Diagnostic Approach: Bulky Ovary with Ascites and Negative CA-125
Proceed directly to surgical exploration with comprehensive staging and intraoperative frozen section, as this presentation requires histopathological diagnosis regardless of negative tumor markers. 1, 2
Why Surgery is the Next Step
Preoperative imaging and tumor markers alone cannot definitively exclude malignancy or establish a diagnosis in this clinical scenario. 2 The combination of a bulky ovary with ascites demands tissue diagnosis, and negative CA-125 does not rule out ovarian cancer since:
- Only 50% of early-stage ovarian cancers produce elevated CA-125 3, 2
- Certain histologic subtypes (particularly mucinous carcinomas) may not elevate CA-125 3
- The negative myositis panel effectively excludes paraneoplastic myositis-associated malignancy 4
Pre-Surgical Workup Required
Before proceeding to surgery, complete the following:
Additional tumor markers:
- Measure CEA and CA 19-9 if mucinous histology is suspected, as a CA-125/CEA ratio ≤25:1 suggests gastrointestinal origin rather than primary ovarian cancer 3, 1, 2
- For patients under 35 years, measure AFP and β-hCG to exclude germ cell tumors 1, 2
Imaging:
- CT scan of chest, abdomen, and pelvis with contrast to assess for metastases and aid surgical planning 1, 2
- Consider FDG-PET/CT for indeterminate lesions when standard imaging is inconclusive 2
Gastrointestinal evaluation:
- If CEA or CA 19-9 are elevated, consider endoscopy/colonoscopy to rule out gastrointestinal primary with ovarian metastases 1, 2
Critical Pitfalls to Avoid
Do NOT attempt percutaneous biopsy or fine-needle aspiration in presumed early-stage disease, as this risks rupturing the cyst and spilling malignant cells into the peritoneal cavity, which would upstage the disease 2
Do NOT delay surgery while pursuing additional non-invasive testing—peritoneal biopsies alone are insufficient and do not provide proof of ovarian origin or degree of malignancy 2
Consider Benign Diagnoses
While malignancy must be excluded surgically, recognize that this presentation can occur with benign conditions:
Meigs syndrome or Demons-Meigs syndrome:
- Ovarian fibroma/fibrothecoma with ascites and pleural effusion can present with markedly elevated CA-125 (even >1800 IU/mL) 5, 6
- Complete resolution occurs after surgical removal of the benign tumor 5, 6
- This mimics malignant ovarian cancer clinically but has benign prognosis 5, 6
Other benign causes of ascites with elevated CA-125:
- Ovarian fibromatosis (rare, nonneoplastic) can present with ascites and slightly elevated CA-125 7
- Ruptured endometrioma can cause extremely high CA-125 (>10,000 IU/mL) with ascites 8
- Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure produce the antigen 3, 9
Ensure referral to a gynecologic oncologist or specialized cancer center for suspected ovarian malignancy to ensure proper comprehensive staging, as this is standard of care 2