Gastrinoma with Local Metastatic Lymph Node Causing Zollinger–Ellison Syndrome: Pathophysiology, Imaging Features, Diagnosis, and Management

on

 Keywords: Gastrinoma, Zollinger–Ellison Syndrome, Neuroendocrine Tumor, Ga-68 DOTATATE PET/CT

Introduction

Gastrinoma is a rare but clinically significant functional neuroendocrine tumor (NET) characterized by autonomous gastrin secretion, resulting in profound gastric acid hypersecretion and the development of Zollinger–Ellison syndrome (ZES). Despite its rarity, gastrinoma remains a critical diagnosis due to its association with refractory peptic ulcer disease, chronic diarrhea, and potential metastatic spread—most commonly to regional lymph nodes and the liver.

With the advent of Ga-68 DOTATATE PET/CT, the diagnostic accuracy for gastrinoma and other neuroendocrine tumors has improved dramatically, allowing precise localization of small primary lesions and metastatic lymph nodes that were previously occult on conventional imaging.

This article presents a comprehensive, expert-level review of gastrinoma with a local metastatic lymph node causing Zollinger–Ellison syndrome, integrating pathophysiology, epidemiology, clinical presentation, imaging features, differential diagnosis, diagnosis, treatment, and prognosis, based on the most authoritative contemporary literature and the provided imaging case.

Pathophysiology of Gastrinoma and Zollinger–Ellison Syndrome

Gastrinomas originate from neuroendocrine cells that secrete gastrin independent of normal regulatory mechanisms. Excessive gastrin stimulates parietal cells via cholecystokinin-B (CCK-B) receptors, leading to:

  • Marked gastric acid hypersecretion
  • Hypertrophy of gastric folds
  • Refractory peptic ulcers
  • Mucosal injury extending beyond the duodenal bulb

The persistently high acid load overwhelms the buffering capacity of the small intestine, causing inactivation of pancreatic enzymes, impaired fat absorption, and secretory diarrhea—a hallmark of ZES.

Approximately 20–30% of gastrinomas are associated with Multiple Endocrine Neoplasia type 1 (MEN1), in which tumors are often multifocal and arise predominantly in the duodenum rather than the pancreas.

Epidemiology

  • Annual incidence of pancreatic neuroendocrine tumors (pNETs): ~0.8 per 100,000
  • Gastrinomas account for ~30–40% of functional pNETs
  • Duodenal gastrinomas are more common than pancreatic gastrinomas
  • Duodenal tumors are typically <1 cm, while pancreatic gastrinomas average 3–4 cm
  • Local lymph node metastasis is common at diagnosis, even with small primary tumors

Clinical Presentation

Patients with gastrinoma classically present with:

  • Refractory or recurrent peptic ulcer disease
  • Ulcers in atypical locations (distal duodenum, jejunum)
  • Chronic abdominal pain
  • Nausea and vomiting
  • Chronic watery diarrhea
  • Gastroesophageal reflux disease resistant to therapy

Case Correlation

The presented 62-year-old woman had:

  • Abdominal pain, vomiting, and intermittent diarrhea
  • History of GERD
  • Multiple non-bleeding duodenal and jejunal ulcers on EGD
  • No NSAID use

These features are classic for Zollinger–Ellison syndrome.

Imaging Features

Figure 1. Contrast-Enhanced CT of the Abdomen and Pelvis

Axial and coronal contrast-enhanced CT images demonstrate marked gastric, duodenal, and jejunal wall thickening with mucosal hyperenhancement and mild surrounding inflammatory changes, suggestive of severe acid-related gastroenteritis rather than primary inflammatory bowel disease.

Key CT Findings in Gastrinoma/ZES:

  • Diffuse gastric and proximal small bowel wall thickening
  • Prominent mucosal enhancement
  • Secondary inflammatory changes
  • Primary tumors often small and difficult to visualize

Figure 2. Ga-68 DOTATATE PET/CT

Ga-68 DOTATATE PET/CT demonstrates two foci of intense somatostatin receptor–avid uptake: one corresponding to a ~1 cm soft tissue lesion in the duodenum, consistent with a primary gastrinoma, and another corresponding to a ~1 cm regional lymph node, indicating local metastatic disease.

