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PubMed2004

Chondroid tumors of the larynx: a clinicopathologic study of 19 cases, including two dedifferentiated chondrosarcomas.

We studied 19 cases of chondroid tumors of the larynx: two chondrometaplastic nodules, two chondromas and 15 chondrosarcomas (including two dedifferentiated chondrosarcomas). One of chondromas recurred 18 months after resection because of inadequate surgical treatment. Chondrosarcomas were separated as low-grade (nine cases), intermediate (three cases), high-grade (one case), and dedifferentiated (two cases) according to histologic appearance. Chondrosarcomas are nearly always histologically low grade, make up the largest numbers of the neoplasms, and arise from the cricoid cartilage. Conservative surgical management, when possible, is advocated to preserve the larynx. Chondrometaplastic nodules are to be distinguished from chondrosarcoma and the rarely occurring chondroma. The nodules are not neoplastic and have a low to nil recurrent potential.

Adult↗

PubMed2003

PAS inclusions, immunoreactive tenascin and proliferative activity in low-grade chondrosarcomas.

To distinguish between chondrosarcoma (grade 1--borderline histology) and enchondroma, we examined six chondrosarcomas (grade 1--borderline histology) which looked like benign lesions. Their diagnosis, albeit based on clinical, radiologic and pathologic examinations, was not easily reached. Moreover, we examined six enchondromas and 11 chondrosarcomas, the diagnoses of which were straightforward. All cartilaginous tumors were studied, placing emphasis on PAS-positive intracytoplasmic globules. Anti-Ki67 proliferation-associated nuclear antigen antibody and tenascin antibody were applied. The following features were observed in low-grade chondrosarcomas: (1) masses of hyalin and/or myxoid cartilage invading spaces around the tumor, (2) host lamellar bone trabeculae surrounded by cartilage on all sides, (3) tumoral resorption of bone trabeculae. Intracytopasmic hyalin globules (ICG) were more frequently found in malignant than in benign neoplasm (p = 0.042). Moreover, tenascin matrix immunoreactivity was more likely to be observed in benign than in malignant neoplasm (p = 0.029). Ki67 immunoreactivity was more frequent in characterized than in low-grade chondrosarcomas or in enchondromas, where it was null (p = 0.0044).

Adolescent↗

PubMed2003

Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma.

In this case of a dedifferentiated chondrosarcoma, we searched for genetic or epigenetic alterations in both components of the tumor, the low grade chondroblastic component, and the high grade osteosacomatouscomponent. To date, only little is known about aberrant patterns of DNA methylation in chondrosarcomas. Microdissection was used as a valuable method for clearly separating the tissues. We examined CpG island methylation of 8 tumor suppressor genes and candidate tumor suppressor genes, which are involved in different pathways: cell cycle (p21WAF1, p16INK4, p14ARF), apoptosis (DAPK, FHIT), DNA repair (hMLH1), and cell adherence (E-Cadherin). We found p16INK4 and E-cadherin promotor methylation in the low grade chondroid compartment of the dedifferentiated chondrosarcoma. P16INK4, FHIT, and E-cadherin were methylated in the highly malignant osteosarcomatous compartment of the tumor. Earlier investigations of this chondrosarcoma showed p53 mutation and p53-LOH in the anaplastic component. As shown in this case, it was accompanied by Rb-LOH. Early methylation of p16IK4 and E-cadherin in the chondroid compartment could point to the monoclonal origin of demonstrated dedifferentiated chondrosarcoma. Further alterations, as shown in p53, Rb and FHIT, are responsible for the "switch" to a high grade anaplastic sarcoma.

Cadherins↗

PubMed2006

Type II collagen, but not aggrecan expression, distinguishes clear cell chondrosarcoma and chondroblastoma.

AIM: Chondroblastoma and clear cell chondrosarcoma are uncommon skeletal neoplasms that have a strong tendency to involve the epiphysis of long bones. They also share some overlapping histological features. Thus, it can be difficult both radiographically and histologically to distinguish these neoplasms. So far there are no immunohistochemical markers available that have been shown to be helpful in differentiating these neoplasms. METHODS: In our study of a series of clear cell chondrosarcomas (n = 15) and chondroblastomas (n = 35), S100, vimentin, aggrecan and collagen type II were detected by immunohistochemistry. RESULTS: We detected immunohistochemical evidence of type II collagen within both the extracellular matrix-rich (chondroid) and matrix-poor areas in all 15 cases of clear cell chondrosarcoma. In contrast, immunohistochemical analysis failed to show staining of collagen type II in any of the 35 chondroblastomas. Other markers, including S100 protein, vimentin and aggrecan proteoglycan were tested in parallel and found to be focally positive in both neoplasms. CONCLUSION: Therefore, our data show that in cases when clear cell chondrosarcoma and chondroblastoma pose a diagnostic challenge, the presence of type II collagen in the extracellular tumour matrix significantly supports the diagnosis of clear cell chondrosarcoma and aids in distinguishing it from chondroblastoma.

