What are peritoneal implants of borderline ovarian tumors and how should they be managed?

Peritoneal Implants in Borderline Ovarian Tumors

Peritoneal implants are extra-ovarian deposits that occur in approximately 20% of serous borderline tumors, and their classification into non-invasive versus invasive types is the single most critical prognostic factor determining patient outcomes and treatment decisions. 1

Definition and Pathologic Classification

Peritoneal implants represent extra-ovarian disease associated with borderline ovarian tumors (also called tumors of low malignant potential). The International Collaboration on Cancer Reporting (ICCR) and WHO 2014 classification mandate that these implants be categorized as either non-invasive or invasive based on specific histopathologic criteria. 1

Non-Invasive Implants

Non-invasive implants lack destructive invasion of underlying tissue and carry a favorable prognosis. 1 They are further subclassified into two distinct types:

• Epithelial-type non-invasive implants resemble detached fragments of serous borderline tumor on peritoneal surfaces, do not infiltrate underlying tissue, and are often present within mesothelial or epithelial-lined spaces or adherent to serosal surfaces 1

• Desmoplastic-type non-invasive implants consist of glands or papillary clusters within predominant fibroblastic or granulation tissue-like stroma, typically located on serosal surfaces or within omental septa, without infiltration of adjacent tissue 1

• Isolated individual or small clusters of eosinophilic epithelial cells within stroma are considered within the spectrum of desmoplastic non-invasive implants rather than invasive disease 1

Invasive Implants

The most widely accepted criterion for diagnosing invasive implants is low-power destructive invasion of underlying tissue, which has been shown to have excellent interobserver reproducibility (κ=0.84) and is the best predictor of adverse patient outcome. 2

Invasive implants demonstrate the following features:

• Markedly crowded epithelial nests, glands, or micropapillary clusters with haphazard arrangement 1
• Nests, glands, and papillae sometimes surrounded by clefts 1
• Destructive invasion correlates with 69% overall survival and 59% disease-free survival, significantly worse than non-invasive implants 2

Expanded criteria for invasive implants (when superficial biopsies lack sufficient tissue to assess classic invasion patterns) include:

• Micropapillary architecture resembling micropapillary serous borderline tumor 1
• Clusters of tumor within clear lacunar spaces 1

Critical caveat: Not all gynecologic pathologists accept these expanded criteria, though they correlate with poor outcomes. 1 When invasive versus non-invasive classification cannot be definitively determined, designate as "indeterminate type" sparingly, and obtain specialist gynecologic pathology consultation with additional tissue sections if available. 1

Mandatory Terminology

When invasive implants are diagnosed, the pathology report must state that these represent "extra-ovarian low-grade serous carcinoma"—this terminology is endorsed by WHO 2014 and is not optional. 1 This designation reflects that invasive implants carry a prognosis analogous to low-grade serous carcinoma and should be confirmed by at least two pathologists, preferably including an experienced gynecologic pathologist. 2

Molecular Evidence and Origin

Large-scale molecular analysis demonstrates that the vast majority of peritoneal implants are clonally related to the primary ovarian tumor rather than representing independent primary peritoneal lesions. 3

• A Danish population-based study showed 95% concordance of KRAS and BRAF mutations between primary tumors and implants (p<0.00001) 3
• All 10 invasive implants analyzed had identical mutational status (KRAS mutation, BRAF mutation, or wild-type) as their corresponding serous borderline tumors 1, 3
• This supports that invasive implants represent metastases from the ovarian tumor, though the total number of invasive implants examined molecularly remains limited 1

Clinical Presentation and Staging

Implants occur in approximately 20-30% of serous borderline tumors and are more common with exophytic neoplasms. 1, 4 Borderline tumors with peritoneal implants have the visual appearance of peritoneal carcinomatosis, but microscopic evaluation fails to reveal frank invasion in non-invasive implants. 1

Specifying the location and size of implants is essential for FIGO staging determination. 1 Non-invasive and invasive implants may coexist in the same patient. 1

Management Approach

Surgical Management

Surgery is the primary treatment for borderline epithelial tumors, and the NCCN guidelines base management decisions on whether invasive implants are present. 1

For patients desiring fertility preservation:

• Unilateral salpingo-oophorectomy (USO) with resection of residual disease is appropriate 1
• Comprehensive surgical staging including lymphadenectomy and omentectomy does not show survival benefit, though upstaging occurs 1
• Lymph node evaluation may be considered case-by-case 1

For patients not desiring fertility preservation:

• Standard ovarian cancer debulking surgery with resection of residual disease 1

Postoperative Management

The presence or absence of invasive implants determines the need for postoperative therapy. 1

For patients with invasive implants:

• Postoperative chemotherapy with carboplatin plus either docetaxel or paclitaxel can be considered (NCCN category 2A recommendation) 1
• Use the same regimens as for grade 1 (low-grade) serous epithelial ovarian cancer 1
• Invasive implants portend less favorable prognosis 1
• Observation is a category 3 recommendation for patients with invasive implants 1

For patients with non-invasive implants only:

• The benefit of postoperative chemotherapy has not been demonstrated 1
• Observation is one of several appropriate approaches and is more strongly recommended than for invasive implants 1
• Non-invasive implants carry favorable prognosis 1

Critical management caveat: The benefit of chemotherapy (intraperitoneal or intravenous) remains controversial in borderline epithelial tumors, and the significance of invasive implants continues to be investigated. 1

Prognostic Implications

The most important adverse prognostic factor for serous borderline tumors is the presence of invasive implants in extra-ovarian tissues. 1 The 5-year survival rate for borderline tumors overall exceeds 80%, but this varies significantly based on implant type. 1

Patients with non-invasive implants have excellent prognosis, with some series showing survival intervals of 10-16 years even with persistent disease and multiple episodes of small-bowel obstruction. 5 In contrast, invasive implants demonstrate survival rates comparable to low-grade serous carcinoma. 2

Special Considerations

Implants generally do not occur with mucinous, endometrioid, clear cell, or Brenner borderline tumors. 1 When an "implant" is present with an ovarian mucinous borderline tumor, alternative diagnoses should be considered. 1

Implants may occur with seromucinous borderline tumors, and the same classification principles for serous tumors apply. 1

Primary peritoneal serous borderline tumors can arise with minimal or absent ovarian involvement, appearing histologically identical to peritoneal implants from ovarian primaries. 4, 5