What is a Krukenberg tumor in the context of a postmenopausal woman with suspected ovarian cancer?

What is a Krukenberg Tumor?

A Krukenberg tumor is a metastatic ovarian malignancy characterized by signet ring cell adenocarcinoma that has spread to one or both ovaries from a primary cancer elsewhere in the body, most commonly the gastrointestinal tract. 1

Definition and Pathologic Characteristics

• Krukenberg tumors are metastatic lesions to the ovary containing mucinous signet ring carcinoma cells within a cellular, nonneoplastic ovarian stroma. 2
• By strict pathologic definition, at least 10% of the tumor must consist of signet ring cells to qualify as a Krukenberg tumor. 3
• These are secondary neoplasms, not primary ovarian cancers, accounting for only 1-2% of all ovarian tumors despite ovarian metastases representing approximately 30% of ovarian malignancies overall. 4

Primary Cancer Origins

The most common primary sites in descending order are:

• Stomach (42.5%) - the classic and most frequent source 4, 2
• Colon-rectum (26.1%) 4
• Breast (9.3%) 4, 3
• Appendix (5%) 4
• Pancreas (rare) 5

In 90.9% of cases with adequate follow-up, a primary gastrointestinal cancer (stomach or colon) is ultimately identified. 2

Clinical Presentation in Postmenopausal Women

For a postmenopausal woman with suspected ovarian cancer, key clinical features include:

• Approximately 39.8% of Krukenberg tumor patients are postmenopausal, and 39.7% are age 50 or older. 4
• The most common presenting symptoms are ascites (51.7%), palpable abdominal/pelvic mass (31.3%), abdominal pain (29.3%), and abdominal distention (28.7%). 4
• Irregular vaginal bleeding occurs in only 9.1% of cases 4, though one case report described menorrhagia as the presenting symptom 6
• Notably, 11.2% of patients are completely asymptomatic at diagnosis. 4

Tumor Characteristics

Physical and imaging findings typically reveal:

• Bilateral ovarian involvement in 64.3% of cases 4, 2
• Tumors are characteristically solid and asymmetrically large 2
• 40.5% have diameter ≥10 cm 4
• 55.3% demonstrate extraovarian extension and 49% show peritoneal involvement at diagnosis 4

Temporal Relationship to Primary Cancer

A critical diagnostic pitfall is that the primary cancer may not be known at the time of ovarian tumor discovery:

• 48.7% of Krukenberg tumors are synchronous (discovered simultaneously with the primary tumor) 4
• In the classic series, the primary gastrointestinal cancer was diagnosed before the ovarian tumor in only 5 of 20 cases (25%) 2
• In 10 cases, the ovarian and gastrointestinal tumors were diagnosed simultaneously 2
• In 5 cases, the primary cancer was not discovered until after the ovarian tumor had been treated 2

Diagnostic Workup Implications

When a postmenopausal woman presents with a suspected ovarian malignancy that could be a Krukenberg tumor:

• Serum tumor markers should include CA-125, but also CEA and CA19-9, particularly when CA-125/CEA ratio is ≤25, as this suggests possible gastrointestinal origin. 1
• Colonoscopy and/or gastroscopy should be strongly considered to identify an occult primary gastrointestinal malignancy. 1
• All women with typical Krukenberg tumors should be considered as having metastatic carcinoma, usually from the stomach, until proven otherwise. 2
• Histopathologic diagnosis requires adequate tissue sampling, not just peritoneal biopsies or cytology, as these do not provide proof of origin or degree of malignancy 1

Treatment and Prognosis

For gastric cancer patients with Krukenberg tumor (single-ovary metastasis), systemic chemotherapy is the main treatment. 1

• Highly selected patients may benefit from systemic chemotherapy combined with surgical resection of both the primary tumor and ovarian metastasis, extending median overall survival from 6-9 months to 19-23.7 months. 1
• The most important prognostic factors are ECOG performance status 0-1, R0 resection (complete removal of primary and metastatic lesions), and postoperative systemic chemotherapy. 1
• The prognosis remains poor overall, with most patients dying within 2 years despite treatment 5, 2

Key Clinical Pitfall

The entity of "primary" Krukenberg tumor (arising de novo in the ovary) is highly controversial and likely does not exist. Even in the two cases from the classic series where no primary cancer was initially found, both patients had bilateral Krukenberg tumors and died with widespread carcinomatosis within 2 years, strongly suggesting an undetected primary source. 2 Therefore, exhaustive search for a primary malignancy is mandatory.