Utility of p16-Ki-67-HMB45 score in sorting benign from malignant Spitz tumors

Abstract

When Spitz nevi have increased vertical thickness (>1.0 mm), show ulceration and deep seated mitoses, the differential diagnostic considerations of atypical Spitz tumor (AST) or a Spitzoid melanoma (SM) enter into consideration. While molecular genetic testing could be employed in the work up of atypical melanocytic proliferations, they are expensive and not available at all institutions. Recently, one study employed the combination of p16, Ki-67 and HMB45 (PKH) immunohistochemistry on adult melanomas and proposed a combination of the three markers with scoring of their result to support a diagnosis of melanoma. We report the utility of this antibody combination scoring in discriminating SM and AST in children. We retrospectively reviewed 30 Spitzoid lesions (7 SM, 9 AST and 14 Spitz nevi) from children. Slides from H&E staining and Immunohistochemistry for p16, Ki-67 and HMB45 were reviewed for all cases. The extent of immunohistochemical expression in the lesional cells was scored following published criteria as follows: p16 scored as 0, 1, 2, 3; Ki-67 scored as 0, 1, 2, 3, 4 and HMB45 scored as 0, 1 and 2. Thus, the total PKH score for the combination of the 3 antibodies for any case could vary from 0 to 9. The result of the immunohistochemical analysis of cases in our study revealed that the PKH score of Spitz nevus and AST was below 4 for each of the case and that of SM was >4 for each of the case. These results are significant as the previously published study found that the PKH score of equal/or >4 correlated with melanoma and less <4 correlated with benign nevi. Independently, the immunostains could be misleading as Ki-67 labeling index tended to be higher in young children (<2 years of age) and HMB45 was occasionally negative in both AST and SM, and p16 could be completely lost in AST.Our study replicates the findings of the published study of adult melanomas and nevi that showed a total PKH score of equal/or>4 is seen in melanoma. Although, the number of SM cases in our study are few, the PKH scoring pattern of malignant and benign cases was congruent with the adult study. We suggest routine use of PKH immunohistochemistry in the work up of atypical Spitzoid lesions in children.