Gastrointestinal Stromal Tumor (GIST) in the Rectum: A Rare Location

Abstract

Gastrointestinal stromal tumor (GIST) is a rare condition that originates in the cells of Cajal and constitutes the most frequent type of malignant mesenchymal tumors in the gastrointestinal tract. Although their incidence is low, GISTs are most common in the stomach and small intestine, although they can occur in other areas, such as the rectum. Although no specific risk factor has been identified, certain genetic conditions such as neurofibromatosis type I increase the likelihood of developing a GIST. Symptoms may vary depending on the location of the tumor and include early satiety, abdominal distention, gastrointestinal disturbances, and bleeding.

The diagnosis is usually made incidentally during radiologic or endoscopic studies and is confirmed by immunohistochemistry studies that identify mutations in cluster of differentiation 117 (c-KIT) and platelet-derived growth factor receptor kinase alpha (PDGRF-α) receptors. These tumors are resistant to conventional chemotherapy and radiotherapy.

Management of the disease preferably involves surgical resection, aiming for complete removal of the tumor. Prognosis after surgery depends on the size of the tumor and its mitotic activity. Periodic follow-up with imaging tests is recommended for several years after resection.

In advanced cases, treatment may include therapy with imatinib, a tyrosine kinase inhibitor that has demonstrated efficacy in GISTs. Primary resistance to treatment can be a challenge, and in advanced rectal tumors, several surgical options can be considered, although resection can be difficult due to the location of the tumor and its adherence to the pelvic floor.

Despite curative resection, recurrence and distant metastasis, especially to the liver, are major concerns, with a reduced median survival in patients with advanced disease.

Keywords

Gastrointestinal Stromal Tumor - GIST - rectum - surgical resection - immunohistochemistry

Introduction

A gastrointestinal stromal tumor (GIST) is a rare entity originating from the cells of Cajal. Although their incidence is rare (14–20 per million), they are the most common type of malignant mesenchymal tumors of the gastrointestinal tract. They are most found in the stomach and small intestines but can arise at other sites. Of these, ∼ 5% are located primarily in the rectum.[1] [2]

These tumors occur equally in both sexes, mostly in the sixth decade of life. No specific risk factor has been identified, but people with neurofibromatosis type I are more likely to develop a GIST, as are those with Carney triad[3] and those with a family history of stromal tumor. Gastrointestinal stromal tumors do not appear to be associated with other malignancies.[4] [5]

They cause unspecific symptoms depending on their location (early satiety, abdominal distension, gastrointestinal disorders, bleeding, obstruction, among others).[6]

Rectal GISTs present with primary symptoms of hematochezia (23.0%), constipation (15.2%), and anal pain (38.5%), similar to those of other rectal tumors.[7] [8]

These tumors are usually diagnosed incidentally during a radiological or endoscopic study, in which lesions of less than 10 mm to large lesions measuring more than 350 mm can be observed.[9]

Gastrointestinal stromal tumors are considered specific entities that can be classified into three categories according to their morphology: epithelioid, spindle cell, or mixed.[10]

To confirm the diagnosis, an immunohistochemical study is necessary.[7] To be called GIST, they must be identified by mutations in the c-KIT receptor (the most sensitive and specific marker) -present in 75 to 80%- and in the platelet-derived growth factor receptor tyrosine kinase alpha (PDGRF-α).[11] [12] present in 75 to 80% and in the PDGRF- α—present in 5 to 10%—these characteristics are what cause GISTs.[6] [13] These characteristics are what make them highly resistant to conventional chemotherapy and radiotherapy. Tumors that do not have these mutations are called wild-type GISTs.[14]

As mentioned, these tumors are usually found incidentally; however, when their surgical protocol is performed, computed tomography (CT) and positron emission tomography (PET) scans are usually of great help. On CT, GISTs are usually seen as an exophytic mass that enhances heterogeneously with intravenous contrast because of their high vascularity, and PET can reveal small metastases and establish baseline metabolic activity, which can later help in the evaluation of effectiveness of therapy. In the anorectal region, magnetic resonance imaging (MRI) can be of great help due to the anatomical detail it offers for planning the surgical approach.[7] [15]

On the other hand, The Canadian Advisory Committee on Gastrointestinal Stromal Tumours recommends that a follow-up CT scan be performed every 3 to 6 months for a minimum of 5 years after resection in patients without residual disease.[16]

If there is a high suspicion that it is a GIST, biopsy is not recommended; however, if it is an undetermined lesion in an accessible location, fine needle aspiration or endoscopic biopsy are the methods of choice. Percutaneous biopsy is not recommended because of the risk of dissemination. Open biopsy is indicated for inaccessible tumors.[17]

Surgical resection is preferred for the management of local disease. The objective is complete macroscopic resection obtaining negative margins with preservation of the pseudocapsule to avoid tumor dissemination.[18] [19]

Particularly with GISTs arising in the rectum, total excision of the mesorectum is the preferred approach. Resecting the lymph nodes along the mesenteric or mesorectal vessels is not necessary.[1] [20]

Prognosis after surgical resection is strongly affected by both tumor size and mitotic activity.[21]

Presentation of the Case

We present the case of a 60-year-old male who was sent for consultation due to diarrhea with 1 year and 6 months of evolution and weight loss of 30 kg in 1 year. He denied bleeding or transrectal mucus output. On physical examination, the abdomen had a palpable tumor in the right iliac fossa, not delimited, without peritoneal irritation; and on rectal examination, a lesion was palpated, 5–6 cm from the anal margin, anterior, renitent, and mobile. A biopsy was taken by anal exploration, which reported inadequate material for diagnosis; thus, a colonoscopy was scheduled ([Fig. 1]), during which a biopsy was taken, which reported an ulcer bed with granulation tissue without neoplasia and inadequate material.

