p16 Expression Is Lost in Severely Atypical Cellular Blue Nevi and Melanoma Compared to Conventional, Mildly, and Moderately Atypical Cellular Blue Nevi

Abstract

Background. Significant decreases in p16 expression have been shown to occur in melanoma compared to Spitz tumors, and loss of p16 staining has been found to correlate with melanoma tumor progression. However, comparison of p16 between atypical cellular blue nevi (CBN) and melanoma has not been reported previously. Methods. p16 immunohistochemical staining was evaluated in 14 atypical CBN, 8 conventional and atypical melanocytic nevi, and 16 melanomas, including 4 malignant CBN. p16 staining intensity was graded on a scale of 0–3 and the percentage of melanocytes stained with p16 was determined. Results. p16 staining was significantly higher in all CBN as a group when compared to melanomas (P = 0.001) and malignant CBN (P = 0.00008). Higher p16 expression was also seen in mildly (P = 0.0002) and moderately atypical (P = 0.02), but not severely atypical, CBN compared to melanomas. Conclusions. p16 immunohistochemical expression is higher in mildly and moderately atypical CBN compared to severely atypical CBN and melanomas. In conjunction with additional markers and histology, p16 staining may be useful in confirming the benign nature of these tumors, but is not useful in distinguishing severely atypical CBN from malignant cases, consistent with the overlapping histologic features between these tumors.

Immunohistochemical Expression of p16 in Melanocytic Lesions: An Updated Review and Meta-analysis

“…A more variable staining pattern is illustrated in primary invasive cutaneous melanoma, in which there is mostly cytoplasmic staining of the invasive cells (Figure 1, d), versus negative staining (Figure 1, f), versus cases in which there is heterogenous positive and negative staining of the invasive cells (Figure 1, h). Multiple studies have also incorporated specialized types of melanocytic lesions, such as Spitz lesions, [58][59][60][61]64,66,68 desmoplastic melanomas, 58,67,71 blue nevus-related lesions, 69,71 and mucosal melanocytic lesions 41,49,62,63 ; 2 studies 43,70 focused on nodal metastases, and a recent study (S. S. Koh, unpublished data, 2018) compared nevi of pregnancy and nevoid melanomas. The wide range of variable results is further highlighted when analyzing studies from Spitz nevi.…”

Problems of Differential Diagnosis in Melanoma Arising from Blue Naevus

“…Immunohistochemical analyses revealed a typical expression for S100 protein, HMB45, Melan A, Tyrosinase (T311) and Mitf and a typical negativity for p53, β Catenin, AE1-AE3, EMA and CK 8/18. The loss of expression of p16 seems to be suggestive for melanoma in blue melanocytic lesions [25]. The high ki 67 index (∼ 10% and focally 25% in our case) is the most important immunohistochemical marker [1] in diagnosis of malignant melanocytic blue lesions.…”

Cellular Blue Nevomelanocytic Lesions: Analysis of Clinical, Histological, and Outcome Data in 37 Cases

“…Classical histologic features for CBN are well described in the literature. 13 The diagnosis of ACBN, thus, still hinges predominately on the pathologist's gestalt of the lesion, with the aforementioned features generally used to support opinions for or against a diagnosis of CBN, ACBN, or BNLM. 3,4,7 We incorporated most characteristics in our histological evaluation in this study.…”