Spinal Metastases from Gastrointestinal Stromal Tumor: A Case Report Open Access

Gastrointestinal stromal tumors (GISTs) are the most common form of gastrointestinal mesenchymal tumors and arise from the interstitial cells of Cajal or related stem cells [1, 2]. It has been reported that 4,000 new cases of GISTs occur in the USA annually, contributing to 2–3% of all gastrointestinal neoplasia [1‒3]. The most common presentations are symptoms due to localized tumor invasion with patients typically presenting between the ages of 40–70, with a median age of 63 years; men and women are equally affected [1, 2, 4, 5]. The primary location of GIST is most commonly in the stomach, with an incidence of 60%–70%, followed by the small intestine (20%–30%), colon and rectum (5%), abdominal cavity, peritoneum, and omentum (5%), esophagus (<5%), and the retroperitoneal space (<3%) [1, 5]. Bone metastasis in GIST is rare, accounting for only 0.47% of cases, with the spine being the most common location of osseous metastasis. To date, there have been only 27 reported cases of metastatic GIST to the spine [2, 6‒9]. Here we review the current literature and report a case of GIST with metastatic spread to the thoracic spine presenting with acute spinal cord compression. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543568).

A 56-year-old female initially presented with a 20-year history of acute on chronic mechanical low back pain. A thoracolumbar X-ray was obtained at an outside institution which demonstrated a subtle compression deformity of the T10 vertebral body with multiple lytic lesions noted throughout the thoracolumbar spine (Fig. 1). She was found to have no neurologic deficits. No further imaging or spinal biopsy was performed at this time and the compression deformity was managed with conservative nonsurgical management. On further oncologic workup due to concern for possible metastatic disease, she was ultimately found to have a tumor with primary location in the gastric fundus and peritoneum along with metastatic lesions within the liver confirmed on liver biopsy.

Histopathological assessment of the gastric and hepatic tumors demonstrated a hypercellular tumor composed of epithelioid and spindle cells (Fig. 2a) with frequent mitotic figures (Fig. 2b). On immunohistochemical analysis, the tumor cells were negative for AE1/AE3 (Fig. 2c) and diffusely positive for CD117 (Fig. 2d) consistent with a diagnosis of GIST. Next-generation sequencing of KIT and platelet-derived growth factor receptor-alpha (PDGFRA) revealed a mutation in an exon 11 mutation in KIT (p. Trp557_Lys 558 deletion). The patient was initiated on a therapeutic regimen consisting of imatinib 400 mg with palliative external beam radiation therapy to T1–T9 of the spine with 3,000 cGy in 300 cGy fractions.

The patient remained stable for 3 years until she returned to the emergency department with 2 weeks of numbness/tingling at the T7 dermatomal level and below, lower extremity weakness, progressive gait instability, and urinary retention. Magnetic resonance imaging (MRI) of the thoracic spine demonstrated a dorsal epidural enhancing mass spanning the T6–T8 levels with associated spinal cord compression and spinal cord signal change (Fig. 3). The lesion was quantified to be SINS score of 12 and Bilsky grade 2. She was started on high-dose steroids with dexamethasone before ultimately undergoing urgent surgical decompression and resection of epidural tumor by way of a T5–T8 decompressive laminectomy. Pathology from the thoracic epidural mass was similar to that previously obtained from liver biopsy demonstrating a hypercellular tumor with extensive necrosis (Fig. 4a) and frequent mitotic figures (Fig. 4b) with findings on immunohistochemical staining of negative AE1/AE3 (Fig. 4c) and diffusely positive CD117 (Fig. 4d) consistent with metastatic GIST. Postoperatively, the patient initially did well with improvement in bilateral lower extremity sensation and bladder function and was discharged to acute rehabilitation. She declined follow-up MRI due to severe claustrophobia. At 2-week follow-up, the patient’s incision had been healing well. The patient unexpectedly passed away at home 6 weeks postoperatively from undetermined causes, prior to the scheduled 3-month follow-up and the initiation of adjuvant therapy.

GISTs arise from the interstitial cells of Cajal or related stem cells and are considered to be the pacemaker cells of the gastrointestinal tract. Interstitial cells of Cajal are located within the subepithelium in the intramuscular layer of the bowel, where they are thought to regulate peristalsis by acting as the intermediary cell type that interfaces with both the autonomic nervous system and GI smooth muscle [10]. While the molecular pathogenic mechanism has not been fully elucidated, the current hypothesis is that the pathogenesis of GISTs is due to activating mutations in either the KIT or PDGFRA genes, resulting in unregulated proliferation throughout the GI tract [1, 2, 10‒12]. It has been previously reported that approximately 78% of GISTs are due to mutations in KIT, while only 6% of cases report a normal KIT gene and a mutated PDGFRA [2, 13]. The most frequent mutations of KIT are located in exon 11, with mutations less frequently reported in exons 9, 13, 17, and 37–39 [2]. While the location of mutations have not been shown to harbor a prognostic implication, there have been previous reports of improved response to therapy with imatinib mesylate, a tyrosine kinase inhibitor, in patients with the exon 11 mutation [2, 5, 12‒14].

