PRAME immunohistochemistry is useful in the evaluation of conjunctival melanomas, nevi, and primary acquired melanosis

Abstract

Background Many dermatopathologists find conjunctival melanocytic proliferations challenging because they are rare relative to their cutaneous counterparts and have nuanced morphology and nomenclature. PRAME immunohistochemistry has been widely adopted for distinguishing cutaneous nevi from melanoma, but limited data exist assessing its utility in evaluating conjunctival specimens. In particular, it is uncertain whether it can predict the risk of melanoma progression in primary acquired melanosis (PAM). Methods Thirty clinically annotated cases (two melanomas, three PAM with atypia, seven PAM without atypia, 15 nevi, two combined nevi, and a diagnostically challenging nevus with atypical features) were retrospectively evaluated with PRAME. Results Strong, diffuse PRAME expression was present in melanomas and PAM with high‐grade atypia, but not in PAM with low‐grade atypia, PAM without atypia, or nevi. Scattered, faintly PRAME‐positive intraepithelial melanocyte nuclei were identified in six nevi. A clonal nevus and nests of heavily pigmented type‐A melanocytes in two additional nevi had cytoplasmic staining. Conclusions PRAME was useful for distinguishing melanoma and its probable precursors from benign conjunctival melanocytic proliferations in our cohort. The data alert us to two diagnostic pitfalls in nevi: scattered, PRAME‐positive intraepithelial melanocytes and cytoplasmic PRAME staining in type‐A melanocytes and melanophages. Larger scale investigations are warranted to further substantiate these promising findings.

PRAME expression in melanocytic lesions of the conjunctiva

“…21 In accordance with our results, a diffuse 4+ PRAME positivity was identified in two of two invasive melanomas, two of two 'high-grade' PAM, none in one 'low-grade' PAM, none of seven PAM without atypia and none of 18 melanocytic naevi. 21 Absent expression of PRAME in most cases of PAM without atypia is consistent with the view that PAM without atypia is not associated with a significantly increased risk of progression to melanoma and possibly does not represent a true clonal neoplasm. 12 Focal 1+ PRAME positivity in three (13%) PAM without atypia seems to correspond to the frequency of focal PRAME positivity in normal conjunctival melanocytes in older patients (see below).…”

“…1,5,6,9,10 In another recent study, 30 conjunctival melanocytic lesions of different types were analysed using the same antibody and the same approach to quantify PRAME positivity as in our study. 21 In accordance with our results, a diffuse 4+ PRAME positivity was identified in two of two invasive melanomas, two of two 'high-grade' PAM, none in one 'low-grade' PAM, none of seven PAM without atypia and none of 18 melanocytic naevi. 21 Absent expression of PRAME in most cases of PAM without atypia is consistent with the view that PAM without atypia is not associated with a significantly increased risk of progression to melanoma and possibly does not represent a true clonal neoplasm.…”

“…To the best of our knowledge, in conjunctival melanocytic lesions PRAME expression has been analysed by immunohistochemistry in only two previous studies. 20,21 In one study, 70 conjunctival melanomas and 12 conjunctival naevi were included and PRAME expression was quantified by immunoreactivity score (from 0 to 12) as a product of the points of staining intensity and percentage of stained cells. 20 Although PRAME was differentially expressed in conjunctival melanomas and naevi, with immunoreactive score ≥ 7 being 100% specific and 76.6% sensitive for conjunctival melanomas, the results cannot be directly correlated with ours.…”

“…1,9 To the best of our knowledge, PRAME expression in conjunctival melanocytic lesions has so far been analysed in two studies, one including 70 conjunctival melanomas and 12 naevi, and another including 30 melanocytic lesions of different types (including only two invasive melanomas). 20,21 As the utility of PRAME expression for separating malignant from benign melanocytic lesions may vary depending on the type and site of melanocytic lesions, data from cutaneous lesions cannot be directly applied to conjunctival melanocytic lesions. 1,[4][5][6][7][8][9][10][11] Our aim was to analyse PRAME expression in a large number of different melanocytic lesions of the conjunctiva in order to test its utility in differentiating between conjunctival naevi, invasive or in-situ melanomas or PAM.…”

Preferentially Expressed Antigen in Melanoma (PRAME) and Human Malignant Melanoma: A Retrospective Study

“…In this scenario, rising attention is being devoted to this marker, and new studies are being conducted in an attempt to increase experiences, report results, and find safer answers [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”