Atypical Endometrial Hyperplasia, Low-grade: "Much ADO About Nothing"

Area of Science:

• Gynecologic pathology
• Oncology
• Molecular pathology

Background:

• Atypical endometrial hyperplasia (AEH) is a precursor to endometrioid carcinoma.
• The 2020 WHO classification categorizes endometrial hyperplasia but omits nuclear atypia grading.
• Accurate risk stratification for AEH is crucial for patient management.

Purpose of the Study:

• To evaluate the reproducibility of grading nuclear atypia in AEH.
• To assess the predictive value of nuclear atypia grade for detecting carcinoma at hysterectomy.
• To investigate the role of key genes in endometrial carcinogenesis within AEH.

Main Methods:

• Retrospective review of 79 AEH biopsies with subsequent hysterectomy.
• Intraobserver and interobserver agreement analysis for nuclear atypia grading.
• Immunohistochemistry for mismatch repair (MMR) status and targeted sequencing of cancer-related genes.
• Correlation of biopsy atypia grade with hysterectomy findings.

Main Results:

• High intraobserver (89-96%) and interobserver (87-91%) agreement for grading nuclear atypia.
• Nuclear atypia grade strongly predicted hysterectomy findings (P=1.6×10-15).
• No carcinoma found in patients with low-grade AEH; 23% and 61% of high-grade AEH patients had uterine high-grade AEH or FIGO grade 1 carcinoma, respectively.
• MMR deficiency observed in 3/79 patients; no significant gene mutation association with atypia grade.

Conclusions:

• Grading nuclear atypia in AEH demonstrates high diagnostic reproducibility.
• Nuclear atypia grading is a reliable predictor of concurrent carcinoma at hysterectomy.
• Low-grade AEH has a minimal risk of associated malignancy, supporting conservative management in select cases.