Only 10–30% of GISTs demonstrate metastatic behavior; however, bony metastasis represents a particularly rare but devastating site with a median overall survival of 18 months [8, 14, 15]. The spine is the most common site of bony metastasis in GIST given the anatomic location of the spine in relation to the GI tract and the vast vascular network of the vertebral column. In patients with spinal involvement, such as the one we report, it has been noted that their average overall survival was half that of their counterparts without involvement (41.78 vs. 82.49 months) [14].

Diagnosis is dependent on radiographic studies, tissue biopsy, and histopathologic characterization in tandem with immunohistochemical analysis. It has been reported that 90–95% of GISTs express CD117, making it the most sensitive diagnostic biomarker [1].

Given the myriad of possible secondary sequelae that could result from this symptomatology such as systemic infection, compromised cardiopulmonary function, and potentially death, immediate surgical intervention is critical to preserve neurological function, improve genitourinary control, maintain spinal column stability, and reduce morbidity secondary to severe pain. Based on a review of the current literature, the best therapeutic approach is management with urgent surgical resection and adjuvant imatinib. It has been previously reported that GIST patients with bony metastasis who underwent combined therapy using this treatment algorithm had an overall survival of 77.78 months compared to those who underwent imatinib chemotherapy alone who had an overall survival of 43.09 months [4, 14]. The difference between these two groups underscores the survival benefit conferred by surgical resection. Bisphosphonates can also be effective in the management of osseous metastases [7]. Systemic therapy with regorafenib, a multikinase inhibitor targeting angiogenic, stromal, and oncogenic pathways, was initiated 2 weeks postoperatively. A postoperative MRI had been scheduled for 6 weeks to assess residual spinal metastatic disease, as the patient declined inpatient imaging. The therapeutic plan included continued regorafenib and adjuvant radiation therapy for any residual disease. Unfortunately, the patient’s unexpected passing precluded further treatment.

Herein, we present a case of metastatic GIST with spinal involvement status post-palliative radiation and imatinib mesylate therapy who presented with numbness/tingling at the T7 dermatomal level and below, progressive gait instability, inability to ambulate, and urinary retention. With urgent surgical intervention, the patient experienced an improvement in all of the aforementioned symptoms with restoration of neurological function and improved GU control. Our experience demonstrates the ability of surgical intervention to reduce morbidity and mortality in patients with this rare, aggressive metastatic disease. The decision to proceed with surgery, made in conjunction with the patient, is congruent with the remainder of the literature, and surgical intervention in the acute presentation of metastatic GIST with spinal involvement continues to be necessary when the spinal lesions result in spinal cord compression and compromised neurological function.

GISTs are the most common form of gastrointestinal mesenchymal tumors. Bony metastasis in GIST is rare, with the spine serving as the most common location of osseous spread. Here we present the case of a patient with metastatic GIST to the thoracic spine presenting with acute spinal cord compression treated with surgical resection in addition to reviewing the literature of previous patients with metastatic GIST to the spine. We recommend that patients undergo surgical resection with adjuvant tyrosine kinase inhibitor.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Conception and design: Pashayar P. Lookian, Luke J. Weisbrod, Landon D. Ehlers, and Miki Katzir. Acquisition of data: Pashayar P. Lookian, Luke J. Weisbrod, Jie Chen, and Tyler R. Teichmeier. Analysis and interpretation of data: Pashayar P. Lookian, Luke J. Weisbrod, and Jordan M. Rasmussen. Drafting the article: Pashayar P. Lookian and Luke J. Weisbrod. Critically revising the article: Pashayar P. Lookian, Luke J. Weisbrod, Jordan M. Rasmussen, Jie Chen, Tyler R. Teichmeier, and Miki Katzir. Reviewed submitted version of manuscript: Pashayar P. Lookian, Luke J. Weisbrod, Jordan M. Rasmussen, Jie Chen, Tyler R. Teichmeier, Landon D. Ehlers, and Miki Katzir. Approved the final version of the manuscript on behalf of all authors: Jordan M. Rasmussen. Administrative/technical/material support: Pashayar P. Lookian and Miki Katzir. Study supervision: Miki Katzir.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of the patient in this case report but are available from the corresponding author (M.K.) upon reasonable request.