Aggrecans↗

PubMed1986

Extraskeletal myxoid chondrosarcoma arising from the retroperitoneum.

A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.

Chondrosarcoma↗

PubMed1985

Periosteal chondroma and periosteal chondrosarcoma.

A clinicopathologic study of 46 patients with periosteal chondroma and 14 patients with periosteal chondrosarcoma revealed that periosteal chondroma tended to affect younger patients and that the lesion was usually smaller. Radiographically, the typical periosteal chondroma was a small, well-marginated tumor on the outer surface of a long bone. Erosion of the cortical surface and marginal buttresses were usually present. Periosteal chondrosarcoma had a more aggressive appearance and was seen as a large mass located superficially on the cortex; the margins of the mass were more irregular than those of chondroma. Histologically, periosteal chondroma frequently showed hypercellularity, plump nuclei, and binucleation. Thus, the differentiation of chondroma from chondrosarcoma is difficult and is based mainly on evidence of invasion. The prognosis in periosteal chondroma is good: only one patient had a local recurrence, none of the tumors underwent malignant change, and excision seems to be curative. However, the prognosis in periosteal chondrosarcoma is not as good: two patients died of metastasis to the lungs after local excision and two patients had recurrences after local resection. Periosteal chondrosarcoma should be treated more aggressively than periosteal chondroma.

Adolescent↗

PubMed2002

Clear cell chondrosarcoma of the larynx: a case report of a rare histologic variant in an uncommon localization.

The authors describe a clear cell chondrosarcoma of the larynx. The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas. Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.

Chondrosarcoma↗

PubMed2002

Chondrosarcoma of the larynx: a clinicopathologic study of 111 cases with a review of the literature.

Chondrosarcomas of the larynx are rare tumors accounting for about 0.5% of all laryngeal primary tumors. A total of 111 laryngeal chondrosarcoma cases, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology. There was a 3.6:1 male/female ratio of patients 25-91 years of age (mean, 64.4 years). Patients presented most frequently with hoarseness (n = 72 patients) present for a mean of 28.2 months. The majority of tumors involved the cricoid cartilage (n = 77) with a mean size of 3.5 cm. All tumors were invasive and malignant by radiology and/or histology (into bone within the ossified laryngeal cartilages in 52 tumors). Most tumors were low-grade lesions: grade 1 (n = 51), grade 2 (n = 54); there were six grade 3 tumors. An associated benign chondroma with (n = 41 tumors) or without ischemia (n = 24 tumors) was noted. All patients had surgery and five had radiation therapy. Wide excision or voice-sparing surgery was used in 73 patients, whereas 37 patients had a laryngectomy. Recurrences occurred in 20 (18%) patients, 10 of whom underwent salvage laryngectomy. At the last follow-up, 102 patients had no evidence of disease (alive or dead, mean 11.2 years) and five patients had evidence of disease (alive, one patient, 6.5 years; dead, four patients, mean 6.4 years). The six patients with high-grade chondrosarcoma were all without disease at the last follow-up (mean, 15.1 years). There was no difference in clinical outcome based on grade (p = 0.210), location (p = 0.078), or treatment (p = 0.607) but was worse for patients with a myxoid-type chondrosarcoma (p = 0.044). Primary laryngeal chondrosarcomas are typically low- to moderate-grade lesions involving the cricoid cartilage, frequently associated with a chondroma. They usually portend an excellent overall long-term prognosis with initial conservative voice-sparing surgery.

Adult↗

PubMed2002

Treatment and outcome of recurrent pelvic chondrosarcoma.

