In an adult woman with a pelvic/abdominal mass that is immunohistochemically positive for carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), and cancer antigen 125 (CA‑125), what is the most likely diagnosis and recommended management?

Immunohistochemical Profile: CEA+, CK7+, CA125+ in Pelvic/Abdominal Mass

This immunohistochemical profile (CEA+, CK7+, CA125+) in an adult woman with a pelvic/abdominal mass most strongly suggests a primary ovarian mucinous adenocarcinoma, though metastatic gastrointestinal adenocarcinoma must be definitively excluded before treatment.

Differential Diagnosis Based on IHC Pattern

Primary Ovarian Mucinous Carcinoma (Most Likely)

• CK7 positivity is typically more extensive than CK20 in primary ovarian mucinous tumors, distinguishing them from metastatic colorectal adenocarcinoma where CK20 staining predominates over CK7 1
• Primary ovarian mucinous carcinomas commonly express CEA, CA19.9, and can show variable CK20 positivity 1
• CA125 positivity supports an ovarian primary, as it is typically positive in ovarian carcinomas and negative or only focally positive in gastrointestinal metastases 1
• Research confirms that 96% of primary ovarian adenocarcinomas are CK7-positive, compared to only 25% of metastatic colorectal carcinomas 2

Metastatic Gastrointestinal Adenocarcinoma (Must Exclude)

• Metastases to the ovaries from gastrointestinal primaries are actually more common than primary mucinous ovarian tumors, making this distinction critical 1
• Metastatic colorectal adenocarcinoma typically shows CK20+/CK7- pattern with strong CEA positivity 1
• The presence of CA125 positivity argues against colorectal origin, as only 10% of gastrointestinal metastases express CA125 1

Other Considerations

• Metastatic pancreatic or biliary adenocarcinoma can mimic primary ovarian mucinous neoplasms and may show diffuse CK7 positivity with variable CK20 and CEA positivity 1
• High-grade serous ovarian carcinoma typically shows CA125 and WT1 positivity but would be less likely to show prominent CEA positivity 1

Critical Diagnostic Algorithm

Step 1: Calculate CA-125/CEA Ratio

• If CA-125/CEA ratio is >25, this strongly favors an ovarian primary over gastrointestinal origin 1, 3
• If CA-125/CEA ratio is ≤25, gastrointestinal primary must be excluded with endoscopy 1

Step 2: Additional IHC Markers to Order

• CK20 staining pattern: Focal/negative favors ovarian primary; diffuse positivity suggests gastrointestinal origin 1, 2
• CDX-2: Diffusely positive in 100% of gastrointestinal metastases but only focally positive in 21% of primary ovarian mucinous carcinomas 4
• DPC4 (SMAD4): Loss of nuclear staining suggests pancreatic primary, as approximately 50% of pancreatic adenocarcinomas show DPC4 inactivation, while virtually all primary ovarian mucinous neoplasms retain DPC4 expression 1
• PAX8: Positive in primary ovarian tumors, negative in gastrointestinal metastases 1

Step 3: Mandatory Gastrointestinal Evaluation

• Measure serum CEA and CA19-9 levels in addition to CA-125 1, 5
• If CEA or CA19-9 is elevated, or if CA-125/CEA ratio is <25, perform colonoscopy and upper endoscopy (gastroscopy) to exclude occult gastrointestinal primary 1
• Consider barium enema or radiologic examination of stomach if endoscopy cannot be performed 1
• Mammography should also be obtained to exclude breast primary 1

Step 4: Imaging Requirements

• CT scan of chest, abdomen, and pelvis with contrast is essential for staging and identifying potential primary sites 1, 5
• Transvaginal ultrasound with color Doppler helps characterize the ovarian mass 1, 5

Management Recommendations

If Primary Ovarian Mucinous Carcinoma Confirmed

• Comprehensive surgical staging with cytoreductive surgery is the primary treatment, including appendectomy which is specifically recommended for mucinous histology 1
• For stage IC disease, postoperative options include observation, carboplatin/paclitaxel, or gastrointestinal-type regimens (5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) 1
• For stages II-IV, chemotherapy options include standard epithelial ovarian cancer regimens or gastrointestinal-type regimens, as mucinous carcinomas are similar to gastrointestinal tumors 1

If Metastatic Disease Identified

• Treatment should be directed at the primary site of origin 1
• Core biopsy (preferred over cytology) must be obtained before initiating any chemotherapy to confirm diagnosis and allow for molecular testing 1

Critical Pitfalls to Avoid

• Do not assume ovarian primary without excluding gastrointestinal origin, as metastases are more common than primary mucinous ovarian tumors 1
• Do not rely on single markers—panels are superior to individual markers, and no marker is totally specific or sensitive 1
• Do not initiate chemotherapy without tissue diagnosis, as treatment differs dramatically based on site of origin 1
• Remember that immunohistochemical results must always be interpreted in conjunction with clinical, gross, and microscopic features 1
• Unexpected positive and negative staining reactions may occur, requiring correlation with all available data 1