharide. In conclusion, our results show increased HS6ST1 and HS6ST2 expression during chondrosarcoma progression and increased HS 6O-sulphation in vitro. As 6O-sulphation plays an important role in signal transduction, altered HS6ST expression might be associated with changes in signal transduction pathways in chondrosarcoma progression.

Shivapathasundram G, Sammons V, Darwish B
Spinal intradural myxoid chondrosarcoma.
J Neurosurg Spine. 2012; 17(4):280-4 [PubMed]

The authors present a rare case of intradural extramedullary spinal chondrosarcoma. This 38-year-old man presented with urinary retention and lower-limb weakness. Magnetic resonance imaging demonstrated a thoracic intradural extramedullary spinal tumor, which was resected. Histopathology revealed a meningeal myxoid chondrosarcoma. Despite adjuvant radiotherapy, the patient had multiple recurrences and metastases and died 18 months following his first surgery. The management of the rare entity of spinal canal chondrosarcoma is discussed.