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Immunohistochemical expression of myoepithelial markers in adenomyoepithelioma of the breast: a unique paradoxical staining pattern of high-molecular weight cytokeratins


To determine which immunohistochemical markers are useful for the identification of neoplastic myoepithelial cells in adenomyoepithelioma of the breast, the expression of seven myoepithelial markers (α-smooth muscle actin (α-SMA), calponin, p63, CD10, cytokeratin 5/6, cytokeratin 14, and S-100) was examined in 19 lesions from 16 patients. The lesion consisted of seven spindle and 12 clear cell lesions. For normal myoepithelial cells, α-SMA, calponin, and p63 were significantly more sensitive than cytokeratin 5/6, cytokeratin 14, and S-100. There was no significant difference in the expression of α-SMA, calponin, p63, and CD10 in neoplastic myoepithelial cells of adenomyoepithelioma regardless of spindle or clear cell types. In spindle cell lesions, high-molecular weight cytokeratins (HMWCK; cytokeratin 5/6 and cytokeratin 14) tended to show higher staining scores and S-100 showed lower staining scores than other markers. In clear cell lesions, HMWCK showed significantly lower staining scores than the other five markers. There was no significant difference in staining scores among the other five markers. HMWCK showed a unique paradoxical staining pattern in clear cell lesions, with diffusely positive inner epithelial cells and completely negative outer myoepithelial cells. Although the sensitivity of HMWCK in clear cell lesions is low, with this unique paradoxical staining pattern and relatively high sensitivity in spindle cell lesions, HMWCK could be useful in diagnosing adenomyoepithelioma. In choosing immunohistochemical markers, any of the seven markers are useful, but combining HMWCK and any one of α-SMA, calponin, and p63 would be a good panel for the diagnosis of adenomyoepithelioma.

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  1. 1.

    Lakhani SR, Hayes M, Eusebi V (2012) Adenomyoepithelioma and adenomyoepithelioma with carcinoma. In: Lakhani SR, Ellis IO, Schnitt SJ et al (eds) WHO Classification of Tumours of the Breast. IARC, Lyon, pp 122–123

  2. 2.

    Hartz PH (1946) Adenomyoepithelioma of sweat gland; report of a case. Am J Clin Pathol 16:385–390

  3. 3.

    Hamperl H (1970) The myoepithelia (myoepithelial cells): normal state, regressive changes, hyperplasia, tumors. Curr Top Pathol 53:161–221

  4. 4.

    Rosen PP (1987) Adenomyoepithelioma of the breast. Hum Pathol 18:1232–1237

  5. 5.

    McLaren BK, Smith J, Schuyler PA, Dupont WD, Page DL (2005) Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions. Am J Surg Pathol 29:1294–1299

  6. 6.

    Nadelman CM, Leslie KO, Fishbein MC (2006) “Benign”, metastasizing adenomyoepithelioma of the breast. A report of 2 cases. Arch Pathol Lab Med 130:1349–1353

  7. 7.

    Kiaer H, Nielsen B, Paulsen S, Sørensen IM, Dyreborg U, Blichert-Toft M (1984) Adenomyoepithelial adenosis and low-grade malignant adenomyoepithelioma of the breast. Virchows Arch A 405:55–67

  8. 8.

    Loose JH, Patchefsky AS, Hollander IJ, Lavin LS, Cooper HS, Katz SM (1992) Adenomyoepithelioma of the breast. A spectrum of biologic behavior. Am J Surg Pathol 16:868–876

  9. 9.

    Rasbridge SA, Millis RR (1998) Adenomyoepithelioma of the breast with malignant features. Virchows Arch 432:123–130

  10. 10.

    Hayes MM (2011) Adenomyoepithelioma of the breast: a review stressing its propensity for malignant transformation. J Clin Pathol 64:477–484

  11. 11.

    Dorpe JV, Pauw AD, Moerman P (1998) Adenoid cystic carcinoma arising in an adenomyoepithelioma of the breast. Virchows Arch 432:119–122

  12. 12.

    Ahmed AA, Heller DS (2000) Malignant adenomyoepithelioma of the breast with malignant proliferation of epithelial and myoepithelial elements. A case report and review of the literature. Arch Pathol Lab Med 124:632–636

  13. 13.

    Zarbo RJ, Oberman HA (1983) Cellular adenomyoepithelioma of the breast. Am J Surg Pathol 7:863–870

  14. 14.

    Tavassoli FA (1991) Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma. Am J Surg Pathol 15:554–568

  15. 15.

    Cameron HM, Hamperl H, Warambo W (1974) Leiomyosarcoma of the breast originating from myothelium (myoepitehlium). J Pathol 114:89–92

  16. 16.

    Weidner N, Levine JD (1988) Spindle-cell adenomyoepithelioma of the breast. A microscopic, ultrastructural, and immunohistochemical study. Cancer 62:1561–1567

  17. 17.

    Choi JS, Bae JY, Jung WH (1996) Adenomyoepithelioma of the breast. Its diagnostic problems and histogenesis. Yonsei Med J 37:284–289

  18. 18.

