Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors arising in the wall of the gastrointestinal tract. They are rare, with an overall incidence of 6.8 cases per million persons in the United States each year.1 However, in patients aged <40 years, there are only 2.6 cases per million persons annually.2 Insertions, deletions, and missense mutations in the KIT and PDGFRA oncogenes cause approximately 85% of GISTs, whereas BRAF V600E missense mutations lead to approximately 1% of cases.3 We and others recently reported that a small subset of GISTs also occur due to kinase fusions (eg, ETV6-NTRK3, FGFR1-TACC1, FGFR1-HOOK3), a previously unappreciated mechanism for GIST tumorigenesis.4–7
GISTs amenable to resection are generally managed surgically, and patients with tumors harboring high-risk features are recommended to receive adjuvant therapy with imatinib, a tyrosine kinase inhibitor that targets the KIT and PDGFRA oncoproteins, but not BRAF, NTRK3, or FGFR1. Risk of recurrence is determined by tumor size, location, mitotic rate, and tumor rupture. Prediction tools, such as the modified NIH method,8 the Armed Forces Institute of Pathology (AFIP; Miettinen criteria),9 and the Memorial Sloan Kettering Cancer Center nomogram,10 stratify risk and predict the likelihood of tumor recurrence after complete resection. If a tumor is considered high risk, adjuvant imatinib is typically recommended based on the ACOSOG Z900111 and SSG XVIII/AIO12 trials, whose cumulative results demonstrated improved relapse-free survival and overall survival (OS) with at least 3 years of adjuvant imatinib. In the era of precision oncology, these recommendations should be provided in conjunction with genomic analyses that may predict imatinib sensitivity or resistance in order to maximize efficacy and minimize toxicity.
This case presentation reminds clinicians that GIST can occur in women of childbearing age and should remain in the differential diagnosis of an adnexal mass. We also review the genomics of GIST, and present a novel tumor mutation to highlight the emerging importance of molecular profiling in dictating personalized cancer treatment, especially during pregnancy.
Dr. Chmielecki has disclosed that she is an employee of AstraZeneca and has equity in Foundation Medicine and AstraZeneca. Dr. Sicklick has disclosed that he receives grant or research support from Foundation Medicine and Novartis Pharmaceuticals, and serves as a consultant for Loxo Oncology. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
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