Successful endoscopic resection of an unusually enlarged and pedunculated type I gastric carcinoid tumour

Abstract

Three distinct gastric carcinoid (GC) tumour types have been described based on differing biological behaviour and prognoses. Type I GC tumours account for the vast majority (70%–80%), are associated with chronic atrophic gastritis and have a low metastatic potential. Type II carcinoid tumours are the least common (5%–10%), are related to Zollinger-Ellison syndrome and occur in relation to multiple neoplasia type I. Sporadic type III tumours (15%–25%) are the most aggressive type, are unrelated to gastrin over secretion and carry the worst prognosis. In this case report, we present a patient with longstanding gastroesophageal reflux disease (GERD) who presented with epigastric abdominal pain and tarry stools and was found to have a large gastric polyp on endoscopy. Despite current literature recommending surgical resection for larger GC tumours, endoscopic resection was successfully used to excise the tumour with pathology demonstrating complete resection with negative margins.

Background

Gastric carcinoids (GCs), which are rare endocrine tumours of the stomach that develop from enterochromaffin-like (ECL) cells in the gastric wall, represent 0.5%–1.7% of all gastric cancers and 7.1% of all gastrointestinal carcinoids.^1–5

Three distinct GC tumours have been classified based on their varied biological behaviour. Type I GCs represent the majority (70%–80%), type II GCs (5%–10%), which are well differentiated, and type III GCs (15%–25%), which demonstrate the most aggressive behaviour.^{4 5} Type I GCs are typically small and multifocal lesions, grow slowly and are mostly benign. They are largely observed in the setting of hypergastrinaemia secondary to achlorhydria in autoimmune chronic atrophic gastritis. Furthermore, type I GCs are more common in women and have a good prognosis, with a 5-year survival of about 96% that does not differ from an age-matched normal population.⁵ Type II GCs are similarly expressed due to excess gastrin levels in the setting of gastrinoma from Zollinger-Ellison syndrome (ZES) in multiple neoplasia type I (MEN-I) and have malignant potential. The majority of type II GCs have a good prognosis, but a small portion behave more aggressively and up to 30% of them metastasise.⁶ Type III GCs are sporadic, typically solitary, ulcerated and often larger when compared with types I and II, usually larger than 1–2 cm. These lesions are not associated with hypergastrinaemia, can have a high malignant potential (>50%) and can be associated with carcinoid syndrome.^1–6 GC tumours can be incidentally identified in the stomach on routine endoscopy and appear as a mucosal or submucosal lesion or may be identified after presentation with symptoms, including dyspepsia, abdominal pain or early satiety.⁷

Here, we report a case of an exceptionally enlarged type I carcinoid tumour in a patient with hypergastrinaemia that was successfully treated by endoscopic resection with negative margins on pathology.

Case presentation

A 63-year-old African-American woman with a previous medical history significant for GERD, hypertension, intraductal carcinoma of the breast status post right partial mastectomy, arthritis and hypothyroidism presented to the emergency department due to a week’s duration of nausea and emesis, which was non-bloody, non-bilious. She also reported tarry stools for the past 1–2 weeks, with associated generalised weakness. She denied any weight loss in that time period. She denied history of non-steroidal anti-inflammatory drugs, alcohol or tobacco use. She had not had any previous endoscopic evaluation, including an esophagoduodenoscopy (EGD) or colonoscopy. She had been compliant with her proton pump inhibitor therapy for her GERD. Her laboratory workup revealed macrocytic anaemia with a haemoglobin of 63 g/L on admission, and, thus, she was subsequently transfused 1 unit of packed red blood cells. The gastroenterology team was consulted for evaluation.

