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Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma. Surgery is the cornerstone of the management of this tumour. The response rate to chemotherapy has been very poor; with the exception of one reported case which showed promising results, overall results are disappointing because no significant radiologic or clinical responses have been noted with chemotherapy. Here we report the case of a 15-year-old girl who presented with extraskeletal myxoid chondrosarcoma in the sacrococcygeal region which was regarded as unresectable. After four cycles of chemotherapy the mass showed complete remission which has lasted >6 months.
Extraskeletal myxoid chondrosarcoma (EMC) is an intermediate sarcoma with indolent clinical features, yet a high tendency for recurrence and development of distant metastases. Wide excision is the primary approach to the management of localised EMC. For unresectable or metastatic EMC, systematic treatment such as chemotherapy has a poor response rate. Here we report an unresectable case of EMC which showed complete remission following systematic chemotherapy.
A 15-year-old girl with an unremarkable past medical history presented with signs of pain and a palpable mass in the sacrococcygeal region for nearly half a year, but no other complaints of discomfort. The local hospital’s preliminary diagnosis was a cyst, and undertook a simple excision. However, after the operation, the wound did not heal and continued to discharge. The patient also suffered from a high grade fever for several weeks. To seek relief, she visited another hospital and underwent a magnetic resonance imaging (MRI) examination. Her doctors identified a large mass (9.5×5.0 cm in size) in the sacrococcygeal region (fig 1, left panel). Subsequently, the patient underwent incisional biopsy, and the pathologist diagnosed the mass as EMC. The pathology report was also sent to another expert pathologist for diagnosis reconfirmation and opinion. The tumour tissues were also analysed by immunohistochemical techniques (fig 2).
Our bone and soft tissue sarcoma collaborative network, comprising pathologists, radiologists, surgeons, radiation therapists and medical oncologists, deemed that the mass was too large and too close to the rectum, making it intractable for surgery. Because radiotherapy of this area might incur severe side effects, we recommended neoadjuvant chemotherapy before surgery. The patient was administered a high dose of ifosfamide (5 g) by continuous intravenous infusion for 3 days, in combination with an intravenous infusion of adriamycin (100 mg) on day 1. Upon completion of the first round of chemotherapy, the patient’s fever settled down, the wound started to heal gradually, and the tumour mass reduced in size. After another three cycles of chemotherapy (same protocol as above, every 3 weeks), the physical mass had completely disappeared, and the patient’s quality of life returned to normal. Subsequent MRI examination of the patient failed to show any tumour mass (fig 1, right panel), indicating complete remission. This remission has now lasted for 6 months, and further follow-up is planned.
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,5 no chemotherapeutic agent or combination of agents have been demonstrated to achieve durable efficacy against EMC to date (table 1). 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.
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.
This work was contributed from departments of pathology and general surgery (Tumor hospital of Fudan University shanghai China); radiotherapy, general surgery and medical oncology of Shanghai Sixth People’s Hospital.
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.