Toward an effective use of β-catenin immunohistochemistry in the evaluation of challenging melanocytic lesions

Excerpt

In this issue, Fouchardiere and colleagues [1] proffer that nuclear β-catenin expression as detected by immunohistochemistry (IHC) can be a helpful screening tool to distinguish an ambiguous dermal melanocytic proliferation as a deep penetrating nevus (DPN) from similar entities on its differential diagnosis, including “blue” melanocytic tumors, spitzoid tumors, nevoid and superficial spreading melanomas (SSM), and pigmented epithelioid melanocytomas (PEM). Firstly, they retrospectively evaluated nuclear β-catenin expression in 178 diagnostically challenging and unambiguous lesions and found that 98/100 of the DPN were positive, along with 2/16 melanomas (one SSM and one nevoid melanoma with a plexiform clone), while all spitzoid, blue, and PEM (n = 30, 26 and 6, respectively) lesions lacked nuclear accumulation of β-catenin. Because nuclear accumulation of β-catenin can drive cyclin D1 expression in other cellular contexts, they also evaluated nuclear and cytoplasmic cyclin D1 expression, which was not significantly different among the diagnostic groups, suggesting that cyclin D1 expression is not entirely dependent upon nuclear β-catenin expression. Secondly, they evaluated nuclear β-catenin IHC expression in a set of 13 diagnostically-ambiguous melanocytic tumors with DPN in the differential diagnosis. Three of four cases with canonical DPN mutation profiles were the only β-catenin-positive cases; there were no false positives by β-catenin IHC. …