Investigations

An EGD was completed and revealed a large, pedunculated, polypoid mass lesion that was ulcerated, friable and bleeding in the body of the stomach with a stalk (figure 1) and antral gastritis. The remaining stomach appeared normal and the scope was advanced into the duodenal bulb and second portion, which appeared normal as well. Further laboratory workup revealed a significantly elevated gastrin level of 1988 pg/mL (normal range 0–115 pg/mL). Chromogranin-A levels were significantly elevated at 300 ng/mL (normal range 0–101.8 ng/mL). Urine 5-Hydroxyindoleacetic acid levels were within normal limits. A diagnosis of pernicious anaemia was confirmed based on the patient’s macrocytosis (mean corpuscular volume 108.7), normal ferritin and decreased vitamin B₁₂ levels of 135 pg/mL (normal range 180–914 pg/mL). The elevated serum gastrin levels as well as corpus predominant atrophic gastritis suggested that the large lesion was likely a type I carcinoid tumour associated with pernicious anaemia and chronic atrophic gastritis.

Figure 1.

Endoscopic image of the lesion showing a large, ulcerated pedunculated polypoid mass of the antral stomach.

Grossly, the polypoid mass appeared rubbery, bumpy and pink in coloration (figure 2). Pathological examination of the removed mass showed a 3.5×3.0×2.8 cm well-differentiated neuroendocrine (carcinoid) tumour, with Ki-67 of less than 3%. There was no residual neuroendocrine tumour on all margins of the resected mass. The gastric mucosa revealed severe chronic inactive gastritis with focal intestinal metaplasia and prominent lymphoid foveolar hyperplasia with superficial erosions. The tumour cells were strongly and diffusely positive for chromogranin-A and synaptophysin (figure 3).

Figure 2.

Rubbery, pink polypoid mass with nodularity.

Figure 3.

Grossly received is a 3.5×3 x 2.8 cm mass with a 0.9×0.8 cm base (deep resection margin). Microscopically, the mass is composed of a submucosal tumour with moderately chronic inactive gastritis, prominent foveolar hyperplasia, focal intestinal metaplasia, and superficial erosions (A). The tumour cells are relatively monotonous arranged in predominantly glandular structures (B). Rare mitotic activity is present (C). No necrosis is seen. The immunohistochemical studies are performed and the tumour cells are diffusely and strongly positive for synaptophysin and chromogranin (D). The ki-67 proliferative index is <3%. The above features are consistent with grade 1 well-differentiated gastric neuroendocrine tumour. The tumour is completely excised with clear margin.

Treatment

Due to the pedunculated nature of the polyp and the patient’s recent gastrointestinal bleed, snare polypectomy was used to directly entangle the base followed by coagulation electrotomy. Due to the very large size of the polyp, a basket had to be used in order to retrieve the mass, which was sent for pathological analysis. Post excision of the lesion, an artery with blood spurting out was observed at the base of the polypectomy site. Haemostasis was achieved by endoscopic injection therapy with epinephrine solution and using two clips. The postoperative course was uneventful. Haemoglobin levels remained within normal range until the day of discharge.

The patient was started on sucralfate 1 g before meals and at bedtime, pantoprazole 40 mg two times per day as well as vitamin B₁₂ 1000 μg intramuscular weekly × 4 doses and then monthly indefinetely. A surgical consult was also placed in case of rebleed. Postprocedure, CT abdomen/pelvis and thorax scans were ordered to rule out any possible metastasis, which were negative for any abdominal, pelvic or thoracic masses or any lymphadenopathy. To complete her workup, a colonoscopy was completed, which was negative for any mass lesions.

Outcome and follow-up

Due to the unusually large size of the type I carcinoid tumour, the patient’s case was presented and discussed at the Multidisciplinary Tumour Conference. Due to the fact that the large carcinoid polyp was entirely resected endoscopically with negative margins, the multidisciplinary team agreed that there was no role for surgery or adjuvant treatment. It was recommended for the patient to follow-up for a repeat EGD in 3–6 months and biannually thereafter. The patient was discharged home in stable and improved condition and scheduled for her follow-up EGD.

Follow-up endoscopy at the 3-month mark failed to reveal the reappearance of any nodules at the original or other sites. The patient remains disease and symptom free after 6 months.

