Chondrosarcoma with Target-Like Chondrocytes: Update on Molecular Profiling and Specific Morphological Features.

This is the first histological and molecular analysis of two chondrosarcomas with target-like chondrocytes that were compared with a group of conventional chondrosarcomas and enchondromas. The unique histological feature of target-like chondrocytes is the presence of unusual hypertrophic eosinophilic APAS-positive perichondrocytic rings (baskets). In the sections stained with Safranin O/Fast green, the outer part of the ring was blue and the material in the lacunar space stained orange, similarly to intercellular regions. Immunohistochemical examination showed strong positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, B-cell lymphoma 2 apoptosis regulator (Bcl-2), p53 and p16. The S-100 protein was positive in 25 % of neoplastic cells. Antibodies against GFAP, D2-40 (podoplanin), CD99, CKAE1.3 and CD10 exhibited weak focal positivity. Pericellular rings/baskets contained type VI collagen in their peripheral part, in contrast to the type II collagen in intercellular interterritorial spaces. Ultrastructural examination revealed that pericellular rings contained an intralacunar component composed of microfibrils with abundant admixture of aggregates of dense amorphous non-fibrillar material. The outer extralacunar zone was made up of a layer of condensed thin collagen fibrils with admixture of non-fibrillar dense material. NGS sequencing identified a fusion transcript involving fibronectin 1 (FN1) and fibroblast growth factor receptor 2 (FGFR2) at the RNA level. At the DNA level, no significant variant was revealed except for the presumably germline variant in the SPTA1 gene.

Periosteal Myxoid Leiomyosarcoma Histologically Mimicking Extraskeletal Myxoid Chondrosarcoma: Report of a Case with Histopathological and Cytopathological Comparison with Extraskeletal Myxoid Chondrosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare variant of leiomyosarcoma, with most cases occurring in the uterus. A case of MLS arising in the periosteal region of the tibia, mimicking extraskeletal myxoid chondrosarcoma (EMC), is described. The evaluation included histological and cytological comparison with EMC. The patient was a 77-year-old man with a palpable mass at the anterior aspect of the right lower leg. After diagnosis by cytopathology and biopsy examination, a wide resection was performed. The resulting cytological smears were composed primarily of spindle-shaped tumor cells in a myxoid and hemorrhagic background. Histologically, the tumor showed abundant myxoid matrix and tumor cells proliferating in a cord-like to reticular pattern, exhibiting a lace-like arrangement that mimicked EMC. Although immunohistochemical findings suggested leiomyosarcoma, a diagnosis of EMC eventually was excluded by the lack of a split signal when assessed for a rearrangement of NR4A3 by chromogenic in situ hybridization. Despite histological similarity to EMC, characteristic cytological findings of EMC such as epithelioid structures with a cord-like pattern and chondroblast-like lacunar structures were not observed in the smears of this patient's MLS. We propose that cytopathological examination of bone and soft tissue lesions is useful as a diagnostic tool in similar cases. A total diagnostic workup, including clinical, radiographic, cytopathological, histopathological, and molecular findings, is needed to ensure an accurate final diagnosis and to reduce diagnostic error.

Structural Features of Heparan Sulfate from Multiple Osteochondromas and Chondrosarcomas.

Multiple osteochondromas (MO) is a hereditary disorder associated with benign cartilaginous tumors, known to be characterized by absence or highly reduced amount of heparan sulfate (HS) in the extracellular matrix of growth plate cartilage, which alters proper signaling networks leading to improper bone growth. Although recent studies demonstrated accumulation of HS in the cytoplasm of MO chondrocytes, nothing is known on the structural alterations which prevent HS from undergoing its physiologic pathway. In this work, osteochondroma (OC), peripheral chondrosarcoma, and healthy cartilaginous human samples were processed following a procedure previously set up to structurally characterize and compare HS from pathologic and physiologic conditions, and to examine the phenotypic differences that arise in the presence of either exostosin 1 or 2 (EXT1 or EXT2) mutations. Our data suggest that HS chains from OCs are prevalently below 10 kDa and slightly more sulfated than healthy ones, whereas HS chains from peripheral chondrosarcomas (PCSs) are mostly higher than 10 kDa and remarkably more sulfated than all the other samples. Although deeper investigation is still necessary, the approach here applied pointed out, for the first time, structural differences among OC, PCS, and healthy HS chains extracted from human cartilaginous excisions, and could help in understanding how the structural features of HS are modulated in the presence of pathological situations also involving different tissues.

Biomarkers of chondrosarcoma.

