Extraskeletal myxoid chondrosarcoma (EMC) is a rare indolent sarcoma of the soft tissue ^[1]. It is twice as likely to be diagnosed in males, typically at 50–60 years of age [2, 3] and is most commonly identified in the proximal lower extremity and limb girdle ^[4]. Approximately half of patients with this neoplasm develop a metastasis ^[5], most frequently to the lung, followed by soft tissue and bone, typically between 6 and 15 years post-diagnosis ^[6]. Diagnoses of these neoplasms can be delayed because of their indolent nature and can have a propensity for misdiagnosis because of their rare and generally asymptomatic presence, especially when found in atypical locations like the foot [7, 8, 9]. We present the following case of a traumatic toe injury that was later diagnosed as an EMC.

An 80-year-old Caucasian female presented to the clinic with complaints of the left 3^rd toe pain and swelling that began after a traumatic impact to the foot while walking. The patient was initially seen in the emergency department and referred for orthopedic evaluation of a questionable non-displaced fracture seen on radiographs. Her medical history included stage T1a endometrial cancer treated with hysterectomy and bilateral salpingo-oophorectomy and invasive ductal breast cancer (estrogen receptor positive) treated with radiation therapy and long-term use of selective estrogen receptor modulators. Notable family medical history includes colon cancer in her mother and prostate cancer in her father. Radiographs demonstrated a fracture through the mid-portion of the third proximal phalanx with a lytic lesion, cortical erosion, and soft-tissue shadowing (Fig. 1). After initial evaluation, magnetic resonance imaging (MRI) was ordered because of the lesion observed on radiographs. MRI with contrast similarly showed an aggressive appearing lytic expansile lesion of the third toe measuring 15×13×14 mm (Fig. 2) expanding through the cortex medially, approximately 14 mm, beyond the cortex with intense uniform post-contrast enhancement and adjacent soft-tissue enhancement. This prompted a referral to orthopedic oncology, and subsequent radionuclide bone scan imaging which showed enhancement at the lesion in question but no concern for metastasis. An open biopsy of the left third toe was performed and curettings of the soft-tissue component were collected for frozen sections. Once frozen section analysis confirmed the presence of carcinoma, wide resection was performed with a third toe amputation. There was no evidence of residual tumor following the procedure. Two months following the amputation, a PET scan and chest computer tomography showed no evidence of metastasis. Follow-up at 2 years showed no evidence of tumor recurrence or metastasis (Fig. 3). Microscopic analysis of the biopsy specimen showed the tumor consisted of anastomosing cords of reniform cells characterized by a thin rim of eosinophilic cytoplasm and present within a myxoid stroma. Nuclei were ovoid with prominent nuclear grooves and no atypical mitotic figures. There were no hyaline chondroid or osteoid matrix, vascular channels or differentiation, or cross striations identified. Immunohistochemical analysis revealed tumor cells focally positive for S100 and KIT proteins, whereas negative for HMB-45, MART-1, pankeratin, GATA3, CAM5.2, CK5/6, 34betaE12, CK7, desmin, EMA, WT-1, and SOX-10. Metastatic breast carcinoma was ruled out by negative GATA-3, EMA, and keratin staining, and myxofibrosarcoma was ruled out because of insufficient cell spindling. The diagnosis of EMC was confirmed from the pathognomonic NR4A3 rearrangement at 9q22.33 ^[10] demonstrated by fluorescent in situ hybridization.

To the best of our knowledge, only 19 cases of EMC in the foot have been previously discussed in the literature [7, 9, 11]. A unique feature of this case was that the EMC was identified incidentally in a patient with a history of the previous malignancies including endometrial cancer and invasive ductal breast carcinoma. The erosive changes and osseous lesions were initially misdiagnosed as a fracture. The indolent nature of EMC that has been demonstrated indicates that it should be considered in the differential diagnosis of incidentally identified masses in the soft tissue of the distal extremities and osseous abnormalities seen on radiographs. This tumor presented with typical histological features of EMC: Elongated malignant cells characterized by ovoid nuclei within eosinophilic cytoplasm and arranged in a cord-like fashion within a myxoid stroma ^[4]. S-100 positivity is considered non-specific for EMC ^[9] but was observed. Negative keratin staining and the NR4A3 rearrangement were characteristic of this case and are confirmatory for EMC ^[12]. The ideal imaging technique for EMC is MRI ^[12]. Once a diagnosis of EMC is confirmed through biopsy, the curative treatment is a complete resection of the lesion, and potential post-operative radiation ^[7]. For this case, identification of the lesion using MRI and complete surgical resection without radiation therapy resulted in symptomatic improvement without metastasis. No chemotherapeutic was used and is known to be generally ineffective for EMC ^[7]. Therefore, the presented case further suggests that the diagnostic and treatment protocol for EMC consisting of MRI, biopsy, and complete surgical resection is effective. Per National Comprehensive Cancer Network recommendations for chondrosarcomas, follow-up should include repeat imaging of the chest and original tumor site, along with complete blood count and physical exam, every 3–6 months for the first 5 years and then annually, ideally up to 10 years following treatment ^[13].

EMC, a rare soft-tissue mass of the bone, can present in atypical locations and is predisposed to misdiagnosis secondary to its indolent and asymptomatic qualities. Radiographic assessment of osseous and soft-tissue abnormalities, including those in the distal lower extremities, should include EMC in differential diagnosis. Successful treatment of this patient with surgical resection is consistent with previously published cases.

Incidentally identified soft-tissue masses of the bone should be evaluated for EMC. This would allow for improved diagnostic accuracy and prompt initiation of treatment. Future cases and their treatments should continue to be reported to allow for an analysis of their unique clinical presentations and treatment outcomes.