Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic...

Area of Science:

• Gynecologic Pathology
• Oncology
• Molecular Pathology

Background:

• Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms with variable behavior.
• While some clinicopathologic features suggest aggressiveness, their predictive power is limited.
• ALK fusions are common drivers, but additional molecular alterations are less understood in uterine IMTs.

Purpose of the Study:

• To evaluate clinicopathologic and molecular features of uterine IMTs.
• To identify predictors of aggressive behavior in uterine IMTs.
• To develop a risk stratification model for uterine IMTs.

Main Methods:

• Retrospective analysis of 11 uterine IMTs with clinicopathologic review.
• Next-generation sequencing and whole-transcriptome RNA sequencing.
• Meta-analysis with literature cases to develop a risk score.

Main Results:

• Aggressive uterine IMTs (5/11) showed additional molecular alterations and copy number changes beyond ALK fusions.
• Non-aggressive IMTs (6/11) had ALK fusions as the sole pathogenic alteration.
• A risk score (age, size, mitoses, borders) correlated with outcomes: 0 points (no aggressive), 1-2 points (21% aggressive), ≥3 points (all aggressive).

Conclusions:

• A novel clinicopathologic risk score aids in stratifying uterine IMT risk.
• A 2-step classification using the score and molecular testing can improve management of uterine IMTs.
• Identifying aggressive uterine IMTs is crucial for appropriate patient management.