Do both invasive and non‑invasive peritoneal implants from a serous borderline ovarian tumor arise by shedding of tumor cells into the peritoneal fluid?

Origin of Peritoneal Implants in Serous Borderline Ovarian Tumors

The evidence strongly supports that both non-invasive and invasive peritoneal implants arise from shedding of tumor cells from the primary ovarian serous borderline tumor into the peritoneal fluid, rather than representing independent primary peritoneal lesions.

Molecular Evidence Supporting the Shedding Mechanism

The most compelling evidence comes from large-scale molecular analysis demonstrating that peritoneal implants are clonally related to the primary ovarian tumor. A population-based cohort study showed that 95% (59 of 62) of peritoneal implant pairs—both non-invasive and invasive—harbored identical KRAS or BRAF mutations present in the associated serous borderline tumor (p < 0.00001) 1. Specifically, all 10 invasive implants examined had the same mutational status (KRAS mutation, BRAF mutation, or wild-type KRAS/BRAF) as the corresponding primary tumor 2, 3.

This molecular concordance provides cogent evidence that peritoneal implants are derived from the primary ovarian tumor rather than arising independently 1. The identical mutational profiles in both invasive and non-invasive implants support a common mechanism of origin via tumor cell shedding into peritoneal fluid 3.

Histopathologic Features Supporting Tumor Cell Dissemination

Non-Invasive Implants

Non-invasive implants demonstrate morphologic features consistent with detached tumor fragments that have implanted on peritoneal surfaces:

• Epithelial-type non-invasive implants resemble detached fragments of the serous borderline tumor involving extra-ovarian tissues 2, 4.
• These implants are often present within mesothelial or epithelial-lined spaces, suggesting they arrived via peritoneal fluid and became trapped in these anatomic compartments 2.
• They lack infiltration of underlying tissue, consistent with passive implantation rather than active invasion 2, 4.

Invasive Implants

Invasive implants, while showing destructive invasion, still originate from the primary tumor via peritoneal dissemination:

• Despite their invasive behavior, molecular analysis confirms they are clonally related to the primary ovarian tumor 2, 3, 1.
• The progression from non-invasive to invasive implants likely represents evolution of implanted tumor cells rather than a different mechanism of spread 5.
• Invasive implants display micropapillary architecture and solid epithelial nests surrounded by clefts, features that correlate with adverse outcomes but do not negate their origin from shed tumor cells 5, 6.

Clinical and Epidemiologic Support

Extra-ovarian implants occur in approximately 20-30% of serous borderline tumors and are more common with exophytic neoplasms 4, 7. The association with exophytic growth patterns supports the shedding mechanism, as exophytic tumors have greater surface area exposed to the peritoneal cavity, facilitating cell release into peritoneal fluid 2.

Important Caveats

While the evidence overwhelmingly supports the shedding mechanism, the number of invasive implants examined by molecular methods in the entire literature remains limited 2. However, the 100% concordance in the available data (10 of 10 invasive implants showing identical mutations) provides strong support for this mechanism 2, 3.

It remains unclear whether invasive implants represent true metastases from the borderline tumor or reflect simultaneous transformation of shed cells 2. The WHO 2014 classification mandates that invasive implants be reported as "extra-ovarian low-grade serous carcinoma," acknowledging their malignant potential regardless of their origin 2, 4, 3.