Department of Pathology and Laboratory Medicine Children's Mercy Hospital, 2401, Gillham Road, 64108, Kansas City, MO, United States.
Department of Pathology and Laboratory Medicine Children's Mercy Hospital, 2401, Gillham Road, 64108, Kansas City, MO, United States.
Pathol Res Pract. 2019 Oct;215(10):152550. doi: 10.1016/j.prp.2019.152550. Epub 2019 Jul 22.
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.
当 Spitz 痣的垂直厚度增加（>1.0mm）、出现溃疡和深部有丝分裂时，需要考虑非典型 Spitz 肿瘤（AST）或 Spitz 样黑素瘤（SM）的鉴别诊断。虽然分子遗传学检测可用于非典型黑色素细胞增生的研究，但这些检测费用昂贵，并非所有机构都能开展。最近，有一项研究在成人黑素瘤中应用了 p16、Ki-67 和 HMB45（PKH）免疫组化，并提出了将这三种标志物结合起来，并对其结果进行评分，以支持黑素瘤的诊断。我们报告了这种抗体组合评分在鉴别儿童 SM 和 AST 中的效用。我们回顾性分析了 30 例 Spitz 样病变（7 例 SM、9 例 AST 和 14 例 Spitz 痣）患儿的资料。对所有病例的 H&E 染色切片和 p16、Ki-67 和 HMB45 的免疫组化染色进行了复习。根据发表的标准，对病变细胞中免疫组化表达的程度进行评分如下：p16 评分为 0、1、2、3；Ki-67 评分为 0、1、2、3、4；HMB45 评分为 0、1。因此，任何病例的 3 种抗体组合的 PKH 评分范围为 0-9。我们研究中病例的免疫组化分析结果表明，Spitz 痣和 AST 的 PKH 评分均低于 4，而 SM 的 PKH 评分均高于 4。这些结果具有重要意义，因为之前的研究发现，PKH 评分等于或>4 与黑素瘤相关，小于 4 与良性痣相关。独立地，免疫组化染色可能具有误导性，因为年轻儿童（<2 岁）的 Ki-67 标记指数往往较高，AST 和 SM 中偶尔 HMB45 为阴性，AST 中 p16 可完全丢失。我们的研究复制了之前发表的成人黑素瘤和痣的研究结果，即等于或>4 的总 PKH 评分见于黑素瘤。尽管我们的研究中 SM 病例数量较少，但恶性和良性病例的 PKH 评分模式与成人研究一致。我们建议在儿童非典型 Spitz 样病变的研究中常规使用 PKH 免疫组化。
