Rectal Gastrointestinal Stromal Tumor Poor Response to Imatinib: A Case Report

ABSTRACT

A 63‐year‐old man presented with persistent constipation lasting 6.5 months. Digital rectal examination revealed a soft‐tissue lesion near the anal verge without bleeding. Further evaluation identified a rectal mass. Treatment with imatinib for 6 months showed no significant response. The patient subsequently underwent surgical resection, with favorable short‐term clinical outcomes.

Key Clinical Message

Rectal gastrointestinal stromal tumors are rare and may present with nonspecific symptoms, including constipation. This case emphasizes the importance of considering GIST in the differential diagnosis of rectal masses and highlights that some tumors show a limited response to neoadjuvant imatinib therapy. This underscores the essential role of surgical resection in management.

1. Introduction

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract and most often arise in the stomach and small intestine [1]. They can occur throughout the GI tract but are uncommon in the colon, rectum, and esophagus. Rectal GISTs account for only a small proportion of all GISTs and are therefore considered rare. Their low incidence, nonspecific clinical presentation, and anatomically constrained location make diagnosis and treatment challenging [2]. GISTs are thought to arise from the interstitial cells of Cajal or their precursor cells. Molecular alterations in the KIT and platelet‐derived growth factor receptor alpha (PDGFRA) tyrosine kinase pathways play a central role in GIST pathogenesis and have important implications for diagnosis, prognosis, and treatment [1, 3]. Histopathological examination, combined with immunohistochemical assessment, particularly of CD117 and DOG1 expression, is central to establishing the diagnosis [3, 4].

Managing rectal GIST is particularly challenging because of the confined pelvic anatomy and the tumor's close relationship to the anal sphincter and adjacent pelvic structures. Surgical resection remains the mainstay of treatment for localized, resectable disease [4, 5]. However, radical procedures may cause substantial functional morbidity, including permanent colostomy. Consequently, neoadjuvant imatinib has increasingly been used in selected patients with locally advanced rectal GIST to reduce tumor burden, facilitate complete resection, and potentially increase the likelihood of sphincter‐preserving surgery [5, 6]. Although many rectal GISTs respond favorably to neoadjuvant imatinib, the magnitude of response varies among patients and is influenced by the tumor's molecular characteristics [6, 7]. In particular, KIT exon 11 mutations are generally associated with a higher likelihood of response to imatinib, whereas certain KIT and PDGFRA mutations may be linked to reduced sensitivity [7]. Therefore, careful assessment of treatment response and timely reassessment of the surgical strategy are important during neoadjuvant treatment. Imaging characteristics may overlap between GISTs and other hypervascular tumors, making accurate localization and characterization essential for establishing an appropriate differential diagnosis. Contrast‐enhanced computed tomography can provide useful information for distinguishing GISTs from other hypervascular neoplasms by evaluating tumor location, enhancement pattern, morphology, and relationship to adjacent structures. Ren et al. demonstrated that contrast‐enhanced CT could help differentiate duodenal GISTs from hypervascular pancreatic neuroendocrine tumors in the pancreatic head [8]. Although this differential diagnosis is anatomically distinct from rectal GIST, it underscores the broader importance of considering other hypervascular tumors when evaluating a suspected GIST and of integrating imaging findings with histopathological and immunohistochemical assessment.

We report a rare case of distal rectal GIST in a 63‐year‐old man with an inadequate response to 6 months of neoadjuvant imatinib, who underwent transanal tumor excision preserving anal sphincter function. Unlike many cases where imatinib led to sufficient tumor reduction for sphincter‐preserving surgery, this case highlights decision‐making challenges from limited response. It showcases individualized, multidisciplinary decision‐making where local surgery was still feasible despite limited neoadjuvant therapy response.

2. Case Presentation

2.1. Presentation and Diagnostic Workup

A 63‐year‐old man was referred to our clinic with a 6.5‐month history of persistent constipation. On clinical examination, no palpable abdominal mass was detected. Digital rectal examination revealed a soft‐tissue lesion near the anal verge without bleeding. Based on the patient's symptoms and clinical findings, colonoscopy was performed. Colonoscopy revealed a submucosal rectal lesion. Further evaluation with endoscopic ultrasonography (EUS) and computed tomography (CT) was subsequently performed. EUS demonstrated a hypoechoic, heterogeneous rectal lesion measuring 41 × 51 mm, located approximately 5 cm from the anal verge and originating from the muscularis propria. The lesion was in close proximity to the urinary bladder. No regional lymphadenopathy was identified, and the lesion had relatively well‐defined borders. Abdominopelvic CT demonstrated a large rectal mass with extension into the perirectal space.