Key PET/CT Features:

  • DOTATATE binds somatostatin receptor subtype 2 (SSTR2)
  • Physiologic uptake: spleen > liver > kidneys > adrenals > pituitary
  • Pathologic uptake: focal, intense uptake exceeding background activity

Differential Diagnosis

  • Nonfunctional neuroendocrine tumor
  • Functional NETs:
    • Insulinoma
    • VIPoma
    • Glucagonoma
    • Somatostatinoma
  • Severe infectious gastroenteritis
  • Medication-induced mucosal injury
  • Ischemic bowel disease

Diagnosis

Definitive diagnosis requires biochemical, imaging, and clinical correlation.

Diagnostic Criteria

  • Fasting serum gastrin level >10× upper limit of normal
  • Gastric pH <2
  • Positive somatostatin receptor imaging

Case Diagnosis

  • Gastrin level: 1154 pg/mL (>10× ULN)
  • Ga-68 DOTATATE PET/CT: focal duodenal lesion + metastatic lymph node

Final Diagnosis:
Gastrinoma with local metastatic lymph node causing Zollinger–Ellison syndrome

Treatment

Medical Management

  • High-dose proton pump inhibitors (PPIs): cornerstone of therapy
  • Control acid hypersecretion and prevent complications

Surgical Management

  • Curative resection for localized disease
  • Lymph node dissection improves long-term outcomes

Advanced Disease

  • Somatostatin analogs
  • Peptide receptor radionuclide therapy (PRRT, e.g., ¹⁷⁷Lu-DOTATATE)
  • Targeted therapies

Prognosis

  • Excellent symptom control with PPIs
  • 10-year survival:
    • Localized disease: >90%
    • Liver metastasis: significantly worse
  • Isolated lymph node metastasis has a favorable prognosis

Quiz

Question 1. Which imaging modality is most sensitive for detecting small gastrinomas?

A. Contrast-enhanced CT
B. MRI
C. Ga-68 DOTATATE PET/CT
D. FDG PET/CT

Answer: C. Explanation: Ga-68 DOTATATE PET/CT targets SSTR2, highly expressed in gastrinomas.

Question 2. What receptor does Ga-68 DOTATATE bind to?

A. Dopamine receptor
B. Serotonin receptor
C. Somatostatin receptor subtype 2
D. HER2 receptor

Answer: C. Explanation: DOTATATE has high affinity for SSTR2.

Question 3. Which feature most strongly suggests Zollinger–Ellison syndrome?

A. Single gastric ulcer
B. NSAID use
C. Refractory ulcers in distal duodenum and jejunum
D. Normal gastrin level

Answer: C. Explanation: Distal, refractory ulcers are classic for ZES.

References

  1. R. T. Jensen et al., “Gastrinoma (duodenal and pancreatic),” Neuroendocrinology, vol. 84, no. 3, pp. 173–182, 2006.
  2. M. S. Hofman et al., “Somatostatin receptor imaging with 68Ga-DOTATATE PET/CT,” Radiographics, vol. 35, no. 2, pp. 500–516, 2015.
  3. T. A. Hope et al., “NANETS/SNMMI procedure standard for PRRT,” J. Nucl. Med., vol. 60, no. 7, pp. 937–943, 2019.
  4. K. Öberg, “Management of functional pancreatic NETs,” Gland Surg., vol. 7, no. 1, pp. 20–27, 2018.
  5. S. U. Dalm et al., “Receptor targeted nuclear imaging,” Int. J. Mol. Sci., vol. 18, no. 2, p. 260, 2017.
  6. E. Cives and J. R. Strosberg, “Gastroenteropancreatic neuroendocrine tumors,” CA Cancer J Clin, vol. 68, pp. 471–487, 2018.
  7. R. Modlin et al., “Neuroendocrine tumor epidemiology,” Lancet Oncol., vol. 9, pp. 61–72, 2008.

Comments

Post a Comment