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Laura M. Chang 1 and David S. Cassarino 2
Academic Editor:M. Clelia and Academic Editor:M. Feinmesser and Academic Editor:P. Quatresooz
1, Department of Dermatology, Southern California Kaiser Permanente, Los Angeles Medical Center (LAMC), Kaiser Permanente, 4867 W Sunset Boulevard, Los Angeles, CA 90027-5969, USA
2, Department of Pathology, Southern California Kaiser Permanente, Los Angeles Medical Center (LAMC), Kaiser Permanente, 4867 W Sunset Boulevard, Los Angeles, CA 90027-5969, USA
Received 15 September 2013; Accepted 21 October 2013; 22 January 2014
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Distinguishing atypical and unusual variants of melanocytic nevi from melanoma by routine histologic examination can be difficult in some cases [1-3]. In particular, differentiating atypical cellular blue nevi (CBN) from melanoma (including melanoma arising in or mimicking a cellular blue nevus, the so-called "malignant cellular blue nevus") can pose a significant diagnostic problem [1], and it has been shown that even experienced dermatopathologists often disagree in differentiating CBN, especially atypical CBN, from melanoma [4]. Like melanoma, CBN often lack maturation, can have dermal mitotic figures, extend deeply in the dermis, and may have perineural and even intralymphatic involvement [5].
Immunohistochemistry is a useful tool in the diagnosis of some cases of melanoma, and markers such as S-100, HMB-45, Melan-A, MITF, and the proliferation marker Ki-67 are often used. Ki-67, in particular, has been found useful to distinguish benign from malignant melanocytic lesions [6], but additional markers would clearly be beneficial. p16 is one of the proteins that regulates the G1/S checkpoint of the cell cycle, and it is the product of the tumor suppressor gene CDKN2 [7]. Since loss of p16 expression has been documented to occur in melanoma [8], p16 may be a potential helpful marker in differentiating atypical melanocytic nevi from melanoma. p16 has been shown to be decreased or absent in melanoma compared to benign melanocytic nevi [9-13], including congenital melanocytic nevi [14]. This loss of p16 staining in melanoma compared to benign nevi has also been found to occur in noncutaneous sites such as the oral mucosa and conjunctiva [15, 16]. Furthermore, p16 has also been shown to be...