Given the patient's symptoms and the identification of a distal rectal submucosal lesion on colonoscopy, further evaluation was performed with EUS and CT to characterize the lesion, determine its layer of origin, assess local extension, and evaluate its relationship with adjacent pelvic structures. EUS demonstrated a hypoechoic, heterogeneous lesion arising from the muscularis propria, measuring 41 × 51 mm and located approximately 5 cm from the anal verge. CT demonstrated a large rectal mass with extension into the perirectal space. The absence of regional lymphadenopathy and the lesion's origin from the muscularis propria favored a mesenchymal tumor such as a GIST. Based on the imaging and endoscopic findings, a tissue biopsy was obtained for histopathological confirmation.

2.2. Surgical Procedure

The patient underwent transanal surgical resection under general anesthesia in the lithotomy position. Given the lesion's distal location and proximity to the anal verge, a transanal approach was chosen to facilitate tumor excision while preserving anal sphincter function. During surgery, two bulky submucosal masses were identified in the distal rectum. The larger measured approximately 4 × 3 cm, and a second, more proximal mass measured approximately 2 × 2 cm. Both lesions were located approximately 1–2 cm from the anal verge. The masses were excised transanally using electrocautery and LigaSure. After tumor excision, the circumferential rectal mucosa was repaired with 2–0 Vicryl sutures. Hemostasis was achieved, and the surgical field was thoroughly irrigated. The resected specimens were submitted for histopathological and immunohistochemical examination.

2.3. Postoperative Course and Follow‐Up

The postoperative course was complicated by a perirectal fluid collection, which was managed conservatively with medical treatment. The patient remained clinically stable, tolerated the prescribed diet, and did not develop fever or other signs of systemic infection. A follow‐up ultrasonographic examination performed 3 weeks after surgery showed no evidence of a persistent perirectal fluid collection. The patient remained clinically stable throughout the available postoperative follow‐up period.

2.4. Histopathological and Immunohistochemical Findings

Histopathological examination of the resected specimens confirmed the diagnosis of rectal GIST. Microscopically, the tumor was composed of spindle cells with wavy nuclei and eosinophilic cytoplasm, arranged in a predominantly storiform pattern with focal areas of nuclear aggregation. Immunohistochemical staining showed positivity for CD117 and CD34, with focal, weak positivity for smooth muscle actin (SMA). S100 expression was reported. Based on the morphological and immunohistochemical findings, the final diagnosis was rectal GIST.

3. Discussion

GISTs are the most common mesenchymal tumors of the gastrointestinal tract and are characterized by activating alterations in the KIT or PDGFRA tyrosine kinase pathways [1, 3]. Rectal GISTs are rare compared with gastric and small‐intestinal GISTs and represent a clinically challenging subgroup because of their anatomical location and the difficulty of achieving complete tumor resection while preserving anorectal function [2, 5]. The present case illustrates these challenges in a patient with a distal rectal GIST who showed an inadequate response to 6 months of neoadjuvant imatinib and subsequently underwent transanal tumor excision with preservation of anal sphincter function. Unlike many previously reported cases in which neoadjuvant imatinib facilitated tumor reduction and sphincter‐preserving surgery, this case highlights the management of a patient in whom the anticipated response was not achieved, yet a sphincter‐preserving surgical option remained feasible.

