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. 2018 May 8;9:1816. doi: 10.1038/s41467-018-04128-5

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Histologic and immunohistochemical features of adenomyoepitheliomas. a−f Representative micrographs of hematoxylin-and-eosin (H&E)-stained adenomyoepitheliomas included in this study. a Low-power magnification of AM2, a multilobulated lesion, of tubular architectural pattern, with well-circumscribed borders (scale bar, 1 mm). b Intermediate-power magnification of AM39 displaying the typical bi-layered glandular architecture of adenomyoepitheliomas, comprising abluminal myoepithelial cells with clear cytoplasm and inner cuboidal epithelial cells with eosinophilic cytoplasm and apical snouts (scale bar, 200 μm). c AM9 displaying areas of comedo-like necrosis (*, scale bar, 200 μm). d AM8 displaying nuclear atypia and mitotic figures (arrowheads, scale bar, 100 μm). e AM5 displaying an adenomyoepithelioma component (lower left corner, *) in association with a larger high-grade myoepithelial carcinoma (**), with large central necrosis in the upper right corner (***, scale bar, 1 mm). f Axillary lymph node metastasis of AM5 (scale bar, 1 mm), where the biphasic architecture is maintained. *, residual lymph node; **, metastatic lesion. g Representative micrographs of estrogen receptor (ER)-negative and ER-positive adenomyoepitheliomas. On the left, H&E stain of each case (scale bars, 100 μm). On the right, ER immunohistochemistry results. Note the internal positive control (*) in the ER-negative case. h Stacked bar plots showing the frequency of histologic features indicative of a more aggressive behavior (nuclear grade, mitotic rate, and necrosis) and of the presence of associated carcinoma according to ER status (ER-positive versus ER-negative comparisons were performed using two-tailed Fisher’s exact tests). The histologic features are color-coded according to the legends. AME, adenomyoepithelioma. i Stacked bar plots showing the frequency of the expression of androgen receptor, HER2, Ki67, and p53 according to ER status (ER-positive versus ER-negative comparisons were performed using two-tailed Fisher’s exact tests). AME, adenomyoepithelioma; AR, androgen receptor; Equiv, equivocal; Neg, negative; Pos, positive