Extraskeletal Myxoid Chondrosarcoma: A Clinicopathologic, Immunohistochemical, and Ploidy Analysis of 23 Cases

Abstract

Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors. Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > 10%, and Ki-67 "hot spot" > 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome. The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested. ) reassessed the clinical features of EMC in a series of 10 patients and showed the "indolent but resilient" nature of this neoplasm; 7 of the patients died of tumor up to 17 years after the initial diagnosis. Seven years later, Meis-Kindblom et al. (4) studied a large series of EMCs, most consultation cases, and showed that older age, larger tumor size, and proximal tumor location were associated with decreased survival by multivariate analysis.The histogenesis of EMC is still a subject of controversy. However, chondroblastic differentiation has been supported by ultrastructural (5-15) and histochemical (16 -18) studies. In addition, cytogenetic and molecular analyses have shown that EMC is a distinct entity with the characteristic translocation t(9;22) involving the EWS gene (22q12) and the TEC gene (9q22) in a majority of the cases (19 -29).We reviewed the clinicopathologic, immunohistochemical, and ploidy features in a series of 23 cases of EMC evaluated at a single institution to identify potential prognostic factors associated with a more aggressive behavior. MATERIALS AND METHODSTwenty-three patients in whom EMC was diagnosed between 1968 and 1996 were included in this study. Eighteen patients with EMC were diagnosed and primarily treated at the Mayo Clinic, and five patients were referred by other institutions for additional treatment or evaluation. Fifteen cases from this series will be described in another article (30).

Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall

“…Not all cases contained sufficient tissue for all studies; overall wide-spectrum cytokeratin was performed in 44 cases, low molecular weight cytokeratin in 27 cases, synaptophysin in 37 cases, chromogranin A in 36 (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) years old), and two older adults 460 years of age. The primary tumors were available for study in 36 cases; for eight patients only metastases (seven to lymph nodes, one to lung) were available.…”

“…50 Synaptophysin expression is uncommon in tumors of the Ewing sarcoma family and is generally considered as evidence of a tumor closer to the 'primitive neuroectodermal tumor' end of that biologic continuum. 51 'Anomalous' synaptophysin expression is extremely unusual, but may be seen in extraskeletal myxoid chondrosarcomas 52,53 and very rarely in melanoma. 54 It is also important to realize that synaptophysin expression may be seen routinely in tissues and tumors not typically thought of as 'neuroendocrine', specifically adrenal cortex and its neoplasms.…”

Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype

“…The tumors were identified from the Mayo Clinic Tissue Registry/Soft Tissue and Bone Sarcoma Database according to established criteria described previously. 29 The material was fixed with 10% formalin and embedded in paraffin. Paraffin sections (4-mm thick) were cut and stored at room temperature until use.…”

Clinical–Pathological Conference: Case 1

“…There is a wide variation in reports for other markers; the most frequently positive at least focally are S-100, neuroendocrine markers (NSE, synaptophysin and chromogranin) in a subgroup of patients and PGP9.5. Cytokeratins, EMA, smooth muscle actin, muscle specific actin, desmin and GFAP are rarely positive [2,3].Occasional cases showed some BCl-2 or c-kit positivity.…”

“…Large atypical or rhabdoid cells, focal hyaline cartilage and cellular spindle cell areas resembling fibrosarcoma have all been described in individual cases but are uncommon features. The cellularity of EMC was described as low in 70% of cases, and the mitotic count is generally low, with 61% of cases showing less than 1 mitosis/10 HPF, and the remaining less than 2/10 HPF [3]. Using immunohistochemistry, the only marker which has been consistently positive in the majority of cases is vimentin.…”