What is a Krukenberg (metastatic ovarian) tumor?

What is a Krukenberg Tumor?

A Krukenberg tumor is a metastatic ovarian malignancy characterized by mucin-secreting signet ring cell adenocarcinoma that has spread to one or both ovaries, most commonly originating from the stomach (70% of cases), followed by colorectal, appendiceal, breast, pancreatic, and cervical primary sites. 1, 2, 3

Definition and Pathologic Features

Krukenberg tumors are defined as metastatic adenocarcinomas to the ovary containing at least 10% signet ring cells. 4 The term specifically refers to this histologic pattern rather than all ovarian metastases from gastrointestinal sources. 3, 5

Key Histopathologic Characteristics:

• Bilateral ovarian involvement occurs in approximately 64-87% of cases 2, 4
• Microscopic features include: 4
  • Discrete tumor lobules separated by striking stromal edema
  • Multiple growth patterns: nests (most common), cords, diffuse sheets, single cells, small clusters, and occasionally glands
  • Mucin-secreting signet ring cells comprising 10-70% of tumor cells
  • Ovarian architecture typically effaced by metastatic disease

Primary Sites of Origin

The stomach is the most common primary site (70%), followed by colorectal cancer (approximately 52% in some series), breast, appendix, pancreas, and rarely cervix. 1, 2, 3, 6

Distinguishing Primary Sites:

• Gastric origin: Most common; may present synchronously or metachronously with the primary tumor 1, 6
• Colorectal origin: CK20 staining more extensive than CK7 in metastatic colonic adenocarcinoma 1
• Pancreatic/biliary origin: Absence of DPC4 staining in approximately 50% of pancreatic adenocarcinomas helps distinguish from primary ovarian mucinous neoplasms 1
• Breast origin: Tumors exhibit nests, cords, and diffuse sheets; positive for GCDFP15, mammoglobin, and GATA3; negative for WT1 1, 4
• Cervical origin: Diffuse p16 immunoreactivity suggests HPV-related cervical adenocarcinoma 1

Clinical Presentation

Krukenberg tumors present primarily (synchronously with the primary cancer) in 69% of patients, with a mean age at diagnosis of 43.5 years. 2 Patients typically present with:

• Pelvic or abdominal masses (often bilateral)
• Abdominal distension and ascites
• Symptoms related to the primary malignancy
• Occasionally discovered incidentally during staging workup

Prognosis and Survival

The prognosis of Krukenberg tumors remains dismal, with median overall survival ranging from 9-50 months depending on treatment and disease extent. 3, 5

Key Prognostic Factors:

Favorable prognostic factors include: 2, 3

• R0 resection (complete cytoreduction with no residual disease)
• Primary breast cancer origin (better than gastric)
• Good ECOG performance status (0-1)
• Absence of ascites
• No peritoneal carcinomatosis or low Peritoneal Cancer Index
• Metachronous presentation (rather than synchronous)
• Adjuvant systemic chemotherapy following complete resection

Poor prognostic factors include: 2, 3

• Peritoneal/omental concomitant metastasis
• Extra-ovarian or extra-pelvic disease
• R1 (microscopic residual) or R2 (gross residual) resection
• Gastric primary site
• Presence of ascites

Treatment Approach

Systemic chemotherapy is the primary treatment modality for Krukenberg tumors, with cytoreductive surgery reserved for highly selected patients who can achieve R0 resection. 1, 3

Surgical Considerations:

Surgery offers survival benefit ONLY when complete (R0) resection of both the primary tumor and ovarian metastases can be achieved. 1, 2, 3 Key points:

• Median overall survival after R0 resection: 19-32 months 1, 2
• Median overall survival with R1/R2 resection or no surgery: 10-11 months 3
• Hazard ratio for R0 resection: 0.09, indicating substantial survival benefit 2
• Diagnostic laparoscopy should be considered before planned debulking to assess resectability and avoid futile laparotomy 3

Optimal Surgical Candidates:

Patients most likely to benefit from cytoreductive surgery include those with: 1, 2, 3

• Single-ovary metastasis or resectable bilateral disease
• ECOG performance status 0-1
• Absence of extensive peritoneal carcinomatosis
• Resectable primary tumor
• No extra-pelvic metastases
• Anticipated ability to achieve R0 resection

Role of HIPEC:

Heated intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery remains controversial but may offer survival benefit for gastric-origin Krukenberg tumors with peritoneal dissemination and low Peritoneal Cancer Index. 3

Diagnostic Workup

When Krukenberg tumor is suspected, comprehensive evaluation must identify the primary site: 1

• Serum tumor markers: CA 125 (elevated in 85% of advanced ovarian disease), CEA, CA 19-9
• Upper endoscopy with biopsy for suspected gastric primary
• Colonoscopy for suspected colorectal primary
• Imaging: CT chest/abdomen/pelvis to identify primary site and assess disease extent
• Immunohistochemistry panel tailored to differential diagnosis

Important Clinical Pitfalls

Common diagnostic errors to avoid: 1

• Do not assume all ovarian masses in patients with known malignancy are metastatic—women with BRCA1/2 mutations or history of breast cancer may develop new primary high-grade serous ovarian carcinomas
• Immunohistochemistry panels are essential—no single marker is specific or sensitive enough for definitive diagnosis
• Always correlate immunostains with clinical history and morphology—unexpected staining patterns occur
• Patients with R1 or R2 resection have survival equivalent to unresected patients—avoid morbid surgery that cannot achieve complete cytoreduction