Discussion

Type I GC tumours are associated with atrophic gastritis and pernicious anaemia, typically present as multiple lesions located in the mucosa, with a diameter <2 cm. Similar to type I GCs, type II GCs occur in the context of hypergastrinaemia but in relation to ZES and MEN-I, typically presenting with a diameter >2 cm. Type III tumours are the most aggressive, present as single and large tumours without gastrin over-secretion.

Many lesions are detected at routine endoscopy as incidental findings. The gold standard for diagnosing GC is endoscopic biopsy and immunohistochemical study for chromogranin-A and synaptophysin.^7–9 Serum chromogranin-A appears to be the most useful diagnostic marker in the diagnosis of GCs with a sensitivity higher than 90%. It is also well correlated to tumour burden, especially in the presence of liver metastasis, making it a valuable marker in follow-up after treatment is initiated.⁹ Further staging can be completed by ultrasound and CT scan. Additionally, it is important to determine the proliferative index Ki-67 and to evaluate the mitotic index in order to reach a more accurate management plan.^{8 9} If margins are positive after endoscopic resection, endoscopic ultrasonography can be used to provide useful information in large tumours >1 cm in terms of exact depth of tumour invasion.¹⁰

Endoscopic mucosal resection and surgical resection are currently the main means of treatment of carcinoid tumours, usually tailored to the type of tumour and underlying stimulus. Multiple studies have demonstrated that endoscopic resection is a minimally invasive technique that can be effectively and safely employed in certain eligible patients.^11–14 Per the American Society for Gastrointestinal Endoscopy, the indications for endoscopic treatment include a diameter <1 cm, few (3–5 lesions) and well-differentiated lesions.¹⁵ Additionally, if excision of pathology specimens has negative margins and negative vessel metastasis, no further surgery is needed. Surgical resection in the form of antrectomy is indicated when endoscopic resection fails or for lesions more than five, larger ≥1 cm and aggressive tumours. Based on these criteria, type I carcinoids can be usually removed by endoscopic resection, while types II and III are typically removed by surgical resection.^{11–14 16}

An alternative strategy is to perform a surgical intervention to reduce the gastrin level, that is, antrectomy. Antrectomy removes antral G cells, which are overactive as a result of the achlorhydria caused by parietal cell destruction and reduces circulating gastrin to a level that does not promote significant ECL cell hyperplasia, thus leading to carcinoid regression and inhibiting additional carcinoid formation.¹⁷ In type II carcinoids, surgical removal of the gastrinoma, if feasible, will likewise remove the source of gastrin hormone and result in the complete cessation of GC growth. For type III carcinoids, which are completely autonomous of gastrin stimulation, complete excision of the primary lesion prior to development of metastases via endoscopic or surgical resection is warranted and should result in long-term cure.

The choice of management for type I GCs remains controversial and includes medical antigastrin therapy (diet, acidification, octreotide), endoscopic surveillance and resection and antrectomy.11–14 16–20 Hung et al recommend that gastric resection should be pursued for any large lesions (>1.5 cm to 2 cm) or lesions that have deeply penetrated the stomach wall into the submucosa or muscularis.²¹ Based on their single-institution experience with type I GC tumours, Dakin et al concluded that while gastric antrectomy is the most efficacious treatment for type I GCs, leading to a significant reduction in serum gastrin levels and regression of carcinoid tumours, simple endoscopic polypectomy for small solitary type I GC tumours is recommended and laparoscopic antrectomy should be reserved for large (>1 cm) tumours, multicentric tumours or tumour recurrence.²²

Alternatively, some studies have demonstrated that type I carcinoid tumours may be successfully treated medically with somatostatin analogues.^23–28 Khuroo and colleagues showed that octreotide-LAR (long acting and repeatable) therapy causes regression of type I GC tumours, with no recurrence of tumours up to 3 years after cessation of therapy, despite persistent hypergastrinaemia. Thus, the authors concluded that octreotide medical treatment should be a consideration for the treatment of type I carcinoids, especially in patients who are at high risk for surgery due to comorbid diseases or who refuse surgery.²⁸

While there is no formal guideline on the follow-up and surveillance of these patients, upper endoscopy performed either two times annually or annually is recommended to excise visualised tumours and to ensure that no single lesion is enlarging.

