Gastrointestinal Stromal Tumour: Cause of Obscure Gastrointestinal Bleeding

Overview

Gastrointestinal stromal tumours (GISTs) are rare tumours. It can cause occult gastrointestinal bleeding when conventional investigations fail to detect the bleeding lesions. Obscure gastrointestinal bleeding also represents a challenge in the quest for the clinical diagnosis and its therapeutic approach. We report a case of gastrointestinal bleeding originated from small bowel gastrointestinal stromal tumour diagnosed by capsule endoscopy and computerized tomography (CT) imaging. This case illustrates the difficulty in diagnosing GISTs and the important role of capsule endoscopy as a non-invasive investigation modality. The treatment options include curative surgical resection and tyrosine kinase inhibitor.

Key words:
obscure gastrointestinal bleeding – gastrointestinal stromal tumour – capsule endoscopy – tyrosine kinase inhibitor

Introduction

Gastrointestinal stromal tumour is an uncommon soft tissue tumour of the gastrointestinal tract. It is increasingly recognized as a subtype of sarcoma with positive c-Kit or CD117 growth factor receptor expression. Some GISTs also express CD34 and heavy caldesmon [1]. Conventional investigations modalities like esophagogastroduodenoscopy and colonoscopy usually fail to detect the bleeding sites leading to obscure hemorrhage. It is estimated that about 5% of the gastrointestinal hemorrhage is obscure in nature and GISTs have been identified as one of the cause [1]. The outcome of malignant GIST is exceptionally poor. This tumour is resistant to radiotherapy and conventional chemotherapeutic agents. Curative surgical resection has been the only available treatment of choice but surgery alone is often inadequate for advanced disease. Recently, the long term survival has markedly improved with the use of c-Kit targeted therapy like, imatinib mesylate, which is a tyrosine kinase inhibitor. CT imaging has an important role in monitoring the disease progression as there are no other established tumour markers for this tumour.

Case report

A 38 year-old female was referred to our hospital for investigation of chronic upper gastrointestinal bleeding. She was presented to a local hospital complaining of passing black stool for 2 months duration. There was no associated abdominal pain, vomiting or anorexia. She had significant weight loss of 6 kg during this period. She also experienced anemic symptoms like lethargy and giddiness. Her past medical history was unremarkable. She took regular hematinics as supplements. Her menstrual flow was normal and regular. There was no significant family history of malignancy and she was a non-smoker. She denied regular use of non-steroidal anti-inflammatory drugs.

Clinical examination was unremarkable except for pallor. Her abdominal examination was normal. There were no features of iron deficiency anemia, abdominal mass, hepatosplenomegaly or lymphadenopathy. Digital rectal examination showed stale melena.

Admission hemoglobin level was 4.4 g/dL (normal range 12.0–16.0 g/dL), reticulocyte count was 7.2% (normal range 0.5–2.5%) and mean corpuscular volume was 94.7 fL (normal range 101.0–119.0 fL). The total serum iron was 5.7 µmol/L whereas total iron binding capacity was 45.7 µmol/L. The coagulation and renal profile were normal.

During this admission she was transfused a total of 6 units of packed cell which resulted in an increased of hemoglobin to 10.2 g/dL. The esophagogastroduodenoscopy (OGDS) revealed normal upper gastrointestinal tract. Colonoscopy performed 6 days later showed a normal mucosa with blood clot and fresh blood throughout the colon up to the caecum and no tumour was seen.

A follow-up study using capsule endoscopy examination revealed evidence of active gastrointestinal bleeding at about 25 cm from the pylorus which was in the region of the jejunum. A contrast enhanced CT abdomen and pelvis showed an enhancing mass which was lobulated and exophytic at D3 junction measuring 4 cm × 5 cm × 6 cm in size. The mass showed significant enhancement on the arterial phase. This finding was suggestive of leiomyoma or sarcoma. There were no other focal lesions seen.

She was counseled for an open laparotomy and a successful ­Whipple’s ­operation was performed.

The tissue specimen was reported as gastrointestinal stromal tumour (GIST) in the duodenum. The immunohistochemistry stained strongly positive for CD117 and negative for S100 (Fig. 1 and 2).

Post laparotomy, the patient was well and requested for further follow up and continuation of therapy in her local hospital. She was advised to follow up with periodic CT scan for monitoring of disease progression. The patient remained well 2 years after the operation and her last follow up was 2 months ago with no recurrence of symptoms.

