Nazarian Rosalynn M, Kapur Payal, Rakheja Dinesh, Piris Adriano, Duncan Lyn M, Mihm Martin C, Hoang Mai P
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Mod Pathol. 2009 Apr;22(4):600-10. doi: 10.1038/modpathol.2009.18. Epub 2009 Feb 27.
The histological features of atypical hidradenoma are worrisome for increased risk of recurrence and possible malignant potential; however, earlier studies with immunohistochemistry or patient follow-up have not been reported. In addition, immunohistochemical analysis of hidradenocarcinoma exists in the literature mainly as case reports and as a single series of six cases. We compare the histological features and Ki-67, phosphorylated histone H3, epidermal growth factor receptor, and Her2/neu expression profiles of 15 atypical and 15 malignant hidradenomas with those of benign hidradenoma and metastasizing adnexal carcinomas. Infiltrative growth pattern, deep extension, necrosis, nuclear pleomorphism, and > or =4 mitoses per 10 high-power fields are specific features of hidradenocarcinomas. Significant difference in mean Ki-67% was observed between benign and malignant hidradenomas (P<0.001), benign and metastasizing adnexal carcinomas (0.002), atypical and malignant hidradenomas (P<0.001), and between atypical hidradenomas and metastasizing adnexal carcinomas (0.002). Significant difference in mean phosphorylated histone H3% was observed between benign and malignant hidradenomas (P<0.001), benign and metastasizing adnexal carcinomas (0.003), atypical and malignant hidradenomas (P<0.001), and between atypical hidradenomas and metastasizing adnexal carcinomas (P<0.001). Mean epidermal growth factor receptor total score was significantly different in benign and atypical hidradenoma when compared with that in metastasizing adnexal carcinoma (P=0.014 and 0.019, respectively). Equivocal or 2+ Her2/neu positivity was observed in one hidradenocarcinoma and in two metastasizing adnexal carcinomas. Receiver operating characteristic curve analysis for Ki-67 and phosphorylated histone H3% positivity reveals statistically significant criterion values of >11.425 and >0.7, respectively, for distinguishing malignant hidradenomas from atypical hidradenomas. Despite the presence of some worrisome histological features, the significantly different immunoprofile from the malignant counterpart suggests that atypical hidradenomas are likely to recur but are unlikely to metastasize. A tumor with Ki-67>11% and/or phosphorylated histone H3>0.7% would likely be a malignant rather than an atypical hidradenoma. The infrequent Her2/neu overexpression in hidradenocarcinoma suggests its limited therapeutic role.
非典型汗腺腺瘤的组织学特征令人担忧，提示复发风险增加及可能的恶性潜能；然而，此前尚未见有关免疫组化或患者随访的早期研究报道。此外，文献中关于汗腺癌的免疫组化分析主要为病例报告及一组6例的系列报道。我们比较了15例非典型汗腺腺瘤、15例恶性汗腺腺瘤与良性汗腺腺瘤及转移性附件癌的组织学特征，以及Ki-67、磷酸化组蛋白H3、表皮生长因子受体和Her2/neu的表达情况。浸润性生长模式、深部浸润、坏死、核异型性以及每10个高倍视野有≥4个核分裂象是汗腺癌的特征性表现。良性与恶性汗腺腺瘤之间（P<0.001）、良性与转移性附件癌之间（0.002）、非典型与恶性汗腺腺瘤之间（P<0.001）以及非典型汗腺腺瘤与转移性附件癌之间（0.002），Ki-67平均百分比存在显著差异。良性与恶性汗腺腺瘤之间（P<0.001）、良性与转移性附件癌之间（0.003）、非典型与恶性汗腺腺瘤之间（P<0.001）以及非典型汗腺腺瘤与转移性附件癌之间（P<0.001），磷酸化组蛋白H3平均百分比存在显著差异。与转移性附件癌相比，良性与非典型汗腺腺瘤的表皮生长因子受体总分有显著差异（分别为P=0.014和0.019）。在1例汗腺癌和2例转移性附件癌中观察到Her2/neu呈可疑阳性或2+阳性。对Ki-67和磷酸化组蛋白H3%阳性进行的受试者工作特征曲线分析显示，区分恶性汗腺腺瘤与非典型汗腺腺瘤的统计学显著标准值分别为>11.425和>0.7。尽管存在一些令人担忧的组织学特征，但与恶性肿瘤明显不同的免疫表型提示非典型汗腺腺瘤可能复发，但不太可能转移。Ki-67>11%和/或磷酸化组蛋白H3>0.7%的肿瘤可能是恶性汗腺腺瘤而非非典型汗腺腺瘤。汗腺癌中Her2/neu过表达不常见，提示其治疗作用有限。