Fig. 1 Tumor from 6 to 13 cm of anal margin, pedicle at 13 cm anterior left; without mucosal alterations.

The patient was protocolized for surgery, and abdominopelvic CT scan ([Fig. 2]) and MRI ([Fig. 3]) were performed.

Fig. 2 Abdominopelvic computed tomography scan. Rectum – sigmoid-dependent tumor lesion with apparent intussusception effect, heterogeneous content, 95 × 88 × 80 mm.

Fig. 3 Magnetic resonance imaging scan. Tumor lesion in upper and middle third of rectum 9.3 × 8.5 × 8.1 cm probably related to gastrointestinal stromal tumor. Lower third of rectum and levator and sphincter complex muscles with preserved signal intensity.

The patient underwent elective ultra-low anterior resection with primary colorectal anastomosis 5 cm from the margin of the anus ([Fig. 4]).

Fig. 4 Ultra-low anterior resection.

Pathology confirmed rectal GIST ([Fig. 5]) measuring 10 × 7.1 × 6.5 cm, pedunculated and ulcerated, with less than 1% mitoses in 10 high-power fields, no neoplasia in proximal, distal, or radial surgical edges, no vascular invasion, necrosis, or hemorrhage.

Fig. 5 Surgical specimen of ultra-low anterior resection of the middle, superior and sigmoid rectum. Gastrointestinal stromal tumor measuring 10 × 7.1 × 6.5 cm, pedunculated and ulcerated.

The result of the immunohistochemistry revealed CD117 positive, CD34 positive, AML positive, PS100 negative, and Ki67 positive < 1% mitosis ([Fig. 6]).

Fig. 6 Immunohistochemical analysis. (A) CD34: positive (++); (B) AML: positive (++); (C) PS100: negative; (D) ki-67: positive < 1% mitosis.

Discussion

The cornerstone of treatment remains resection. For the treatment of advanced GIST, imatinib, which is a small molecule tyrosine kinase inhibitor with activity against Abelson leukemia virus (ABL), breakpoint cluster region (BCR)-ABL, stem cell factor receptor (KIT), PDGFR-α, platelet-derived growth factor receptor beta (PDGFR-β), ARG, and possibly colony-stimulating factor-1 receptor (CSF1R), is also indicated as neoadjuvant or adjuvant therapy.[22]

Gastrointestinal stromal tumors are sensitive to imatinib by two mechanisms, as the drug inhibits the activity of wild-type KIT kinase and the growth of a line of gastrointestinal stromal tumor cells; however, if there is no response to treatment within 6 months, we speak of a tumor with primary resistance.[23] [24]

If the tumor is located in the rectum and is in an advanced stage, it is usually a bulky entity. There is still no standardized technique, but a local resection (minimally invasive transanal resection) can be performed, although its use is limited by the distance to the dentate line, which must be close; a low anterior resection (LAR), an abdominoperineal resection (APR) or even a pelvic exenteration.[7] [25] [26]

Consideration must be given to the confined pelvic space and the fact that the tumor is often densely adherent to the pelvic floor, which can require cruciate surgery to achieve a complete surgical resection.[20]

The cause of death following curative resection is distant metastasis rather than local recurrence, with the most common site being the liver. Gastrointestinal stromal tumors metastasize to lymph nodes only rarely. Almost all patients undergoing resection for advanced disease have subsequent recurrence, regardless of the quality of the procedure. It has been observed that the median survival of patients with advanced disease is 18 to 24 months.[27] [28]

Conclusion

Gastrointestinal stromal tumor is a rare but important entity, as it is the most common type of mesenchymal tumor in the gastrointestinal tract. Although its incidence is low, its diagnosis and management are critical due to its malignant potential and resistance to conventional treatments such as chemotherapy and radiotherapy.

Gastrointestinal stromal tumors can occur in various locations of the gastrointestinal tract, with the most common being the stomach and small intestine. Although no specific risk factor has been identified, certain genetic conditions may increase the likelihood of developing GIST.

The diagnosis is usually made incidentally during radiologic or endoscopic studies, confirmed by immunohistochemical studies that identify mutations in c-KIT and PDGRF-α receptors. Primary management involves surgical resection, aiming for complete removal of the tumor. In advanced cases, imatinib therapy may be considered, although primary resistance to treatment can be a challenge.

Despite curative resection, recurrence and distant metastasis are major concerns, especially in the liver. Therefore, periodic long-term follow-up is recommended to detect and treat possible recurrences.

Conflict of Interests

The authors have no conflicts of interest to declare.

Ethical Responsibilities

Informed consent was not requested for the publication of this case, because no personal data that would allow the patient to be identified are published in this article.

The work is not a research study, although it complies with current ethical regulations, and no data referring to the patient appears in the text or in the figures.

Authors' Contributions

Conceptualization; Nadab David Mitre-Reyes

Investigation; Yulia Angélica Morales-Chomina, Luz del Carmen Mendoza Namur, Kevin Joseph Fuentes-Calvo

Methodology Kevin Joseph Fuentes-Calvo

Supervision;Nadab David Mitre-Reyes

Visualization; Alan Guerrero-Gomez

Writing – original draft; Nadab David Mitre-Reyes, Kevin Joseph Fuentes-Calvo

Writing – review & editing; Nadab David Mitre-Reyes, Kevin Joseph Fuentes-Calvo

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Publication History

Received: 25 July 2024

Accepted: 25 November 2024

Article published online:
26 March 2025