Extraskeletal Myxoid Chondrosarcoma: Clinical and Molecular Characteristics and Outcomes of Patients Treated at Two Institutions

Abstract

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics.Methods: This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database.Results: 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival.Chiusole et al. EMC Treatment and OutcomesConclusion: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.

Extraskeletal Myxoid Chondrosarcoma: State of the Art and Current Research on Biology and Clinical Management

“…Hemorrhagic and necrotic degeneration can also be found and signal characteristics in T1-weighted MR vary accordingly, from low- to intermediate- and high-intensity signals [ 11 , 12 , 13 ]. Metastases are usually pulmonary, however, extra-pulmonary metastases can occur, with lymph node involvements seen more often than in other soft tissue sarcoma (STS) subtypes [ 14 , 15 ].…”

High-dose-rate interstitial brachytherapy as a suitable option for metastatic extraskeletal myxoid chondrosarcoma – a case report

“…Extraskeletal myxoid chondrosarcoma can develop distant metastasis, similar to other STS. The most common metastasis site is the lung, although lymph node metastases are seen more often in EMC than in other STS sub-types [ 15 , 16 ]. Recurrent or metastatic STS is treated using a standard palliative EBRT regimen (for example, 30 Gy/10 frac-tions, 20 Gy/5 fractions, etc.).…”

Case Report: Gene Heterogeneity in the Recurrent and Metastatic Lesions of a Myxoid Chondrosarcoma Patient With Aggressive Transformation

“…EMC was a low-grade malignancy primary affecting the limbs and limb girdles while seldomly affecting the foot, with 5-years, 10-years, and 15-years survival rates of 82–90%, 65–70%, and 58–60%, respectively ( Meis-Kindblom et al, 1999 ; Stacchiotti et al, 2020 ). Despite the indolent behavior and a long clinical course, EMC has a high rate of local recurrences and distant metastasis ( Chiusole et al, 2020 ). Here we report a rare EMC deriving from the foot, which developed aggressive during the clinical course with recurrences and multiple metastases ( Figure 1 ).…”

“…This neoplasm is always described as low-grade tumor because it has an indolent course throughout the prolonged natural history. Nevertheless, recent studies revealed that EMC may be a more aggressive malignant tumor neoplasm owing to the high rate of local recurrence and distant metastasis even after radical resection ( Meis-Kindblom et al, 1999 ; Hisaoka and Hashimoto, 2005 ; Chiusole et al, 2020 ). For patients with repeated recurrences, the interval between recurrences was gradually shortened, suggesting that the EMC may become more invasive after relapsed ( Paioli et al, 2021 ).…”

“…For patients with repeated recurrences, the interval between recurrences was gradually shortened, suggesting that the EMC may become more invasive after relapsed ( Paioli et al, 2021 ). Several clinical features have been shown to be associated with the poor prognosis, including age, tumor size, tumor location, high grade, metastasis, and inappropriate initial surgery ( Meis-Kindblom et al, 1999 ; Kawaguchi et al, 2003 ; Chiusole et al, 2020 ; Paioli et al, 2021 ). However, the prognostic significance of these factors vary in different studies and the mechanism of invasive progression of EMC was seldomly discussed.…”