Reassure, resect or retreat?

July 16, 2015 By: Bjorn Rembacken

Reassure, resect or retreat?

What's the diagnosis and management of this nodule likely to be?

This video clip shows a nodule that was found on the greater curve of the stomach in a 35-year-old man referred for a gastroscopy because of symptoms of reflux oesophagitis.

You take a full set of samples and after the examination the patient asks what the management of the lesion is likely to be.

What do you tell the patient?

a) This is probably a hyperplastic polyp and eradication of any Helicobacter pylori may well induce spontaneous regression. You tell the patient that he will most likely be offered another examination in a year to reassess the stomach after treatment to eradicate Helicobacter pylori.

b) This is probably a gastrointestinal stromal tumour (GIST). You tell the patient that he is likely to be offered an assessment by endoscopic ultrasonography (EUS) and, as the lesion is small, it is likely that surveillance will be offered.

c) This is probably a neuroendocrine tumour (NET). You tell the patient that it is likely to require surgical resection.

d) This is probably an early gastric cancer. You tell the patient that he is likely to be offered an attempt at endoscopic resection.

e) This is probably an advanced gastric cancer. You tell the patient that he is likely to be offered a gastrectomy. 

Discussion

This is a firm nodule covered with a relatively normal-looking mucosa. The differential diagnosis thus rests between a NET and a GIST, both of which arise below the surface mucosa. Endoscopically, the lesion looks more like a NET with its typical dilated vessels close to the head of the polyp. The incidence of NETs is increasing and is now around 5.25/100,000/year.1 Up to 30% of NETs are found in the stomach,2 where they are subclassified into three distinct groups:

  • Type 1 NETs are the most common type (they account for 70%–80% of all gastric NETs). Type 1 NETs are associated with achlorhydria (e.g. due to chronic atrophic gastritis or pernicious anaemia), where high levels of gastrin induce hyperplasia of histamine-secreting cells in the gastric body that are called enterochromaffin-like (ECL) cells. The continuous stimulation of the ECL cells to grow ultimately leads to the growth of multiple small carcinoid tumours in the gastric body. In this case, the patient has symptoms of reflux oesophagitis, which eliminates the possibility that the lesion is a type 1 NET. Patients with atrophic gastritis and achlorhydria are unlikely to complain of heartburn!
  • Rarely, NETs are associated with pancreatic or duodenal gastrinomas as part of the Zollinger–Ellison syndrome or multiple endocrine neoplasia type 1 (MEN 1). These are called type 2 NETs and they only account for about 5% of cases. Patients with type 2 carcinoids have high gastrin levels and high acid levels and therefore present with symptoms of peptic ulcer disease, diarrhoea or reflux esophagitis.3 Endoscopically, type 2 NETs appear similar to type 1 NETs, with multiple, small gastric nodules. However, there is no gastric atrophy in the surrounding mucosa of type 2 NETs. For this reason, it is important to not only sample the lesion but also the surrounding mucosa in cases of suspected NETs. Type 2 NETs are more aggressive than type 1 NETs—at the time of diagnosis, up to 30% of patients have lymph-node metastases and up to 10% have liver metastases.4
  • Finally, sporadic NETs of the stomach (type 3 gastric NETs) are usually single, large (>1 cm in 70%) and aggressive. In more than 70% of cases, there are lymph-node metastases and/or distant metastases at the time of diagnosis.5

 

As this is a single, large lesion with dilated vessels leading up to the head of the polyp, the best guess for endoscopic diagnosis is that this is a type 3 NET!  To save time, I would now set in motion the standard ‘carcinoid workup’. This workup includes measurement of plasma chromogranin A (pCgA) levels. CgA is produced by all cells derived from the neural crest and high levels are found particularly in patients with metastatic disease. In addition, you should request a ‘gut hormone screen’ (measurement of gastrin, glucagon, vasointestinal peptide, somatostatin and pancreatic polypeptide levels). Finally, you should request either an ‘octreotide scan’ (somatostatin receptor scintigraphy) or, even better, a PET/CT scan using peptides that bind to somatostatin receptors (68Gallium-DOTA-TOC/NOC/TATE).6

What about management of gastric NETs? As type 1 NETs are usually benign, it has been recommended that patients who have up to six nodules that are no larger than 2 cm may be managed endoscopically.7 However, patients with a larger lesion or more than six carcinoids are considered for local surgical resection.8 Of course, an antrectomy would eliminate the source of the hypergastrinaemia and may also result in tumour regression.9

In patients who have type 2 NETs (secondary to an endocrine syndrome), somatostatin analogs may result in regression of the gastric NET.10 However, treatment is also aimed at finding and resecting the primary duodenal or pancreatic tumour that is driving the syndrome.

Type 3 NETs are managed in the same way as gastric cancers, with at least a partial gastrectomy and lymph-node dissection. After resection, the mitotic rate within the tumour is assessed by immunohistochemistry. This allows the tumour to be graded according to the WHO classification (grade 1, ≤2%; grade 2, 3–20%; grade 3, >20%).

In this particular case, a subtotal gastrectomy was carried out and revealed a WHO grade 2 sporadic (type 3) NET that was confined to the mucosa and submucosa. However, 2 out of 25 lymph nodes contained metastatic disease!

 

References 

  1. Yao JC, Hassan M, Phan A, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26: 3063–3072. 
  2. Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717–1751. 
  3. Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore). 2000; 79: 379–411.
  4. Norton JA, Melcher ML, Gibril F, et al. Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery 2004; 136: 1267–1274. 
  5. Rindi G, Bordi C, Rappel S, et al. Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg 1996; 20: 168–172. 
  6. Rockall AG and Reznek RH. Imaging of neuroendocrine tumours (CT/MR/US). Best Pract Res Clin Endocrinol Metab 2007; 21: 43–68. 
  7. Hou W and Schubert ML. Treatment of gastric carcinoids. Curr Treat Options Gastroenterol 2007; 10: 123–133. 
  8. Ruszniewski P, Delle Fave G, Cadiot G, et al. Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 2006; 84: 158–164. 
  9. Hirschowitz BI, Griffith J, Pellegrin D, et al. Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy. Gastroenterology 1992; 102: 1409–1418. 
  10. Tomassetti P, Migliori M, Caletti G, et al. Treatment of type II gastric carcinoid tumors with somatostatin analogs. N Engl J Med 2000; 343: 551–554.

 

 

Answer

 

Correct answer: c.

 

 

About the author

Bjorn Rembacken is at Leeds Teaching Hospitals NHS Trust, Leeds, UK. He was born in Sweden and qualified from Leicester University in 1987. He undertook his postgraduate education in Leicester and in Leeds. His MD was dedicated to inflammatory bowel disease. Dr Rembacken was appointed Consultant Gastroenterologist, Honorary Lecturer at Leeds University and Endoscopy Training Lead in 2005. Follow Bjorn on Twitter @Bjorn_Rembacken

 

Comments

Mohamed, July 21, 2015 13:25
why not do eus , and see the layer of origin, and stage if lymphadenopathy is present , do CEA and chromogranin,

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