Little has been published about the outcome of patients with recurrent chondrosarcoma of the pelvis. The current study is a review of patients with surgically treated locally recurrent pelvic chondrosarcoma at one institution. Twenty-one patients had surgical resection of recurrent pelvic chondrosarcoma between July 1974 and July 1996. There were nine women and 12 men with a mean age of 46 years (range, 24-67 years) at first recurrence. Patients were followed up for a minimum of 3.3 years and median of 12 years from first (index) recurrence or until death. The mean time to index recurrence was 27 months (range, 5-87 months). In three cases (14%), the tumor at index recurrence was a higher grade than the initial lesion. There were six additional tumors that became a higher grade during subsequent recurrences. Fifteen of the 21 patients (71%) had a second local recurrence. Five patients (24%) had distant metastasis. At death or final followup, 11 patients (52%) had no evidence of disease, two patients (10%) are alive with disease, and eight patients (38%) died of their disease. The three patients with high-grade tumors at index recurrence all died of disease. The treatment of recurrent pelvic chondrosarcoma is a challenging problem. Tumor-free margins may require radical surgery, and the best chance of cure is at the time of initial resection. With aggressive surgical intervention, approximately 50% of patients with recurrent pelvic chondrosarcoma can achieve long-term survival.

Adult↗

PubMedDate not supplied

FDG-PET in differential diagnosis and grading of chondrosarcomas.

PURPOSE: The purpose of this work was to investigate the usefulness of PET with [18F]2-deoxy-2-fluoro-D-glucose (FDG) in the differential diagnosis and grading of chondrosarcomas. METHOD: Four enchondromas, one osteochondroma, and six chondrosarcomas were prospectively studied by FDG-PET. The significance of the standardized uptake value (SUV) was evaluated in comparison with clinical, radiological, and histopathological findings of the tumors. RESULTS: The SUV ranged from 0.7 to 1.3 (mean 0.96+/-0.22) in benign cartilage tumors and from 1.3 to 3.3 (2.23+/-0.80) in chondrosarcomas. This SUV difference between benign and malignant tumors was statistically significant (p = 0.011) in contrast to considerable overlap of clinical and radiological findings. Among chondrosarcomas, the SUV of one Grade I tumor was 1.3; those of four Grade II tumors were 1.3, 1.9, 2.5, and 3.1; and that of one Grade III tumor was 3.3. CONCLUSION: Our preliminary study showed that FDG-PET could be an objective and quantitative adjunct in the differential diagnosis and grading of chondrosarcomas.

Adult↗

PubMed2002

Dedifferentiated chondrosarcomas of the larynx: a report of two cases and review of the literature.

OBJECTIVE: To analyze the long-term clinical outcome of dedifferentiated chondrosarcoma or chondrosarcoma with additional malignant mesenchymal component (CAMMC) of the larynx and compare the results with those of axial chondrosarcomas. STUDY DESIGN/METHODS: Two patients with CAMMC of the larynx (0.03%) were retrospectively identified within the archives of the Armed Forces Institute of Pathology between 1970 and 2001. We compared the clinical and histologic features of these two cases with those reported in the English literature (Medline 1966-2001) (Table I). RESULTS: Patient no. 1 was a 67-year-old man who presented with a 12-month history of hoarseness and was found to have a 4-cm mass involving the cricoid cartilage. Enucleation was performed and histologically demonstrated a dedifferentiated chondrosarcoma. Without additional intervention, the patient died after 136 months without evidence of disease. Patient no. 2 was a 41-year-old man who also presented with a 12-month history of hoarseness and dysphagia and was found to have a 5-cm mass involving the cricoid cartilage. A total laryngectomy was performed for the dedifferentiated chondrosarcoma. He is alive without evidence of disease at last contact (91 mo). CONCLUSION: CAMMC of the larynx are rare tumors but have a better prognosis than their axial counterparts (mean, 6 mo). Initial voice-sparing surgery can be followed with more aggressive surgery if recurrences develop.

Adult↗

PubMed2004

Cricoid chondrosarcoma presenting as arytenoid hypertelorism.

