Atypical Placental Site Nodule and Related Lesions: Interobserver Reproducibility

Area of Science:

• Gynecologic Pathology
• Trophoblastic Neoplasia
• Diagnostic Reproducibility

Background:

• Placental site nodule (PSN) and atypical placental site nodule (APSN) are intermediate trophoblastic lesions.
• APSN is characterized by worrisome histologic features and can precede trophoblastic neoplasia, such as epithelioid trophoblastic tumor (ETT).
• Current diagnostic criteria for APSN lack consensus, impacting diagnostic consistency.

Purpose of the Study:

• To assess the interobserver reproducibility of diagnosing APSN, PSN, and ETT.
• To evaluate the reliability of specific worrisome histologic features used in APSN diagnosis.
• To propose potential criteria for improving APSN diagnostic accuracy and reducing overdiagnosis.

Main Methods:

• Five expert pathologists reviewed whole slide images (H&E and Ki-67/AE1-AE3 stains) of 50 cases with index diagnoses of APSN, PSN, or ETT.
• Pathologists independently recorded diagnostic impressions and the presence of seven worrisome histologic features.
• Interobserver agreement was quantified using Fleiss' kappa (κ) and intraclass correlation coefficients (ICC).

Main Results:

• Diagnostic consensus was achieved in 96% of cases, with 75% agreement with the index diagnosis.
• Overall reproducibility was fair (κ=0.46), with lower agreement for APSN (κ=0.34) compared to PSN (κ=0.58).
• Substantial agreement was observed for extensive lesional tissue (κ=0.76) and Ki-67 index (ICC=0.62); other features showed moderate reproducibility.
• Cases with higher agreement typically showed 3-6 worrisome features for APSN, <2 for PSN, and ≥6 for ETT.

Conclusions:

• APSN diagnosis presents diagnostic challenges, reflected in fair interobserver reproducibility.
• Consultation among experts improves diagnostic agreement.
• A threshold of ≥3 worrisome features may be a reasonable criterion to avoid APSN overdiagnosis, with extensive lesional tissue and Ki-67 proliferation being key reproducible features.