Discussion

Obscure gastrointestinal (GI) bleeding is uncommon but represents a tremendous diagnostic and therapeutic challenge. It is referred as clinically evident GI blood loss without identifiable site of bleeding by at least esophagogastroduodenoscopy (OGDS) and colonoscopy. These examinations can readily detect the lesion in 95% of gastrointestinal hemorrhage [2]. In cases of recurrent significant GI bleeding, the focus of the care is aimed to the identification of the site and determination of the cause of bleeding as well which allow institution of appropriate therapy.

Our case illustrated a clinical scenario of chronic overt and obscure GI bleeding failed to be diagnosed by colonoscopy and esophagogastroduodenoscopy. Further investigation by capsule endoscopy successfully identified the source of bleeding in the small bowel. This procedure is safe and painless but cost is a concern. In such case, it has the potential to become a useful diagnostic tool to avoid further invasive examinations.

From the review of literature, the lesions most commonly identified in the small bowel are tumours and vascular ectasias [3]. Tumours are the most common pathology found in the small intestine among patients between the ages of 30 to 50 years-old [4].

In one study, capsule endoscopy is significantly superior to push enteroscopy in detecting the source of blee­ding from small bowel [5]. The pathology reported in this study includes angiodysplasia, inflammatory small bowel lesion, GISTs, small bowel polyps, carcinoid tumour and lipoma. The detection rate was 82% and the diagnostic yield was 66% .

GIST is an uncommon visceral sarcoma that arises predominantly in the GI tract. They are mesenchymal tumours of the gastrointestinal tract with variable malignant potential. The reported annual incidence is about 1.2 cases per million populations [6,7]. Their distribution in the small intestine includes 17.7% in the duodenum, 47.6% in the jejunum and the remaining in the ileum. Based on immunohistochemistry and electron microscopy examination, GIST may have several components including myogenic, neural attributes, mixed features or undifferentiated types. The exact cellular origin of GIST has been proposed to be the interstitial cell of Cajal which is the intestinal pacemaker cell. Recently, expression of CD117 in the tumour cells was universally identified. The tumour can be recognized by the presence of the c-kit proto-oncogene, the critical factor in the pathogenesis of GIST due to its constitutive activation of kit receptor tyrosine kinase [2].

GIST arises predominantly from the stomach and small intestine. It can present with GI bleeding when the primary tumour size is more than 5 cm. The tumour is more common in men with peak incidence at the age of 50 years old. In women, the peak incidence is in older age group. Our patient presented at a relatively younger age and a 5 cm × 5 cm primary tumour was resected. Studies have shown that the estimated 5-year disease free survival is negatively influenced by male sex, non-gastric primary tumour site, tumour size of more than 5 cm, tumour rupture and mitotic index of more than 5/50 per high power field [4]. The prognosis is better if the tumour can be completely resected. Further improvement had been observed with adjuvant chemotherapy using imatinib mesylate (Glivec), a selective tyrosine kinase inhibitor [8]. It has been shown to be a promising treatment in selected high-risk cases and patient with overtly malignant disease [9]. In addition, it is generally well tolerated.

As the long term survival markedly improved with treatment, radiological imaging has become increasingly important for monitoring the effects of treatment and detecting tumour progression. A study involving 113 patients with primary and advanced GISTs with follow up to 37 months of imatinib treatment showed clinical meaningful regression of tumour on CT scan imaging. It typically showed exophytic, large and hypervascular mass at diagnosis and became homogenous and hypo-attenuating with disappearance of enhancing tumour nodules and tumour vessels along with the treatment [3]. The development of a nodule within the treated tumour is unique to GIST and indicates recurrence regardless of changes in tumour size.

Our patient chose to continue her follow-up and treatment in another hospital; however, she remained in good health during her recent follow up. Nonetheless, she needs a lifelong follow up to monitor the disease progression. Despite complete resection, GISTs have a tendency to recur.

In conclusion, the role of capsule endoscopy as a diagnostic tool in cases of obscure GI bleeding is promising, as shown in our case. It provides adequate information for the initial diagnosis of GISTs. GISTs should be considered when occult bleeding is suspected in the small intestine. Although, the diagnosis can be made histologically, the presence of CD117 is pathonogmonic. Imatinib as an adjuvant chemotherapy should be used only in well selected cases of GISTs with higher risk of recurrence. Collection of data and case records of GIST should be integrated as part of observational evidence to enhance the understanding of the natural history of the disease.

Harris Ngow Abdullah MD (USM), M.MED(INTERNAL MEDICINE) (UKM)
Assistant Professor Physician and Cardiologist
International Islamic University Malaysia
Kulliyah of Medicine
harrisngow@gmail.com
Wan Khairina WMN MBBS (Adelaide), M.MED(Pediatric)
Pediatrician Hospital Tengku Ampuan Afzan
Ministry Of Health Malaysia

rinmohd@yahoo.com