Clinical outcome prediction is major concern to patients with cancer. Various molecular markers in various carcinomas have been identified in the past few decades. However, accurate predictors in chondrosarcoma have not been developed, even though chondrosarcoma is the second most common primary bone tumour. Chondrosarcoma is the cartilage-forming malignancy and shows a wide spectrum of clinicopathological behaviours. The majority of chondrosarcoma grows slowly and rarely metastasises, and adequate surgery leads to a good prognosis. However, wide surgical excision is acquired in high-grade chondrosarcoma, because this tumour is highly resistant to chemotherapy and radiotherapy. To decide best therapy, accurate diagnostic markers are also necessary in chondrosarcoma. It is reported that angiogenesis and lymphangiogenesis increase by chondrosarcoma staging, and they are promoted by leptin and adiponectin. Several microRNAs to regulate vascular endothelial growth factor (VEGF)-A and VEGF-C are also reported. Alpha-methylacyl-CoA racemase and periostin are proposed as new biomarkers for differential diagnosis of enchondroma and chondrosarcoma. This review summarises that chondrosarcoma diagnostic markers are currently reported.

[Significance of SATB2 in the pathologic diagnosis of osteosarcoma].

OBJECTIVE: To investigate the role of SATB2 in the pathological diagnosis and differential diagnosis of osteosarcoma. METHODS: Immunostaining of SATB2 was performed in 47 cases of osteosarcomas, 5 osteoblastomas, 4 fibrous dysplasias, 5 myositis ossificans, 10 chondroblastomas, 8 chondrosarcomas, 5 Ewing sarcomas, 5 undifferentiated pleomorphic sarcomas, 6 fibrosarcomas and 2 leiomyosarcomas. RESULTS: All osteoblastomas (5/5) and myositis ossificans (5/5), 83.0%(39/47) of osteosarcomas and 2/10 of chondroblastomas showed nuclear immunoreactivity for SATB2. SATB2 staining was negative in all cases of fibrous dysplasia, chondrosarcomas, Ewing sarcomas and all bone primary spindle cell sarcomas(undifferentiated pleomorphic sarcoma, fibrosarcoma and leiomyosarcoma). CONCLUSION: SATB2 is a reliable osteoblastic marker for differential diagnosis of osteosarcoma and non-osteoid sarcoma, although with a limited role in separating osteosarcoma from non-malignant osteoblastic lesions.

Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of Glioblastoma in the Central Nervous System.

BACKGROUND: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer. CASE: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found. CONCLUSION: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy.

Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism.

[Histopathological diagnostic concordance in bone and soft tissue sarcomas between two comprehensive cancer centers from eastern and western Europe: a collaborative experience]. / La concordance du diagnostic histopathologique des sarcomes osseux et des tissus mous entre deux centres anticancéreux de l'Europe de l'Est et de l'Ouest : une expérience de collaboration.

INTRODUCTION: This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe - not specialized in this area of pathology - and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. MATERIALS AND METHODS: The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. RESULTS: Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies - not affecting the management of the patient - were observed in 18 cases (20.4%). A major discordance in grading - potentially changing the management of the patient - was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). DISCUSSIONS: Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular biology was decisive in one case. Most grading discrepancies resulted from the appreciation of the mitotic index. CONCLUSIONS: The profile of the sarcomatous pathology in the northwest region of Romania does not appear to differ significantly from other parts of Europe or the world, but a prospective epidemiological study would be necessary to confirm this assessment. The expansion of immunohistochemical antibody panel, the over-specialization of pathologists and, in the future, the establishment of a national network of referral centers in sarcoma pathology, are required for a high level of histological diagnosis in Eastern Europe. A periodic external audit, continuing this trans-European collaboration between the two centers, would be beneficial for monitoring progress.

ERG expression in chondrogenic bone and soft tissue tumours.

AIM: We studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation. METHODS: Formalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%-25%), 2+ (26%-50%), 3+ (>51%). RESULTS: Nuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG. CONCLUSIONS: In this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.

NY-ESO-1 is a sensitive and specific immunohistochemical marker for myxoid and round cell liposarcomas among related mesenchymal myxoid neoplasms.

