Initial radiographs demonstrated an aggressive lesion in the
Initial radiographs demonstrated an aggressive lesion in the medial condyle of the distal right femur (Figs. 1A and B). CT obtained to characterize matrix showed an aggressive lesion with a focus of dense linear matrix (Fig. 2) with intervening lucent areas. The lesion was felt to be indeterminate at the time, with overall features suspicious for an aggressive lesion such as a high-grade osteosarcoma. Much less likely considerations included secondary malignant degeneration of a cartilaginous lesion such as an enchondroma into chondrosarcoma, given the question of possible cartilaginous component on CT. Whole body Tc-99 MDP bone scan demonstrated abnormal uptake in the right femoral lesion, but no other abnormal areas (Fig. 3). A subsequent MRI demonstrated a large soft tissue mass associated with the osseous lesion and abnormal marrow signal intensity extending to the proximal femoral neck (Figs. 4A–C). Staging PET scan demonstrated metastasis to the lungs and right inguinal and external iliac lymph nodes (Fig. 5).
The incisional biopsy specimen from the right leg consisted of multiple fragments of pink tan soft tissue with focal calcifications. Hematoxylin and eosin stained microscopic sections demonstrated epithelioid SEA0400 in cords and solid sheets amid a myxoid to cartilaginous stroma (Fig. 6A and B). Focal areas showed bone arising from endochondral ossification of the cartilage. The tumor cells expressed cytokeratins and S-100. Cytogenetic analysis was remarkable for a clonal t(X;19)(q13;p13.3) translocation. Bone marrow aspirate also showed metastatic disease.
This patient was treated with vincristine, adriamycin, and cytoxan, alternating with ifosfamide and etoposide, following the Children\'s Oncology Group Ewings sarcoma protocol AEWS-0031. The patient initially showed decrease in size of the knee mass, radiographic resolution of most of the pulmonary nodules, and resolution of the bone marrow disease by morphologic assessment of a bone marrow aspirate 2 months later. However, he developed a new right mid-thigh lesion the following month, proven to be malignant mixed tumor by fine needle aspiration. He then developed numerous firm pink keloid-like nodules on the right knee and leg, the largest being 2cm in height. Subsequent follow up radiographic and PET imaging (Fig. 6) showed progression of disease. He received additional treatment with an aurora kinase inhibitor and subsequently with the combination of irinotecan, temozolomide, and temsirolimus, but he died of progressive disease 7 months from diagnosis.
Discussion Although the nomenclature is evolving, the term “mixed tumor” refers to the presence of both epithelial and mesenchymal, often chondroid, elements . These tumors most commonly occur in the salivary glands, where they are known as “pleomorphic adenomas” and exhibit benign characteristics. Less commonly, mixed tumors occur as primary skin neoplasms and are termed “chondroid synringomas”, and may exhibit more aggressive clinical behavior [3,6,7]. The origin of these tumors in somatic soft tissue and bone is controversial, but recent evidence suggests rearrangement of the EWSR1 gene at 22q12 is common in this category  The present case demonstrated typical histologic and immunophenotypic characteristics of mixed tumor, and a novel t(X;19)(q13;p13.3) translocation. It remains to be seen whether t(X;19) produces a fusion gene with analogous pathogenetic mechanisms to the more common EWSR1 fusions. Malignant forms of mixed tumor can occur at any site but primary MMT of bone is extremely rare [4,5,1]. Of the reported cases of primary MMT of bone, the average age at presentation ranged between 25 and 44 years . The limited number of reports of this entity in older adult patients occurring in other sites suggests that this lesion may have a period of relatively slow, indolent growth followed by more rapid progression of local invasion and distal metastasis . Treatment recommendations for this lesion are not specific to this tumor, but suggest it be treated as a high-grade sarcoma; there are no reports, however, of a successful treatment regimen.