Gastrointestinal stromal tumour masquerading as a diverticular bleed

Abstract

Gastrointestinal stromal tumours (GISTs) only account for a small percentage of gastrointestinal malignancies with a wide range of clinical presentations depending on the location and size of the tumour. Herein, we present the case of a 55-year-old woman with occult gastrointestinal bleeding (GIB) despite imaging and two separate oesophagogastroduodenoscopy colonoscopies. On double-balloon enteroscopy, an oozing diverticular-appearing lesion in the ileum was identified which on laparoscopy was connected to a large pelvic GIST. This case highlights the importance of considering GISTs in patients with occult GIB, as a high index of suspicion is required for diagnosis.

Background

While gastrointestinal stromal tumours (GISTs) remain the most common mesenchymal malignancy of the gastrointestinal (GI) tract, they only account for 1%–2% of primary GI malignancies overall.^{1 2} Seventy per cent of GISTs are asymptomatic and discovered incidentally.^{1 3} Its rarity, non-specific clinical presentation with resemblance to more commonly encountered conditions, and need for surgical resection and immunohistopathology make it an elusive diagnostic challenge.

Case presentation

A 55-year-old woman with type II diabetes, dyslipidemia, obesity and endometrial cancer status post hysterectomy and bilateral salpingo-oophorectomy presented with 1 year history of occult gastrointestinal bleeding (GIB) and severe iron deficiency anaemia. Initial oesophagogastroduodenoscopy (OGD) was consistent with chronic duodenitis without evidence of ulceration, bleeding or arteriovenous malformations. Similarly, colonoscopy revealed an ascending colon tubular adenoma but otherwise no clear source of bleeding. Contrast-enhanced (oral and intravenous) CT of her abdomen and pelvis obtained at the time of initial evaluation was unremarkable except for postsurgical pelvic changes with scarring, scant perihepatic fluid and distal colon diverticulosis. Given persistent haemoccult positive stool and refractory anaemia (haemoglobin 58 g/L, haematocrit 19.6%) despite multiple transfusions and iron supplementation she was referred to our academic medical centre for further evaluations.

Investigations

Repeat OGD colonoscopy was performed but remained noncontributory. Oral double-balloon enteroscopy was performed revealing a 1 cm diverticular-appearing lesion at 315 cm from the pylorus. The luminal mucosa surrounding the defect was intact without ulceration; however, intermittent oozing was observed both intraluminally and within the defect. No additional biopsies taken given unknown aetiology, with referral for surgical evaluation.

Laparoscopic evaluation revealed a defect on the antimesenteric aspect of ileum with fistulisation to an adjacent 12×12×3.5 cm smooth inflamed pelvic mass (figures 1 and 2) adherent to anterior abdominal wall. Both the involved segment of ileum and the pelvic mass were resected. Surgical pathology showed a 1.5 cm transmural small bowel defect with serosal inflammation in direct communication with the haemorrhagic centre of the intact pelvic mass. Pathological evaluation of the proximal, distal and mesenteric margins of the small bowel segment were free of tumour. The other margins especially in regions adherent to adjacent structures could not be assessed due to fragmented nature of the specimen. Further pathology revealed a spindle cell neoplasm (figure 3). Immunohistochemistry was diffusely positive for CD117, DOG1, and characteristically negative for Desmin, CD3 and S100 consistent with GIST of small bowel origin. Mitotic rate of >10/high power field (HPF) was reported. Additional molecular analysis revealed exon 11 PV559A mutation predicting response to imatinib and regorafenib. Staging positron emission tomography/CT was negative for evidence of distant metastases.

Figure 1.

View of luminal defect on double-balloon enteroscopy.

Figure 2.

Gross photograph of disrupted pelvic mass. Green arrow demarcates the stalk connecting mass to diverticulum. Blue arrows shows irregular margins of the mass disrupted at time of excision.

Figure 3.

High power view—tumour is composed of uniform spindle to epithelioid cells with eosinophilic cytoplasm.

Treatment

This tumour had multiple high-grade characteristics which confer a high risk of recurrence and metastasis. Specifically, this was a small bowel GIST, >10 cm in size, with mitotic index >10 (ie, any index ≥5 is considered high risk) with difficult to assess margins. As such, she was considered to be at significant risk of recurrence and thus started on imatinib 400 mg/day with plan for semiannual surveillance imaging.

Outcome and follow-up

Patient completed 6 months and 1 year imaging follow-up without evidence of recurrence. She reported tolerating the treatment with imatinib well.

