Subclassification of pleomorphic sarcomas: How and why should we care?

Pleomorphic sarcomas are a heterogeneous group of mesenchymal neoplasms with widely varied clinical behavior but overlapping histologic appearances. The following guidelines are helpful when approaching the diagnosis of a pleomorphic sarcoma. (1) Be aware of the relative incidence of the various sarcoma types: several pleomorphic sarcomas are relatively common (e.g., dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma), whereas others are exceptionally rare. (2) Pay attention to anatomic location: some pleomorphic sarcomas have a predilection for somatic soft tissues, especially the thigh (e.g., undifferentiated pleomorphic sarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma), whereas other pleomorphic sarcomas most often arise in the retroperitoneum (e.g., dedifferentiated liposarcoma). (3) Carefully sample the resection specimen, paying particular attention to areas with differences in gross appearances (e.g., fleshy, fibrous, mucoid, or gritty). (4) Search for histologic clues (i.e., myxoid stroma, lipoblasts, and osteoid matrix, in order to diagnose myxofibrosarcoma, pleomorphic liposarcoma, and extraskeletal osteosarcoma, respectively); these critical diagnostic features may be limited in extent. (5) Apply immunohistochemistry judiciously, after generating a differential diagnosis; always exclude metastatic sarcomatoid carcinoma and melanoma before diagnosing a pleomorphic sarcoma. This review will present an approach to the diagnosis of pleomorphic sarcomas, emphasizing differential diagnosis and the application of ancillary studies (immunohistochemistry and FISH), when relevant.