Serum Tumor Markers for Abdominal Mass or Epigastric Pain
For patients presenting with an abdominal mass or unexplained epigastric pain, the selection of tumor markers depends critically on clinical context: CA 125 for suspected ovarian/pelvic masses in women, chromogranin A for suspected neuroendocrine tumors, and AFP/beta-hCG for young patients with concern for germ cell tumors, while routine tumor marker panels are not indicated for uncomplicated epigastric pain without a mass. 1
Clinical Algorithm for Tumor Marker Selection
For Pelvic/Lower Abdominal Mass in Women
- CA 125 should be measured when imaging reveals a suspicious pelvic mass, particularly in postmenopausal women or those with ascites 1
- AFP and beta-hCG should be ordered for women younger than 35 years with a pelvic mass to assess for germ cell tumors 1
- Inhibin can be measured if clinically indicated for suspected sex cord-stromal tumors 1
- The NCCN explicitly states that HE4 and CA 125 combined (ROMA algorithm) are not recommended for determining malignancy status of an undiagnosed pelvic mass, despite FDA approval 1
For Suspected Neuroendocrine Tumors
- Chromogranin A is elevated in 60% or more of patients with functioning or nonfunctioning pancreatic neuroendocrine tumors and should be measured when these are suspected 1
- Critical caveat: Proton pump inhibitors cause spuriously elevated chromogranin A levels; patients must discontinue PPIs for at least 1 week before testing 1
- False elevations also occur with renal failure, liver failure, hypertension, and chronic gastritis 1
- 24-hour urinary 5-HIAA should be ordered for suspected midgut carcinoid tumors (usually raised in 70% of patients) 1
For Functioning Pancreatic Neuroendocrine Tumors
When specific syndromes are suspected based on symptoms, order targeted markers 1:
- Gastrinoma: Fasting gastrin levels with gastric secretion studies (must be off PPIs for ≥1 week) 1
- Insulinoma: Fasting insulin, glucose, and C-peptide during supervised 48-72 hour fast; insulin >3 mcIU/mL when glucose <40-45 mg/dL with insulin/glucose ratio ≥0.3 indicates insulinoma 1
- Glucagonoma: Fasting pancreatic glucagon and enteroglucagon 1
- VIPoma: Fasting vasoactive intestinal peptide 1
- Somatostatinoma: Fasting somatostatin 1
For Uncomplicated Epigastric Pain Without Mass
Tumor markers are NOT indicated as initial testing 2, 3, 4
- The British Society of Gastroenterology and American College of Radiology recommend H. pylori breath or stool testing as the baseline investigation for chronic epigastric pain without alarm features 2, 4
- Endoscopy is reserved for patients ≥55 years with persistent symptoms, or any age with alarm features (weight loss, dysphagia, bleeding, vomiting, anemia) 2, 3
- Routine tumor marker screening in this population leads to false positives and unnecessary anxiety without improving outcomes 2, 4
Common Pitfalls to Avoid
- Do not order chromogranin A in patients actively taking PPIs—this is the most common cause of false-positive results and will lead to unnecessary imaging and procedures 1
- Do not order CA 125 in premenopausal women with simple ovarian cysts—physiologic cysts commonly elevate CA 125, leading to overtreatment 1
- Do not order broad tumor marker panels (CEA, CA 19-9, etc.) for undifferentiated abdominal pain—these lack specificity and generate false positives that complicate rather than clarify diagnosis 2, 4
- Do not skip imaging before ordering tumor markers—ultrasound or CT should characterize the mass first to guide appropriate marker selection 1, 5
When Imaging Should Precede Tumor Markers
- For suspected intra-abdominal masses, contrast-enhanced CT or ultrasound should be performed first to characterize the mass location, size, and organ of origin 5
- For pelvic masses, ultrasound is the initial imaging modality, with CT useful for assessing metastases and MRI for determining malignant potential when ultrasound is equivocal 1
- Tumor markers should then be selected based on imaging findings and clinical suspicion rather than ordered reflexively 1, 5