AME of the breast is characterized by microscopically biphasic proliferation of epithelial and myoepithelial cells. The AME of breast is a very rare tumor that was already reported in 1970 [3
]. The majority of AME are benign, but malignant transformation may occur in AME. Both benign and malignant AME are inclined to local recurrence after surgery and may even recur several years after the initial surgery [5
]. The guidelines of malignant AME have been not established yet. However we can use the term 'malignant AME' that has infiltrating margins, markedly increased mitotic counts and distinctly cytologic atypia in case of not having definite metastasizing evidence [7
]. Also distant metastasis and local recurrence are the most obvious evidences of malignancy. Subsequently, malignant transformation of AME can be divided into three different types according to the main malignant cell types: 1) completely epithelial type; 2) malignant spindle cell type; or 3) both epithelial and myoepithelial type. Malignant epithelial carcinoma arising AME is similar to infiltrating ductal carcinoma, mucoepidermoid carcinoma or adenosquamous carcinoma. Myoepithelial carcinoma or malignant myoepithelioma is purely composed of infiltrating myoepithelial cells with predominantly spindle features.
Microscopically, myoepithelial carcinoma shows infiltrating patterned spindle tumor cells with prominent cytologic atypia, increased mitotic activity (more than 3-4/10 HPF) and definitely infiltrating tumor borders. On immunohistochemistry, spindle tumor cells represent strong positivity of myoepithelial markers, such as smooth muscle actin, calponin, S-100 or p63, and of epithelial markers, such as cytokeratin or epithelial membrane antigen.
Treatment of malignant AME or myoepithelial carcinoma has not been established yet except only complete surgical resection because of the rarity of this tumor. Up to date, several cases of local recurrence or metastasis have been reported so myoepithelial carcinoma should be carefully examined and needed to close follow up. The effectiveness of adjuvant Tamoxifen therapy has not come out.
The differential diagnosis of myoepithelial carcinoma should be included spindle cell carcinoma, fibromatosis and variety of myofibroblastic tumors. The obviously atypical spindle cells which show positivity of myoepithelial and epithelial markers with infiltrating margins are helpful in distinguishing from the spindle cell carcinoma and myofibroblastic tumors. Our case showed also biphasic pattern of immunohistochemistry of strong positivity for myoepithelial markers, such as smooth muscle actin, calponin, p63, and for epithelial marker, such as pancytokeratin. Also it demonstrated definite infiltrating tumor margins with high mitotic rates (4-5/10 HPF) and prominent cytologic atypia. So it could be diagnosed with myoepithelial carcinoma. Also there was a central lesion which showed biphasic proliferation of inner epithelilal and outer myoepithelial cells which could be diagnosed with AME. Consequently, our case is a myoepithelial carcinoma arising in AME. Interestingly, in our case, a contralateral invasive micropapillary carcinoma was found.
Han et al. [8
] researched molecular abnormalities of malignant AME and reported the point mutation of p53
gene in this myoepithelial cells, but not in intraluminal epithelial cells or adjacent normal ductal epithelium. Also Jones et al. [9
] were performed comparative genomic hybridization (CGH) analysis on a malignant AME case in another study. Furthermore, Angèle et al. [10
] have also reported that p53 protein was negative in benign myoepithelial lesions but overexpressed in 44.4% of malignant myoepithelial tumors of the breast. Recently some molecular studies of AME have been trying to identify the molecular pathway of tumorigenesis of AME, but due to the rarity of AME or malignant AME, the pathway has not been established yet.
In conclusion, our case is a rare case of myoepithelial carcinoma arising in AME with contralateral invasive micropapillary carcinoma. Despite the definite diagnosis of malignant AME can be possible throughout various immunohistochemistry, pathologists who are unaware of myoepithelial lesions can make a misdiagnosis of malignant AME. Finally, in case of malignant AME or malignant myoepithelial tumors, close follow up and in some cases, adequate further treatment with adjuvant chemotherapy or radiotherapy should be considered.