Soft tissue sarcomas are a diverse group of rare malignancies originating from mesenchymal tissue. As a rare type of soft tissue sarcoma, EMC was defined as an independent clinical pathology by Enzinger and Shiraki in 1972.1
Cytogenetic studies have demonstrated the association of EMC with recurrent chromosomal translocations t(9;22)(q22;q11-12) and t(9;17)(q22;q11) that generate EWS/CHN and RBP56/CHN fusion genes, respectively.2
Ultrastructural studies of EMC have also provided evidence of neuroendocrine differentiation markers, such as class III b-tubulin and microtubule associated protein-2.3
The estimated incidence of EMC is 2.5% among all soft tissue sarcomas. It occurs commonly in middle aged adults and is usually developed in the deep parts of proximal extremities and limb girdles.4
McGrory et al
suggested that EMC is an intermediate grade neoplasm with a tendency toward recurrence and metastasis.5
In fact, about half of the EMC cases would develop metastasis, and the most common metastatic sites are lung, soft tissue, lymph node, bone and brain.6
As identified in a multivariate analysis, Meis-Kindblom et al
concluded in their review of 117 EMC cases that clinical features, such as older patient age, larger tumour size, and tumour location in the proximal extremity or limb girdle, are adverse prognostic factors. Moreover, the survival of EMC patients is adversely affected by metastasis, but not local recurrence.6
Surgery is the principle treatment modality for soft tissue sarcoma. Several clinical studies have reported the aggressive control of localised EMC as a primary management approach.6–8
However, despite seemingly promising local treatment, there is still a significant portion of EMC patients whose tumour is unresectable or has already metastasised to distant organs. For these patients, the treatments are palliative only, and the majority of patients with metastatic soft tissue sarcoma are incurable, although surgical resection of pulmonary metastases may render selected patients free of disease.
The response of advanced or metastatic soft tissue sarcoma to chemotherapy is often unsatisfactory. There is an updated meta-analysis confirming the marginal efficacy of chemotherapy in localised resectable soft tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. Most patients receiving a standard first line doxorubicin containing regimen may have a response rate of 15–30%.9
Although these benefits can be further improved with the addition of ifosfamide, such a combination regimen must be carefully weighed against associated toxicities. According to a recent study of patients with metastatic soft tissue sarcoma, routine addition of ifosfamide to standard doxorubicin containing regimens is not recommended, as compared with doxorubicin based monotherapy. However, it is reasonable to employ this combination in patients with symptomatic, locally advanced or inoperable soft tissue sarcoma because their combined effects may render such tumours resectable.10
To the best of our knowledge, apart from a single complete remission case reported by McGrory et al
no chemotherapeutic agent or combination of agents have been demonstrated to achieve durable efficacy against EMC to date (). For example, Saleh et al
failed to observe any significant responses in seven patients treated with chemotherapy.11
Consistent with this result, Patel et al
also reviewed their experience in treating EMC over the past three decades. With a median of four chemotherapy cycles, no objective response was noted in 10 patients who received mainly doxorubicin and dacarbazine based regimens, or in three patients treated with ifosfamide as second line chemotherapy.12
It was not until 1995 that Rubinger et al
documented a partial response to interferon-α-2b with stable residual disease which lasted for 12 months after the completion of therapy.13
Subsequently, McGrory et al
found that two out of six patients responded to multi-agent chemotherapy for systemic disease (one complete response and one partial response). These patients were followed for up to 6 years with no sign of disease progression. Unfortunately, the protocols regarding the use of these agents were unavailable.5
In a recent study conducted by Drilon et al
, 21 patients received 32 evaluable courses of chemotherapy, with doxorubicin containing regimens comprising the largest subgroup. No significant radiologic or clinical responses were noted, however.7
Based on these data, it is apparent that long term success in the treatment of patients with unresectable or metastatic EMC is currently limited due to the lack of effective chemotherapy regimens.
Outcomes of chemotherapy for extraskeletal myxoid chondrosarcoma
Development of effective chemotherapy is urgently needed to prolong the long term survival of these patients. In the case reported here, we attempted to administer a high dosage of ifosfamide (10 g/m2) and adriamycin (80 mg/m2) in a combined regimen to alleviate an inoperable EMC. To our surprise, after four cycles of chemotherapy, the tumour showed complete remission which has endured for more than 6 months—an astonishing clinical outcome for a patient with EMC. A close follow-up is underway to determine whether this strategy can indeed offer a long period of disease-free survival. Although one might argue that such fascinating results obtained from a single exceptional case is possibly due to random chance or other unique patient specific factors, our experience nevertheless opens up new avenues for devising current treatment strategies, especially for patients with unresectable or metastatic EMC.
- The main finding of this report is the dramatic results obtained with the chemotherapeutic protocol of high dosage ifosfamide and adriamycin in combination that was used to treat a patient with extraskeletal myxoid chondrosarcoma.
- We emphasise the need to try this chemotherapeutic protocol to treat this particular cancer type, in an effort to achieve an optimal result.