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Aberrant expression of HMB45 and negative PRAME expression in halo nevi
Kristen N Ruby1, Zhongze Li2, Shaofeng Yan1
1Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Background:
Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP).
Methods:
PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity.
Results:
Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME.
Conclusion:
Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.
Insights
Aberrant HMB45 expression is common in halo nevi, mimicking melanoma. Negative PRAME staining helps distinguish halo nevi from melanoma, aiding diagnosis.
Area of Science:
- Dermatopathology
- Immunohistochemistry
- Melanoma Diagnosis
Background:
- Cutaneous nevi typically exhibit HMB45 gradient and negative PRAME.
- Melanomas often display irregular HMB45 and positive PRAME staining.
- Halo nevi can show atypical HMB45 patterns, complicating melanoma differentiation.
Purpose of the Study:
- To investigate HMB45 and PRAME expression in nevi with the halo phenomenon (NHP).
- To clarify diagnostic challenges in distinguishing NHP from melanoma.
Main Methods:
- Evaluated HMB45 and PRAME staining in 20 NHP and 16 conventional nevi.
- Defined HMB45 gradient as superficial melanocyte positivity.
- Defined aberrant HMB45 expression as superficial and deep melanocyte positivity.
Main Results:
- Aberrant HMB45 expression occurred in 50% of NHP cases.
- Conventional nevi predominantly showed HMB45 gradients (93.7%).
- PRAME staining was negative in all NHP and conventional nevus cases.
Conclusions:
- Aberrant HMB45 expression in NHP is a frequent diagnostic pitfall.
- Negative PRAME immunostaining is a useful marker to differentiate halo nevus from melanoma.

