Malignant fibrous histiocytoma phenotype in pleomorphic sarcoma differentiation in recurrent disease

Two cases of pleomorphic sarcoma with malignant fibrous histiocytoma phenotype that recurred following therapy with a distinctly different, more mature histologic appearance and immunohistochemical profile are reported. The first case recurred predominantly as extraosseous osteosarcoma at the same site 17 months after wide local excision. The second case recurred as widespread pulmonary, mediastinal, and hepatic metastatic disease 5 years after wide local excision and adjuvant local radiotherapy and chemotherapy with doxorubicin hydrochloride (Adriamycin) and cyclophosphamide (Cytoxan). Fine-needle aspiration of the pulmonary metastatic lesions showed predominantly spindle cells without any large, pleomorphic giant cells typical of malignant fibrous histiocytoma. The patient was treated by radiotherapy to the lung and mediastinum and by chemotherapy with ifosfamide and mesna. Biopsy of a metastatic scrotal skin nodule 9 months later showed a malignant spindle cell lesion with the histologic appearance and immunohistochemical phenotype of leiomyosarcoma. Retrospective immunohistochemical evaluation of the primary tumor showed focal desmin expression, suggesting focal leiomyosarcomatous differentiation. However, the large proportion of the primary tumor had the phenotype of malignant fibrous histiocytoma. These two cases illustrate an unusual finding of "differentiation" rather than "dedifferentiation" in a recurrent sarcoma. The transformation to osteosarcoma and differentiated leiomyosarcoma demonstrates the potential for phenotypic changes in soft-tissue sarcomas and suggests that the malignant fibrous histiocytoma phenotype and more-differentiated sarcomas such as extraosseous osteosarcoma or leiomyosarcoma are related in a common pathway in differentiation from a primitive mesenchymal stem cell.