Introduction Scott Kilpatrick and Omar Sangueza

Due to their absolute rarity (< 1% of all malignant neoplasms), compounded by the realization that a malignant diagnosis often leads to adverse consequences (i.e. amputation), the diagnosis of bone and soft tissue tumors has always been difficult. Further apprehension may be related to the fact that many sarcomas (and pseudosarcomas) affect children. In this brief presentation, we will present to you a series of ten cases, illustrating important but often common differential diagnostic dilemmas, providing practical guidelines for their resolution. When possible, correlation with clinical and radiologic features cannot be over-emphasized. Some neoplasms are virtually non-existent in children (e.g. liposarcoma) while others tend to be extremely rare in adults (e.g. lipoblastoma). Radiographs, including computed tomography (CT) scans and magnetic resonance imaging (MRI), provide information regarding anatomic location, size, and bony involvement, homogeneity vs. heterogeneity, content, and relationships to neurovascular structures. Combining clinical and radiographic information helps the pathologist provide a more accurate and definitive diagnosis. It is our opinion that ancillary studies, such as immunohistochemistry, are useful diagnostic aids but should never supplant thoughtful scrutiny of pertinent clinical and morphologic features. Following intensive scientific investigation, the initial enthusiasm associated with the discovery of specific immunohistochemical and molecular markers is virtually always replaced by a more realistic perspective. The immunohistochemical marker CD99, initially reported as highly specific for Ewing's sarcoma, has now been convincingly documented in most cases of mesenchymal chondrosarcoma, synovial sarcoma and a few examples of small cell osteosarcoma, rhabdomyosarcoma and desmoplastic small round cell tumor. [1, 2, 3, 4] Cytokeratin positivity is sometimes observed in rhabdomyosarcoma. [5] Desmin, an immunohistochemical marker usually associated with rhabdomyosarcoma, is often expressed by the blastemal portion of Wilm's tumor. [6] Cytogenetic and molecular analyses have yielded similar surprisingly nonspecific results. The most frequent Ewing's sarcoma translocation, t(11;22)(q24;q12) with the EWS-FLI1 fusion product, has been reported in phenotypically classic examples of mesenchymal chondrosarcoma, embryonal and alveolar rhabdomyosarcoma, polyphenotypic tumor of childhood, and neuroblastoma. [7, 8, 9, 10] Both the EWS-FLI1 and the EWS-ERG fusion transcripts have been described in cases of intra-abdominal desmoplastic small round cell tumor. [11, 12] For these reasons, immunohistochemical and molecular studies should be considered ancillary not definitive tests. The "gold standard" for diagnosis remains light microscopy. This should not imply that knowledge and application of these ancillary tests are not helpful for the pathologist faced with a challenging case, but such data should only be interpreted with the complete knowledge of the pertinent clinical and microscopic features. As summarized by Dehner, "…the gold standard for pathologic diagnosis is predicated on the microscopic features of the tumor. 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