{"paper_id":"df00ae1c-e3ab-4896-b0e4-a6710820666b","body_text":"Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors originating predominantly in the gastrointestinal tract, particularly in the stomach and small intestine. Extra‐gastrointestinal GISTs, although rare, may occur in atypical locations such as the pelvis, where they can closely resemble gynecologic tumors. This case report highlights a patient whose large pelvic GIST presented similarly to a primary ovarian tumor (OT), complicating the diagnostic and therapeutic approach.\nSolid‐organ transplant recipients have an approximately twofold to fourfold higher overall cancer risk than the general population, largely attributed to chronic immunosuppression and impaired immune surveillance [ 1 ,  2 ]. Although uncommon, GIST has been reported in transplant patients in the literature (≈16 cases collated in a recent review) [ 3 ]. Our case adds to this small body of evidence by describing an extra‐GI pelvic GIST in a patient with dual solid‐organ transplants. We also discuss transplant‐specific diagnostic and pharmacologic considerations relevant to this presentation.\n\nA 39‐year‐old female with a history of Type 1 diabetes mellitus (DM) complicated by end‐stage diabetic nephropathy, requiring kidney transplantation and immunosuppressive therapy, as well as a liver transplant due to alcoholic liver disease, presented with several months of progressive abdominal bloating and discomfort. Initial gynecological evaluation included a pelvic ultrasound, which revealed a large right adnexal mass measuring 18.8 × 12.8 × 9.8 cm, indicative of a possible ovarian involvement. Subsequent CT imaging demonstrated a complex pelvic tumor exerting mass effect on surrounding organs, concerning for a gynecologic malignancy (Figure  1 ).\nCoronal image of CT scan demonstrating large midline lower abdomen/pelvic mass with cystic areas measuring up to 19 × 12 × 13 cm, with mass effect on pelvic organs and bowel loops.\nThe patient underwent in‐depth endoscopic evaluation to identify the primary tumor site, which was unrevealing. After counseling, the patient elected for a total abdominal hysterectomy–bilateral salpingo‐oophorectomy (TAH‐BSO); this was based on her strong family history, no desire for future fertility, and avoidance of reoperation. She subsequently underwent exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and extensive tumor debulking. Intraoperative findings revealed a large right pelvic mass with extensive adhesions, as well as friable tumor implants on the rectal surface and small bowel, along with mesenteric lymphadenopathy. Postoperative pathology confirmed a diagnosis of high‐grade GIST with epithelioid features, positive for DOG1 and CD117, and a Ki 67 index greater than 30% (Figure  2 ). The tumor was classified as pT4 pN0, indicating no lymph node involvement. Margins were reported as no gross residual disease (macroscopic cytoreduction) without implying R0. Postsurgical complications included recurrent gastrointestinal bleeding, which was managed endoscopically. Molecular testing of the tumor identified a KIT Exon 9 mutation, leading to the initiation of imatinib therapy, which was subsequently titrated based on the patient′s tolerance.\nCross‐section of pathology images showing: (a) interface of spindle neoplasm with areas of tumor cell necrosis and hemorrhage; (b) increased mitotic activity, including atypical mitotic figures; (c) DOG1 positivity; (d) CD 117 positivity.\n(a)\n(b)\n(c)\n(d)\n\nGISTs are rare neoplasms, representing about 1% of gastrointestinal tumors yet making up 80% of mesenchymal cancers. Postulated to arise from the interstitial cells of Cajal, they can develop in standard digestive tract locations such as the stomach, small and large intestines, or less common sites like the omentum, mesentery, retroperitoneum, and pancreas. When arising from extra‐gastrointestinal sites like the ovaries, GISTs can mimic primary OTs or metastatic ovarian tumors (M‐OTs). This is particularly true when they present with significant mass effect or abdominal discomfort, and often lead to a misdiagnosis as gynecologic neoplasms [ 4 – 6 ]. Table  1  below provides a differential diagnosis of pelvic masses with an emphasis on GIST.\nDifferential diagnosis of pelvic mass with emphasis on gastrointestinal stromal tumor (GIST).\nPrognostic markers for ovarian GIST include younger age and nonmetastatic disease. GISTs mimicking OTs have been noted to occur more frequently in younger women and are less likely to be associated with elevated tumor markers, indicating a better prognosis compared with older women with M‐OTs, who may exhibit elevated markers and a worse prognosis [ 1 ]. Additionally, a systematic review found that patients with metastatic ovarian GISTs (GIST M‐OTs) had significantly higher recurrence and mortality rates compared with those with GISTs mimicking primary ovarian tumors (GIST‐OTs), with recurrence occurring in 54.5% of GIST M‐OT patients versus only 6.8% of GIST‐OT patients [ 4 ]. Prognosis was also noted to be significantly better in cases with complete resection, achieved in over 90% of GIST‐OTs but in only about 57% of GIST M‐OTs [ 4 ].