What tumor markers are elevated in appendiceal cancers, including carcinoid tumors and adenocarcinomas?

Tumor Markers for Appendiceal Cancers

For appendiceal cancers, chromogranin A is the primary tumor marker for carcinoid tumors, while 5-HIAA is useful for serotonin-producing tumors; adenocarcinoid/goblet cell carcinoids may show limited elevation of these markers and should be managed according to colon cancer protocols. 1

Carcinoid Tumors of the Appendix

• Chromogranin A (CgA) is the most useful general marker for appendiceal carcinoid tumors, with elevated levels associated with recurrence and poorer survival outcomes 1
• CgA levels elevated twice the normal limit or higher correlate with shorter survival times in patients with metastatic neuroendocrine tumors (hazard ratio 2.8) 1
• 5-Hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite measured in 24-hour urine samples, is particularly useful for serotonin-producing appendiceal carcinoids 1
• Platelet serotonin has shown the highest discriminating capacity for diagnosing carcinoid tumors, especially for foregut carcinoids that produce small amounts of serotonin 2
• Chromogranin B (CgB) may be elevated when CgA is in the reference range, making it a useful additional marker 1
• Pancreastatin, a post-translational product of CgA, is specifically elevated in metastatic neuroendocrine tumors and not affected by conditions that commonly elevate CgA 1

Important Considerations and Limitations

• CgA levels can be falsely elevated in several conditions including:
  • Renal or hepatic insufficiency 1
  • Concurrent use of proton pump inhibitors 1
  • Atrophic gastritis 1
• 5-HIAA measurements require strict dietary restrictions for 48 hours before and during collection:
  • Avoid foods including avocados, bananas, cantaloupe, eggplant, pineapples, plums, tomatoes, nuts, kiwi, dates, grapefruit 1
  • Avoid coffee, alcohol, and smoking 1
  • Medications that can increase 5-HIAA include acetaminophen, ephedrine, diazepam, nicotine, guaifenesin, and phenobarbital 1
• Rising CgA levels in an asymptomatic patient with stable imaging does not necessarily indicate need for new therapy 1

Adenocarcinoid/Goblet Cell Carcinoids

• These tumors show features of both adenocarcinoma and neuroendocrine tumors 3, 4
• Conventional neuroendocrine markers have limited diagnostic value:
  • CgA is only slightly elevated in some cases 3
  • Urinary 5-HIAA is typically normal 3
  • Somatostatin receptor scintigraphy (Octreoscan) is positive in only a subset of patients with metastatic disease 3
• Ki67 proliferation index >20% appears to predict more aggressive tumor behavior 3
• These tumors should be managed according to colon cancer protocols rather than typical carcinoid protocols 1

Surveillance Recommendations

• For typical appendiceal carcinoids ≤2cm without aggressive features:
  • Follow-up examinations as clinically indicated 1
  • Some institutions recommend examination at 1 year post-appendectomy and then with decreasing frequency 1
• For larger tumors or those with aggressive features:
  • Monitoring with CgA and 5-HIAA (if elevated at baseline) every 3-6 months 1
  • CT or MRI imaging once yearly for up to 10 years 1
• Somatostatin receptor scintigraphy (Octreoscan) is not routinely recommended for surveillance after definitive resection but may be useful to assess disease location and burden in cases of suspected recurrence 1