The diagnostic evaluation of rectal GIST typically includes endoscopy, cross‐sectional imaging, and tissue sampling. Endoscopic ultrasonography is particularly useful for determining the layer of origin of a rectal submucosal lesion, while CT and pelvic MRI provide information on tumor size, local extension, and relationships to adjacent pelvic structures [4, 5]. Because the imaging appearance of GIST may overlap with other mesenchymal or hypervascular tumors, careful assessment of tumor location, morphology, enhancement characteristics, and relationships to adjacent structures is important when establishing the differential diagnosis. Ren et al. demonstrated that contrast‐enhanced CT characteristics can help differentiate duodenal GISTs from hypervascular pancreatic neuroendocrine tumors arising in the pancreatic head [9]. Although this specific differential diagnosis is anatomically distinct from rectal GIST, the study underscores the broader importance of distinguishing GIST from other hypervascular neoplasms by integrating imaging findings with pathological evaluation. Histopathological and immunohistochemical assessment remains essential for definitive diagnosis, with CD117 and DOG1 among the most useful markers for confirming GIST [3, 4]. In the present case, EUS demonstrated a lesion arising from the muscularis propria, and biopsy showed a spindle‐cell neoplasm favoring GIST. Immunohistochemical findings, including CD117 and CD34 positivity, supported the diagnosis.

Neoadjuvant imatinib has become an important treatment strategy for selected patients with locally advanced rectal GIST. The rationale is to reduce tumor volume and facilitate complete resection, potentially enabling a less extensive operation and preserving anal sphincter function [5, 6]. Previous studies have reported favorable outcomes with neoadjuvant imatinib in rectal GIST. Machlenkin et al. reported that preoperative imatinib could reduce tumor size and facilitate sphincter‐preserving surgery in selected patients [6]. Similarly, multicenter studies have demonstrated meaningful tumor responses and suggested that neoadjuvant treatment may improve the feasibility of organ‐preserving surgery [8, 10]. These reports contrast with the present case, in which 6 months of neoadjuvant imatinib did not yield a satisfactory clinical response. Nevertheless, the lack of an adequate response did not preclude a sphincter‐preserving procedure, as the tumor remained amenable to transanal excision given its distal location and surgical accessibility.

Response to imatinib varies among patients, and the molecular characteristics of GIST play a key role in determining treatment sensitivity. KIT exon 11 mutations are generally associated with a favorable response to imatinib, whereas certain KIT and PDGFRA mutations may be linked to reduced sensitivity or primary resistance [7]. Molecular characterization may therefore be particularly relevant when neoadjuvant therapy is considered and when an expected response is not observed. In the present case, molecular testing for KIT and PDGFRA mutations was not available. Consequently, the biological basis for the inadequate response to imatinib cannot be determined, and the patient should not be classified as having molecularly confirmed imatinib resistance (Table 1).

TABLE 1.

Comparison of the present case with selected published studies of neoadjuvant imatinib and sphincter‐preserving surgery in rectal GIST.

Study	Patients	Neoadjuvant imatinib	Response	Sphincter‐preserving surgery	Main finding
Machlenkin et al. [6]	9	Yes	1 CR, 6 PR, 2 SD	7 underwent surgery	Neoadjuvant imatinib enabled tumor response and R0 resection in most operated patients
Cavnar et al. [5]	47	Perioperative use in 24	—	More common in neoadjuvant group	Neoadjuvant imatinib was associated with organ preservation and improved oncologic outcomes
Yang et al. [8]	100	Yes	75 PR, 18 SD, 7 PD	—	Most patients showed tumor response; neoadjuvant imatinib reduced tumor size
Fujimoto et al. [11]	5	Yes, 4–12 months	Tumor reduction in all patients	5/5	Sphincter‐preserving surgery was feasible after neoadjuvant imatinib
Present case	1	Yes, 6 months	Inadequate response	Yes, transanal excision	Sphincter‐preserving surgery remained feasible despite inadequate response

The duration of neoadjuvant imatinib therapy should be individualized based on tumor response, anatomical considerations, and the likelihood of achieving an R0 resection [4]. In published series of rectal GIST, treatment durations have varied considerably, and prolonged therapy may be considered when continued tumor response is observed [8, 10]. However, continuation of neoadjuvant therapy should be reconsidered if the response is inadequate or there is evidence of disease progression. In the present case, the patient had received imatinib for approximately 6 months without a satisfactory response, so definitive surgical treatment was selected. Because pretreatment and post‐treatment tumor measurements were not available, the response could not be quantified using standardized radiological criteria. Thus, the present case demonstrates an inadequate clinical response rather than providing definitive evidence of primary imatinib resistance.