Discussion

While GISTs remain the most common mesenchymal malignancy of the GI tract, they only account for 1%–2% of primary GI malignancies overall.^{1 2} Epidemiologically, GISTs are frequently diagnosed in the fifth and sixth decades of life, show male predominance, with higher prevalence among African-Americans, Asians and Pacific Islanders.^3–6 Patients with type 1 neurofibromatosis and germline KIT mutations also have an increased prevalence of GISTs.^{7 8} They can arise anywhere along the GI tract with 1% occurring in the oesophagus, 55% in the stomach, 5% in the duodenum, 30% in the jejunum or ileum, and 5% in the rectum with rare cases involving the omentum, mesentery or peritoneum.^{3 9 10} While most GISTs are <5 cm, they can grow significantly. Metastatic potential has been associated with tumour location, size and mitotic index; in general gastric GISTs <5 cm with <5 mitoses/HPF have the least malignant potential while small-intestinal GISTs >5 cm with >5 mitoses/HPF have the highest.^{5 9–11} Common sites of metatasis include peritoneal cavity and the liver, with the axial skeleton rarely involved.^{10 11} Metastatic disease can occur with a long delay—one report of liver metastesis 42 years after diagnosis—highlighting the necessity of long-term monitoring.^{9 10}

Clinical presentation varies depending on size and location of the tumour with GIB secondary to mucosal ulceration being the most common.^{11 12} Larger tumours can present with mass effect including nausea, fullness, abdominal distension and obstruction.¹¹ Contrast-enhanced CT and CT enterography are the initial diagnostic modalities of choice with employment of endoscopy or endoscopic ultrasound (EUS) in cases necessitating better characterisation of the lesion.^{13 14} Pathological evaluation using molecular and immunohistochemical techniques are diagnostic as GISTs originate from intestinal cells of Cajal, and 95% possess a gain of function mutation in tyrosine kinase receptor protein KIT detected by CD117 antibody.^{3 5 7} As seen in this case, ~90% of mutations occur in exon 11 of KIT gene permitting the use of targeted therapies like imatinib.¹⁰

Although at first this case is a classic presentation of GIST, a few points merit further discussion. First, despite its large dimensions, the tumour was not detected on initial radiographs. This may have occurred due to small size of the lesion at the time of imaging with more rapid interim growth or as a result of previous intrapelvic surgery with scarring distorting the pelvic anatomy. Most GISTs are highly vascular and show homogeneous contrast enhancement especially when smaller in size, while larger ones are more heterogeneous owing to central haemorrhage, necrosis or myxohyaline degeneration.^{11 14} A valuable teaching point here is that in setting of ongoing occult bleeding, repeat imaging (preferably with CT enterography) should have occurred to look for evolution of a previously small lesion, one with central necrosis, or one that had been missed. Second, the diverticular appearance of the lesion reported herein on endoscopy is misleading and can lead to misdiagnosis if the index of suspicion is low. Since GISTs commonly evolve from the outer muscularis layers, they tend to show exophytic growth with extension into the peritoneal cavity; overtime, many larger GISTs grow towards the luminal surface as well leading to mucosal ulceration and bleeding.^{10 11} Rarely and as seen in this case, larger small-intestinal GISTs can form central cavitation and fistulate into the intestinal lumen.¹⁰

In general, preoperative biopsy is discouraged for low operative risk individuals, as sample acquisition is largely inadequate (ie, successful in 20%–30% of cases) and risks rupture as well as dissemination.³ In cases requiring preoperative diagnosis (eg, metastatic disease where neoadjuvant imatinib may be used), EUS-guided fine-needle aspiration is the preferred modality.¹⁵ The management of GISTs is complex and beyond the scope of this paper but a few points need to be highlighted. In brief, non-metastatic GISTs can be resected surgically. Consideration for adjuvant imatinib and long-term follow-up is warranted especially in this case given the small bowel origin of the tumour, dimensions >10 cm and mitotic index >5 which are high-grade features associated with increased risk of progression.³ Moreover, the possibility of rapid interval growth given negative prior imaging and haemorrhagic necrosis of the pelvic mass suggest more aggressive features, further necessitating adjuvant therapy. In metastatic or surgically unresectable GISTs, imatinib is the modality of choice with an improved 5-year survival.^{6 10 16}

Learning points.

• While rare, gastrointestinal stromal tumours (GISTs) should be considered in all patients with occult gastrointestinal bleed.

• Repetition, pursuit of additional workup, and referal to a centre with highly specialised serives can prove fruitful in rare cases and be lifesaving.

• The advent of immunohistopathological techniques has transformed the diagnosis and treatment of GISTs with much improved outcomes.