Gastrointestinal Stromal Tumor With Chondrosarcomatous Dedifferentiation Following Imatinib Therapy

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, followed by schwannomas, lipomas, leiomyomas, and vascular tumors. They arise more often in the stomach, followed by the small bowel, esophagus, and rectum. Imatinib mesylate, a tyrosine kinase inhibitor with activity against ABL, BCR-ABL, platelet-derived growth factor receptor-alpha (PDGFRA), and c-KIT (CD117), constitutes the cornerstone of treatment for inoperable or metastatic GIST. Cases showing disease progression or resistance to imatinib mesylate may retain their morphology or present unusual morphologic and immunohistochemical characteristics. We herein describe a case of a 67-year-old patient with a previous history of GIST of the stomach, with local recurrence, who was admitted with a workup of lung nodule on chest computed tomography as part of the routine follow-up. The nodule was resected which showed a malignant tumor composedof epithelioid cells, with an abrupt transition to chondrosarcoma. Epithelioid cells were immunostained for CD117, DOG1, and Vimentin, whereas chondrosarcomatous cells expressed only Vimentin. These findings were consistent with metachronous pulmonary metastasis of the previously diagnosed GIST with chondrosarcomatous dedifferentiation. No KIT or PDGFRA mutation was detected. A review of all accessible pertinent papers disclosed 26 similar cases with unusual morphological and immunohistochemical findings, either post-imatinib treatment or, less commonly, de novo, with heterogeneous differentiation. Awareness of the histological and immunohistochemical changes in GISTs post imatinib therapy is essential to avoid a severe diagnostic pitfall.