Surgical resection remains the cornerstone of treatment for localized rectal GIST [4, 5]. The optimal surgical approach depends on tumor size, location, relationship to the anal sphincter, and the ability to achieve complete tumor removal without tumor rupture. Historically, extensive procedures such as abdominoperineal resection were commonly performed for distal rectal GISTs. However, recognition that lymph node metastases are uncommon and that preservation of anorectal function is clinically important has encouraged the development of more conservative surgical approaches in appropriately selected patients [2, 4].

Transanal and other local approaches have been increasingly investigated for distal rectal GISTs. A retrospective study comparing transanal and nontransanal approaches found that transanal surgery can yield favorable oncological and functional outcomes in selected patients with primary rectal GIST [12]. Similarly, sphincter‐preserving surgery after neoadjuvant imatinib has been reported in patients with rectal GIST, demonstrating that tumor reduction and careful surgical selection can allow avoidance of radical surgery in selected cases [11]. In the present case, the tumor was located approximately 5 cm from the anal verge and arose from the muscularis propria. Given its distal location and the goal of preserving anal sphincter function, a transanal approach was chosen. The tumor was excised directly through the anal route, and the rectal wall defect was subsequently closed.

An additional consideration when evaluating GISTs is the differential diagnosis of hypervascular tumors on imaging. GISTs may show prominent enhancement due to their vascularity, and their imaging appearance can overlap with other hypervascular neoplasms. Ren et al. demonstrated that contrast‐enhanced CT characteristics can help differentiate duodenal GISTs from hypervascular pancreatic neuroendocrine tumors arising in the pancreatic head [9]. Although this specific differential diagnosis does not directly apply to a rectal lesion, the study underscores the importance of carefully evaluating tumor location, morphology, enhancement characteristics, and relationship to adjacent structures when considering GIST in the differential diagnosis of a hypervascular mass. Ultimately, pathological and immunohistochemical confirmation remains essential.

The present case is clinically relevant because most published reports on neoadjuvant imatinib for rectal GIST emphasize tumor response and the potential for organ preservation [5, 6, 8, 10]. In contrast, our case illustrates a different clinical scenario in which the anticipated response to neoadjuvant imatinib was inadequate, necessitating definitive surgery. Importantly, the case also shows that an inadequate response to neoadjuvant therapy does not necessarily preclude a sphincter‐preserving surgical approach. In carefully selected patients, a transanal approach may provide direct access to a distal rectal tumor while avoiding the morbidity associated with more radical procedures [11, 12]. Thus, treatment decisions should be individualized based on tumor location, response to systemic therapy, surgical feasibility, and the patient's functional goals.

This case has several limitations. First, it involves a single patient and therefore cannot establish the superiority of transanal surgery or the optimal management strategy for rectal GIST. Second, pretreatment tumor measurements and detailed imaging data before and after imatinib were unavailable, preventing objective assessment of the degree of response. Third, molecular testing for KIT and PDGFRA mutations was not performed, so the mechanism underlying the inadequate response to imatinib remains unknown. Fourth, the available postoperative follow‐up is relatively limited, and long‐term oncological outcomes, including local recurrence and distant metastasis, cannot yet be adequately assessed. Finally, because the case represents an individual clinical course, its findings should be generalized cautiously to other patients with rectal GIST. Despite these limitations, this case underscores the importance of continuous reassessment during neoadjuvant imatinib therapy and multidisciplinary treatment planning for rectal GIST. When the expected response to imatinib is not achieved, definitive surgery should not necessarily be delayed, particularly when a technically feasible sphincter‐preserving procedure can achieve complete tumor removal. Further prospective studies and molecularly characterized cohorts are needed to identify predictors of inadequate response to neoadjuvant imatinib and to clarify the optimal selection and timing of sphincter‐preserving surgery in patients with rectal GIST.

4. Conclusion

Rectal gastrointestinal stromal tumors are rare and may present with nonspecific symptoms, including constipation. This case emphasizes the importance of considering GIST in the differential diagnosis of rectal masses and highlights that some tumors show a limited response to neoadjuvant imatinib therapy. This underscores the essential role of surgical resection in management.

Author Contributions

Narges Mesbah: writing – review and editing, writing – original draft. Majid Einakchi: resources. Alireza Samimi: writing – original draft, writing – review and editing. Tooraj Zandbaf: software, data curation, investigation.

Funding

The authors have nothing to report.

Consent

The patient's written consent was obtained for the publication of this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data supporting this research are available from the author(s) on reasonable request.