Do Krukenberg tumors require a functional ovary to metastasize?

Krukenberg Tumors Do NOT Require Functional Ovaries to Metastasize

Krukenberg tumors are metastatic deposits to the ovary that do not require functional ovarian tissue to develop—they represent hematogenous or lymphatic spread of malignant cells (most commonly gastric adenocarcinoma with signet ring cells) that colonize the ovarian stroma, and can occur in postmenopausal women with atrophic ovaries or even after oophorectomy if microscopic ovarian remnants remain. 1, 2

Mechanism of Spread

• Krukenberg tumors spread to the ovaries through hematogenous and lymphatic routes, not through direct peritoneal seeding 2
• The ovary serves as a target organ due to its rich vascular supply and hormonal microenvironment, but functional ovarian activity is not a prerequisite for metastatic colonization 1, 2
• These tumors can develop in postmenopausal women with non-functioning ovaries, demonstrating that hormonal activity is not required for metastatic spread 3

Clinical Evidence

• Krukenberg tumors occur across a wide age range (41-76 years in breast cancer metastases), including postmenopausal patients with atrophic ovaries 3
• The tumors are bilateral in approximately 87% of cases, further supporting hematogenous dissemination rather than dependence on functional ovarian tissue 3
• Metastases can appear years to decades after the primary tumor (ranging from 2 months to 284 months in breast cancer cases, and up to 9 years in gallbladder cancer), indicating that ovarian function is irrelevant to the metastatic process 4, 3

Pathophysiology

• The metastatic cells efface normal ovarian architecture and replace it with tumor lobules separated by edema, demonstrating that they destroy rather than require functional ovarian tissue 3
• Histologically, Krukenberg tumors are defined by at least 10% signet ring cells within metastatic adenocarcinoma, with primary sites most commonly being stomach (most frequent), colon, breast, and rarely gallbladder 1, 2, 4, 3
• The ovarian stroma provides a receptive microenvironment for metastatic colonization, but this is independent of hormonal function 2

Clinical Implications

• Bilateral oophorectomy should be considered in gastric cancer patients with single-ovary Krukenberg metastasis, as the contralateral ovary remains at risk regardless of its functional status 5
• Systemic chemotherapy combined with surgical resection (R0 resection of primary and ovarian metastases) can extend median overall survival from 6-9 months to 19-23.7 months in highly selected patients 5, 6
• The most important prognostic factors are ECOG performance status 0-1, R0 resection, and postoperative systemic chemotherapy—not ovarian functional status 5, 6

Common Pitfall to Avoid

The misconception that Krukenberg tumors require functional ovaries can lead to inadequate surveillance in postmenopausal patients with gastrointestinal malignancies. Routine gynecological examinations should be performed regardless of menopausal status, as late metastases can occur even after prolonged disease-free intervals 4.