Morphologic and Molecular Differences of BAP1 Melanocytomas and BAP1 Inactivated Melanomas

Area of Science:

• Oncology
• Dermatopathology
• Genetics

Background:

• BAP1 inactivated melanocytomas are intermediate-grade melanocytic tumors with potential overlap with melanoma.
• Distinguishing between BAP1 inactivated melanocytomas and melanomas is difficult due to shared morphologic features.
• Limited outcome-based data exists for differentiating these BAP1-inactivated entities.

Purpose of the Study:

• To identify distinct morphologic and molecular features differentiating BAP1 inactivated melanomas from BAP1 inactivated melanocytomas.
• To provide diagnostic criteria for challenging melanocytic tumors with BAP1 inactivation.

Main Methods:

• Comparative analysis of 20 BAP1 inactivated melanomas and 23 BAP1 inactivated melanocytomas.
• Evaluation of clinical follow-up data (n=17 for melanomas).
• Assessment of genomic (pathogenic variants, tumor mutational burden) and morphologic features.

Main Results:

• BAP1 inactivated melanomas exhibited ulceration, tumor necrosis, subcutaneous invasion, and higher mitotic activity (≥4/mm²).
• Melanomas showed significantly more pathogenic variants (6.6 vs. 2.4) and higher tumor mutational burden (31.2 vs. 7.8 m/Mb) compared to melanocytomas.
• Specific pathogenic variants (TERT-promoter, CDKN2A, CDK4, MYC, SWI/SNF, PI3K-AKT) were exclusive to BAP1 inactivated melanomas.

Conclusions:

• Morphologic and molecular features identified can aid in diagnosing BAP1 inactivated melanomas.
• Ulceration, necrosis, deep invasion, high mitotic rate, and specific genetic alterations are key indicators of melanoma in BAP1-inactivated tumors.
• These findings offer valuable criteria for challenging melanocytic tumor assessments.