    Catena F, Santini D, Saverio SD, Ansaloni L, Taffurelli M (2008) Adenomyoepithelioma of the breast: an intricate diagnostic problem. Breast Care 3:125–127

  19. 19.

    Popnikolov NK, Ayala AG, Graves K, Gatalica Z (2003) Benign myoepithelial tumors of the breast have immunophenotypic characteristics similar to metaplastic matrix-producing and spindle cell carcinomas. Am J Clin Pathol 120:161–167

  20. 20.

    Hungermann D, Buerger H, Oehlschlegel C, Herbst H, Boecker W (2005) Adenomyoepithelial tumours and myoepithelial carcinomas of the breast—a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells. BMC Cancer 5:92

  21. 21.

    Mukai K, Schollmeyer JV, Rosai J (1981) Immunohistochemical localization of actin. Application in surgical pathology. Am J Surg Pathol 5:91–97

  22. 22.

    Nakajima T, Kameya T, Watanabe S, Hirota T, Sato Y, Shimosato Y (1982) An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol 6:715–727

  23. 23.

    Dewar R, Fadare O, Gilmore H, Gown AM (2011) Best practices in diagnostic immunohistochemistry. Myoepithelial markers in breast pathology. Arch Pathol Lab Med 135:422–429

  24. 24.

    Lazard D, Sastre X, Frid MG, Glukhova MA, Thiery JP, Koteliansky VE (1993) Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue. Proc Natl Acad Sci 90:999–1003

  25. 25.

    Barbareschi M, Pecciarini L, Cangi MG, Macrí E, Rizzo A, Viale G, Doglioni C (2001) p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25:1054–1060

  26. 26.

    Reis-Filpho JS, Schmitt FC (2002) Taking advantage of basic research: p63 is a reliable myoepithelial and stem cell marker. Adv Anat Pathol 9:280–289

  27. 27.

    Moritani S, Kushima R, Sugihara H, Bamba M, Kobayashi TK, Hattori T (2002) Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections. Mod Pathol 15:397–405

  28. 28.

    Gillett CE, Bobrow LG, Millis RR (1990) S100 protein in human mammary tissue immunoreactivity in breast carcinoma, including Paget’s disease of the nipple, and value as a marker of myoepithelial cells. J Pathol 160:19–24

  29. 29.

    Hilson JB, Schnitt SJ, Collins LC (2009) Phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells. Biologic and diagnostic implications. Am J Surg Pathol 33:227–232

  30. 30.

    Hilson JB, Schnitt SJ, Collins LC (2010) Phenotypic alterations in myoepithelial cells associated with benign sclerosing lesions of the breast. Am J Surg Pathol 34:896–900

  31. 31.

    Otterbach F, Bánkfalvi Ά, Bergner S, Decker T, Krech R, Boecker W (2000) Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 37:232–240

  32. 32.

    Gusterson BA, Ross DT, Heath VJ, Stein T (2005) Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res 7:143–148

  33. 33.

    Su L, Morgan PR, Lane B (1996) Expression of cytokeratin messenger RNA versus protein in the normal mammary gland and in breast cancer. Hum Pathol 27:800–806

  34. 34.

    Clarke CL, Sandle J, Parry SC, Reis-Filho JS, O’Hare MJ, Lakhani SR (2004) Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype. J Pathol 204:147–152

  35. 35.

    Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W, Sjöström B, Dahlqvist Å, Coates PJ (2002) Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol 198:417–427

  36. 36.

    Reis-Filho JS, Simpson PT, Martins A, Preto A, Gärtner F, Schmitt FC (2003) Distribution of p63, cytokeratin 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443:122–132

  37. 37.

    Boecker W, Stenman G, Loening T, Andersson MK, Bankfalvi A, Holstein S, Heegaard S, Lange A, Berg T, Samoilova V, Tiemann K, Buchwalow I (2013) Mod Pathol 26:1086–1100

  38. 38.

    Diaz NM, McDivitt RW, Wick MR (1991) Pleomorphic adenoma of the breast: a clinicopathologic and immunohistochemical study of 10 cases. Hum Pathol 22:1206–1214

  39. 39.

    Sato K, Ueda Y, Shimasaki M, Ozaki M, Nitta N, Chada K, Ishikawa Y, Katsuda S (2005) Pleomorphic adenoma (benign mixed tumor) of the breast: a case report and review of the literature. Pathol Res Pract 201:333–339

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This study was supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

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The authors declare that they have no conflicts of interest.

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Correspondence to Suzuko Moritani.

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Moritani, S., Ichihara, S., Yatabe, Y. et al. Immunohistochemical expression of myoepithelial markers in adenomyoepithelioma of the breast: a unique paradoxical staining pattern of high-molecular weight cytokeratins. Virchows Arch 466, 191–198 (2015). https://doi.org/10.1007/s00428-014-1687-2

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  • Adenomyoepithelioma
  • Myoepithelial cells
  • Immunohistochemistry
  • Cytokeratin 5/6
  • Cytokeratin 14
  • Paradoxical staining pattern