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PRAME expression in genital melanocytic lesions - Potential diagnostic pitfall of intermediate expression in atypical
Joanna Ka Man Ng1, Paul Cheung Lung Choi1, Chit Chow1
1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
Introduction:
The Preferentially Expressed Antigen in Melanoma (PRAME) immunostain has seen significant diagnostic use in confirming malignancy for melanocytic lesions. However, the expression of PRAME in genital melanocytic lesions have not been reported. In this study, PRAME staining was performed on a cohort of genital melanocytic lesions, aiming to investigate the diagnostic role of PRAME in genital melanocytic lesions and its expression in atypical genital nevi.
Methodology:
A cohort including genital invasive melanoma, melanoma-in-situ, atypical genital nevus (AGN), compound nevus, intradermal nevus, blue nevus, lentigo and melanosis was retrieved with histology reviewed and PRAME immunostaining performed.
Results:
A total of 66 cases were reviewed. The average proportion expression of PRAME were 56.75 % and 57.43 % for invasive melanoma and melanoma-in-situ, with average H-scores of 153.5/300 and 163.14/300 respectively, which were greater than AGN (3.25 %, 7.75/300, p<0.001), compound/intradermal nevi, lentigo/melanosis, and background junctional melanocytes (<1 %, <1/300, p<0.001). The different cutoffs of PRAME expression, the sensitivity and specificity were 65.22 % and 100 % (>100/300); 69.57 % and 95.83 % (>10/300); and 82.61 % and 93.75 % (≥1/300) respectively. Low level PRAME expression was seen in half of the cases of AGN (n=2/4, 50 %), and at low cutoffs (>10/300 and ≥1/300) unable to differentiate invasive melanoma from AGN (p>0.05).
Conclusions:
For genital melanocytic lesions, PRAME immunostain shows high specificity at strong and diffuse staining. AGN not uncommonly display low level expression. Focal and/or weak PRAME expression should not be considered as an absolute indication of malignancy, and comprehensive histological assessment remains the key to accurate diagnosis of melanocytic lesions.
Insights
Preferentially Expressed Antigen in Melanoma (PRAME) immunostaining is highly specific for genital melanomas, but low expression in atypical genital nevi requires careful histological evaluation for accurate diagnosis.
Area of Science:
- Dermatopathology
- Oncology
- Immunohistochemistry
Background:
- Preferentially Expressed Antigen in Melanoma (PRAME) immunostaining aids in diagnosing melanocytic lesions.
- PRAME expression in genital melanocytic lesions has not been previously reported.
- This study investigates PRAME's diagnostic utility in the genital area.
Purpose of the Study:
- To evaluate the diagnostic role of PRAME immunostaining in genital melanocytic lesions.
- To assess PRAME expression patterns in atypical genital nevi.
- To determine the sensitivity and specificity of PRAME for distinguishing melanoma from benign lesions in the genital region.
Main Methods:
- A cohort of 66 genital melanocytic lesions, including invasive melanoma, melanoma-in-situ, atypical genital nevi (AGN), and various benign nevi, was analyzed.
- Histological review and PRAME immunostaining were performed on all cases.
- Statistical analysis was used to compare PRAME expression levels and assess diagnostic performance at different cutoffs.
Main Results:
- PRAME expression was significantly higher in invasive melanoma (56.75%) and melanoma-in-situ (57.43%) compared to AGN (3.25%) and benign lesions (<1%).
- PRAME immunostaining demonstrated high specificity (up to 100%) at certain expression cutoffs.
- Approximately 50% of atypical genital nevi showed low-level PRAME expression, hindering differentiation from melanoma at lower cutoffs.
Conclusions:
- PRAME immunostaining is highly specific for genital melanomas, particularly with strong and diffuse staining.
- Low-level PRAME expression in atypical genital nevi is common and can complicate diagnosis.
- Comprehensive histological assessment remains crucial for accurate diagnosis, as focal or weak PRAME expression alone is not definitive for malignancy.