BACKGROUND: Arytenoid hypertelorism (arytenoid cartilages spaced too widely apart) appears to be the most common initial recognizable physical finding of cricoid chondrosarcoma. Nine cases from the Center for Voice Disorders are presented. With arytenoid hypertelorism caused by cricoid chondrosarcoma, usually the posterior larynx is open. In fact, patients with arytenoid hypertelorism caused by cricoid chondrosarcoma may be aphonic even though the anterior membranous vocal folds make contact during attempted phonation. METHODS: Between 1991 and 2002, nine patients were diagnosed with cricoid chondrosarcoma. Patients' charts and video examinations were retrospectively evaluated for symptoms and the presence of arytenoid hypertelorism on endoscopic evaluation. Two were women, and seven were men, with a mean age of 70 (range 53-72) years at diagnosis. RESULTS: Eight (88%) patients had aphonia or dysphonia caused by arytenoid hypertelorism as their presenting symptom. Six were diagnosed after failed medialization laryngoplasty or other laryngeal rehabilitation surgery. All nine patients had a low-grade tumor. The initial treatment in eight patients was hemicricoidectomy, and one patient had a total laryngectomy. In four cases, a second procedure was needed 1 to 6 years later because of recurrence. Seven patients are alive without clinically significant disease; one is alive with moderate disease, and one has died from an unrelated cause. CONCLUSIONS: Severely dysphonic, elderly patients presenting with arytenoid hypertelorism of unknown cause should be evaluated by fiberoptic laryngoscopy and by computed tomography scan to rule out cricoid chondrosarcoma. Because these tumors behave so benignly, the authors recommend conservative surgery (unilateral hemicricoidectomy) as the diagnostic/treatment modality of choice.

Aged↗

PubMed2004

Scapular chondrosarcomas have high rates of local recurrence and metastasis.

This is the first report of a large series of patients with scapular chondrosarcomas. The grade distributions, locations of the tumors in the scapula, surgical techniques, status of margins, chondrosarcoma subtypes, Enneking stages, adjuvant therapies, local recurrence rates, metastasis rates, and survival prognoses of patients with scapular chondrosarcoma were evaluated. Forty-seven patients treated between 1921 and 1999 were analyzed retrospectively. Grade 3 disease was significantly associated with a poorer survival prognosis when compared with Grades 1 or 2 disease. Patients with tumors smaller than 5 cm were treated mainly with partial scapulectomy, and patients with tumors larger than 5 cm often were treated with total scapulectomy. The survival prognoses of patients with intralesional resections at initial surgery showed a tendency toward poorer survival when compared with patients with wide resections at initial surgery. Metastasis and local recurrence (21.3% and 40.4%) were higher in scapular chondrosarcomas than rates reported for patients with general chondrosarcomas, and local recurrence or metastasis was associated with limited survival. The 5- and 15-year survival probabilities subsequent to diagnosis were 79% and 53%, respectively. The high rates of local recurrence and metastasis likely were caused by the difficult anatomic relationships encountered during scapular resections. This study shows the importance of wide margins which must be achieved to provide local disease control.

Adolescent↗

PubMed2004

Genetics of chondrosarcoma and related tumors.

PURPOSE OF REVIEW: The burgeoning body of information on the genetic changes present in and underlying the development and biology of human cancers has carried implications regarding the possible genetic events that are responsible for not only the genesis of these cancers but also the hope of the cure for these cancers. Chondrosarcomas are a group of tumors that fall into this category. The purpose of this review is to summarize the genetic findings in these tumors. RECENT FINDINGS: The histopathologic variability of chondrosarcomas is reflected in the complexity and lack of specificity of their cytogenetic and molecular genetic findings, except for extraskeletal myxoid chondrosarcomas. These are characterized in the preponderant number of cases by a translocation, t(9;22)(q22;q12), and in a small number of cases by variant translocations t(9;17)(q22;q11) and t(9;15)(q22;q21). These translocations lead to the formation of abnormal fusion genes and gene products (proteins). In each of these translocations, the CHN gene is involved, resulting in the chimeric fusion genes EWS/CHN, RBP56/CHN, and TCF12/CHN, respectively. The specific translocations and their associated molecular genetic changes are diagnostic of extraskeletal myxoid chondrosarcomas. The abnormal proteins resulting from these fusion genes aberrantly affect gene transcription and cellular signaling pathways thought to be responsible for initiating sarcoma formation. In skeletal (central) chondrosarcomas of varying histopathologic types, the cytogenetic and molecular genetic findings are variable, complex, and apparently lacking in specificity. These changes may reflect a stepwise process (or processes) of oncogenesis involving an array of genes. SUMMARY: Although some cartilaginous tumors are characterized by specific or recurrent chromosome alterations and molecular genetic changes, much is yet to be learned about the nature and sequence of these genetics events and about their unique role in the stepwise process involved in the development and biology of each tumor type, both malignant and nonmalignant. Until such time, some of the genetic changes, particularly the presence of specific translocations, can be of definite diagnostic value.

Bone Neoplasms↗

PubMed1999

Abl expression, tumour grade, and apoptosis in chondrosarcoma.

