Background: The immunohistochemical hallmarks of gastrointestinal stromal tumors (GISTs) are positivity for CD117 (c-kit) and CD34; however, CD117 is not specific for GISTs, and the list of CD117+ tumors/tissues is increasing. Also, MDM2 is known to be amplified in several types of mesenchymal tumors, including liposarcoma.
Methods: We report a spindle cell sarcoma arising in the mediastinum that morphologically and immunohistochemically mimicked GIST to illustrate the potential diagnostic pitfalls of ancillary studies in sarcoma and their appropriate use in conjunction with clinical content. Clinical information was obtained from electronic medical databases. Cytological, histological, and ancillary studies were retrieved from the archives of the Department of Anatomic Pathology at Moffitt Cancer Center. Literature of the last 20 years was reviewed. The role of biomarkers and their molecular testing in the prognosis and prediction of GIST is also discussed.
Results: A 75-year-old woman with a history of well-differentiated liposarcoma of the trunk/inguinal canal 5 years earlier developed a 5.5-cm heterogeneously enhancing mediastinal mass by computed tomography. Fine-needle aspiration biopsy revealed spindle cells with moderate pleomorphism and immunohistochemically reactive to CD117 and CD34 suggestive of GIST, but the clinical picture was unusual for GIST. Mutational analyses for KIT and platelet-derived growth factor receptor alpha (PDGFRα) were negative; DOG1 was not immunoactive, and this was believed to rule out GIST. An additional study of MDM2 by fluorescent in situ hybridization was positive, suggesting that this tumor was a dedifferentiated liposarcoma vs a spindle cell sarcoma not otherwise specified.
Conclusions: CD117+/CD34+ sarcoma is not diagnostic for GIST. KIT and PDGFRα mutational analyses are important in confirming a diagnosis of GIST and predicting its response to imatinib therapy. MDM2+ sarcoma is not diagnostic for liposarcoma. Although MDM2 is almost always positive in well-differentiated liposarcoma, which is useful in differentiating benign from atypical/well-differentiated lipomatous tumor, it should not be used in differentiating liposarcoma from other sarcomas.