Myxoid and round cell liposarcomas constitute approximately one-third of all liposarcomas, a relatively common group of fat-derived soft tissue sarcomas. The histomorphology is a continuum between highly differentiated myxoid and poorly differentiated round cell components. The gold standard of diagnosis is dependent on histomorphology and/or identification of t(12;16)(q13;p11) translocation by cytogenetics or demonstration of DDIT3 rearrangements by fluorescence in situ hybridization. There are currently no diagnostic immunohistochemical stains available. The broad range of myxoid neoplasms in the differential diagnosis includes a variety of sarcomas. Given the notable differences in disease biology among myxoid neoplasms, which range from benign to aggressive, an accurate diagnosis is imperative for proper treatment and prognostication. Prompted by our recent study showing frequent expression of the cancer testis antigen NY-ESO-1 in myxoid and round cell liposarcomas, we sought to evaluate the utility of NY-ESO-1 as an immunohistochemical marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms within the differential diagnosis. Formalin-fixed, paraffin-embedded blocks were obtained for the following mesenchymal myxoid neoplasms (n=138): myxoid and round cell liposarcoma (n=38); well-differentiated liposarcoma (n=12); lipoma (n=20; 4 with myxoid change); extra-cardiac soft tissue myxoma (n=39); extraskeletal myxoid chondrosarcoma (n=12); myxofibrosarcoma (n=10: 5 low grade, 2 intermediate grade, 3 high grade); and low-grade fibromyxoid sarcoma (n=7). Utilizing standard immunohistochemistry protocols, full sections were stained with NY-ESO-1 (clone E978), and staining was assessed for intensity (1-2+), percentage of tumor positivity, and location. In all, 36/38 (95%) of the myxoid and round cell liposarcomas demonstrated NY-ESO-1 immunoreactivity. The majority of the positive cases (34/36; 94%) showed strong, homogenous staining (>50% tumor positivity), and two cases (6%) showed weak (1+ intensity), patchy staining (20-30% tumor positivity). Immunoreactivity was predominantly cytoplasmic. All the other neoplasms evaluated were negative for NY-ESO-1. NY-ESO-1 appears to be a sensitive and a specific marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms. The assessment of NY-ESO-1 expression by immunohistochemistry in the appropriate setting provides a cheaper, faster, and more accessible confirmatory test.

Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the spectrum of tumors associated with SMARCB1 germline mutations.

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.

Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia.

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.

A novel sarcoma with dual differentiation: clinicopathologic and molecular characterization of a combined synovial sarcoma and extraskeletal myxoid chondrosarcoma.

We report on an unusual case of a 43-year-old woman who developed a malignant soft tissue tumor of the arm with overlapping morphology between synovial sarcoma (SS) and extraskeletal myxoid chondrosarcoma (EMC). The tumor recurred 7 years after the initial diagnosis and continued to demonstrate both SS and EMC histology. Immunophenotypically, the primary and recurrent tumors were both positive, focally, for cytokeratin, S-100, bcl-2, and epithelial membrane antigen. At the time of recurrence, the primary and recurrent tumors were further characterized for genetic and molecular abnormalities. Intriguingly, fluorescence in situ hybridization of the primary tumor revealed rearrangements of both the SS18 and EWSR1 genes. Furthermore, reverse transcriptase-polymerase chain reaction studies of both the primary tumor and the recurrence confirmed the presence of both SS18-SSX2 and EWSR1-NR4A3 (exon 3) gene fusions, characteristic of SS and EMC, respectively. This is the first reported case of a remarkable soft tissue sarcoma that exhibits overlapping morphologic features between SS and EMC and that also harbors a combination of SS18-SSX2 and EWS-NR4A3 gene fusions. This case supports the fact that specific, reproducible gene fusions frequently direct, cooperatively or competitively, basic histogenetic processes to produce tumor phenotypes.

Characterization of a new human cell line (CH-3573) derived from a grade II chondrosarcoma with matrix production.

Chondrosarcomas are malignant cartilage-forming tumors that represent the third most common malignant solid tumor of bone. In patients with grades II and III, local recurrence, increasing tumor size and dedifferentiation have been associated with lower survival rates. These biologically poorly-understood neoplasms vary considerably in clinical presentation and biological behavior. Cytogenetic studies have shown that heterogeneity is related to karyotypic complexity; moreover, alterations in the 9p21 locus and TP53 gene are related to disease progression. Despite the relatively high frequency of chondrosarcoma only a limited number of cell lines exist in the scientific community, limiting the possibility to study hypothesis-derived research or primary drug interaction necessary for pre-clinical studies. We report a chondrosarcoma cell line, CH-3573, derived from a primary tumor that may serve as a useful tool for both in vitro and in vivo models to study the molecular pathogenesis. In addition, xenograft passages in nude mice were studied to characterize the genetic stability over the course of tumor progression. In contrary to other reported cell lines, an important feature of our established cell line was the retained matrix production, a characteristic feature of a conventional grade II chondrosarcoma. The cell line (CH-3573) was characterized by pathological, immunohistochemical and molecular genetic methods.

Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors- clinical and histological correlation.

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

Increased levels of hypoxia-inducible factor-1α are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma.