\nImmunohistochemical profile, particularly DOG1 and CD117 positivity, is crucial in differentiating GISTs from other tumors [ 7 ,  8 ]. Beyond immunohistochemistry, molecular profiling plays a key role [ 9 ]. Most GISTs harbor activating mutations in  KIT  (Exon 11 being the most common) or  PDGFRA , which drive tumorigenesis and influence response to tyrosine kinase inhibitors, such as imatinib. Additionally, recurrence risk is significantly impacted by factors such as tumor size, location, and mitotic rate, with tumors larger than 5 cm or those exceeding 5 mitoses per 50 high‐power fields (HPF) carrying a higher risk of recurrence and metastasis [ 6 ]. For our patient′s resection status, to avoid ambiguity, we state complete macroscopic cytoreduction (no gross residual disease) rather than implying R0 margins, and we explicitly note pT4 due to intraoperative rupture, which drives high‐recurrence risk and informs the adjuvant KIT‐inhibitor strategy.\nBeyond tumor‐intrinsic risk, the patient′s posttransplant immunosuppression added distinct diagnostic and therapeutic considerations. Solid‐organ transplant recipients have a ~2× overall increase in cancer risk versus the general population, attributed to chronic immunosuppression and impaired immune surveillance [ 1 ,  2 ]. GIST after kidney transplantation is rare but documented in the literature [ 3 ]. Although the mechanistic link between immunosuppression and mesenchymal tumorigenesis remains incompletely defined, the transplant setting may lower barriers to tumor emergence [ 3 ] and complicate recognition when masses arise in atypical locations (e.g., pelvis mimicking ovarian neoplasm). Maintaining GIST in the differential for large pelvic masses in transplant recipients is prudent, particularly when gynecologic markers are noncontributory. These data support interpreting our case within a recognized, if uncommon, transplant‐oncology context rather than implying causality.\nAdjuvant treatment with the tyrosine kinase inhibitor (TKI) Imatinib remains the cornerstone of postoperative GIST management [ 10 ]. Additionally, imatinib remains the first‐line standard of care for metastatic GIST. However, dose adjustments may be necessary based on tolerability, as seen in our patient. Studies show that molecular profiling for mutations in KIT or PDGFRA genes is essential [ 9 ]. Although imatinib is typically administered at a standard dose of 400 mg daily, patients with different KIT mutations show variable responses. Patients with KIT Exon 9 mutations may benefit from higher dosing (800 mg daily), unlike those with KIT Exon 11 mutations, who generally respond well to standard dosing [ 11 ,  12 ]. This difference stems from the distinct molecular mechanisms by which these mutations affect imatinib binding and efficacy [ 11 – 13 ].\nIn the metastatic setting, a meta‐analysis of the EORTC‐ISG‐AGITG 62005 and SWOG S0033 Phase III trials demonstrated significant progression‐free survival (PFS) benefit for patients with KIT Exon 9‐mutated GIST when treated with high‐dose imatinib (800 mg daily) compared with standard dose (400 mg daily) [ 11 ]. However, this analysis did not demonstrate a statistically significant overall survival (OS) benefit. Another retrospective analysis [ 14 ] suggests that higher imatinib doses did not demonstrate improved survival outcomes compared with the lower dose in patients with KIT Exon 9 mutations. Conversely, in the adjuvant setting, the benefit of higher dosing for Exon 9‐mutated GIST remains less established, with current evidence not showing robust OS improvements [ 15 ]. As such, mutation‐specific and context‐dependent treatment approaches for GIST patients remain important. Additionally, two transplant‐specific issues warrant emphasis. First, drug–drug interactions: imatinib inhibits CYP3A4 and can increase tacrolimus exposure [ 16 ,  17 ], mandating trough monitoring and close collaboration with transplant pharmacology. Second, choice/adjustment of maintenance immunosuppression: meta‐analytic data suggest sirolimus regimens are associated with lower malignancy incidence overall [ 18 ], though potential trade‐offs (including mortality signals) require individualized assessment with the transplant team.\n\nWhen GISTs in atypical locations, such as the pelvis, mimic OTs due to their presentation and mass effect on surrounding pelvic structures, it can lead to diagnostic delays, particularly if the initial presentation resembles gynecologic pathology. As such, atypically presenting GISTs require a multidisciplinary approach in their diagnosis and management to optimize patient outcomes. The ability to distinguish GISTs from ovarian malignancies and other pelvic tumors through a combination of imaging, histology, and molecular profiling is critical, as is careful management with TKIs in patients with extensive comorbidities. Understanding the unique presentation, diagnostic process, and multidisciplinary management is crucial for optimizing outcomes, particularly in complex cases involving significant coexisting conditions. In solid‐organ transplant recipients, chronic immunosuppression should be treated as a clinical context that can alter presentation, risk stratification, and pharmacology, potentially complicating management of pelvic GIST. For high‐risk/ruptured disease, guideline‐concordant adjuvant imatinib remains the reference approach when tolerated; when intolerance or KIT Exon 9 biology necessitates, a carefully monitored alternative is reasonable. Future reports that include agent class, trough levels, and graft function may clarify the immunosuppression–GIST relationship.\n\nThe patient′s consent was obtained.\n\nThe authors declare no conflicts of interest.\n\nNo funding was received for this manuscript.","source_license":"CC-BY-4.0","license_restricted":false}