# PRAME Expression in Melanoacanthomas: Expanding the Spectrum of Positive Melanocytes in Sun-Exposed Skin

**Authors:** Francesco Fortarezza, Anna Poputchikova, Federica Pezzuto, Christian Ciolfi, Vincenza Guzzardo, Paolo Del Fiore, Gerardo Cazzato, Franco Bassetto, Mauro Alaibac, Angelo Paolo Dei Tos

PMC · DOI: 10.3390/dermatopathology13010014 · 2026-03-23

## TL;DR

This study shows that strong PRAME expression in melanoacanthomas is linked to sun exposure, not cancer, helping avoid misdiagnosis in skin pathology.

## Contribution

The study identifies a link between strong PRAME expression in melanoacanthomas and chronic sun exposure, not malignancy.

## Key findings

- Strong PRAME expression was more common in melanoacanthomas on sun-exposed skin.
- High-intensity PRAME expression correlated with increasing solar elastosis.
- PRAME positivity was not associated with features of malignancy in melanoacanthomas.

## Abstract

PRAME is a marker commonly used in pathology to help distinguish malignant melanoma from benign melanocytic lesions. However, PRAME can also be detected in some benign conditions, and the reasons for this are not fully understood. In this study, we analyzed PRAME expression in melanoacanthoma, a benign skin lesion, focusing on the possible influence of sun exposure. We found that while overall PRAME positivity was relatively frequent, strong PRAME expression was more commonly observed in lesions arising on sun-exposed skin and in areas showing chronic sun damage. Importantly, this increased expression was not associated with features of malignancy. These findings suggest that strong PRAME expression in melanoacanthoma may reflect long-term ultraviolet exposure rather than malignant transformation. Our results highlight the importance of interpreting PRAME staining in the context of lesion type and sun damage to avoid diagnostic misinterpretation in dermatology and dermatopathology.

PRAME (Preferentially Expressed Antigen in Melanoma) is increasingly used as an immunohistochemical marker in the evaluation of melanocytic lesions; however, its expression in benign melanocytic proliferations remains incompletely characterized. This study investigated PRAME expression in melanoacanthomas, with particular emphasis on its relationship with ultraviolet exposure and chronic solar damage. A consecutive series of melanoacanthomas was retrospectively analyzed. Melanocytes were identified and quantified using SOX10 immunohistochemistry, while PRAME-positive melanocytes were counted and graded semiquantitatively according to nuclear staining intensity. PRAME expression was correlated with lesion site (photoexposed versus non-photoexposed skin) and with the degree of solar elastosis. Eighty-four cases were evaluated, of which 25 (29.8%) showed at least focal PRAME positivity in melanocytes. Overall melanocytic density assessed by SOX10 did not differ significantly between photoexposed and non-photoexposed lesions. Similarly, stratification based on total PRAME-positive melanocyte counts, irrespective of staining intensity, revealed no significant association with photoexposure. In contrast, analysis restricted to melanocytes with strong nuclear PRAME expression demonstrated a significant enrichment in photoexposed lesions compared with non-photoexposed sites (p < 0.01). Moreover, high-intensity PRAME expression showed a positive association with increasing grades of solar elastosis. These findings indicate that strong PRAME expression in melanoacanthoma could be associated with chronic sun damage and may reflect non-specific, ultraviolet-related modulation rather than malignant transformation, underscoring the importance of contextual interpretation of PRAME immunohistochemistry in diagnostic practice.

## Linked entities

- **Genes:** PRAME (PRAME nuclear receptor transcriptional regulator) [NCBI Gene 23532]
- **Diseases:** melanoacanthoma (MONDO:0006579), malignant melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** SOX10 (SRY-box transcription factor 10) [NCBI Gene 6663] {aka DOM, PCWH, SOX-10, WS2E, WS4, WS4C}, RARA (retinoic acid receptor alpha) [NCBI Gene 5914] {aka NR1B1, RAR, RARalpha}, PRAME (PRAME nuclear receptor transcriptional regulator) [NCBI Gene 23532] {aka CT130, MAPE, OIP-4, OIP4}, RARS1 (arginyl-tRNA synthetase 1) [NCBI Gene 5917] {aka ArgRS, DALRD1, HLD9, RARS}
- **Diseases:** pigmented seborrheic keratoses (MESH:D017492), benign nevi (MESH:D009506), melanocytic hyperplasia (MESH:D006965), acanthotic epidermal lesions (MESH:D004814), dysplastic nevi (MESH:D004416), benign skin lesion (MESH:D012871), acanthosis (MESH:D000052), keratinocytic lesion (MESH:C580062), benign lesions (MESH:D001932), pigmented keratoses (MESH:D007642), benign melanocytic lesions (MESH:D009508), cutaneous carcinogenesis (MESH:D063646), cancer (MESH:D009369), Solar elastosis (MESH:D000092130), actinic (MESH:C579880), squamoproliferative lesions (MESH:D009059), Skin Tumours (MESH:D012878), malignant melanoma (MESH:D008545), papillomatosis (MESH:D010212), lentigo maligna (MESH:D018327), testis antigen (MESH:D013736), injury to (MESH:D014947), elastosis (MESH:D005148)
- **Chemicals:** RA (MESH:D014212), retinoid (MESH:D012176), hematoxylin (MESH:D006416), H&amp;E (MESH:D006371), formalin (MESH:D005557), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024871/full.md

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Source: https://tomesphere.com/paper/PMC13024871