Hypoxia-inducible factor (HIF)-1α is a key nuclear transcription factor that regulates the cellular response to hypoxia, and is important for solid tumor growth and survival. However, the underlying role of HIF-1α in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF-1α in chondrosarcoma, and its association with clinicopathologic features, Bcl-xL expression, apoptosis index (AI), and overall survival of patients with chondrosarcoma. Our results shown that the protein levels of HIF-1α were increased, and the mRNA and protein levels of Bcl-xL were also increased in SW1353 cells under hypoxic conditions. In eight patients with chondrosarcoma, increased expression of HIF-1α and Bcl-xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20 (58.8%) showed high HIF-1α protein expression as compared to benign cartilage tumors. Increased HIF-1α expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF-1α expression was significantly associated with Bcl-xL expression and AI. More significantly, the survival rate of patients with HIF-1α high tumors was significantly lower than that of patients with HIF-1α low tumors. These findings suggest that increased HIF-1α levels mediated up-regulation of Bcl-xL play a prominent role in evasion of apoptosis and tumor progression, and can be predictive for the prognosis in human chondrosarcoma.

Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors: clinical and histological correlation

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

Gadd45ß expression in chondrosarcoma: a pilot study for diagnostic and biological implications in histological grading.

BACKGROUND: Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45ß (GADD45ß) is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45ß in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45ß in pathological grading of chondrosarcoma. METHODS: Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1) were used for immunohistochemical analysis to investigate the expression of GADD45ß. Quantitative analysis was performed to compare the number of GADD45ß positive cells and pathological grading. RESULTS: Over 70% of the cells in enchondromas expressed GADD45ß. On the other hand, the expression of GADD45ß decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%). CONCLUSIONS: The association of GADD45ß expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45ß may be a specific diagnostic parameter for chondrosarcoma cell differentiation.

Chondrosarcoma of the temporomandibular joint: a case report in a child.

This article reports a rare case of a temporomandibular joint (TMJ) chondrosarcoma in a child. Chondrosarcoma is a malignant cartilaginous neoplasm that resembles synovial chondromatosis. In the head and neck region, chondrosarcoma is uncommon, corresponding to 6.4% to 12% of all reported cases. The majority of patients with chondrosarcoma are in the third to fourth decades of life. A Pubmed search showed that 20 TMJ chondrosarcoma cases had been reported up to 2008. The present case was of an 11-year-old girl referred to an Oral Disease Center and presenting with a preauricular swelling on the right side and normal ENT evaluation. The patient was healthy. Discrete pain and mild limitation of mouth opening were observed. A panoramic radiograph as well as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI) revealed an osteolytic lesion in the right TMJ. The skull base and adjacent spaces were preserved but adjacent anatomic structures were displaced. After an incisional biopsy, the patient underwent high condylectomy. Microscopic findings showed a tumor exhibiting cartilaginous tissue proliferation with cellular pleomorphism, nuclear hyperchromasia, and mixoid changes in the matrix. The immunohistochemical analysis of the expression of Ki-67 and Cyclin B1 proteins (cellular proliferation markers) revealed a very low proliferative cell index. The 3.5 years of clinical and imaging follow-up have shown no evidence of recurrence or metastasis, but signs of myofascial disorders could be observed. It is concluded that cartilaginous lesions in the jaws must be regarded with suspicion, since benign and malignant lesions may show similar clinical features. This case emphasized the importance of interdisciplinary approaches to minimize the possibility of misdiagnosis.

Extraskeletal myxoid chondrosarcoma of the perineum.

Extraskeletal myxoid chondrosarcoma is an aggressive tumor with significant metastatic potential. A 40-year-old man presented with an asymptomatic mass at the left ischial fossa. Magnetic resonance imaging showed a 9x6-cm mass with variable signal intensity and cystic formations. A computed tomography scan of the chest showed multiple pulmonary nodules. A computed tomography-guided core needle biopsy was consistent with low-grade extraskeletal myxoid chondrosarcoma. Despite the presence of lung metastases, wide resection of the primary tumor was performed. Wide resection included the perineal mass and the adjacent ischiopubic ramus. Postoperative recovery was uneventful. One month postoperatively, thoracotomy was performed, and approximately 20 pulmonary nodules were excised. Histological analysis of the excised specimens was consistent with extraskeletal myxoid chondrosarcoma metastases. Two years postoperatively, the patient is alive without evidence of local recurrence or distant disease. Extraskeletal myxoid chondrosarcoma is an unusual soft tissue sarcoma with ultrastructural and molecular features distinct from that of skeletal myxoid chondrosarcoma. The EWS-CHN gene fusion is highly specific to extraskeletal myxoid chondrosarcoma; the gene fusion is positive in >or=75% of cases. Treatment should include wide excision for local tumor control. Resection of the lung metastases is feasible. Because of the prolonged survival of patients with extraskeletal myxoid chondrosarcoma, long-term follow-up is recommended for early detection of local recurrence or distant metastases.