Surgical Exploration with Intraoperative Frozen Section is the Next Step
When MRI suggests ovarian carcinoma but biopsy/FNAC is not feasible and CA125 is normal, proceed directly to surgical exploration with comprehensive staging, utilizing intraoperative frozen section to guide the extent of surgery. 1, 2
Why Surgery is the Definitive Next Step
Preoperative imaging alone is insufficient for precise staging or definitive diagnosis - surgical exploration with histopathological examination is necessary for confirmation of diagnosis and staging, except in cases with obvious stage IV disease 1
Fine-needle aspiration should be avoided in presumed early-stage disease to prevent rupturing the cyst and spilling malignant cells into the peritoneal cavity 1
Normal CA125 does not exclude malignancy - CA125 is elevated in only ~50% of early-stage ovarian cancers, though it reaches ~85% sensitivity in advanced disease 2, 3, 4
Intraoperative frozen section can guide the extent of surgery by providing rapid preliminary diagnosis, though interpretation may be difficult for distinguishing well-differentiated adenocarcinomas from borderline tumors 1
Pre-Surgical Workup to Complete First
Before proceeding to surgery, ensure the following are completed:
CT scan of chest/abdomen/pelvis with contrast (unless contraindicated) to assess for metastases and aid surgical planning 1, 2
Additional tumor markers if mucinous histology suspected: Measure CEA and CA19-9, as a CA125/CEA ratio ≤25:1 suggests gastrointestinal origin rather than primary ovarian cancer 2, 5
For young women (<35 years): Measure AFP and β-hCG to exclude germ cell tumors 1, 2
FDG-PET/CT may be useful for indeterminate lesions when standard imaging is inconclusive 1
Surgical Approach and Staging Requirements
The surgical procedure must include comprehensive staging components:
Total hysterectomy with bilateral salpingo-oophorectomy (for postmenopausal women or when fertility preservation is not desired) 6
Complete surgical staging procedures: Multiple peritoneal biopsies, omental sampling, pelvic and para-aortic lymph node assessment, peritoneal washings for cytology 6
Adequate tissue sampling is critical - peritoneal biopsies alone are insufficient and do not provide proof of ovarian origin or degree of malignancy 1
Proper surgical staging is an independent prognostic factor for improved disease-free and overall survival, and distinguishes true early-stage disease from occult advanced disease (found in 16-42% of presumed early cases) 6
Critical Pitfalls to Avoid
Do not delay surgery for tissue diagnosis - attempting percutaneous biopsy risks tumor spillage and upstaging in early disease 1
Do not rely on CA125 alone - normal values occur in 50% of early-stage cancers and can be elevated in benign conditions (endometriosis, PID, benign cysts) 2, 5, 3
Ensure adequate surgical expertise - referral to a gynecologic oncologist or specialized cancer center is standard for suspected ovarian malignancy to ensure proper staging 1
For mucinous tumors, rule out gastrointestinal primary - consider gastrointestinal tract evaluation (endoscopy/colonoscopy) if CEA or CA19-9 are elevated, as metastases to the ovary can mimic primary ovarian cancer 1, 2
Special Consideration for MRI Findings
MRI features suggesting malignancy include: Solid components, irregular walls, thick septa, papillary projections, intense enhancement, bilateral involvement, and secondary signs like ascites or peritoneal disease 7, 8
Even with normal CA125, MRI findings of malignancy warrant surgical exploration - one case report demonstrated that even slightly elevated CA125 (48 U/mL) in a borderline tumor with concerning MRI features progressed to metastatic disease 8