Background/Objectives: Extra-gastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors arising outside the gastrointestinal tract, making up <5% of all GISTs. Rectovaginal EGISTs are particularly uncommon, with limited available data. This study systematically reviews the clinicopathological features, management, and outcomes of rectovaginal EGISTs. Methods: A systematic review of the English-language literature was conducted for studies on rectovaginal EGISTs (search date: 15 January 2025). Results: Thirty-one studies, including 40 female patients (mean age: 55.2 ± 15.4 years), met the inclusion criteria. Presenting symptoms included vaginal bleeding (24.3%), palpable mass (13.5%), constipation (10.8%), and abdominal pain (8.1%); however, the majority of patients (45.9%) were asymptomatic. Surgical excision was undertaken in 95% of patients, more often via local resection (61.1%). A high-grade mitotic index (>5/50 HPF) was noted in 63.2%. CD117, DOG-1, and vimentin was expressed in all cases, while CD34 was positive in 97.1%. Adjuvant therapy with tyrosine kinase inhibitors (TKIs) was administered in 57.5%, and neoadjuvant therapy was rare (8.6%). Recurrence occurred in 39.4% over a median follow-up of 40 ± 61.5 months, with a median disease-free survival (DFS) of 48 months. One death occurred 13 months postoperatively. Conclusions: Rectovaginal EGISTs are exceedingly rare and often asymptomatic, complicating preoperative diagnosis. Surgical resection remains the cornerstone of treatment, complemented by stage-specific neoadjuvant or adjuvant TKI therapy. The challenging location predisposes to recurrence, underscoring the need for further studies to optimize management and improve outcomes.

Gastrointestinal stromal tumors or GISTs are the most common mesenchymal tumors of the gastrointestinal tract; only a few cases have been reported at other sites. The prognosis of GISTs depends on their size and mitotic rate. Surgical removal is the treatment of choice although imatinib shows clinical benefits. We present a rare case of a GIST in a 64-year-old female patient treated for vaginal bleeding. During diagnostic hysteroscopy, an intra-uterus polyp and a large vaginal mass were identified and multiple biopsies were obtained. Initially, the histological examination of the first lesion suggested that it was an intra-uterus, benign adenomatous polyp but later the second lesion indicated a malignant vaginal neoplasm. The patient was operated on and the postoperative course was uneventful. The histological analysis of the specimen finally revealed a GIST. Vaginal GISTs are extremely rare tumors and in most cases, diagnosis is achieved only histologically in the removed specimen. Additional treatment options and prognosis are similar to those of gastric GISTs.

Gastrointestinal stromal tumors (GISTs) arising from the gynecological tract are extremely rare. A case of GIST with an unusual presentation as a vaginal mass is presented with comprehensive literature review, aiming to gain a better understanding of the diagnostic and treatment strategy of the disease.

A 78-year-old woman presented with persistent vaginal bleeding and difficulty in micturition. Although the tumor mass was diagnosed, the results of preoperative evaluations are uncertain.

Preoperative evaluation included the computed tomography examination (a 6.3×5.3 cm cervical mass lesion with rectal and vaginal invasion), colonoscopy (an external compression with an intact mucosa), tumor markers, and biopsy (spindle cell tumor). Postoperative histopathology confirmed the diagnosis of GIST.

Posterior exenteration with complete resection was performed. The patient received postoperative adjuvant imatinib therapy.

The patient has survived without the disease for more than 3 years.

It is still a challenge to diagnose GISTs in women with rectovaginal mass preoperatively. Efforts should be made, including a high suspicion and an assistance of immunohistochemistry. A precise diagnosis may offer a better surgical and treatment plan, especially on the preservation of reproductive organs and accessibility of targeted therapy.

Rectal gastrointestinal stromal tumors are rare. To date, 12 gastrointestinal stromal tumors have been reported as pelvic vaginal masses. We describe a rectovaginal tumor in a 39-year-old woman. The tumor frequently recurred after multiple surgical excisions and interrupted imatinib treatment without metastasizing. Magnetic resonance tomography demonstrated a partial response under imatinib. The patient was alive with stable disease under imatinib 44 months from initial diagnosis. Molecular analysis showed a somatic 6-base pair deletion in exon 11 of c-KIT (W557_K558del) in both the primary tumor and the third recurrence; the recurrence had an additional exon 17 mutation (N822K). Comparative genomic hybridization analysis of the primary tumor showed loss of 14q and gain of 1q. Recurrence showed complete loss of nuclear p16 expression. Molecular studies and p16 status confirmed the typical characteristics of gastrointestinal stromal tumors with an aggressive phenotype underscoring the need for a special interdisciplinary treatment and for achieving complete local excision with free margins.