What are Krukenberg tumors?

Krukenberg Tumors

Krukenberg tumors are metastatic ovarian tumors characterized by the presence of signet ring cells, typically originating from gastrointestinal primary cancers, most commonly gastric cancer, and associated with poor prognosis and survival outcomes. 1

Definition and Pathological Features

Krukenberg tumors are defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells 2. These tumors represent a specific pattern of metastatic spread to the ovaries with distinctive histopathological characteristics:

• Presence of signet ring cells (at least 10% of tumor cells)
• Typically bilateral ovarian involvement (in approximately 80-87% of cases)
• Characteristic histological patterns including nests, cords, diffuse sheets, and single cell infiltration 2

Primary Origins

While originally described as metastases from gastric cancer, Krukenberg tumors can originate from various primary sites:

• Stomach (most common primary site)
• Colorectal tract
• Pancreas
• Biliary tract
• Breast (less common but possible) 2
• Other gastrointestinal sites

The Japanese classification of gastric carcinoma specifically mentions Krukenberg tumors as a form of distant metastasis from gastric cancer, classified as M1 disease 1.

Clinical Presentation

Patients with Krukenberg tumors typically present with:

• Abdominal or pelvic pain
• Abdominal distension
• Ascites (common)
• Palpable adnexal masses
• Symptoms related to the primary tumor site
• In rare cases, hormonal manifestations (such as virilization) 3

Diagnosis

Diagnosis of Krukenberg tumors requires:

1. Histopathological examination: Identification of signet ring cells in ovarian tissue
2. Imaging studies: CT scans of thorax, abdomen and pelvis to identify the primary tumor and extent of disease
3. Tumor markers:
   • CEA (often elevated in colorectal primaries)
   • CA-125 (may be elevated)
   • Specific markers related to suspected primary sites

Prognosis and Outcomes

Krukenberg tumors are associated with extremely poor prognosis:

• Median overall survival of approximately 19 months after diagnosis 4
• Nearly universal mortality due to disease progression
• Virtually 0% disease-free survival in cases of colorectal origin 4
• Presence of peritoneal carcinomatosis in approximately 76% of cases, further worsening prognosis 4

Treatment Approaches

The Chinese Society of Clinical Oncology (CSCO) guidelines indicate that for gastric cancer patients with ovarian metastasis (Krukenberg tumors), systemic chemotherapy is the main treatment 1. However, treatment options may include:

1. Cytoreductive surgery (CRS):

   • Complete resection of all visible disease (R0 CRS) shows the best survival outcomes
   • May include removal of primary tumor and bilateral oophorectomy

2. Systemic chemotherapy:

   • Used as primary treatment or adjuvant therapy
   • Results are conflicting regarding survival benefit

3. Hyperthermic intraperitoneal chemotherapy (HIPEC):

   • May provide benefit when combined with CRS
   • Shows fewer adverse effects than systemic chemotherapy 5

Some retrospective studies have shown that systemic chemotherapy combined with surgical resection of the primary tumor and/or ovarian metastasis could provide survival benefits, extending median overall survival from 6-9 months to 19-23.7 months 1.

Key Prognostic Factors

The most important prognostic factors for patients with Krukenberg tumors include:

• ECOG performance score of 0-1
• R0 resection (complete removal of all visible disease)
• Ability to receive postoperative systemic chemotherapy 1
• Absence of peritoneal carcinomatosis

Clinical Pitfalls and Considerations

1. Misdiagnosis as primary ovarian cancer: Krukenberg tumors can be mistaken for primary ovarian neoplasms, delaying appropriate treatment.

2. Failure to identify the primary site: Comprehensive evaluation is needed to identify the primary tumor for optimal treatment planning.

3. Bilateral ovarian involvement: The high rate of bilateral involvement (80-87%) means unilateral oophorectomy is usually insufficient.

4. Poor response to standard treatments: These tumors generally respond poorly to conventional chemotherapy regimens.

5. Rapid disease progression: The aggressive nature of these tumors requires prompt diagnosis and treatment initiation.

In summary, Krukenberg tumors represent a challenging clinical entity with poor outcomes despite multimodal treatment approaches. Early identification of the primary tumor and aggressive treatment with complete cytoreductive surgery when feasible, combined with appropriate systemic therapy, offers the best chance for extending survival in these patients.