It is well known that breast and salivary gland tissues share embryologic similarities [2
]. Similar to the salivary glands, the breast has modified sweat or apocrine glands, and some tumors arising in the breast are subject to development of salivary type tumors, such as pleomorphic adenoma, adenoid cystic carcinoma, adenomyoepithelioma, and ACC. Matoso et al. [2
] emphasized that breast tumors with salivary gland differentiation originate from a malignant transformation of terminal duct-lobular units with metaplastic changes. Furthermore, the immunohistochemical profile of the tumor reported herein was identical to that of salivary ACC [3
]. The significance of acinar cell differentiation in breast carcinomas is not clear. Lysozyme can be detected in mammary epithelium during lactation and lactating lobules share a similar immunophenotype with breast ACC [3
Previous reports have shown that the pathogenesis of ACC is related to MGA or secretory carcinoma (SC) [3
]. However, these reports noted no relationship between MGA or SC and ACC based on a lack of ETV6 rearrangement in ACC [6
]. Therefore, ACC is a distinct entity other than one variant or a related lesion [5
Peintinger et al. [7
] described the differential points of MGA, pointing out that ACC of the breast has a microglandular growth pattern, luminal eosinophilic colloid-like secretory materials, and diffuse and intense positive immunoreactivity for the S-100 protein. These features are similar to carcinoma arising in MGA. However, ACC shows immunoreactivity for EMA, lysozyme, amylase, and α-1-antichymotrypsin. While the glands in MGA are surrounded by a basal lamina, the neoplastic glands of ACC do not possess a basal lamina.
Microscopically, ACC of the breast reveals two morphologically distinct cell populations focally merging into one another [3
]. The present tumor showed a diffuse infiltrative growth pattern with small acinar or glandular structures mixed with solid nests (). The solid nests, commonly observed in in situ
and invasive ductal carcinoma, were focally recognized in the present case. These large solid tumor cell nests showed central comedo-like necrosis, which is reminiscent of ductal carcinoma in situ
(). This feature was initially interpreted as ordinary invasive ductal carcinoma. However, these cells were also cytologically and immunohistochemically closely similar to typical acinar cells. Both glandular and solid tumor cell populations were strongly positive for lysozyme (), α-1-antitrypsin, and EMA. The tumor cells were negative for GCDFP 15, estrogen receptor, progesterone receptor, and HER2/neu. Re-evaluation of the present case led to a diagnosis of pure ACC, due to the immunohistochemical results. And special stains in this case showed results similar to a previously described tumors [7
]. Damiani et al. [3
] studied acinar cell differentiation in salivary gland tumors and noted the presence of zymogen-type granules. Zymogen is only one of the components in ACC, as amylase, lysozyme and α-1-antichymotrypsin are also constituents of salivary gland acinar cells. They found amylase expression in all breast tumors studied, as well as in all studied cases of ACC of the parotid gland. However, amylase was negative in ordinary breast carcinomas.
In this case, electron microscopy demonstrated numerous variable sized electron dense zymogen granules in the cytoplasm, that were consistent with acinar cell granules. Intense immunohistochemical expression of lysozyme and α-1-antitrypsin combined with ultrastructural findings of numerous zymogen granules confirmed the diagnosis of ACC of the breast.
Damiani et al. [3
] described six patients with ACC of the breast. All patients were 35-80 years (mean-age, 56 years). The tumor size ranged from 2 to 5 cm. All patients were treated with surgery. Axillary dissection was performed in three cases, and lymph node metastases were found in two. Of the six patients, one was alive and well after 5 years, three were alive and well after 1 year, one had a recurrence after 4 years, and one was lost to follow-up. These cases demonstrate that primary ACC of the breast can be associated with a poor prognosis, particularly when the tumor is high grade with additional adverse prognostic features. The present case was a high grade invasive solid tumor with a high mitotic count for small limited foci. Therefore, the prognosis of this case might be unfavorable. Peintinger et al. [7
] suggested that ACC of the breast belongs to a group of clinically low-grade malignant tumors, even with some unfavorable prognostic parameters such as high mitotic activity and steroid hormone receptor negativity.
In summary, this case was histologically, immunohistochemically, and ultrastructurally typical of pure ACC of the breast.