Could a patient with a history of mucinous cystic neoplasm of the liver and elevated CEA (Carcinoembryonic Antigen) and CA 19-9 (Cancer Antigen 19-9) levels, with a biopsy showing well-differentiated adenocarcinoma metastatic in peritoneal nodules, have peritoneal carcinomatosis or peritoneal seeding from a malignant liver condition?

Diagnostic Evaluation of Peritoneal Adenocarcinoma in the Setting of Hepatic Mucinous Cystic Neoplasm

Yes, this represents peritoneal carcinomatosis from malignant transformation of the hepatic mucinous cystic neoplasm (MCN), and the elevated CEA and CA 19-9 support but do not definitively establish this diagnosis. 1, 2

Understanding the Clinical Context

The combination of a known hepatic MCN with peritoneal nodules showing well-differentiated adenocarcinoma creates a critical diagnostic scenario requiring differentiation between:

• Peritoneal seeding from malignant MCN (biliary cystadenocarcinoma with peritoneal carcinomatosis)
• Metastatic adenocarcinoma from an occult gastrointestinal primary
• Primary peritoneal carcinomatosis from another source

Limitations of Tumor Markers

CEA and CA 19-9 cannot reliably distinguish between simple hepatic cysts and MCNs, nor can they differentiate benign from malignant MCNs. 2

• CA 19-9 in cyst fluid has only 19% accuracy for distinguishing simple from malignant cysts (AUC 0.71) 2
• CEA in cyst fluid has only 22% accuracy for distinguishing benign from malignant cysts (AUC 0.71) 2
• CA 19-9 can be elevated in 6-100% of benign biliary cystadenomas and 28-73% of malignant cystadenocarcinomas 2
• Serum CEA is elevated in up to 49% of cystadenomas (benign) and up to 75% of cystadenocarcinomas (malignant) 2

The elevated markers in your patient are consistent with malignant transformation but are non-specific. 2

Critical Immunohistochemical Analysis Required

The peritoneal biopsy must be analyzed with a specific immunohistochemical panel to determine the primary origin. 1

For Hepatobiliary Origin (MCN/Cholangiocarcinoma):

• CK7+/CK20-/CRP+ phenotype strongly suggests cholangiocarcinoma or MCN origin 1
• Negative CDX2 or SATB2 (excludes intestinal/gastric origin) 1
• Negative TTF1 (excludes pulmonary origin) 1
• Negative GATA3 (excludes breast origin) 1
• CK19 positivity supports biliary origin 1

For Gastrointestinal Origin:

• CK7-/CK20+ or CK7+/CK20+ with positive CDX2 suggests colorectal or gastric primary 1
• CEA and COX-2 positivity supports gastrointestinal origin 1

For Ovarian/Peritoneal Origin:

• CK7+/CK20+ with WT-1 positivity suggests ovarian origin 1

Essential Diagnostic Workup

Perform contrast-enhanced MRI of the abdomen to assess for worrisome features of malignant MCN and evaluate the extent of peritoneal disease. 1, 2

Worrisome features for malignant MCN include: 1

• Thick septations or nodularity (especially >1 cm)
• Mural nodules
• Upstream biliary dilatation
• Perfusional changes

Complete gastrointestinal evaluation is mandatory to exclude metastatic disease from an occult GI primary: 1

• Upper endoscopy (exclude gastric primary) 1
• Colonoscopy (exclude colorectal primary) 1
• Consider endoscopic ultrasound if pancreatic involvement suspected 1

Obtain chest/abdomen/pelvis CT to evaluate for additional metastatic sites and assess resectability. 1, 3

Peritoneal Carcinomatosis from Hepatic MCN

Peritoneal carcinomatosis from malignant hepatic MCN (biliary cystadenocarcinoma) is a documented but rare entity. 4

• Peritoneal seeding can occur from rupture or surgical manipulation of malignant MCNs 4
• One case report documented peritoneal carcinomatosis developing 18 months post-operatively after cyst aspiration of a hepatic cystadenocarcinoma 4
• The mechanism involves intraperitoneal spillage of malignant cells during surgical procedures 4, 5

Clinical Decision Algorithm

1. Obtain immunohistochemistry on peritoneal biopsy immediately - CK7, CK20, CRP, CDX2, SATB2, TTF1, GATA3, CK19 1

2. If CK7+/CK20-/CRP+ with negative GI/lung/breast markers → Diagnosis is peritoneal carcinomatosis from malignant hepatic MCN 1

3. If CK7-/CK20+ or positive CDX2 → Complete GI evaluation with endoscopy/colonoscopy to identify occult primary 1

4. Perform MRI to assess hepatic lesion characteristics and peritoneal disease burden 1, 2

5. Calculate Peritoneal Carcinomatosis Index (PCI) on imaging to assess tumor burden - this guides surgical candidacy 3

Treatment Implications

If confirmed as peritoneal carcinomatosis from malignant MCN, consider cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in selected patients with low-volume disease. 3, 6, 5

Selection criteria for aggressive treatment: 5

• Low-grade malignancy
• Absence of liver metastases beyond the primary MCN
• Low-volume peritoneal disease (low PCI score)
• Good performance status

For patients with high-volume disease or poor performance status, systemic chemotherapy similar to cholangiocarcinoma protocols should be considered. 1

Critical Pitfall to Avoid

Do not rely solely on elevated CEA and CA 19-9 to establish the diagnosis - these markers are non-specific and can be elevated in both benign and malignant hepatic cystic lesions. 2 The diagnosis must be confirmed through immunohistochemical analysis of the peritoneal biopsy combined with comprehensive imaging and exclusion of alternative primary sites. 1