In this case report, the patient had an unusually enlarged type I carcinoid tumour, with a size of 3.5 cm in its greatest dimension. In conjunction with type I GCs, our patient’s tumour had been mostly asymptomatic, and only became symptomatic once it significantly increased in size. The patient had hypergastrinemia, with a medical history of GERD and laboratory workup demonstrating elevated serum gastrin levels. Additionally, histology demonstrated gastric mucosa with severe chronic inactive gastritis and focal intestinal metaplasia with prominent lymphoid foveolar hyperplasia with superficial erosions. Unlike typical type I tumours that are generally small and multiple, our patient’s tumour was single, ulcerated and very large, measuring up to 3.5×3×2.8 cm in size. To our knowledge, this is the first case of an unusually enlarged type I polypoid carcinoid tumour of the stomach that has been completely excised, tumour free, by endoscopic intervention. Despite the large size of the tumour, its pedunculated nature allowed for the consideration of endoscopic resection. One of our concerns with endoscopic resection was that it would become trapped in and occlude the oesophagus on retrieval if endoscopically resected and removed. However, we were able to successfully resect the lesion in whole endoscopically with negative margins, and successfully retrieve it using an endoscopic basket. Additionally, it was crucial to ensure postprocedure that the tumour was limited to the mucosa and submucosa without involving the muscularis propria or serosa on pathological evaluation.

While the general consensus on type I GC tumours is that they are relatively benign with a tendency towards distant spread of less than 5%, metastatic progression has been described.^{29 30} Thus, it is crucial not to overlook this possibility when considering endoscopic removal. A study examining prognostic factors in 20 patients with type I GCs identified several factors associated with metastasis: tumour size of ≥1 cm, elevated Ki-67 index of tumour proliferation and high serum gastrin levels (mean value 2138.4 mL/L).³⁰ In our case, while the tumour size was ≥1 cm, the ki-67 proliferative index was less than 3%, and serum gastrin levels, while elevated, did not exceed the mean value associated with metastasis. Thus, the likelihood of metastasis in our patient was low based on the above criteria, especially considering the negative margins achieved on pathological examination. This was further confirmed by negative CT scans and colonoscopy. Therefore, the decision was made to monitor the patient with surveillance endoscopy at the 3-month mark to exclude the formation of new lesions given the persistent hypergastrinaemia.

To our knowledge, this is the first report of a significantly enlarged type I carcinoid tumour of the stomach that was completely excised with clear margins, endoscopically. In this case, the pedunculated nature of the mass lesion, its association with chronic atrophic gastritis predicting a type I carcinoid and, thus, a histologically less aggressive tumour and, finally, the patient’s anaemic status justified the endoscopic resection and repeated follow-up endoscopies as a treatment strategy. This report demonstrates the feasibility of en bloc endoscopic resection of even large carcinoids, sparing the patient the morbidity and potential mortality associated with surgical intervention.

Patient’s perspective.

When I first found out that I had a mass in my stomach, I felt a sudden sense of doom and the first thing I imagined was that it was cancer and I regretted not coming in sooner. But my medical team eased many of my worries. They walked me through the plan and answered all of my questions. I was very grateful that my medical team was able to remove the mass just with an EGD and I did not have to undergo surgery to have it removed. I am older and I worried about having surgery, and I did not want that. I was very relieved when I learnt of the negative pathology report and that I did not have to undergo any surgery.

Learning points.

• Endoscopic resection of significantly enlarged type I gastric carcinoid (GC) tumours is possible if certain criteria are met, including having a pedunculated lesion, which makes snaring of the lesion feasible.

• For lesions with negative margins postresection, endoscopic follow-up with sampling for histology is considered a sufficient option.

• A multidisciplinary discussion is crucial to ascertain the follow-up requirements for a patient with an enlarged type I GC that is endoscopically removed, without further surgical intervention

Ethics statements

Patient consent for publication

Obtained.