Esophageal MKRN1::BRAF fusion GIST mimicking leiomyoma: Surgical management via enucleation

Background Gastrointestinal Stromal Tumors (GISTs) of the esophagus are exceptionally rare, representing less than 2% of all GISTs. While most are driven by KIT or PDGFRA mutations, a rare subset of “wild-type” GISTs harbor BRAF fusions. These tumors present a major diagnostic challenge, as they typically lack KIT expression by immunohistochemistry and may show weak or multifocal expression of DOG1 and, as in the present case, DOG1 expression may be lost altogether. Case Presentation We report the case of a 41-year-old male presenting with paroxysmal epigastric pain. Imaging revealed a 41 × 31 × 49 mm solid-cystic mass in the lower esophagus. Initial biopsies showed a spindle cell proliferation with an atypical immunohistochemical phenotype. Given this diagnostic uncertainty, expert pathological review was obtained at two referral centers in France. This review revealed a profile negative for KIT but positive for smooth muscle actin (SMA) and h-caldesmon, initially suggesting a leiomyoma. However, retained diffuse CD34 positivity prompted molecular testing. Targeted RNA-sequencing identified an MKRN1::BRAF fusion. The patient underwent a right transthoracic extramucosal enucleation. Final pathology confirmed an R0 resection of a 5-cm tumor with intermediate risk of recurrence. Conclusion MKRN1::BRAF fusion GISTs represent a distinct molecular entity with important diagnostic and therapeutic implications. This case supports enucleation as a feasible organ-preserving option in selected well-circumscribed esophageal GISTs when an R0 resection can be achieved without tumor rupture, sparing patients the morbidity associated with esophagectomy; longer-term surveillance is needed to confirm durability of this outcome.