Henna Xing, D. Karikios and C. P’Ng
Background: A minority (4%-15%) of Gastrointestinal Stromal Tumours (GISTs) lack common gene mutations and undergo dedifferentiation, either de novo or following chronic imatinib treatment, exhibiting remarkable histological and immunophenotypic changes and possible heterologous differentiation. Given the lack of the usual immunophenotype and molecular signature, dedifferentiated GISTs represent a diagnostic challenge and potential pitfall with no concrete guidelines for its management and associated poor prognosis. In our patient’s case, molecular testing also detected a rare somatic TP53 mutation, making it an extremely rare form of an already rare tumour. Aim: To illustrate dedifferentiated GIST as a potential diagnostic pitfall and clinical challenge through the case of a 41-year-old, imatinib-naïve male who presented with upper gastrointestinal bleeding and was subsequently diagnosed with dedifferentiated GIST. Methods: The dedifferentiated component showed a loss of CD117 and DOG-1 expression that was otherwise present in the conventional component, thus confirming the diagnosis. Further immunohistochemistry excluded other high-grade spindle cell neoplasms, and molecular testing confirmed our diagnosis. Results and Conclusion: This case illustrated the necessity of sufficient sampling to successfully identify and diagnose a dedifferentiated GIST, and the importance of considering dedifferentiated GIST as a differential diagnosis when high-grade spindle cell neoplasms occur in the gastrointestinal tract as they can be erroneously misdiagnosed due to their heterogenous morphology, lack of CD117 and DOG-1 staining, and rarity. This case also demonstrated the need for concrete guidelines and further research into the clinical presentations, diagnostic and management pathways to improve patients’ quality of life, treatment success and prognosis.