AIMS: To determine whether Abl immunoreactivity correlates with grade and cell kinetics (apoptosis and mitosis) in chondrosarcoma. METHODS: Sections from 16 chondrosarcomas were stained immunohistochemically using a polyclonal antibody to the c-Abl/Bcr-Abl oncoprotein. Apoptotic indices and mitotic indices were assessed in all tumours. Sections from 24 paraffin wax blocks of human fetal rib (gestational ages, 15-42 weeks) were also stained to determine whether the Abl protein is synthesised consistently throughout endochondral ossification. RESULTS: Abl staining in immature fetal rib chondrocytes at all stages of development was predominantly nuclear, and 70% of cells showed moderate to strong staining. Abl immunoreactivity was minimal or absent in hypertrophic chondrocytes about to undergo apoptosis at the growth plate. There was strong Abl staining in grade 1 and grade 2 chondrosarcomas but staining was greatly reduced or absent in grade 3 chondrosarcomas. There was a very significant linear correlation between apoptotic index (mean, 0.68%; range, 0-3.2%) and mitotic index (mean, 0.23%; range, 0-0.9%), and both indices were significantly lower in grade 1 than in grade 2 and grade 3 chondrosarcomas. CONCLUSIONS: These data suggest that abl gene expression is associated with differentiation and apoptosis inhibition in fetal and neoplastic chondrocytes. However, these putative effects cannot be ascribed solely to the Abl protein, because several additional factors contribute to the regulation of both differentiation and apoptosis.

Apoptosis↗

PubMed1992

Chondrosarcoma: MR imaging with pathologic correlation.

Magnetic resonance (MR) images of 21 surgically confirmed chondrosarcomas were retrospectively reviewed in conjunction with plain radiographs and computed tomographic scans and correlated with pathologic findings. The tumors appeared lobulated, and signal intensity, as analyzed visually (intermediate on T1-weighted, high on T2-weighted images), was similar for all lesions, regardless of pathologic type. Size of lesion was not an indicator of grade. The appearances of mesenchymal and dedifferentiated chondrosarcomas mimicked that of conventional chondrosarcoma. Extraskeletal chondrosarcoma was visualized as a lobulated soft-tissue mass. In all cases, MR imaging accurately depicted intraosseous and soft-tissue extent of tumor noted at surgery and pathologic examination. Histologic type or grade of chondrosarcoma generally cannot be characterized on the basis of visual analysis of signal intensity noted on routine MR images. However, MR imaging is excellent for exact delineation of tumor extent.

Bone Neoplasms↗

PubMedDate not supplied

Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features.

Distinction of enchondroma versus intramedullary chondrosarcoma affecting the appendicular skeleton (proximal to the metacarpals and metatarsals) is a frequent diagnostic dilemma. The authors studied a large series of patients with these lesions (92 with enchondromas, 95 with chondrosarcomas) using statistical assessment of both clinical parameters and numerous radiologic manifestations on images from multiple modalities to identify differentiating features. Multiple clinical and imaging parameters demonstrated statistically significant differences between enchondroma and chondrosarcoma, particularly pain related to the lesion, deep endosteal scalloping (greater than two-thirds of cortical thickness), cortical destruction and soft-tissue mass (at computed tomography or magnetic resonance imaging), periosteal reaction (at radiography), and marked uptake of radionuclide (greater than the anterior iliac crest) at bone scintigraphy. All of these features strongly suggested the diagnosis of chondrosarcoma. These criteria allow distinction of appendicular enchondroma and chondrosarcoma in at least 90% of cases.

Adult↗

PubMed1992

Chondrosarcomas of the skull base: MR imaging features.

The magnetic resonance (MR) images from 17 patients with chondrosarcomas of the skull base were retrospectively reviewed to characterize the size, location, signal intensity, and extension of these tumors. Eleven patients with chondrosarcomas received intravenously administered gadopentetate dimeglumine. In 16 patients, computed tomographic (CT) scans were obtained to evaluate intratumorous mineralization and bone erosion. On short repetition time (TR)/echo time (TE) MR images, chondrosarcomas generally had low to intermediate signal intensity; on long TR/TE MR images, they generally had very high signal intensity. Signal heterogeneity on long TR/TE MR images was seen in 10 of 17 tumors (59%) and was caused by matrix mineralization, fibrocartilaginous elements, or both. Matrix mineralization was demonstrated with CT in seven of the 16 chondrosarcomas. Chondrosarcomas showed marked enhancement after administration of gadopentetate dimeglumine in either a heterogeneous (n = 8) or homogeneous (n = 3) pattern. The information about the size and extent of these neoplasms was important in the choice of surgical approaches for gross total resection of tumor.

Adult↗