Figure 1: Gross appearance of the tumor; well-circumscribed tumor surrounded by a thin capsule.
Figure 2: Irregular small glandular structures (HE x200).
Figure 3: Prominent smooth muscle differentiation (HE x200).
Figure 4: Fibroadenomatous area within the adenomyoepithelioma (HE x100).
Figure 5: Strong staining for EMA in the epithelial and myoepithelial cells (B-SA, DAB x200).
Figure 6: SMA decorated the outer myoepithelial layer (B-SA, DAB x200).
Figure 7: Estrogen receptor expression in the inner epithelial layer (B-SA, DAB x400).
Table 1: Adenomyoepithelioma of the breast; immunohistochemical findings.
The majority of AMEs is grossly well circumscribed and they can even be encapsulated. However, AMEs may have lobulated, somewhat irregular appearance which may grossly mimic malignancy[10]. The typical histologic appearance of an AME consists of acinar structures composed of an inner layer of epithelial cells with eosinophilic cytoplasm and a prominent peripheral layer of myoepithelial cells with clear cytoplasm[1,2]. Minimal pleomorphism and low mitotic rate (usually less than 3 mitotic figures per 10 HPFs), as noted in this case, may be seen in both elements[11]. Moreover, focal apocrine, squamous, mucinous, sebaceous or even chondroid and oseeous metaplasia may be encountered[1,2,9,12]. Coexistent areas of fibroadenoma in this case support the hypothesis that myoepithelial overgrowth from benign breast lesions give rise to AME, and as might be expected smooth muscle differentiation may be encountered. Immunohistochemically, consistent with the current case, myoepithelial cells exhibit positive reactions for SMA, smooth muscle myosin, vimentin, EMA, cytokeratin 14, S100 protein, calponin and p63, while the luminal epithelial cells are strongly positive for cytokeratin, EMA and CEA. Contrary to normal myoepithelial cells, luminal cells possess receptors for ovarian steroid hormones and actively cycle in response to hormonal levels, however their growth regulation is largely unknown[1,2,11-14]. On the other hand, AME’s resemblance to usual ductal carcinoma -not uncommonly and as noted in the current case- and differentiation from its malignant counterparts are the most challenging issues complicating the diagnosis. In these circumstances, careful examination for myoepithelial differentiation verified by immunohistochemistry may be helpful.
AME is regarded as either a benign or a low-grade malignant lesion. The biologic behavior of AME still remains uncertain. In fact the presence of two-cell lineages alone is of no help in differentiating benign from malignant AME. Although high mitotic activity, cellular pleomorphism, high cellularity, necrosis, reactive stromal response (desmoplasia) and infiltrating (rather than pushing) borders (if present), are suggestive of a malignant behaviour, quite often some malignant AMEs have only one of the above characteristic features[1,2,6,12,15,16]. Malignant change may involve only one cellular element, more often epithelial component rather than the myoepithelial component[1,2]. Several cases with local recurrences and distant metastases to lung, liver, brain, bone, thyroid, chest wall and lymph nodes have been reported[6,8,13,17-19].
In conclusion, AME is an unusual breast neoplasm mostly with a benign course, but has a potential for local recurrence, and may simulate malignant lesions. Furthermore, malignant change of one or both cellular components may also occur. Therefore, it should be considered in the differential diagnosis of solid lesions of the breast and complete excision is necessary for accurate diagnosis and treatment of this unusual breast lesion with long term follow-up.
1) Rosen PP. Myoepithelial neoplasms. In Rosen PP (ed). Rosen’s Breast Pathology. 2nd ed. Philadelphia, Lippincott Williams&Wilkins, 2001. p.121-134.
2) Tavassoli FA. Miscellaneous Lesions. In Tavassoli FA (ed). Pathology of the Breast. 2nd ed. Norwalk, Appleton& Lange, 1992. p.595-609.
3) Tamura G, Monma N, Suzuki Y, Satodate R, Abe H. Adenomyoepithelioma (myoepithelioma) of the breast in a male. Hum Pathol 1993;24:678-681.
4) Berna JD, Arcas I, Balleter A, Bas A. Adenomyoepithelioma of the breast in a male. Am J Roentgenol 1997;169:917-918.
5) Loose JH, Patchefsky AS, Hollander IJ, Lavin LS, Cooper HS, Katz SM. Adenomyoepithelioma of the breast. A spectrum of biologic behavior. Am J Surg Pathol 1992;16:868-879.
6) Choi JS, Bae JY, Jung WH. Adenomyoepithelioma of the breast. Yonsei Med J 1996;37:284-289.
7) Hamperl H. The myothelia (myoepithelial cells). Normal state; regressive changes; hyperplasia; tumors. Curr Top Pathol 1970;53:161-220.
8) Bult P, Verwiel JMM, Wobbes T, Kooy-Smits MM, Biert J, Holland R. Malignant adenomyoepithelioma of the breast with metastasis in the thyroid gland 12 years after excision of the primary tumor. Case report and review of the literature. Virchows Arch 2000;436:158-166.
9) Gill TS, Clarke D, Douglas-Jones AG, Sweetland HM, Mansel RE. Adenomyoepithelioma of the breast: a diagnostic dilemma. Eur J Surg Oncol 2000;26:316-318.
10) Felipo F, Del Agua C, Eguizabal C, Vaquero M. Benign adenomyoepithelioma of the breast: a case with gross mimicking of malignancy. Breast J 2002;8:383-384.
11) McLaren BK, Smith J, Schuyler PA, Dupont WD, Page DL. Adenomyoepithelioma: Clinical, histologic, and immunohistologic evaluation of a series of related lesions. Am J Surg Pathol 2005;29:1294-1299.
12) Gatti G, Viale G, Simsek S, Zurrida S, Intra M, Caldarella P, et al. Adenomyoepithelioma of the breast, presenting as a cancer. Tumori 2004;90:337-339.
13) Kihara M, Yokomise H, Irie A, Kobayashi S, Kushida Y, Yamauchi A. Malignant adenomyoepithelioma of the breast with lung metastases: report of a case. Surg Today 2001;31:899-903.
14) Rosen PP. Adenomyoepithelioma of the breast. Hum Pathol 1987;18:1232-1237.
15) Harigopal M, Park K, Chen X, Rosen PP. Pathologic quiz case:a rapidly increasing breast mass in a postmenopausal woman. Malignant adenomyoepithelioma. Arch Pathol Lab Med 2004;128:235-236.
16) Dorpe JV, De Pauw A, Moerman P. Adenoid cystic carcinoma arising in an adenomyoepithelioma of the breast. Virchows Arch 1998;432:119-122.
17) Chen PC, Chen CK, Nicastri AD, Wait RB. Myoepithelial carcinoma of the breast with distant metastasis and accompanied by adenomyoepitheliomas. Histopathol 1994;24:543-548.