Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism

Area of Science:

• Genetics
• Pathology
• Oncology

Background:

• Cherubism is a rare genetic disorder causing jaw granulomas.
• Disease severity varies, with recurrence post-surgery being a major concern.
• Current prognostic indicators for cherubism are lacking.

Purpose of the Study:

• To evaluate the osteoclastogenesis phenotype in cherubism.
• To identify prognostic indicators for disease aggressiveness.
• To correlate histologic findings with cherubism evolution.

Main Methods:

• Histologic examination of giant multinucleated cells (GMCs) for nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity.
• Classification of cherubism aggressiveness into mild, moderate, and severe based on 1-year post-surgery evolution.
• Comparison of GMC phenotype across different aggressiveness grades.

Main Results:

• GMCs in mild and moderate cherubism lesions were negative for TRAP activity and NFATc1 nuclear localization.
• GMCs in severe cherubism lesions showed positive TRAP activity and NFATc1 nuclear localization, indicating osteoclast-like features.
• No other significant histopathologic differences were observed among the groups.

Conclusions:

• TRAP activity and NFATc1 nuclear localization are associated with aggressive cherubism.
• These markers can aid in prognosis and management of cherubism.
• NFATc1 localization suggests potential benefit from anticalcineurin treatment in aggressive cases.