Preferentially Expressed Nuclear Antigen in Melanoma Expression in Melanocytic Activation (Melanotic Macule) of the Nail Unit. A Potential Diagnostic Pitfall? A Study of 3 Cases.

Recent studies have argued that melanocyte preferentially expressed nuclear antigen in melanoma (PRAME) is a sensitive and specific immunohistochemical marker of melanoma, including acral melanoma. In addition, loss of p16 expression has recently been suggested to have diagnostic utility in acral melanocytic tumors. The purpose of this study was to report PRAME expression in 3 cases of melanocytic activation (MAN). There were 2 men and 1 woman ranging in age at diagnosis from 46 years to 78 years (mean 61, 6 years). All cases involved a single digit. One lesion was in the fingernail (fifth finger), whereas the remaining 2 lesions were in the toenails (hallux). All the patient presented with a longitudinal melanonychia. The width of the lesions varied from 3 mm (2 cases) to 4 mm (1 case). The duration of the lesions before diagnosis varied from 12 to 24 months. Distinction of MAN from melanoma in situ is not always easy. Some morphological misleading features are illustrated in this study: (1) the suprabasal location of matrix melanocytes with long and thick dendrites within the 2-4 germinative cell layers; (2) the microconfluence of 2 melanocytes and rare melanocytes with a relatively large nucleus, however in a general context of melanocyte scarcity; and (3) the occasional nonspecific nuclear microphtalmia-associated transcription factor (MITF) staining of keratogeneous cells. Such staining could suggest a pagetoid spread of melanocytes in the keratogenous zone. PRAME antibody revealed a strong and diffuse staining in all cases. In addition, all cases were p16 negative. In this study, the melanocyte count inferior to 9 melanocytes/mm and the lack of nuclear atypia or confluence of melanocytes permitted a confident diagnosis of MAN. Limitations of our study lie largely in the small number of cases. Despite this, the expression of PRAME in some MAN seems to hamper its diagnostic value in differentiating benign from malignant lesion.