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Updated: Aug 24, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Histopathologic and molecular characterization of BAP-1-inactivated melanoma
Elisabeth M Miller1, Konstantinos Linos2,3, Carlos E Bacchi4
1Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA.
Background:
BRCA1-associated protein 1 (BAP-1) is a deubiquitylase that functions as a tumor suppressor, regulating multiple cellular processes including cell cycle control, differentiation, cell death, and DNA repair. BAP-1-inactivated melanocytic tumors (BIMTs) have recently been described and are characterized by epithelioid cytomorphology, are often clonal in appearance, and typically do not recur or show malignant transformation on follow-up.
Aim:
To describe the histopathologic and molecular characterization of five cases of BAP-1-inactivated cutaneous malignant melanomas.
Methods:
The archives at two separate institutions were retrospectively searched for tumors classified as melanoma with loss of BAP-1 via immunohistochemistry. Five cases were identified. These cases were classified as malignant melanoma based on cytomorphology, immunohistochemistry, and ancillary molecular testing. The clinical demographics were recorded, along with the histomorphologic features of each case. Genomic analysis for all cases was performed via OncoScan.
Results:
The five reviewed cases consisted of two females and three males ranging from 67 to 74 years in age. Molecular characterization of each case was performed using OncoScan. Microarray assay showed that there was a complete deletion of 3p in all cases, BRAF V600E mutation in two cases, NRAS missense variant in one case, and loss of 9p in three cases. All cases showed malignant copy number alterations.
Conclusions:
Herein we describe five cases of BAP-1-inactivated melanomas confirmed by histomorphology and immunohistochemistry, all of which show malignant copy number profiles including loss of 3p. In addition, we provide a case of a likely BIMT showing progression to BAP-1-inactivated melanoma on a 16-year follow-up.
Insights
BAP-1-inactivated melanomas, characterized by 3p deletion, present with malignant copy number alterations. One case showed progression from a likely BAP-1-inactivated melanocytic tumor to melanoma over 16 years.
Area of Science:
- Oncology
- Dermatopathology
- Cancer Genomics
Background:
- BRCA1-associated protein 1 (BAP-1) is a tumor suppressor deubiquitylase.
- BAP-1-inactivated melanocytic tumors (BIMTs) are rare, epithelioid neoplasms.
- BIMTs typically exhibit benign clinical behavior.
Observation:
- This study investigated five cases of BAP-1-inactivated cutaneous malignant melanomas.
- Histomorphologic and molecular analyses were performed.
- Immunohistochemistry confirmed BAP-1 loss in all cases.
Findings:
- All five cases demonstrated malignant copy number alterations, including complete deletion of 3p.
- BRAF V600E mutations were present in two cases; NRAS variants in one.
- One case showed progression from a likely BIMT to BAP-1-inactivated melanoma over 16 years.
Implications:
- BAP-1 inactivation in melanoma is associated with specific genomic alterations, notably 3p deletion.
- These findings aid in distinguishing BAP-1-inactivated melanomas from BIMTs.
- Understanding the genomic profile of BAP-1-inactivated melanoma is crucial for diagnosis and prognosis.
