A 75-year-old woman presented with a left breast mass of 1 month's duration. She was referred for bilateral mammography and left breast ultrasonography. The patient stated that she had a normal mammogram 1 year prior to this presentation and had no prior history of breast abnormalities. Her past medical history was significant for multiple medical problems, including rheumatoid arthritis, asthma, migraine headache, recurrent urinary tract infections, congestive heart failure, and depression. She had no family history of breast cancer. On physical examination, a 1.5 × 2.0-cm mobile mass was palpated in the left subareolar area. There was central nipple inversion without dimpling of the overlying skin or nipple discharge. No axillary masses or lymph nodes were palpated bilaterally. The right breast was unremarkable except for central nipple inversion.
Mammography of the left breast showed a 2.5 × 2.0-cm, dense, oval mass with well-defined margins in the subareolar area. An ultrasound of the left breast showed a 1.9 × 1.8 × 1.7-cm mass with heterogenous echogenicity 2 cm from the areolar margin. The patient underwent a fine-needle aspiration of the left breast mass 2 months later at another institution, which showed a vascular spindle cell neoplasm, interpreted as a malignant neoplasm, favoring a malignant hemangiopericytoma. A cell-block preparation from the fine-needle aspiration showed sheets of neoplastic cells with marked pleomorphism. The patient underwent mastectomy with axillary node dissection. On sectioning of the breast, a well-demarcated, soft, hemorrhagic, partly cystic mass with a nodular cut surface measuring 4.5 × 3.0 × 2.0 cm was seen 1.5 cm from the inverted nipple.
On histology, the tumor showed a biphasic growth pattern with dark compact areas of hyperchromatic cells with a high nucleus-cytoplasmic ratio alternating with a paler zone composed of large polygonal pale cells with vesicular nuclei and ill-defined cytoplasm (Figure, A, arrows, hematoxylin-eosin, original magnification ×20). Both components were poorly differentiated with areas of necrosis and brisk mitotic activity. The mitoses were more frequent in the paler staining areas (Figure, B, arrow, hematoxylin-eosin, original magnification ×40). Immunohistochemistry for cytokeratin (AE1/AE3) stained only cells in the darker compact zone, with complete absence of staining in the pale light zone (Figure, C, hematoxylin-eosin, original magnification ×40). Note the presence of necrosis (arrow). Staining for S100 (Figure, D, hematoxylin-eosin, original magnification ×40), vimentin, and CD10 showed an opposite staining pattern, with reactivity only in the pale zone and complete absence of staining in the darker zones. Immunostains for desmin and CD34 were negative in both parts of the tumor. An immunostain for K903 showed focal reactivity in the darker compact zone. The axillary lymph nodes and nipple sections showed no tumor. The tumor was negative for estrogen and progesterone hormone receptors and lacked Her-2/neu overexpression.
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Pathologic Diagnosis: Malignant Adenomyoepithelioma
Mammary adenomyoepithelial neoplasms are uncommon and are usually associated with benign behavior.1,2 Rare examples of malignant adenomyoepithelioma with metastasis have been reported in the literature.3 Adenomyoepithelial tumors have been reported in women aged 27 to 80 years (mean age, 60 years). The tumors can be peripheral or centrally located near the areola. Grossly, adenomyoepitheliomas are well-circumscribed, firm to hard, and nodular, but they may be soft or have ill-defined margins and occasionally contain small cysts. The tumor size varies from 0.5 to 5 cm (median size, 1.5 cm). Histologically, benign adenomyoepitheliomas have a distinctive and balanced proliferation of epithelial elements composed of round to oval or tubular glands admixed with sheets of polygonal myoepithelial cells with clear vacuolated cytoplasm. The epithelial cells have scanty cytoplasm and dark hyperchromatic nuclei with infrequent mitoses. The myoepithelial cells vary from polygonal to spindle cell myoid growth pattern and rarely exhibit atypia. Malignancy can develop in the epithelial component, myoepithelial component, or in both components. Tumors composed almost exclusively of myoepithelial cells are called myoepitheliomas. Rare examples of purely malignant myoepitheliomas have been reported.4 Malignancy arising in both the epithelial and myoepithelial components is exceptionally rare, and fewer than 12 cases have been published in the literature to date.5 The presence of necrosis, marked cytologic atypia, and mitotic activity is usually associated with malignant transformation. In the case presented, the mitoses were present an average of greater than 5 per 10 high-power fields with large areas of necrosis, and the tumor exhibited irregular margins. Lymph node metastasis and distant metastasis to lung and brain, although rare, have been reported.5 The metastatic tumor in 1 reported case contained both epithelial and myoepithelial components and showed osseous or squamous metaplasia.6 Adenomyoepitheliomas exhibit a characteristic multinodular growth pattern with surrounding satellite nodules, features that contribute to local recurrence even in the more common benign adenomyoepithelial tumors owing to incomplete excision of the tumor. Immunohistochemistry is very useful in confirming the diagnosis. The epithelial elements stain with antibodies to cytokeratins and carcinoembryonic antigen. The myoepithelial cells stain with S100 and actin. More recently, C10 and p63 have been used as reliable markers of myoepithelial phenotype.7
References
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